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1.	Aglago, Elom K., et al. (author) Folate intake and colorectal cancer risk according to genetic subtypes defined by targeted tumor sequencing 2024 In: American Journal of Clinical Nutrition. - : Elsevier. - 0002-9165 .- 1938-3207. Journal article (peer-reviewed)abstract Background: Folate is involved in multiple genetic, epigenetic, and metabolic processes, and inadequate folate intake has been associated with an increased risk of cancer.Objective: We examined whether folate intake is differentially associated with colorectal cancer (CRC) risk according to somatic mutations in genes linked to CRC using targeted sequencing.Design: Participants within 2 large CRC consortia with available information on dietary folate, supplemental folic acid, and total folate intake were included. Colorectal tumor samples from cases were sequenced for the presence of nonsilent mutations in 105 genes and 6 signaling pathways (IGF2/PI3K, MMR, RTK/RAS, TGF-β, WNT, and TP53/ATM). Multinomial logistic regression models were analyzed comparing mutated/nonmutated CRC cases to controls to compute multivariable-adjusted odds ratios (ORs) with 95% confidence interval (CI). Heterogeneity of associations of mutated compared with nonmutated CRC cases was tested in case-only analyses using logistic regression. Analyses were performed separately in hypermutated and nonhypermutated tumors, because they exhibit different clinical behaviors.Results: We included 4339 CRC cases (702 hypermutated tumors, 16.2%) and 11,767 controls. Total folate intake was inversely associated with CRC risk (OR = 0.93; 95% CI: 0.90, 0.96). Among hypermutated tumors, 12 genes (AXIN2, B2M, BCOR, CHD1, DOCK3, FBLN2, MAP3K21, POLD1, RYR1, TET2, UTP20, and ZNF521) showed nominal statistical significance (P < 0.05) for heterogeneity by mutation status, but none remained significant after multiple testing correction. Among these genetic subtypes, the associations between folate variables and CRC were mostly inverse or toward the null, except for tumors mutated for DOCK3 (supplemental folic acid), CHD1 (total folate), and ZNF521 (dietary folate) that showed positive associations. We did not observe differential associations in analyses among nonhypermutated tumors, or according to the signaling pathways.Conclusions: Folate intake was not differentially associated with CRC risk according to mutations in the genes explored. The nominally significant differential mutation effects observed in a few genes warrants further investigation.
2.	Bolstad, Courtney J, et al. (author) Nightmare frequency is a risk factor for suicidal ideation during the COVID-19 pandemic. 2024 In: Journal of Sleep Research. - : WILEY. - 0962-1105 .- 1365-2869. ; , s. e14165- Journal article (peer-reviewed)abstract The association between nightmare frequency (NMF) and suicidal ideation (SI) is well known, yet the impact of the COVID-19 pandemic on this relation is inconsistent. This study aimed to investigate changes in NMF, SI, and their association during the COVID-19 pandemic. Data were collected in 16 countries using a harmonised questionnaire. The sample included 9328 individuals (4848 women; age M[SD] = 46.85 [17.75] years), and 17.60% reported previous COVID-19. Overall, SI was significantly 2% lower during the pandemic vs. before, and this was consistent across genders and ages. Most countries/regions demonstrated decreases in SI during this pandemic, with Austria (-9.57%), Sweden (-6.18%), and Bulgaria (-5.14%) exhibiting significant declines in SI, but Italy (1.45%) and Portugal (2.45%) demonstrated non-significant increases. Suicidal ideation was more common in participants with long-COVID (21.10%) vs. short-COVID (12.40%), though SI did not vary by COVID-19 history. Nightmare frequency increased by 4.50% during the pandemic and was significantly higher in those with previous COVID-19 (14.50% vs. 10.70%), during infection (23.00% vs. 8.10%), and in those with long-COVID (18.00% vs. 8.50%). The relation between NMF and SI was not significantly stronger during the pandemic than prior (rs = 0.18 vs. 0.14; z = 2.80). Frequent nightmares during the pandemic increased the likelihood of reporting SI (OR = 1.57, 95% CI 1.20-2.05), while frequent dream recall during the pandemic served a protective effect (OR = 0.74, 95% CI 0.59-0.94). These findings have important implications for identifying those at risk of suicide and may offer a potential pathway for suicide prevention.
3.	Brauer, M, et al. (author) Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021 2024 In: Lancet (London, England). - : Elsevier B.V.. - 1474-547X .- 0140-6736. ; 403:10440, s. 2162-2203 Journal article (peer-reviewed)
4.	Chen, YL, et al. (author) Super-enhancer-driven IRF2BP2 enhances ALK activity and promotes neuroblastoma cell proliferation 2024 In: Neuro-oncology. - 1523-5866. Journal article (peer-reviewed)
5.	Chen, Zhishan, et al. (author) Fine-mapping analysis including over 254 000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes 2024 In: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1 Journal article (peer-reviewed)abstract Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.
6.	Desai, Trishna A., et al. (author) Identifying proteomic risk factors for overall, aggressive, and early onset prostate cancer using Mendelian Randomisation and tumour spatial transcriptomics 2024 In: EBioMedicine. - : Elsevier. - 2352-3964. ; 105 Journal article (peer-reviewed)abstract Background Understanding the role of circulating proteins in prostate cancer risk can reveal key biological pathways and identify novel targets for cancer prevention. Methods We investigated the association of 2002 genetically predicted circulating protein levels with risk of prostate cancer overall, and of aggressive and early onset disease, using cis- pQTL Mendelian randomisation (MR) and colocalisation. Findings for proteins with support from both MR, after correction for multiple -testing, and colocalisation were replicated using two independent cancer GWAS, one of European and one of African ancestry. Proteins with evidence of prostate -speci fi c tissue expression were additionally investigated using spatial transcriptomic data in prostate tumour tissue to assess their role in tumour aggressiveness. Finally, we mapped risk proteins to drug and ongoing clinical trials targets. Findings We identi fi ed 20 proteins genetically linked to prostate cancer risk (14 for overall [8 speci fi c], 7 for aggressive [3 speci fi c], and 8 for early onset disease [2 speci fi c]), of which the majority replicated where data were available. Among these were proteins associated with aggressive disease, such as PPA2 [Odds Ratio (OR) per 1 SD increment = 2.13, 95% CI: 1.54 - 2.93], PYY [OR = 1.87, 95% CI: 1.43 - 2.44] and PRSS3 [OR = 0.80, 95% CI: 0.73 - 0.89], and those associated with early onset disease, including EHPB1 [OR = 2.89, 95% CI: 1.99 - 4.21], POGLUT3 [OR = 0.76, 95% CI: 0.67 - 0.86] and TPM3 [OR = 0.47, 95% CI: 0.34 - 0.64]. We con fi rmed an inverse association of MSMB with prostate cancer overall [OR = 0.81, 95% CI: 0.80 - 0.82], and also found an inverse association with both aggressive [OR = 0.84, 95% CI: 0.82 - 0.86] and early onset disease [OR = 0.71, 95% CI: 0.68 - 0.74]. Using spatial transcriptomics data, we identi fi ed MSMB as the genome-wide top -most predictive gene to distinguish benign regions from high grade cancer regions that comparatively had fi ve -fold lower MSMB expression. Additionally, ten proteins that were associated with prostate cancer risk also mapped to existing therapeutic interventions. Interpretation Our fi ndings emphasise the importance of proteomics for improving our understanding of prostate cancer aetiology and of opportunities for novel therapeutic interventions. Additionally, we demonstrate the added bene fi t of in-depth functional analyses to triangulate the role of risk proteins in the clinical aggressiveness of prostate tumours. Using these integrated methods, we identify a subset of risk proteins associated with aggressive and early onset disease as priorities for investigation for the future prevention and treatment of prostate cancer.
7.	Korman, Maria, et al. (author) Estimation bias and agreement limits between two common self-report methods of habitual sleep duration in epidemiological surveys 2024 In: Scientific Reports. - : NATURE PORTFOLIO. - 2045-2322. ; 14:1 Journal article (peer-reviewed)abstract Accurate measurement of habitual sleep duration (HSD) is crucial for understanding the relationship between sleep and health. This study aimed to assess the bias and agreement limits between two commonly used short HSD self-report methods, considering sleep quality (SQ) and social jetlag (SJL) as potential predictors of bias. Data from 10,268 participants in the International COVID Sleep Study-II (ICOSS-II) were used. Method-Self and Method-MCTQ were compared. Method-Self involved a single question about average nightly sleep duration (HSDself), while Method-MCTQ estimated HSD from reported sleep times on workdays (HSDMCTQwork) and free days (HSDMCTQfree). Sleep quality was evaluated using a Likert scale and the Insomnia Severity Index (ISI) to explore its influence on estimation bias. HSDself was on average 42.41 +/- 67.42 min lower than HSDMCTQweek, with an agreement range within +/- 133 min. The bias and agreement range between methods increased with poorer SQ. HSDMCTQwork showed less bias and better agreement with HSDself compared to HSDMCTQfree. Sleep duration irregularity was - 43.35 +/- 78.26 min on average. Subjective sleep quality predicted a significant proportion of variance in HSDself and estimation bias. The two methods showed very poor agreement and a significant systematic bias, both worsening with poorer SQ. Method-MCTQ considered sleep intervals without adjusting for SQ issues such as wakefulness after sleep onset but accounted for sleep irregularity and sleeping in on free days, while Method-Self reflected respondents' interpretation of their sleep, focusing on their sleep on workdays. Including an SQ-related question in surveys may help bidirectionally adjust the possible bias and enhance the accuracy of sleep-health studies.
8.	Menushenkov, A. P., et al. (author) Direct evidence of real-space pairing in BaBiO3 2024 In: Physical Review Research. - : American Physical Society. - 2643-1564. ; 6:2 Journal article (peer-reviewed)abstract The parent compound BaBiO3 of bismuthate high-temperature superconductors (HTSCs) BaBi(Pb)O3 and Ba(K)BiO3 with perovskitelike structure exhibits unusual electronic and structural properties, which can be satisfactorily explained if we assume that all charge carriers are in the paired state. However, the prior experiments and the first-principle calculations only indirectly indicate the existence of paired charge carriers in BaBiO3. In this work, we report the direct evidence of initially paired electrons and holes in the upper antibonding Bi 6s-O 2p sigma* orbital of the neighboring octahedral complexes in the ground state of BaBiO3 using the time-resolved x-ray absorption spectroscopy (XAS) to monitor the electron dynamics after the femtosecond resonant 633 nm laser excitation. We observe strong changes in the oxygen K-edge XAS preedge region, defined by the Bi 6s-O 2p sigma* orbitals. We interpret them as a fast (<= 0.3 ps) breaking of charge carrier pairs and slower (0.3-0.8 ps) lattice rearrangement from the distorted monoclinic structure into the new metastable state with a cubic lattice, which persists at least up to 60 ps after the excitation. Analysis of the intermediate state at the fast excitation shows that the bond disproportionation and monoclinic distortion of BaBiO3 structure are energetically favorable due to the charge carrier pairing. Thus the compound BaBiO3 forms a new quantum state that we define as a local pair density wave. Taking into account a large number of similarities between bismuthate and cuprate high-temperature superconductors, we believe that our work will give a new impetus to understanding the nature of superconductivity in perovskite HTSCs.
9.	Pan, L, et al. (author) Single Cell Atlas: a single-cell multi-omics human cell encyclopedia 2024 In: Genome biology. - 1474-760X. ; 25:1, s. 104- Journal article (peer-reviewed)
10.	Papadimitriou, Nikos, et al. (author) Body size and risk of colorectal cancer molecular defined subtypes and pathways : mendelian randomization analyses 2024 In: EBioMedicine. - : Elsevier. - 2352-3964. ; 101 Journal article (peer-reviewed)abstract Background: Obesity has been positively associated with most molecular subtypes of colorectal cancer (CRC); however, the magnitude and the causality of these associations is uncertain.Methods: We used Mendelian randomization (MR) to examine potential causal relationships between body size traits (body mass index [BMI], waist circumference, and body fat percentage) with risks of Jass classification types and individual subtypes of CRC (microsatellite instability [MSI] status, CpG island methylator phenotype [CIMP] status, BRAF and KRAS mutations). Summary data on tumour markers were obtained from two genetic consortia (CCFR, GECCO).Findings: A 1-standard deviation (SD:5.1 kg/m2) increment in BMI levels was found to increase risks of Jass type 1MSI-high,CIMP-high,BRAF-mutated,KRAS-wildtype (odds ratio [OR]: 2.14, 95% confidence interval [CI]: 1.46, 3.13; p-value = 9 × 10−5) and Jass type 2non-MSI-high,CIMP-high,BRAF-mutated,KRAS-wildtype CRC (OR: 2.20, 95% CI: 1.26, 3.86; p-value = 0.005). The magnitude of these associations was stronger compared with Jass type 4non-MSI-high,CIMP-low/negative,BRAF-wildtype,KRAS-wildtype CRC (p-differences: 0.03 and 0.04, respectively). A 1-SD (SD:13.4 cm) increment in waist circumference increased risk of Jass type 3non-MSI-high,CIMP-low/negative,BRAF-wildtype,KRAS-mutated (OR 1.73, 95% CI: 1.34, 2.25; p-value = 9 × 10−5) that was stronger compared with Jass type 4 CRC (p-difference: 0.03). A higher body fat percentage (SD:8.5%) increased risk of Jass type 1 CRC (OR: 2.59, 95% CI: 1.49, 4.48; p-value = 0.001), which was greater than Jass type 4 CRC (p-difference: 0.03).Interpretation: Body size was more strongly linked to the serrated (Jass types 1 and 2) and alternate (Jass type 3) pathways of colorectal carcinogenesis in comparison to the traditional pathway (Jass type 4).Funding: Cancer Research UK, National Institute for Health Research, Medical Research Council, National Institutes of Health, National Cancer Institute, American Institute for Cancer Research, Brigham and Women's Hospital, Prevent Cancer Foundation, Victorian Cancer Agency, Swedish Research Council, Swedish Cancer Society, Region Västerbotten, Knut and Alice Wallenberg Foundation, Lion's Cancer Research Foundation, Insamlingsstiftelsen, Umeå University. Full funding details are provided in acknowledgements.
11.	Potapov, Anton M., et al. (author) Global fine-resolution data on springtail abundance and community structure 2024 In: Scientific Data. - : Nature Publishing Group. - 2052-4463. ; 11:1 Journal article (peer-reviewed)abstract Springtails (Collembola) inhabit soils from the Arctic to the Antarctic and comprise an estimated ~32% of all terrestrial arthropods on Earth. Here, we present a global, spatially-explicit database on springtail communities that includes 249,912 occurrences from 44,999 samples and 2,990 sites. These data are mainly raw sample-level records at the species level collected predominantly from private archives of the authors that were quality-controlled and taxonomically-standardised. Despite covering all continents, most of the sample-level data come from the European continent (82.5% of all samples) and represent four habitats: woodlands (57.4%), grasslands (14.0%), agrosystems (13.7%) and scrublands (9.0%). We included sampling by soil layers, and across seasons and years, representing temporal and spatial within-site variation in springtail communities. We also provided data use and sharing guidelines and R code to facilitate the use of the database by other researchers. This data paper describes a static version of the database at the publication date, but the database will be further expanded to include underrepresented regions and linked with trait data.
12.	Song, Jiao-Jiao, et al. (author) Relocalization of uranium 5f electrons in the antiferromagnetic heavy-fermion superconductor UPd2Al3 : Insights from angle-resolved photoemission spectroscopy 2024 In: Physical Review B. - : American Physical Society. - 2469-9950 .- 2469-9969. ; 109:20 Journal article (peer-reviewed)abstract We investigate the antiferromagnetic heavy fermion superconductor UPd2⁢Al3, employing angle-resolved photoemission spectroscopy to unravel the complex electronic structure of its U 5⁢? electrons. We observe unexpected characteristics that challenge the conventional temperature-dependent behavior of heavy fermion systems, revealing unexpected characteristics. At temperatures above the anticipated coherence temperature (?*), we observe itinerant U 5⁢? electrons at temperatures higher than previously postulated. Additionally, a previously unidentified dispersionless band emerges around 600 meV below the Fermi energy, potentially linked to spin-orbit splitting within the U 5⁢? states. Hybridization between the 5⁢? electrons and conduction band was observed with an energy dispersion of 10 meV at low temperatures, suggesting that U 5⁢? electrons near and at the Fermi surface have an itinerant nature. Temperature-dependent 5⁢?−5⁢? resonance spectra reveal that the 5⁢? electron spectrum weight increases with lowering temperature and begins to decrease at temperatures significantly higher than the Néel temperature (??). We further show that the competition between the Kondo effect and Ruderman-Kittel-Kasuya-Yosida (RKKY) interactions may be responsible for the relocalization of 5⁢? electrons, making relocalization a precursor to the establishment of magnetic order at lower temperatures. Our experiments also provide evidence that 5⁢? electrons with the same orbital are involved in both the Kondo effect and RKKY interactions, suggesting that the two coexist at lower temperatures.
13.	Sun, YW, et al. (author) Overall and cause-specific mortality among patients diagnosed with gastric precancerous lesions in Sweden between 1979 and 2014: an observational cohort study 2024 In: BMC medicine. - 1741-7015. ; 22:1, s. 333- Journal article (peer-reviewed)
14.	Thomas, Claire E., et al. (author) Epidemiologic factors in relation to colorectal cancer risk and survival by genotoxic colibactin mutational signature 2024 In: Cancer Epidemiology, Biomarkers and Prevention. - : American Association For Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 33:4, s. 534-546 Journal article (peer-reviewed)abstract BACKGROUND: The genotoxin colibactin causes a tumor single-base substitution (SBS) mutational signature, SBS88. It is unknown whether epidemiologic factors' association with colorectal cancer risk and survival differs by SBS88.METHODS: Within the Genetic Epidemiology of Colorectal Cancer Consortium and Colon Cancer Family Registry, we measured SBS88 in 4,308 microsatellite stable/microsatellite instability low tumors. Associations of epidemiologic factors with colorectal cancer risk by SBS88 were assessed using multinomial regression (N = 4,308 cases, 14,192 controls; cohort-only cases N = 1,911), and with colorectal cancer-specific survival using Cox proportional hazards regression (N = 3,465 cases).RESULTS: 392 (9%) tumors were SBS88 positive. Among all cases, the highest quartile of fruit intake was associated with lower risk of SBS88-positive colorectal cancer than SBS88-negative colorectal cancer [odds ratio (OR) = 0.53, 95% confidence interval (CI) 0.37-0.76; OR = 0.75, 95% CI 0.66-0.85, respectively, Pheterogeneity = 0.047]. Among cohort studies, associations of body mass index (BMI), alcohol, and fruit intake with colorectal cancer risk differed by SBS88. BMI ≥30 kg/m2 was associated with worse colorectal cancer-specific survival among those SBS88-positive [hazard ratio (HR) = 3.40, 95% CI 1.47-7.84], but not among those SBS88-negative (HR = 0.97, 95% CI 0.78-1.21, Pheterogeneity = 0.066).CONCLUSIONS: Most epidemiologic factors did not differ by SBS88 for colorectal cancer risk or survival. Higher BMI may be associated with worse colorectal cancer-specific survival among those SBS88-positive; however, validation is needed in samples with whole-genome or whole-exome sequencing available.IMPACT: This study highlights the importance of identification of tumor phenotypes related to colorectal cancer and understanding potential heterogeneity for risk and survival.
15.	van Weelderen, Romy E., et al. (author) Optimized cytogenetic risk-group stratification of KMT2A-rearranged pediatric acute myeloid leukemia 2024 In: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 8:12, s. 3200-3213 Journal article (peer-reviewed)abstract A comprehensive international consensus on the cytogenetic risk-group stratification of KMT2A-rearranged (KMT2A-r) pediatric acute myeloid leukemia (AML) is lacking. This retrospective (2005-2016) International Berlin-Frankfurt-Münster Study Group study on 1256 children with KMT2A-r AML aims to validate the prognostic value of established recurring KMT2A fusions and additional cytogenetic aberrations (ACAs) and to define additional, recurring KMT2A fusions and ACAs, evaluating their prognostic relevance. Compared with our previous study, 3 additional, recurring KMT2A-r groups were defined: Xq24/KMT2A::SEPT6, 1p32/KMT2A::EPS15, and 17q12/t(11;17)(q23;q12). Across 13 KMT2A-r groups, 5-year event-free survival probabilities varied significantly (21.8%-76.2%; P < .01). ACAs occurred in 46.8% of 1200 patients with complete karyotypes, correlating with inferior overall survival (56.8% vs 67.9%; P < .01). Multivariable analyses confirmed independent associations of 4q21/KMT2A::AFF1, 6q27/KMT2A::AFDN, 10p12/KMT2A::MLLT10, 10p11.2/KMT2A::ABI1, and 19p13.3/KMT2A::MLLT1 with adverse outcomes, but not those of 1q21/KMT2A::MLLT11 and trisomy 19 with favorable and adverse outcomes, respectively. Newly identified ACAs with independent adverse prognoses were monosomy 10, trisomies 1, 6, 16, and X, add(12p), and del(9q). Among patients with 9p22/KMT2A::MLLT3, the independent association of French-American-British-type M5 with favorable outcomes was confirmed, and those of trisomy 6 and measurable residual disease at end of induction with adverse outcomes were identified. We provide evidence to incorporate 5 adverse-risk KMT2A fusions into the cytogenetic risk-group stratification of KMT2A-r pediatric AML, to revise the favorable-risk classification of 1q21/KMT2A::MLLT11 to intermediate risk, and to refine the risk-stratification of 9p22/KMT2A::MLLT3 AML. Future studies should validate the associations between the newly identified ACAs and outcomes and unravel the underlying biological pathogenesis of KMT2A fusions and ACAs.
16.	Vollset, SE, et al. (author) Burden of disease scenarios for 204 countries and territories, 2022-2050: a forecasting analysis for the Global Burden of Disease Study 2021 2024 In: Lancet (London, England). - 1474-547X .- 0140-6736. ; 403:10440, s. 2204-2256 Journal article (peer-reviewed)
17.	Wang, Fang, et al. (author) Emerging contaminants: A One Health perspective 2024 In: Innovation. - 2666-6758. ; 5 Research review (peer-reviewed)abstract Environmental pollution is escalating due to rapid global development that often prioritizes human needs over planetary health. Despite global efforts to mitigate legacy pollutants, the continuous introduction of new substances remains a major threat to both people and the planet. In response, global initiatives are focusing on risk assessment and regulation of emerging contaminants, as demonstrated by the ongoing efforts to establish the UN's Intergovernmental Science-Policy Panel on Chemicals, Waste, and Pollution Prevention. This review identifies the sources and impacts of emerging contaminants on planetary health, emphasizing the importance of adopting a One Health approach. Strategies for monitoring and addressing these pollutants are discussed, underscoring the need for robust and socially equitable environmental policies at both regional and international levels. Urgent actions are needed to transition toward sustainable pollution management practices to safeguard our planet for future generations.
18.	Yin, Anyue, et al. (author) Quantitative modeling of tumor dynamics and development of drug resistance in non-small cell lung cancer patients treated with erlotinib 2024 In: CPT. - : John Wiley & Sons. - 2163-8306. ; 13:4, s. 612-623 Journal article (peer-reviewed)abstract Insight into the development of treatment resistance can support the optimization of anticancer treatments. This study aims to characterize the tumor dynamics and development of drug resistance in patients with non-small cell lung cancer treated with erlotinib, and investigate the relationship between baseline circulating tumor DNA (ctDNA) data and tumor dynamics. Data obtained for the analysis included (1) intensively sampled erlotinib concentrations from 29 patients from two previous pharmacokinetic (PK) studies, and (2) tumor sizes, ctDNA measurements, and sparsely sampled erlotinib concentrations from 18 patients from the START-TKI study. A two-compartment population PK model was first developed which well-described the PK data. The PK model was subsequently applied to investigate the exposure-tumor dynamics relationship. To characterize the tumor dynamics, models accounting for intra-tumor heterogeneity and acquired resistance with or without primary resistance were investigated. Eventually, the model assumed acquired resistance only resulted in an adequate fit. Additionally, models with or without exposure-dependent treatment effect were explored, and no significant exposure-response relationship for erlotinib was identified within the observed exposure range. Subsequently, the correlation of baseline ctDNA data on EGFR and TP53 variants with tumor dynamics' parameters was explored. The analysis indicated that higher baseline plasma EGFR mutation levels correlated with increased tumor growth rates, and the inclusion of ctDNA measurements improved model fit. This result suggests that quantitative ctDNA measurements at baseline have the potential to be a predictor of anticancer treatment response. The developed model can potentially be applied to design optimal treatment regimens that better overcome resistance.
19.	Yu, Hao, et al. (author) Association of genetic variation in COL11A1 with adolescent idiopathic scoliosis 2024 In: eLIFE. - : eLife Sciences Publications, Ltd. - 2050-084X. ; 12 Journal article (peer-reviewed)abstract Adolescent idiopathic scoliosis (AIS) is a common and progressive spinal deformity in children that exhibits striking sexual dimorphism, with girls at more than fivefold greater risk of severe disease compared to boys. Despite its medical impact, the molecular mechanisms that drive AIS are largely unknown. We previously defined a female-specific AIS genetic risk locus in an enhancer near the PAX1 gene. Here, we sought to define the roles of PAX1 and newly identified AIS-associated genes in the developmental mechanism of AIS. In a genetic study of 10,519 individuals with AIS and 93,238 unaffected controls, significant association was identified with a variant in COL11A1 encoding collagen (α1) XI (rs3753841; NM_080629.2_c.4004C>T; p.(Pro1335Leu); p=7.07E-11, OR = 1.118). Using CRISPR mutagenesis we generated Pax1 knockout mice (Pax1-/-). In postnatal spines we found that PAX1 and collagen (α1) XI protein both localize within the intervertebral disc-vertebral junction region encompassing the growth plate, with less collagen (α1) XI detected in Pax1-/- spines compared to wild-type. By genetic targeting we found that wild-type Col11a1 expression in costal chondrocytes suppresses expression of Pax1 and of Mmp3, encoding the matrix metalloproteinase 3 enzyme implicated in matrix remodeling. However, the latter suppression was abrogated in the presence of the AIS-associated COL11A1P1335L mutant. Further, we found that either knockdown of the estrogen receptor gene Esr2 or tamoxifen treatment significantly altered Col11a1 and Mmp3 expression in chondrocytes. We propose a new molecular model of AIS pathogenesis wherein genetic variation and estrogen signaling increase disease susceptibility by altering a PAX1-COL11a1-MMP3 signaling axis in spinal chondrocytes.
20.	Zhang, Jingqi, et al. (author) Ultrauniform, strong, and ductile 3D-printed titanium alloy through bifunctional alloy design 2024 In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 383:6683, s. 639-645 Journal article (peer-reviewed)abstract Coarse columnar grains and heterogeneously distributed phases commonly form in metallic alloys produced by three-dimensional (3D) printing and are often considered undesirable because they can impart nonuniform and inferior mechanical properties. We demonstrate a design strategy to unlock consistent and enhanced properties directly from 3D printing. Using Ti−5Al−5Mo−5V−3Cr as a model alloy, we show that adding molybdenum (Mo) nanoparticles promotes grain refinement during solidification and suppresses the formation of phase heterogeneities during solid-state thermal cycling. The microstructural change because of the bifunctional additive results in uniform mechanical properties and simultaneous enhancement of both strength and ductility. We demonstrate how this alloy can be modified by a single component to address unfavorable microstructures, providing a pathway to achieve desirable mechanical characteristics directly from 3D printing.
21.	Zhong, Yi, et al. (author) Orbital Controls on North Pacific Dust Flux During the Late Quaternary 2024 In: Geophysical Research Letters. - 0094-8276. ; 51:4 Journal article (peer-reviewed)abstract Airborne mineral dust is sensitive to climatic changes, but its response to orbital forcing is still not fully understood. Here, we present a reconstruction of dust input to the Subarctic Pacific Ocean covering the past 190 kyr. The dust composition record is indicative of source moisture conditions, which were dominated by precessional variations. In contrast, the dust flux record is dominated by obliquity variations and displays an out-of-phase relationship with a dust record from the mid-latitude North Pacific Ocean. Climate model simulations suggest precession likely drove changes in the aridity and extent of dust source regions. Additionally, the obliquity variations in dust flux can be explained by meridional shifts in the North Pacific westerly jet, driven by changes in the meridional atmospheric temperature gradient. Overall, our findings suggest that North Pacific dust input was primarily modulated by orbital-controlled source aridity and the strength and position of the westerly winds.
22.	Alaggio, R, et al. (author) Correction: "The 5th edition of The World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms" Leukemia. 2022 Jul;36(7):1720-1748 2023 In: Leukemia. - 1476-5551. ; 37:9, s. 1944-1951 Journal article (other academic/artistic)
23.	Argirion, Ilona, et al. (author) Comparative Analysis of the Humoral Immune Response to the EBV Proteome across EBV-Related Malignancies 2023 In: Cancer Epidemiology, Biomarkers and Prevention. - : American Association For Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 32:5, s. 687-696 Journal article (peer-reviewed)abstract Background: Epstein-Barr virus (EBV) is linked to multiple cancers, including classical Hodgkin lymphoma (cHL), endemic Burkitt lymphoma (eBL), nasopharyngeal carcinoma (NPC), and extranodal natural killer/T-cell lymphoma (NKTCL).Methods: Anti-EBV IgG and IgA antibody responses target-ing 202 sequences from 86 EBV proteins were measured using the same EBV whole proteome array across four case-control studies investigating EBV-positive cHL, eBL, NPC, and NKTCL (407 cases/620 controls). We grouped EBV-targeted antibodies into pathways by immunoglobulin type (IgA and IgG) and life-cycle stage (latent, immediate early lytic, early lytic, late lytic, and glycoprotein) and evaluated their associ-ation with each cancer type. In an additional analysis, we focused on the subset of 46 individual antibodies repre-senting the top candidates for each cancer and compared their associations across the four cancer types using multivariable linear regression models.Results: IgA antibody responses targeting all EBV life-cycle stages were associated with NPC but limited to anti-early lytic stage for cHL. NPC and eBL were associated with IgG antibodies across the viral life cycle; cHL with antibodies in the early lytic, late lytic and glyco-protein stages; and NKTCL with antibodies in the latent, immediate early lytic and early lytic phases. EBNA3A, BBLF1, BDLF4, and BLRF2 IgG antibodies were associated with all cancer types.Conclusions: Our observed similarities and differences across four EBV-associated cancers may inform EBV-related oncogenesis.Impact: Understanding the comparative humoral immune response across EBV-related cancers may aid in identifying shared etiologic roles of EBV proteins and inform unique pathogenic processes for each cancer.
24.	Ayeni, O. R., et al. (author) Clinical and Radiographic Criteria Define "Acceptable" Surgical Correction of Hip Femoroacetabular Impingement Syndrome as Well as Postoperative Complications: An International Modified Delphi Study 2023 In: Arthroscopy-the Journal of Arthroscopic and Related Surgery. - : Elsevier BV. - 0749-8063. ; 39:5, s. 1198-1210 Journal article (peer-reviewed)abstract Objectives: To develop recommendations for clinical and radiographic criteria to help define the "acceptable" surgical correction of femoroacetabular impingement syndrome (FAIS) and identify/define complications postoperatively. Methods: A 3-phase modified Delphi study was conducted involving a case-based survey; a Likert/multiple choice-based survey concerning radiographic and physical examination characteristics to help define FAIS correction, as well as the prevalence and definition of potential postoperative complications; and 2 consensus meetings. Results: Of the 75 experts invited, 54 completed the Phase I survey, 50 completed the Phase II survey (72% and 67% response rate), and 50 participated in the Phase III consensus meetings. For both typical and atypical (complex) cases, there was consensus that fluoroscopy with multiple views and dynamic hip assessment should be used intraoperatively (96% and 100%, respectively). For typical FAIS cases, the Expert Panel agreed that Dunn lateral and anteroposterior radiographs were the most important radiographs to evaluate the hip postoperatively (88%, consensus). When asked about evaluating the correction of cam impingement postoperatively, 87% voted that they use subjective evaluation of the "sphericity" of the femoral head. In the case of focal and global pincer-type FAIS, there was consensus that the reduction or elimination of the crossover sign (84%) and lateral center-edge angle (91%) were important to inform the extent of the FAIS correction. There was consensus for recommending further investigation at 6 months postoperatively if hip pain had increased/plateaued (92% agreed); that additional investigation and treatment should occur between 6 and 12 months (90% agreed); and that a reoperation may be recommended at 12 months or later following this investigation period (89% agreed). Conclusions: This consensus project identified the importance of using fluoroscopy and dynamic hip assessment intraoperatively; Dunn lateral and anteroposterior view radiographs postoperatively; evaluating the "sphericity" of the femoral head for cam-type correction and the use of dynamic hip assessment; reducing/eliminating the crossover sign for focal pincertype FAIS; evaluating the lateral center-edge angle for global pincer-type FAIS; and avoiding overcorrection of pincer-type FAIS. In cases in which postoperative hip pain increased/plateaued, further investigation and treatment is warranted between 6 and 12 months, and a reoperation may be recommended at a minimum of 12 months depending on the cause of the hip pain. Clinical Relevance: Hip arthroscopy surgeons have yet to reach a firm agreement on what constitutes an "acceptable" or "good" surgery radiographically and how they can achieve desired clinical outcomes. Although this was a comprehensive effort, more study is needed to determine therapeutic thresholds that can be universally applied.
25.	Boakye, K., et al. (author) Urbanization and physical activity in the global Prospective Urban and Rural Epidemiology study 2023 In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 13:1 Journal article (peer-reviewed)abstract Urbanization may influence physical activity (PA) levels, although little evidence is available for low- and middle- income countries where urbanization is occurring fastest. We evaluated associations between urbanization and total PA, as well as work-, leisure-, home-, and transport-specific PA, for 138,206 adults living in 698 communities across 22 countries within the Prospective Urban and Rural Epidemiology (PURE) study. The 1-week long-form International PA Questionnaire was administered at baseline (2003-2015). We used satellite-derived population density and impervious surface area estimates to quantify baseline urbanization levels for study communities, as well as change measures for 5- and 10-years prior to PA surveys. We used generalized linear mixed effects models to examine associations between urbanization measures and PA levels, controlling for individual, household and community factors. Higher community baseline levels of population density (- 12.4% per IQR, 95% CI - 16.0, - 8.7) and impervious surface area (- 29.2% per IQR, 95% CI - 37.5, - 19.7), as well as the rate of change in 5-year population density (- 17.2% per IQR, 95% CI - 25.7, - 7.7), were associated with lower total PA levels. Important differences in the associations between urbanization and PA were observed between PA domains, country-income levels, urban/rural status, and sex. These findings provide new information on the complex associations between urbanization and PA.
26.	Broadaway, K Alaine, et al. (author) Loci for insulin processing and secretion provide insight into type 2 diabetes risk. 2023 In: American Journal of Human Genetics. - : Elsevier. - 0002-9297 .- 1537-6605. ; 110:2, s. 284-299 Journal article (peer-reviewed)abstract Insulin secretion is critical for glucose homeostasis, and increased levels of the precursor proinsulin relative to insulin indicate pancreatic islet beta-cell stress and insufficient insulin secretory capacity in the setting of insulin resistance. We conducted meta-analyses of genome-wide association results for fasting proinsulin from 16 European-ancestry studies in 45,861 individuals. We found 36 independent signals at 30 loci (p value < 5 × 10-8), which validated 12 previously reported loci for proinsulin and ten additional loci previously identified for another glycemic trait. Half of the alleles associated with higher proinsulin showed higher rather than lower effects on glucose levels, corresponding to different mechanisms. Proinsulin loci included genes that affect prohormone convertases, beta-cell dysfunction, vesicle trafficking, beta-cell transcriptional regulation, and lysosomes/autophagy processes. We colocalized 11 proinsulin signals with islet expression quantitative trait locus (eQTL) data, suggesting candidate genes, including ARSG, WIPI1, SLC7A14, and SIX3. The NKX6-3/ANK1 proinsulin signal colocalized with a T2D signal and an adipose ANK1 eQTL signal but not the islet NKX6-3 eQTL. Signals were enriched for islet enhancers, and we showed a plausible islet regulatory mechanism for the lead signal in the MADD locus. These results show how detailed genetic studies of an intermediate phenotype can elucidate mechanisms that may predispose one to disease.
27.	Bustamante, Mercedes, et al. (author) Ten new insights in climate science 2023 2023 In: Global Sustainability. - : CAMBRIDGE UNIV PRESS. - 2059-4798. ; 7 Research review (peer-reviewed)abstract Non-technical summary We identify a set of essential recent advances in climate change research with high policy relevance, across natural and social sciences: (1) looming inevitability and implications of overshooting the 1.5 degrees C warming limit, (2) urgent need for a rapid and managed fossil fuel phase-out, (3) challenges for scaling carbon dioxide removal, (4) uncertainties regarding the future contribution of natural carbon sinks, (5) intertwinedness of the crises of biodiversity loss and climate change, (6) compound events, (7) mountain glacier loss, (8) human immobility in the face of climate risks, (9) adaptation justice, and (10) just transitions in food systems.Technical summary The Intergovernmental Panel on Climate Change Assessment Reports provides the scientific foundation for international climate negotiations and constitutes an unmatched resource for researchers. However, the assessment cycles take multiple years. As a contribution to cross- and interdisciplinary understanding of climate change across diverse research communities, we have streamlined an annual process to identify and synthesize significant research advances. We collected input from experts on various fields using an online questionnaire and prioritized a set of 10 key research insights with high policy relevance. This year, we focus on: (1) the looming overshoot of the 1.5 degrees C warming limit, (2) the urgency of fossil fuel phase-out, (3) challenges to scale-up carbon dioxide removal, (4) uncertainties regarding future natural carbon sinks, (5) the need for joint governance of biodiversity loss and climate change, (6) advances in understanding compound events, (7) accelerated mountain glacier loss, (8) human immobility amidst climate risks, (9) adaptation justice, and (10) just transitions in food systems. We present a succinct account of these insights, reflect on their policy implications, and offer an integrated set of policy-relevant messages. This science synthesis and science communication effort is also the basis for a policy report contributing to elevate climate science every year in time for the United Nations Climate Change Conference.Social media summary We highlight recent and policy-relevant advances in climate change research - with input from more than 200 experts.
28.	Cai, W. L., et al. (author) Angular Dependent Auto-Oscillations by Spin-Transfer and Spin-Orbit Torques in Three-Terminal Magnetic Tunnel Junctions 2023 In: Ieee Electron Device Letters. - : Institute of Electrical and Electronics Engineers (IEEE). - 0741-3106 .- 1558-0563. ; 44:5, s. 861-864 Journal article (peer-reviewed)abstract Spintronic oscillators are promising candidates for neuromorphic computing due to their true miniaturization, non-linearity and synchronization properties. However, spin torque nano-oscillators are excited by current-induced spin-transfer torque which may cause high power consumption and reliability problems. Spin Hall nano-oscillators can realize higher energy efficiency, while their relatively low power emission limits their further applications. Here, we demonstrate three-terminal magnetic tunnel junction based spin torque nano-oscillators excited by the combination of spin-transfer and spin-orbit torques under different angle configurations. Thanks to the large spin Hall angle (-0.278) of W, the ratio between threshold current density of spin-transfer and spin-orbit torques for auto-oscillations can reach 0.6, indicating their high energy efficiency. Furthermore, we observe that the ratio has a sine function dependence on the angle between the spin-polarization directions of spin-transfer and spin-orbit torques. Our work could benefit the development of high-efficiency spintronic oscillators and their large network designs.
29.	Chang, Kuang Yu, et al. (author) Observational constraints reduce model spread but not uncertainty in global wetland methane emission estimates 2023 In: Global Change Biology. - 1354-1013. ; 29:15, s. 4298-4312 Journal article (peer-reviewed)abstract The recent rise in atmospheric methane (CH4) concentrations accelerates climate change and offsets mitigation efforts. Although wetlands are the largest natural CH4 source, estimates of global wetland CH4 emissions vary widely among approaches taken by bottom-up (BU) process-based biogeochemical models and top-down (TD) atmospheric inversion methods. Here, we integrate in situ measurements, multi-model ensembles, and a machine learning upscaling product into the International Land Model Benchmarking system to examine the relationship between wetland CH4 emission estimates and model performance. We find that using better-performing models identified by observational constraints reduces the spread of wetland CH4 emission estimates by 62% and 39% for BU- and TD-based approaches, respectively. However, global BU and TD CH4 emission estimate discrepancies increased by about 15% (from 31 to 36 TgCH4 year−1) when the top 20% models were used, although we consider this result moderately uncertain given the unevenly distributed global observations. Our analyses demonstrate that model performance ranking is subject to benchmark selection due to large inter-site variability, highlighting the importance of expanding coverage of benchmark sites to diverse environmental conditions. We encourage future development of wetland CH4 models to move beyond static benchmarking and focus on evaluating site-specific and ecosystem-specific variabilities inferred from observations.
30.	Cong, Lin, et al. (author) Mild cognitive impairment among rural-dwelling older adults in China : A community-based study 2023 In: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:1, s. 56-66 Journal article (peer-reviewed)abstract Background: Epidemiological studies of mild cognitive impairment (MCI) and subtypes of MCI have rarely focused on rural residents in China.Methods: This population-based study included 5068 participants (age >= 60 years) who were living in rural communities. We defined MCI, amnestic MCI (aMCI), and non-amnestic MCI (naMCI) following the Petersen's criteria that integrated neuropsychological assessments with in-person clinical evaluations.Results: The overall prevalence of MCI, aMCI, and naMCI was 26.48%, 22.30%, and 4.18%, respectively. The prevalence of MCI increased with age. The adjusted odds ratio (OR) of MCI was 0.71 (95% confidence interval [CI] 0.61 to 0.82) for primary school (vs. illiteracy), 0.30 (0.24 to 0.39) for middle school or above, 1.35 (1.09 to 1.67) for being farmers, 0.65 (0.54 to 0.78) for alcohol consumption, 1.43 (1.20 to 1.70) for stroke history, and 1.14 (0.95 to 1.36) for any apolipoprotein E (APOE) epsilon 4 allele (vs epsilon 3/epsilon 3).Conclusions: MCI affects over one-fourth of rural older adults in China. Overall MCI was associated with demographic factors, non-alcohol consumption, and stroke, but not with APOE genotype and cardiometabolic factors.
31.	Figiel, S., et al. (author) Spatial transcriptomic analysis of virtual prostate biopsy reveals confounding effect of heterogeneity on genomic signature scoring 2023 In: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 83 Journal article (other academic/artistic)
32.	Figiel, Sandy, et al. (author) Spatial transcriptomic analysis of virtual prostate biopsy reveals confounding effect of tissue heterogeneity on genomic signatures 2023 In: Molecular Cancer. - : Springer Nature. - 1476-4598. ; 22:1, s. 162- Journal article (other academic/artistic)abstract Genetic signatures have added a molecular dimension to prognostics and therapeutic decision-making. However, tumour heterogeneity in prostate cancer and current sampling methods could confound accurate assessment. Based on previously published spatial transcriptomic data from multifocal prostate cancer, we created virtual biopsy models that mimic conventional biopsy placement and core size. We then analysed the gene expression of different prognostic signatures (OncotypeDx®, Decipher®, Prostadiag®) using a step-wise approach with increasing resolution from pseudo-bulk analysis of the whole biopsy, to differentiation by tissue subtype (benign, stroma, tumour), followed by distinct tumour grade and finally clonal resolution. The gene expression profile of virtual tumour biopsies revealed clear differences between grade groups and tumour clones, compared to a benign control, which were not reflected in bulk analyses. This suggests that bulk analyses of whole biopsies or tumour-only areas, as used in clinical practice, may provide an inaccurate assessment of gene profiles. The type of tissue, the grade of the tumour and the clonal composition all influence the gene expression in a biopsy. Clinical decision making based on biopsy genomics should be made with caution while we await more precise targeting and cost-effective spatial analyses.
33.	Graham, SE, et al. (author) Author Correction: The power of genetic diversity in genome-wide association studies of lipids 2023 In: Nature. - 1476-4687. ; 618:7965, s. E19-E20 Journal article (other academic/artistic)
34.	Lensink, Marc F., et al. (author) Impact of AlphaFold on structure prediction of protein complexes: The CASP15-CAPRI experiment 2023 In: Proteins. - : WILEY. - 0887-3585 .- 1097-0134. Journal article (peer-reviewed)abstract We present the results for CAPRI Round 54, the 5th joint CASP-CAPRI protein assembly prediction challenge. The Round offered 37 targets, including 14 homodimers, 3 homo-trimers, 13 heterodimers including 3 antibody-antigen complexes, and 7 large assemblies. On average similar to 70 CASP and CAPRI predictor groups, including more than 20 automatics servers, submitted models for each target. A total of 21 941 models submitted by these groups and by 15 CAPRI scorer groups were evaluated using the CAPRI model quality measures and the DockQ score consolidating these measures. The prediction performance was quantified by a weighted score based on the number of models of acceptable quality or higher submitted by each group among their five best models. Results show substantial progress achieved across a significant fraction of the 60+ participating groups. High-quality models were produced for about 40% of the targets compared to 8% two years earlier. This remarkable improvement is due to the wide use of the AlphaFold2 and AlphaFold2-Multimer software and the confidence metrics they provide. Notably, expanded sampling of candidate solutions by manipulating these deep learning inference engines, enriching multiple sequence alignments, or integration of advanced modeling tools, enabled top performing groups to exceed the performance of a standard AlphaFold2-Multimer version used as a yard stick. This notwithstanding, performance remained poor for complexes with antibodies and nanobodies, where evolutionary relationships between the binding partners are lacking, and for complexes featuring conformational flexibility, clearly indicating that the prediction of protein complexes remains a challenging problem.
35.	Li, Q., et al. (author) Discovery of new strains for furfural degradation using adaptive laboratory evolution in Saccharomyces cerevisiae 2023 In: Journal of Hazardous Materials. - 0304-3894. ; 459 Journal article (peer-reviewed)abstract In industrial production, the excessive discharge of furfural can pose harm to soil microorganisms, aquatic an-imals and plants, as well as humans. Therefore, it is crucial to develop efficient and cost-effective methods for degrading furfural in the environment. Currently, the use of Saccharomyces cerevisiae for furfural degradation in water has shown effectiveness, but there is a need to explore improved efficiency and tolerance in S. cerevisiae for this purpose. In this study, we isolated and evolved highly efficient furfural degradation strains, namely YBA_08 and F60C. These strains exhibited remarkable capabilities, degrading 59% and 99% furfural in the YPD medium after 72 h of incubation, significantly higher than the 31% achieved by the model strain S288C. Through analysis of the efficient degradation mechanism in the evolutionary strain F60C, we discovered a 326% increase in the total amount of NADH and NADPH. This increase likely promotes faster furfural degradation through intracel-lular aldehyde reductases. Moreover, the decrease in NADPH content led to a 406% increase in glutathione content at the background level, which protects cells from damage caused by reactive oxygen species. Mutations and differential expression related to cell cycle and cell wall synthesis were observed, enabling cell survival in the presence of furfural and facilitating rapid furfural degradation and growth recovery. Based on these findings, it is speculated that strains YBA_08 and F60C have the potential to contribute to furfural degradation in water and the production of furfuryl alcohol, ethanol, and FDCA in biorefinery processes.
36.	Li, Xing-Yu, et al. (author) Comparative Study of Dayside Pulsating Auroras Induced by Ultralow-Frequency Waves 2023 In: Universe. - : MDPI AG. - 2218-1997. ; 9:6 Journal article (peer-reviewed)abstract Pulsating auroras are usually observed with ultralow-frequency (ULF) waves in the Pc 3-5 band (period 10-600 s). These auroras are thought to result from interactions between energetic electrons and chorus waves, but their relationship with ULF waves remains an open question. In this study, we investigated this question by conducting a comparative study on two ULF wave events with pulsating auroras observed near the magnetic footprints. Conjugate observations from the Magnetospheric Multiscale mission and the Chinese Yellow River Station were used. In both events, lower-band chorus waves were observed, which were suggested to be connected with the auroral pulsations by wavelet analysis. The intensity of these waves oscillates at the period of the ULF waves, but the physics laid behind them differs by events. During the event of 22 January 2019, compressional ULF waves changed the threshold for the whistler anisotropy instability periodically, affecting the emission of chorus waves. In the event on 10 January 2016, poloidal ULF waves modulated the chorus wave generation by regulating electron temperature anisotropy through drift resonance. ULF waves in these events may originate from perturbations in the solar wind. We highlight the role of ULF waves in the solar wind-magnetosphere-ionosphere coupling, which requires further study.
37.	Luo, Yifei, et al. (author) Technology Roadmap for Flexible Sensors 2023 In: ACS Nano. - : American Chemical Society. - 1936-0851 .- 1936-086X. ; 17:6, s. 5211-5295 Research review (peer-reviewed)abstract Humans rely increasingly on sensors to address grand challenges and to improve quality of life in the era of digitalization and big data. For ubiquitous sensing, flexible sensors are developed to overcome the limitations of conventional rigid counterparts. Despite rapid advancement in bench-side research over the last decade, the market adoption of flexible sensors remains limited. To ease and to expedite their deployment, here, we identify bottlenecks hindering the maturation of flexible sensors and propose promising solutions. We first analyze challenges in achieving satisfactory sensing performance for real-world applications and then summarize issues in compatible sensor-biology interfaces, followed by brief discussions on powering and connecting sensor networks. Issues en route to commercialization and for sustainable growth of the sector are also analyzed, highlighting environmental concerns and emphasizing nontechnical issues such as business, regulatory, and ethical considerations. Additionally, we look at future intelligent flexible sensors. In proposing a comprehensive roadmap, we hope to steer research efforts towards common goals and to guide coordinated development strategies from disparate communities. Through such collaborative efforts, scientific breakthroughs can be made sooner and capitalized for the betterment of humanity.
38.	Matsui, Kentaro, et al. (author) Associations between changes in habitual sleep duration and lower self-rated health among COVID-19 survivors : findings from a survey across 16 countries/regions 2023 In: BMC Public Health. - : BioMed Central (BMC). - 1471-2458. ; 23:1 Journal article (peer-reviewed)abstract BACKGROUND: Self-rated health (SRH) is widely recognized as a clinically significant predictor of subsequent mortality risk. Although COVID-19 may impair SRH, this relationship has not been extensively examined. The present study aimed to examine the correlation between habitual sleep duration, changes in sleep duration after infection, and SRH in subjects who have experienced SARS-CoV-2 infection.METHODS: Participants from 16 countries participated in the International COVID Sleep Study-II (ICOSS-II) online survey in 2021. A total of 10,794 of these participants were included in the analysis, including 1,509 COVID-19 individuals (who reported that they had tested positive for COVID-19). SRH was evaluated using a 0-100 linear visual analog scale. Habitual sleep durations of < 6 h and > 9 h were defined as short and long habitual sleep duration, respectively. Changes in habitual sleep duration after infection of ≤ -2 h and ≥ 1 h were defined as decreased or increased, respectively.RESULTS: Participants with COVID-19 had lower SRH scores than non-infected participants, and those with more severe COVID-19 had a tendency towards even lower SRH scores. In a multivariate regression analysis of participants who had experienced COVID-19, both decreased and increased habitual sleep duration after infection were significantly associated with lower SRH after controlling for sleep quality (β = -0.056 and -0.058, respectively, both p < 0.05); however, associations between current short or long habitual sleep duration and SRH were negligible. Multinomial logistic regression analysis showed that decreased habitual sleep duration was significantly related to increased fatigue (odds ratio [OR] = 1.824, p < 0.01), shortness of breath (OR = 1.725, p < 0.05), diarrhea/nausea/vomiting (OR = 2.636, p < 0.01), and hallucinations (OR = 5.091, p < 0.05), while increased habitual sleep duration was significantly related to increased fatigue (OR = 1.900, p < 0.01).CONCLUSIONS: Changes in habitual sleep duration following SARS-CoV-2 infection were associated with lower SRH. Decreased or increased habitual sleep duration might have a bidirectional relation with post-COVID-19 symptoms. Further research is needed to better understand the mechanisms underlying these relationships for in order to improve SRH in individuals with COVID-19.
39.	Murphy, Neil, et al. (author) Body mass index and molecular subtypes of colorectal cancer 2023 In: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 115:2, s. 165-173 Journal article (peer-reviewed)abstract Background: Obesity is an established risk factor for colorectal cancer (CRC), but the evidence for the association is inconsistent across molecular subtypes of the disease.Methods: We pooled data on body mass index (BMI), tumor microsatellite instability status, CpG island methylator phenotype status, BRAF and KRAS mutations, and Jass classification types for 11 872 CRC cases and 11 013 controls from 11 observational studies. We used multinomial logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for covariables.Results: Higher BMI was associated with increased CRC risk (OR per 5 kg/m(2) = 1.18, 95% CI = 1.15 to 1.22). The positive association was stronger for men than women but similar across tumor subtypes defined by individual molecular markers. In analyses by Jass type, higher BMI was associated with elevated CRC risk for types 1-4 cases but not for type 5 CRC cases (considered familial-like/Lynch syndrome microsatellite instability-H, CpG island methylator phenotype-low or negative, BRAF-wild type, KRAS-wild type, OR = 1.04, 95% CI = 0.90 to 1.20). This pattern of associations for BMI and Jass types was consistent by sex and design of contributing studies (cohort or case-control).Conclusions: In contrast to previous reports with fewer study participants, we found limited evidence of heterogeneity for the association between BMI and CRC risk according to molecular subtype, suggesting that obesity influences nearly all major pathways involved in colorectal carcinogenesis. The null association observed for the Jass type 5 suggests that BMI is not a risk factor for the development of CRC for individuals with Lynch syndrome.
40.	Nilsen, SM, et al. (author) Gestational age at birth and hospitalisations for infections among individuals aged 0-50 years in Norway: a longitudinal, register-based, cohort study 2023 In: EClinicalMedicine. - 2589-5370. ; 62, s. 102108- Journal article (peer-reviewed)
41.	Park, Kyoung Chul, et al. (author) The Highly Operational Team (HOT) toward f-Block Materials 2023 In: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 62:32 Journal article (other academic/artistic)
42.	Potapov, Anton M., et al. (author) Globally invariant metabolism but density-diversity mismatch in springtails 2023 In: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1 Journal article (peer-reviewed)abstract Soil life supports the functioning and biodiversity of terrestrial ecosystems. Springtails (Collembola) are among the most abundant soil arthropods regulating soil fertility and flow of energy through above- and belowground food webs. However, the global distribution of springtail diversity and density, and how these relate to energy fluxes remains unknown. Here, using a global dataset representing 2470 sites, we estimate the total soil springtail biomass at 27.5 megatons carbon, which is threefold higher than wild terrestrial vertebrates, and record peak densities up to 2 million individuals per square meter in the tundra. Despite a 20-fold biomass difference between the tundra and the tropics, springtail energy use (community metabolism) remains similar across the latitudinal gradient, owing to the changes in temperature with latitude. Neither springtail density nor community metabolism is predicted by local species richness, which is high in the tropics, but comparably high in some temperate forests and even tundra. Changes in springtail activity may emerge from latitudinal gradients in temperature, predation and resource limitation in soil communities. Contrasting relationships of biomass, diversity and activity of springtail communities with temperature suggest that climate warming will alter fundamental soil biodiversity metrics in different directions, potentially restructuring terrestrial food webs and affecting soil functioning.
43.	Qi, L., et al. (author) Techno-economic assessment of implementing photovoltaic water villas in Maldives 2023 In: iScience. - : Elsevier Inc.. - 2589-0042. ; 26:5 Journal article (peer-reviewed)abstract Solar energy is considered to be an effective measure to alleviate the shortage of power supply in the Maldives. In this paper, a roof photovoltaic (PV) system integrated into water villas in the Maldives was investigated. Three islands—Ayada Maldives, Angaga Island Resort, and JA Manafaru, located in the southern, central, and northern parts of Maldives—were selected for a case study. The potential of PV installations in Ayada Maldives, Angaga Island Resort, and JA Manafaru reaches 1,410, 445, and 742 kW, with corresponding annual power generation of 2.04, 0.64, and 1.12 GWh, respectively. The profits over the life cycle of 25 years of the above three studied islands are 4.86, 1.52, and 2.90 million USD, respectively, with payback periods in the range of 6–7 years.
44.	Qin, Ning, 1990, et al. (author) Flux regulation through glycolysis and respiration is balanced by inositol pyrophosphates in yeast 2023 In: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 186:4, s. 748-763.e15 Journal article (peer-reviewed)abstract Although many prokaryotes have glycolysis alternatives, it's considered as the only energy-generating glucose catabolic pathway in eukaryotes. Here, we managed to create a hybrid-glycolysis yeast. Subsequently, we identified an inositol pyrophosphatase encoded by OCA5 that could regulate glycolysis and respiration by adjusting 5-diphosphoinositol 1,2,3,4,6-pentakisphosphate (5-InsP7) levels. 5-InsP7 levels could regulate the expression of genes involved in glycolysis and respiration, representing a global mechanism that could sense ATP levels and regulate central carbon metabolism. The hybrid-glycolysis yeast did not produce ethanol during growth under excess glucose and could produce 2.68 g/L free fatty acids, which is the highest reported production in shake flask of Saccharomyces cerevisiae. This study demonstrated the significance of hybrid-glycolysis yeast and determined Oca5 as an inositol pyrophosphatase controlling the balance between glycolysis and respiration, which may shed light on the role of inositol pyrophosphates in regulating eukaryotic metabolism.
45.	Qiu, Xia, et al. (author) Individual participant data meta-analysis to compare EPDS accuracy to detect major depression with and without the self-harm item 2023 In: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13 Journal article (peer-reviewed)abstract Item 10 of the Edinburgh Postnatal Depression Scale (EPDS) is intended to assess thoughts of intentional self-harm but may also elicit concerns about accidental self-harm. It does not specifically address suicide ideation but, nonetheless, is sometimes used as an indicator of suicidality. The 9-item version of the EPDS (EPDS-9), which omits item 10, is sometimes used in research due to concern about positive endorsements of item 10 and necessary follow-up. We assessed the equivalence of total score correlations and screening accuracy to detect major depression using the EPDS-9 versus full EPDS among pregnant and postpartum women. We searched Medline, Medline In-Process and Other Non-Indexed Citations, PsycINFO, and Web of Science from database inception to October 3, 2018 for studies that administered the EPDS and conducted diagnostic classification for major depression based on a validated semi-structured or fully structured interview among women aged 18 or older during pregnancy or within 12 months of giving birth. We conducted an individual participant data meta-analysis. We calculated Pearson correlations with 95% prediction interval (PI) between EPDS-9 and full EPDS total scores using a random effects model. Bivariate random-effects models were fitted to assess screening accuracy. Equivalence tests were done by comparing the confidence intervals (CIs) around the pooled sensitivity and specificity differences to the equivalence margin of delta = 0.05. Individual participant data were obtained from 41 eligible studies (10,906 participants, 1407 major depression cases). The correlation between EPDS-9 and full EPDS scores was 0.998 (95% PI 0.991, 0.999). For sensitivity, the EPDS-9 and full EPDS were equivalent for cut-offs 7-12 (difference range - 0.02, 0.01) and the equivalence was indeterminate for cut-offs 13-15 (all differences - 0.04). For specificity, the EPDS-9 and full EPDS were equivalent for all cut-offs (difference range 0.00, 0.01). The EPDS-9 performs similarly to the full EPDS and can be used when there are concerns about the implications of administering EPDS item 10.
46.	Shen, Liyan, et al. (author) Clinical Uncertainty Influences Antibiotic Prescribing for Upper Respiratory Tract Infections : A Qualitative Study of Township Hospital Physicians and Village Doctors in Rural Shandong Province, China 2023 In: Antibiotics. - : MDPI. - 2079-6382. ; 12:6 Journal article (peer-reviewed)abstract Objective: This study aimed to explore how clinical uncertainty influences antibiotic prescribing practices among township hospital physicians and village doctors in rural Shandong Province, China.Methods: Qualitative semi-structured interviews were conducted with 30 township hospital physicians and 6 village doctors from rural Shandong Province, China. A multi-stage random sampling method was used to identify respondents. Conceptual content analysis together with Colaizzi's method were used to generate qualitative codes and identify themes.Results: Three final thematic categories emerged during the data analysis: (1) Incidence and treatment of Upper Respiratory Tract Infections (URTIs) in township hospitals and village clinics; (2) Antibiotic prescribing practices based on the clinical experience of clinicians; (3) Influence of clinical uncertainty on antibiotic prescribing. Respondents from both township hospitals and village clinics reported that URTIs were the most common reason for antibiotic prescriptions at their facilities and that clinical uncertainty appears to be an important driver for the overuse of antibiotics for URTIs. Clinical uncertainty was primarily due to: (1) Diagnostic uncertainty (establishing a relevant diagnosis is hindered by limited diagnostic resources and capacities, as well as limited willingness of patients to pay for investigations), and (2) Insufficient prognostic evidence. As a consequence of the clinical uncertainty caused by both diagnostic and prognostic uncertainty, respondents stated that antibiotics are frequently prescribed for URTIs to prevent both prolonged courses or recurrence of the disease, as well as clinical worsening, hospital admission, or complications.Conclusion: Our study suggests that clinical uncertainty is a key driver for the overuse and misuse of prescribing antibiotics for URTIs in both rural township hospitals and village clinics in Shandong province, China, and that interventions to reduce clinical uncertainty may help minimize the unnecessary use of antibiotics in these settings. Interventions that use clinical rules to identify patients at low risk of complications or hospitalization may be more feasible in the near-future than laboratory-based interventions aimed at reducing diagnostic uncertainty.
47.	Suzuki, Toshiyasu, et al. (author) b-Catenin Drives Butyrophilin-like Molecule Loss and gd T-cell Exclusion in Colon Cancer 2023 In: CANCER IMMUNOLOGY RESEARCH. - : AMER ASSOC CANCER RESEARCH. - 2326-6066. ; 11:8, s. 1137-1155 Journal article (peer-reviewed)abstract Intraepithelial lymphocytes (IEL) expressing y8 T-cell receptors (y8TCR) play key roles in elimination of colon cancer. However, the precise mechanisms by which progressing cancer cells evade immu-nosurveillance by these innate T cells are unknown. Here, we investigated how loss of the Apc tumor suppressor in gut tissue could enable nascent cancer cells to escape immunosurveillance by cytotoxic y8IELs. In contrast with healthy intestinal or colonic tissue, we found that y8IELs were largely absent from the micro-environment of both mouse and human tumors, and that butyr-ophilin-like (BTNL) molecules, which can critically regulate y8IEL through direct y8TCR interactions, were also downregulated in tumors. We then demonstrated that 13-catenin activation through loss of Apc rapidly suppressed expression of the mRNA encoding the HNF4A and HNF4G transcription factors, preventing their binding to promoter regions of Btnl genes. Reexpression of BTNL1 and BTNL6 in cancer cells increased y8IEL survival and activation in coculture assays but failed to augment their cancer-killing ability in vitro or their recruitment to orthotopic tumors. However, inhibition of 13-catenin signaling via genetic deletion of Bcl9/Bcl9L in either Apc-deficient or mutant 13-catenin mouse models restored Hnf4a, Hnf4g, and Btnl gene expression and y8 T-cell infiltration into tumors. These observations highlight an immune-evasion mechanism specific to WNT-driven colon cancer cells that disrupts y8IEL immunosurveillance and furthers cancer progression.
48.	Tian, Ruiyi, et al. (author) Clonal Hematopoiesis and Risk of Incident Lung Cancer 2023 In: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 0732-183X. ; 41:7, s. 1423-1433 Journal article (peer-reviewed)abstract PURPOSE: To prospectively examine the association between clonal hematopoiesis (CH) and subsequent risk of lung cancer. METHODS: Among 200,629 UK Biobank (UKBB) participants with whole-exome sequencing, CH was identified in a nested case-control study of 832 incident lung cancer cases and 3,951 controls (2006-2019) matched on age and year at blood draw, sex, race, and smoking status. A similar nested case-control study (141 cases/652 controls) was conducted among 27,975 participants with whole-exome sequencing in the Mass General Brigham Biobank (MGBB, 2010-2021). In parallel, we compared CH frequency in published data from 5,003 patients with solid tumor (2,279 lung cancer) who had pretreatment blood sequencing performed through Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets. RESULTS: In UKBB, the presence of CH was associated with increased risk of lung cancer (cases: 12.5% v controls: 8.7%; multivariable-adjusted odds ratio [OR], 1.36; 95% CI, 1.06 to 1.74). The association remained robust after excluding participants with chronic obstructive pulmonary disease. No significant interactions with known risk factors, including polygenic risk score and C-reactive protein, were identified. In MGBB, we observed similar enrichment of CH in lung cancer (cases: 15.6% v controls: 12.7%). The meta-analyzed OR (95% CI) of UKBB and MGBB was 1.35 (1.08 to 1.68) for CH overall and 1.61 (1.19 to 2.18) for variant allele frequencies ≥ 10%. In Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets, CH with a variant allele frequency ≥ 10% was enriched in pretreatment lung cancer compared with other tumors after adjusting for age, sex, and smoking (OR for lung v breast cancer: 1.61; 95% CI, 1.03 to 2.53). CONCLUSION: Independent of known risk factors, CH is associated with increased risk of lung cancer.
49.	Ugai, Tomotaka, et al. (author) Molecular characteristics of early-onset colorectal cancer according to detailed anatomical locations : comparison with later-onset cases 2023 In: American Journal of Gastroenterology. - : Wolters Kluwer. - 0002-9270 .- 1572-0241. ; 118:4, s. 712-726 Journal article (peer-reviewed)abstract INTRODUCTION:Early-onset colorectal cancer diagnosed before the age of 50 years has been increasing. Likely reflecting the pathogenic role of the intestinal microbiome, which gradually changes across the entire colorectal length, the prevalence of certain tumor molecular characteristics gradually changes along colorectal subsites. Understanding how colorectal tumor molecular features differ by age and tumor location is important in personalized patient management.METHODS:Using 14,004 cases with colorectal cancer including 3,089 early-onset cases, we examined microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and KRAS and BRAF mutations in carcinomas of the cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum and compared early-onset cases with later-onset cases.RESULTS:The proportions of MSI-high, CIMP-high, and BRAF-mutated early-onset tumors were lowest in the rectum (8.8%, 3.4%, and 3.5%, respectively) and highest in the ascending colon (46% MSI-high; 15% CIMP-high) or transverse colon (8.6% BRAF-mutated) (all Ptrend<0.001 across the rectum to ascending colon). Compared with later-onset tumors, early-onset tumors showed a higher prevalence of MSI-high status and a lower prevalence of CIMP-high status and BRAF mutations in most subsites. KRAS mutation prevalence was higher in the cecum compared with that in the other subsites in both early-onset and later-onset tumors (P < 0.001). Notably, later-onset MSI-high tumors showed a continuous decrease in KRAS mutation prevalence from the rectum (36%) to ascending colon (9%; Ptrend<0.001), followed by an increase in the cecum (14%), while early-onset MSI-high cancers showed no such trend.DISCUSSION:Our findings support biogeographical and pathogenic heterogeneity of colorectal carcinomas in different colorectal subsites and age groups.
50.	Ugai, Tomotaka, et al. (author) Prognostic role of detailed colorectal location and tumor molecular features : analyses of 13,101 colorectal cancer patients including 2994 early-onset cases 2023 In: Journal of gastroenterology. - : Springer. - 0944-1174 .- 1435-5922. ; 58, s. 229-245 Journal article (peer-reviewed)abstract Background: The pathogenic effect of colorectal tumor molecular features may be influenced by several factors, including those related to microbiota, inflammation, metabolism, and epigenetics, which may change along colorectal segments. We hypothesized that the prognostic association of colon cancer location might differ by tumor molecular characteristics.Methods: Utilizing a consortium dataset of 13,101 colorectal cancer cases, including 2994 early-onset cases, we conducted survival analyses of detailed tumor location stratified by statuses of microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and KRAS and BRAF oncogenic mutation.Results: There was a statistically significant trend for better colon cancer-specific survival in relation to tumor location from the cecum to sigmoid colon (Ptrend = 0.002), excluding the rectum. The prognostic association of colon location differed by MSI status (Pinteraction = 0.001). Non-MSI-high tumors exhibited the cecum-to-sigmoid trend for better colon cancer-specific survival [Ptrend < 0.001; multivariable hazard ratio (HR) for the sigmoid colon (vs. cecum), 0.80; 95% confidence interval (CI) 0.70–0.92], whereas MSI-high tumors demonstrated a suggestive cecum-to-sigmoid trend for worse survival (Ptrend = 0.020; the corresponding HR, 2.13; 95% CI 1.15–3.92). The prognostic association of colon tumor location also differed by CIMP status (Pinteraction = 0.003) but not significantly by age, stage, or other features. Furthermore, MSI-high status was a favorable prognostic indicator in all stages.Conclusions: Both detailed colonic location and tumor molecular features need to be accounted for colon cancer prognostication to advance precision medicine. Our study indicates the important role of large-scale studies to robustly examine detailed colonic subsites in molecular oncology research.

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