| 1. |
- Kanai, M, et al.
(author)
-
- 2023
-
swepub:Mat__t
|
|
| 2. |
- Niemi, MEK, et al.
(author)
-
- 2021
-
swepub:Mat__t
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Appeltans, W., et al.
(author)
-
The Magnitude of Global Marine Species Diversity
- 2012
-
In: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 22:23, s. 2189-2202
-
Journal article (peer-reviewed)abstract
- Background: The question of how many marine species exist is important because it provides a metric for how much we do and do not know about life in the oceans. We have compiled the first register of the marine species of the world and used this baseline to estimate how many more species, partitioned among all major eukaryotic groups, may be discovered. Results: There are similar to 226,000 eukaryotic marine species described. More species were described in the past decade (similar to 20,000) than in any previous one. The number of authors describing new species has been increasing at a faster rate than the number of new species described in the past six decades. We report that there are similar to 170,000 synonyms, that 58,000-72,000 species are collected but not yet described, and that 482,000-741,000 more species have yet to be sampled. Molecular methods may add tens of thousands of cryptic species. Thus, there may be 0.7-1.0 million marine species. Past rates of description of new species indicate there may be 0.5 +/- 0.2 million marine species. On average 37% (median 31%) of species in over 100 recent field studies around the world might be new to science. Conclusions: Currently, between one-third and two-thirds of marine species may be undescribed, and previous estimates of there being well over one million marine species appear highly unlikely. More species than ever before are being described annually by an increasing number of authors. If the current trend continues, most species will be discovered this century.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- Furukawa, T. A., et al.
(author)
-
Dismantling, optimising, and personalising internet cognitive behavioural therapy for depression: a systematic review and component network meta-analysis using individual data
- 2021
-
In: Lancet Psychiatry. - : Elsevier BV. - 2215-0374 .- 2215-0366. ; 8:6, s. 500-511
-
Journal article (peer-reviewed)abstract
- Findings We identified 76 RCTs, including 48 trials contributing individual participant data (11 704 participants) and 28 trials with aggregate data (6474 participants). The participants' weighted mean age was 42.0 years and 12 406 (71%) of 17 521 reported were women. There was suggestive evidence that behavioural activation might be beneficial (iMD -1.83 [95% credible interval (CrI) -2.90 to -0.80]) and that relaxation might be harmful (1.20 [95% CrI 0.17 to 2.27]). Baseline severity emerged as the strongest prognostic factor for endpoint depression. Combining human and automated encouragement reduced dropouts from treatment (incremental odds ratio, 0.32 [95% CrI 0.13 to 0.93]). The risk of bias was low for the randomisation process, missing outcome data, or selection of reported results in most of the included studies, uncertain for deviation from intended interventions, and high for measurement of outcomes. There was moderate to high heterogeneity among the studies and their components. 511
|
|
| 10. |
- Huyghe, Jeroen R., et al.
(author)
-
Discovery of common and rare genetic risk variants for colorectal cancer
- 2019
-
In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:1, s. 76-
-
Journal article (peer-reviewed)abstract
- To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 x 10(-8), bringing the number of known independent signals for CRC to similar to 100. New signals implicate lower-frequency variants, Kruppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.
|
|
| 11. |
- 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.
|
|
| 12. |
- Das, A., et al.
(author)
-
Genomic predictors of response to PD-1 inhibition in children with germline DNA replication repair deficiency
- 2022
-
In: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 28:1, s. 125-135
-
Journal article (peer-reviewed)abstract
- Cancers arising from germline DNA mismatch repair deficiency or polymerase proofreading deficiency (MMRD and PPD) in children harbour the highest mutational and microsatellite insertion–deletion (MS-indel) burden in humans. MMRD and PPD cancers are commonly lethal due to the inherent resistance to chemo-irradiation. Although immune checkpoint inhibitors (ICIs) have failed to benefit children in previous studies, we hypothesized that hypermutation caused by MMRD and PPD will improve outcomes following ICI treatment in these patients. Using an international consortium registry study, we report on the ICI treatment of 45 progressive or recurrent tumors from 38 patients. Durable objective responses were observed in most patients, culminating in a 3 year survival of 41.4%. High mutation burden predicted response for ultra-hypermutant cancers (>100 mutations per Mb) enriched for combined MMRD + PPD, while MS-indels predicted response in MMRD tumors with lower mutation burden (10–100 mutations per Mb). Furthermore, both mechanisms were associated with increased immune infiltration even in ‘immunologically cold’ tumors such as gliomas, contributing to the favorable response. Pseudo-progression (flare) was common and was associated with immune activation in the tumor microenvironment and systemically. Furthermore, patients with flare who continued ICI treatment achieved durable responses. This study demonstrates improved survival for patients with tumors not previously known to respond to ICI treatment, including central nervous system and synchronous cancers, and identifies the dual roles of mutation burden and MS-indels in predicting sustained response to immunotherapy. © 2022, The Author(s).
|
|
| 13. |
- Adam, J., et al.
(author)
-
Fumarate Hydratase Deletion in Pancreatic beta Cells Leads to Progressive Diabetes
- 2017
-
In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 20:13, s. 3135-3148
-
Journal article (peer-reviewed)abstract
- We explored the role of the Krebs cycle enzyme fumarate hydratase (FH) in glucose-stimulated insulin secretion (GSIS). Mice lacking Fh1 in pancreatic beta cells (Fh1 beta KO mice) appear normal for 6-8 weeks but then develop progressive glucose intolerance and diabetes. Glucose tolerance is rescued by expression of mitochondrial or cytosolic FH but not by deletion of Hif1 alpha or Nrf2. Progressive hyperglycemia in Fh1bKO mice led to dysregulated metabolism in b cells, a decrease in glucose-induced ATP production, electrical activity, cytoplasmic [Ca2+](i) elevation, and GSIS. Fh1 loss resulted in elevated intracellular fumarate, promoting succination of critical cysteines in GAPDH, GMPR, and PARK 7/DJ-1 and cytoplasmic acidification. Intracellular fumarate levels were increased in islets exposed to high glucose and in islets from human donors with type 2 diabetes (T2D). The impaired GSIS in islets from diabetic Fh1bKO mice was ameliorated after culture under normoglycemic conditions. These studies highlight the role of FH and dysregulated mitochondrial metabolism in T2D.
|
|
| 14. |
- Arneth, A., et al.
(author)
-
Historical carbon dioxide emissions caused by land-use changes are possibly larger than assumed
- 2017
-
In: Nature Geoscience. - : Springer Science and Business Media LLC. - 1752-0894 .- 1752-0908. ; 10:2, s. 79-84
-
Research review (peer-reviewed)abstract
- The terrestrial biosphere absorbs about 20% of fossil-fuel CO 2 emissions. The overall magnitude of this sink is constrained by the difference between emissions, the rate of increase in atmospheric CO 2 concentrations, and the ocean sink. However, the land sink is actually composed of two largely counteracting fluxes that are poorly quantified: fluxes from land-use change and CO 2 uptake by terrestrial ecosystems. Dynamic global vegetation model simulations suggest that CO 2 emissions from land-use change have been substantially underestimated because processes such as tree harvesting and land clearing from shifting cultivation have not been considered. As the overall terrestrial sink is constrained, a larger net flux as a result of land-use change implies that terrestrial uptake of CO 2 is also larger, and that terrestrial ecosystems might have greater potential to sequester carbon in the future. Consequently, reforestation projects and efforts to avoid further deforestation could represent important mitigation pathways, with co-benefits for biodiversity. It is unclear whether a larger land carbon sink can be reconciled with our current understanding of terrestrial carbon cycling. Our possible underestimation of the historical residual terrestrial carbon sink adds further uncertainty to our capacity to predict the future of terrestrial carbon uptake and losses.
|
|
| 15. |
- Bowden, John A., et al.
(author)
-
Harmonizing lipidomics : NIST interlaboratory comparison exercise for lipidomics using SRM 1950-Metabolites in Frozen Human Plasma
- 2017
-
In: Journal of Lipid Research. - 0022-2275 .- 1539-7262. ; 58:12, s. 2275-2288
-
Journal article (peer-reviewed)abstract
- As the lipidomics field continues to advance, self-evaluation within the community is critical. Here, we performed an interlaboratory comparison exercise for lipidomics using Standard Reference Material (SRM) 1950-Metabolites in Frozen Human Plasma, a commercially available reference material. The interlaboratory study comprised 31 diverse laboratories, with each laboratory using a different lipidomics workflow. A total of 1,527 unique lipids were measured across all laboratories and consensus location estimates and associated uncertainties were determined for 339 of these lipids measured at the sum composition level by five or more participating laboratories. These evaluated lipids detected in SRM 1950 serve as community-wide benchmarks for intra-and interlaboratory quality control and method validation. These analyses were performed using nonstandardized laboratory-independent workflows. The consensus locations were also compared with a previous examination of SRM 1950 by the LIPID MAPS consortium.jlr While the central theme of the interlaboratory study was to provide values to help harmonize lipids, lipid mediators, and precursor measurements across the community, it was also initiated to stimulate a discussion regarding areas in need of improvement.
|
|
| 16. |
- Martins, Inês S., et al.
(author)
-
Widespread shifts in body size within populations and assemblages
- 2023
-
In: Science. - 0036-8075 .- 1095-9203. ; 381:6662, s. 1067-1071
-
Journal article (peer-reviewed)abstract
- Biotic responses to global change include directional shifts in organismal traits. Body size, an integrative trait that determines demographic rates and ecosystem functions, is thought to be shrinking in the Anthropocene. Here, we assessed the prevalence of body size change in six taxon groups across 5025 assemblage time series spanning 1960 to 2020. Using the Price equation to partition this change into within-species body size versus compositional changes, we detected prevailing decreases in body size through time driven primarily by fish, with more variable patterns in other taxa. We found that change in assemblage composition contributes more to body size changes than within-species trends, but both components show substantial variation in magnitude and direction. The biomass of assemblages remains quite stable as decreases in body size trade off with increases in abundance.
|
|
| 17. |
- Toreti, A, et al.
(author)
-
Narrowing uncertainties in the effects of elevated CO2 on crops
- 2020
-
In: Nature Food. - : Springer Science and Business Media LLC. - 2662-1355. ; 1, s. 775-782
-
Journal article (peer-reviewed)abstract
- Plant responses to rising atmospheric carbon dioxide (CO2) concentrations, together with projected variations in temperature and precipitation will determine future agricultural production. Estimates of the impacts of climate change on agriculture provide essential information to design effective adaptation strategies, and develop sustainable food systems. Here, we review the current experimental evidence and crop models on the effects of elevated CO2 concentrations. Recent concerted efforts have narrowed the uncertainties in CO2-induced crop responses so that climate change impact simulations omitting CO2 can now be eliminated. To address remaining knowledge gaps and uncertainties in estimating the effects of elevated CO2 and climate change on crops, future research should expand experiments on more crop species under a wider range of growing conditions, improve the representation of responses to climate extremes in crop models, and simulate additional crop physiological processes related to nutritional quality.
|
|
| 18. |
- Dams-O'Connor, K., et al.
(author)
-
Alzheimer's Disease-Related Dementias Summit 2022: National Research Priorities for the Investigation of Post-Traumatic Brain Injury Alzheimer's Disease and Related Dementias
- 2023
-
In: Journal of Neurotrauma. - : Mary Ann Liebert Inc. - 0897-7151 .- 1557-9042. ; 40:15-16, s. 1512-1523
-
Journal article (peer-reviewed)abstract
- Traumatic Brain Injury (TBI) is a risk factor for Alzheimer's disease and Alzheimer's disease related dementias (AD/ADRD) and otherwise classified post-traumatic neurodegeneration (PTND). Targeted research is needed to elucidate the circumstances and mechanisms through which TBI contributes to the initiation, development, and progression of AD/ADRD pathologies including multiple etiology dementia (MED). The National Institutes of Health hosts triennial ADRD summits to inform a national research agenda, and TBI was included for a second time in 2022. A multidisciplinary expert panel of TBI and dementia researchers was convened to re-evaluate the 2019 research recommendations for understanding TBI as an AD/ADRD risk factor and to assess current progress and research gaps in understanding post-TBI AD/ADRD. Refined and new recommendations were presented during the MED special topic session at the virtual ADRD Summit in March 2022. Final research recommendations incorporating broad stakeholder input are organized into four priority areas as follows: (1) Promote interdisciplinary collaboration and data harmonization to accelerate progress of rigorous, clinically meaningful research; (2) Characterize clinical and biological phenotypes of PTND associated with varied lifetime TBI histories in diverse populations to validate multimodal biomarkers; (3) Establish and enrich infrastructure to support multimodal longitudinal studies of individuals with varied TBI exposure histories and standardized methods including common data elements (CDEs) for ante-mortem and post-mortem clinical and neuropathological characterization; and (4) Support basic and translational research to elucidate mechanistic pathways, development, progression, and clinical manifestations of post-TBI AD/ADRDs. Recommendations conceptualize TBI as a contributor to MED and emphasize the unique opportunity to study AD/ADRD following known exposure, to inform disease mechanisms and treatment targets for shared common AD/ADRD pathways.
|
|
| 19. |
|
|
| 20. |
- Hesser, Hugo, et al.
(author)
-
Predicting Response to Therapist-Assisted Internet-Delivered Cognitive Behavior Therapy for Depression or Anxiety Within an Open Dissemination Trial
- 2016
-
In: Behavior Therapy. - : Elsevier. - 0005-7894 .- 1878-1888. ; 47:2, s. 155-165
-
Journal article (peer-reviewed)abstract
- Therapist-assisted Internet-delivered cognitive behavior therapy (ICBT) is efficacious for treating anxiety and depression, but predictors of response to treatment when delivered in clinical practice are not well understood. In this study, we explored demographic, clinical, and program variables that predicted modules started and symptom improvement (i.e., Generalized Anxiety Disorder-7 or Patient Health Questionnaire-9 total scores over pre-, mid-, and posttreatment) within a previously published open dissemination trial (Hadjistavropoulos et al., 2014). The sample consisted of 195 patients offered 12 modules of therapist-assisted ICBT for depression or generalized anxiety; ICBT was delivered by therapists working in six geographically dispersed clinics. Consistent across ICBT for depression or generalized anxiety, starting fewer modules was associated with more phone calls from therapists reflecting that therapists tended to call patients who did not start modules as scheduled. Also consistent for both ICBT programs, greater pretreatment condition severity and completion of more modules was associated with superior ICBT-derived benefit. Other predictors of response to treatment varied across the two programs. Younger age, lower education, taking psychotropic medication, being in receipt of psychiatric care and lower comfort with written communication were associated with either fewer program starts or lower symptom improvement in one of the two programs. It is concluded that monitoring response to ICBT may be particularly important in patients with these characteristics. Research directions for identifying patients who are less likely to benefit from ICBT are discussed.
|
|
| 21. |
- Hesser, Hugo, et al.
(author)
-
Therapeutic Alliance in Internet-Delivered Cognitive Behaviour Therapy for Depression or Generalized Anxiety
- 2017
-
In: Clinical Psychology and Psychotherapy. - : John Wiley & Sons. - 1063-3995 .- 1099-0879. ; 24:2, s. 451-461
-
Journal article (peer-reviewed)abstract
- There has been limited research on therapeutic alliance in the context of therapist-assisted Internet-delivered cognitive behaviour therapy (ICBT) when delivered in clinical practice. The present study investigated therapeutic alliance in ICBT delivered to patients seeking treatment for symptoms of depression (n=83) or generalized anxiety (n=112) as part of an open dissemination trial. ICBT was provided by 27 registered therapists or 28 graduate students working in six geographically dispersed clinics; therapist-assistance was delivered primarily through secure messages and occasionally telephone calls. The Generalized Anxiety Disorder-7 and Patient Health Questionnaire-9 were collected pre-, mid- and post-treatment, and the Therapeutic Alliance Questionnaire was assessed mid- and post-treatment. Therapeutic alliance ratings were high both at mid-treatment and post-treatment (above 80%). There was no relationship between therapeutic alliance ratings and improvement on primary outcomes. Among patients treated for depression, lower ratings of mid-treatment alliance were associated with concurrent treatment by a psychiatrist and fewer phone calls and emails from their therapist. Among patients treated for generalized anxiety, ratings of mid-treatment alliance were higher among registered providers as compared to graduate students. Multiple directions for future research on therapeutic alliance in ICBT are offered, including suggestions for developing a new measure of therapeutic alliance specific to ICBT and measuring therapeutic alliance throughout the treatment process.
|
|
| 22. |
- Hesser, Hugo, et al.
(author)
-
Therapist-assisted Internet-delivered cognitive behavior therapy for depression and anxiety : Translating evidence into clinical practice
- 2014
-
In: Journal of Anxiety Disorders. - : Elsevier. - 0887-6185 .- 1873-7897. ; 28:8, s. 884-893
-
Journal article (peer-reviewed)abstract
- This dissemination study examined the effectiveness of therapist-assisted Internet-delivered Cognitive Behavior Therapy (ICBT) when offered in clinical practice. A centralized unit screened and coordinated ICBT delivered by newly trained therapists working in six geographically dispersed clinical settings. Using an open trial design, 221 patients were offered 12 modules of ICBT for symptoms of generalized anxiety (n=112), depression (n=83), or panic (n=26). At baseline, midpoint and post-treatment, kpatients completed self-report measures. On average, patients completed 8 of 12 modules. Latent growth curve modeling identified significant reductions in depression, anxiety, stress and impairment (d=.65-.78), and improvements in quality of life (d=.48-.66). Improvements in primary symptoms were large (d=.91-1.25). Overall, therapist-assisted ICBT was effective when coordinated across settings in clinical practice, but further attention should be given to strategies to improve completion of treatment modules.
|
|
| 23. |
- Zhukova, Nataliya, et al.
(author)
-
WNT activation by lithium abrogates TP53 mutation associated radiation resistance in medulloblastoma
- 2014
-
In: Acta neuropathologica communications. - : Springer Science and Business Media LLC. - 2051-5960. ; 2
-
Journal article (peer-reviewed)abstract
- TP53 mutations confer subgroup specific poor survival for children with medulloblastoma. We hypothesized that WNT activation which is associated with improved survival for such children abrogates TP53 related radioresistance and can be used to sensitize TP53 mutant tumors for radiation. We examined the subgroup-specific role of TP53 mutations in a cohort of 314 patients treated with radiation. TP53 wild-type or mutant human medulloblastoma cell-lines and normal neural stem cells were used to test radioresistance of TP53 mutations and the radiosensitizing effect of WNT activation on tumors and the developing brain. Children with WNT/TP53 mutant medulloblastoma had higher 5-year survival than those with SHH/TP53 mutant tumours (100% and 36.6%±8.7%, respectively (p<0.001)). Introduction of TP53 mutation into medulloblastoma cells induced radioresistance (survival fractions at 2Gy (SF2) of 89%±2% vs. 57.4%±1.8% (p<0.01)). In contrast, beta-catenin mutation sensitized TP53 mutant cells to radiation (p<0.05). Lithium, an activator of the WNT pathway, sensitized TP53 mutant medulloblastoma to radiation (SF2 of 43.5%±1.5% in lithium treated cells vs. 56.6±3% (p<0.01)) accompanied by increased number of gammaH2AX foci. Normal neural stem cells were protected from lithium induced radiation damage (SF2 of 33%±8% for lithium treated cells vs. 27%±3% for untreated controls (p=0.05). Poor survival of patients with TP53 mutant medulloblastoma may be related to radiation resistance. Since constitutive activation of the WNT pathway by lithium sensitizes TP53 mutant medulloblastoma cells and protect normal neural stem cells from radiation, this oral drug may represent an attractive novel therapy for high-risk medulloblastomas.
|
|
