| 1. |
|
|
| 2. |
|
|
| 3. |
- Axfors, Cathrine, et al.
(author)
-
Association between convalescent plasma treatment and mortality in COVID-19 : a collaborative systematic review and meta-analysis of randomized clinical trials
- 2021
-
In: BMC Infectious Diseases. - : BioMed Central (BMC). - 1471-2334. ; 21:1
-
Research review (peer-reviewed)abstract
- Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, ). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I-2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Hirsch, S. D., et al.
(author)
-
The role of CDHR3 in susceptibility to otitis media
- 2021
-
In: Journal of Molecular Medicine. - : Springer Nature. - 0946-2716 .- 1432-1440. ; 99:11, s. 1571-1583
-
Journal article (peer-reviewed)abstract
- Abstract: Otitis media (OM) is common in young children and can cause hearing loss and speech, language, and developmental delays. OM has high heritability; however, little is known about OM-related molecular and genetic processes. CDHR3 was previously identified as a locus for OM susceptibility, but to date, studies have focused on how the CDHR3 p.Cys529Tyr variant increases epithelial binding of rhinovirus-C and risk for lung or sinus pathology. In order to further delineate a role for CDHR3 in OM, we performed the following: exome sequencing using DNA samples from OM-affected individuals from 257 multi-ethnic families; Sanger sequencing, logistic regression and transmission disequilibrium tests for 407 US trios or probands with OM; 16S rRNA sequencing and analysis for middle ear and nasopharyngeal samples; and single-cell RNA sequencing and differential expression analyses for mouse middle ear. From exome sequence data, we identified a novel pathogenic CDHR3 splice variant that co-segregates with OM in US and Finnish families. Additionally, a frameshift and six missense rare or low-frequency variants were identified in Finnish probands. In US probands, the CDHR3 p.Cys529Tyr variant was associated with the absence of middle ear fluid at surgery and also with increased relative abundance of Lysobacter in the nasopharynx and Streptomyces in the middle ear. Consistent with published data on airway epithelial cells and our RNA-sequence data from human middle ear tissues, Cdhr3 expression is restricted to ciliated epithelial cells of the middle ear and is downregulated after acute OM. Overall, these findings suggest a critical role for CDHR3 in OM susceptibility. Key messages: • Novel rare or low-frequency CDHR3 variants putatively confer risk for otitis media. • Pathogenic variant CDHR3 c.1653 + 3G > A was found in nine families with otitis media. • CDHR3 p.Cys529Tyr was associated with lack of effusion and bacterial otopathogens. • Cdhr3 expression was limited to ciliated epithelial cells in mouse middle ear. • Cdhr3 was downregulated 3 h after infection of mouse middle ear.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- Musso, G., et al.
(author)
-
Association of non-alcoholic fatty liver disease with chronic kidney disease : a systematic review and meta-analysis
- 2014
-
In: PLoS Medicine. - : Public Library of Science. - 1549-1277 .- 1549-1676. ; 11:7, s. e1001680-
-
Journal article (peer-reviewed)abstract
- Background:Chronic kidney disease (CKD) is a frequent, under-recognized condition and a risk factor for renal failure and cardiovascular disease. Increasing evidence connects non-alcoholic fatty liver disease (NAFLD) to CKD. We conducted a meta-analysis to determine whether the presence and severity of NAFLD are associated with the presence and severity of CKD.Methods and Findings:English and non-English articles from international online databases from 1980 through January 31, 2014 were searched. Observational studies assessing NAFLD by histology, imaging, or biochemistry and defining CKD as either estimated glomerular filtration rate (eGFR) andlt;60 ml/min/1.73 m2 or proteinuria were included. Two reviewers extracted studies independently and in duplicate. Individual participant data (IPD) were solicited from all selected studies. Studies providing IPD were combined with studies providing only aggregate data with the two-stage method. Main outcomes were pooled using random-effects models. Sensitivity and subgroup analyses were used to explore sources of heterogeneity and the effect of potential confounders. The influences of age, whole-body/abdominal obesity, homeostasis model of insulin resistance (HOMA-IR), and duration of follow-up on effect estimates were assessed by meta-regression. Thirty-three studies (63,902 participants, 16 population-based and 17 hospital-based, 20 cross-sectional, and 13 longitudinal) were included. For 20 studies (61% of included studies, 11 cross-sectional and nine longitudinal, 29,282 participants), we obtained IPD. NAFLD was associated with an increased risk of prevalent (odds ratio [OR] 2.12, 95% CI 1.69-2.66) and incident (hazard ratio [HR] 1.79, 95% CI 1.65-1.95) CKD. Non-alcoholic steatohepatitis (NASH) was associated with a higher prevalence (OR 2.53, 95% CI 1.58-4.05) and incidence (HR 2.12, 95% CI 1.42-3.17) of CKD than simple steatosis. Advanced fibrosis was associated with a higher prevalence (OR 5.20, 95% CI 3.14-8.61) and incidence (HR 3.29, 95% CI 2.30-4.71) of CKD than non-advanced fibrosis. In all analyses, the magnitude and direction of effects remained unaffected by diabetes status, after adjustment for other risk factors, and in other subgroup and meta-regression analyses. In cross-sectional and longitudinal studies, the severity of NAFLD was positively associated with CKD stages. Limitations of analysis are the relatively small size of studies utilizing liver histology and the suboptimal sensitivity of ultrasound and biochemistry for NAFLD detection in population-based studies.Conclusion:The presence and severity of NAFLD are associated with an increased risk and severity of CKD.Please see later in the article for the Editors Summary. © 2014 Musso et al.
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
- Shein, K.A., et al.
(author)
-
State of the Climate in 2005
- 2006
-
In: Bulletin of American Meteorological Society. ; 87:6, s. 1-102
-
Journal article (peer-reviewed)
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
- Lazarus, J.V., et al.
(author)
-
A cross-sectional study of the public health response to non-alcoholic fatty liver disease in Europe
- 2020
-
In: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 72:1, s. 14-24
-
Journal article (peer-reviewed)abstract
- Background & AimsNon-alcoholic fatty liver disease (NAFLD) is a growing public health problem worldwide and has become an important field of biomedical inquiry. We aimed to determine whether European countries have mounted an adequate public health response to NAFLD and non-alcoholic steatohepatitis (NASH).MethodsIn 2018 and 2019, NAFLD experts in 29 European countries completed an English-language survey on policies, guidelines, awareness, monitoring, diagnosis and clinical assessment in their country. The data were compiled, quality checked against existing official documents and reported descriptively.ResultsNone of the 29 participating countries had written strategies or action plans for NAFLD. Two countries (7%) had mentions of NAFLD or NASH in related existing strategies (obesity and alcohol). Ten (34%) reported having national clinical guidelines specifically addressing NAFLD and, upon diagnosis, all included recommendations for the assessment of diabetes and liver cirrhosis. Eleven countries (38%) recommended screening for NAFLD in all patients with either diabetes, obesity and/or metabolic syndrome. Five countries (17%) had referral algorithms for follow-up and specialist referral in primary care, and 7 (24%) reported structured lifestyle programmes aimed at NAFLD. Seven (24%) had funded awareness campaigns that specifically included prevention of liver disease. Four countries (14%) reported having civil society groups which address NAFLD and 3 countries (10%) had national registries that include NAFLD.ConclusionsWe found that a comprehensive public health response to NAFLD is lacking in the surveyed European countries. This includes policy in the form of a strategy, clinical guidelines, awareness campaigns, civil society involvement, and health systems organisation, including registries.Lay summaryWe conducted a survey on non-alcoholic fatty liver disease with experts in European countries, coupled with data extracted from official documents on policies, clinical guidelines, awareness, and monitoring. We found a general lack of national policies, awareness campaigns and civil society involvement, and few epidemiological registries.
|
|
| 16. |
- Poorter, Lourens, et al.
(author)
-
Wet and dry tropical forests show opposite successional pathways in wood density but converge over time
- 2019
-
In: Nature Ecology & Evolution. - : Nature Publishing Group. - 2397-334X. ; 3:6, s. 928-934
-
Journal article (peer-reviewed)abstract
- Tropical forests are converted at an alarming rate for agricultural use and pastureland, but also regrow naturally through secondary succession. For successful forest restoration, it is essential to understand the mechanisms of secondary succession. These mechanisms may vary across forest types, but analyses across broad spatial scales are lacking. Here, we analyse forest recovery using 1,403 plots that differ in age since agricultural abandonment from 50 sites across the Neotropics. We analyse changes in community composition using species-specific stem wood density (WD), which is a key trait for plant growth, survival and forest carbon storage. In wet forest, succession proceeds from low towards high community WD (acquisitive towards conservative trait values), in line with standard successional theory. However, in dry forest, succession proceeds from high towards low community WD (conservative towards acquisitive trait values), probably because high WD reflects drought tolerance in harsh early successional environments. Dry season intensity drives WD recovery by influencing the start and trajectory of succession, resulting in convergence of the community WD over time as vegetation cover builds up. These ecological insights can be used to improve species selection for reforestation. Reforestation species selected to establish a first protective canopy layer should, among other criteria, ideally have a similar WD to the early successional communities that dominate under the prevailing macroclimatic conditions.
|
|
| 17. |
- Smith-Byrne, Karl, et al.
(author)
-
Identifying therapeutic targets for cancer among 2074 circulating proteins and risk of nine cancers
- 2024
-
In: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
-
Journal article (peer-reviewed)abstract
- Circulating proteins can reveal key pathways to cancer and identify therapeutic targets for cancer prevention. We investigate 2,074 circulating proteins and risk of nine common cancers (bladder, breast, endometrium, head and neck, lung, ovary, pancreas, kidney, and malignant non-melanoma) using cis protein Mendelian randomisation and colocalization. We conduct additional analyses to identify adverse side-effects of altering risk proteins and map cancer risk proteins to drug targets. Here we find 40 proteins associated with common cancers, such as PLAUR and risk of breast cancer [odds ratio per standard deviation increment: 2.27, 1.88-2.74], and with high-mortality cancers, such as CTRB1 and pancreatic cancer [0.79, 0.73-0.85]. We also identify potential adverse effects of protein-altering interventions to reduce cancer risk, such as hypertension. Additionally, we report 18 proteins associated with cancer risk that map to existing drugs and 15 that are not currently under clinical investigation. In sum, we identify protein-cancer links that improve our understanding of cancer aetiology. We also demonstrate that the wider consequence of any protein-altering intervention on well-being and morbidity is required to interpret any utility of proteins as potential future targets for therapeutic prevention.
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
- Anderberg, C., et al.
(author)
-
Deficiency for endoglin in tumor vasculature weakens the endothelial barrier to metastatic dissemination
- 2013
-
In: Journal of Experimental Medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 210:3, s. 563-579
-
Journal article (peer-reviewed)abstract
- Therapy-induced resistance remains a significant hurdle to achieve long-lasting responses and cures in cancer patients. We investigated the long-term consequences of genetically impaired angiogenesis by engineering multiple tumor models deprived of endoglin, a co-receptor for TGF-β in endothelial cells actively engaged in angiogenesis. Tumors from endoglin-deficient mice adapted to the weakened angiogenic response, and refractoriness to diminished endoglin signaling was accompanied by increased metastatic capability. Mechanistic studies in multiple mouse models of cancer revealed that deficiency for endoglin resulted in a tumor vasculature that displayed hallmarks of endothelial-to-mesenchymal transition, a process of previously unknown significance in cancer biology, but shown by us to be associated with a reduced capacity of the vasculature to avert tumor cell intra- and extravasation. Nevertheless, tumors deprived of endoglin exhibited a delayed onset of resistance to anti-VEGF (vascular endothelial growth factor) agents, illustrating the therapeutic utility of combinatorial targeting of multiple angiogenic pathways for the treatment of cancer.
|
|
| 22. |
- Barregård, Lars, 1948, et al.
(author)
-
Human and Methodological Sources of Variability in the Measurement of Urinary 8-Oxo-7,8-dihydro-2 '-deoxyguanosine
- 2013
-
In: Antioxidants and Redox Signaling. - : Mary Ann Liebert Inc. - 1523-0864 .- 1557-7716. ; 18:18, s. 2377-2391
-
Journal article (peer-reviewed)abstract
- Aims: Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is a widely used biomarker of oxidative stress. However, variability between chromatographic and ELISA methods hampers interpretation of data, and this variability may increase should urine composition differ between individuals, leading to assay interference. Furthermore, optimal urine sampling conditions are not well defined. We performed inter-laboratory comparisons of 8-oxodG measurement between mass spectrometric-, electrochemical- and ELISA-based methods, using common within-technique calibrants to analyze 8-oxodG-spiked phosphate-buffered saline and urine samples. We also investigated human subject- and sample collection-related variables, as potential sources of variability. Results: Chromatographic assays showed high agreement across urines from different subjects, whereas ELISAs showed far more inter-laboratory variation and generally overestimated levels, compared to the chromatographic assays. Excretion rates in timed 'spot' samples showed strong correlations with 24 h excretion (the 'gold' standard) of urinary 8-oxodG (r(p) 0.67-0.90), although the associations were weaker for 8-oxodG adjusted for creatinine or specific gravity (SG). The within-individual excretion of 8-oxodG varied only moderately between days (CV 17% for 24 h excretion and 20% for first void, creatinine-corrected samples). Innovation: This is the first comprehensive study of both human and methodological factors influencing 8-oxodG measurement, providing key information for future studies with this important biomarker. Conclusion: ELISA variability is greater than chromatographic assay variability, and cannot determine absolute levels of 8-oxodG. Use of standardized calibrants greatly improves intra-technique agreement and, for the chromatographic assays, importantly allows integration of results for pooled analyses. If 24 h samples are not feasible, creatinine- or SG-adjusted first morning samples are recommended.
|
|
| 23. |
|
|
| 24. |
- Cortez, Daniel, et al.
(author)
-
ECG-derived spatial QRS-T angle is strongly associated with hypertrophic cardiomyopathy
- 2017
-
In: Journal of Electrocardiology. - : Elsevier BV. - 0022-0736 .- 1532-8430. ; 50:2, s. 195-202
-
Journal article (peer-reviewed)abstract
- Introduction: ECG-derived vectorcardiography (VCG) has diagnostic and prognostic value in various diseases. Hypertrophic cardiomyopathy (HCM), a genetic disease with unexplained left ventricular hypertrophy, is one of the most common causes of sudden cardiac death (SCD) in young persons. Genotype positive status is associated with increased risk of systolic dysfunction, heart failure, and (SCD). Herein, we aimed to determine the diagnostic utility of derived VCG parameters in a large cohort of genotyped HCM patients. Methods: Between 1997 and 2007, genetic testing was performed on 1053 unrelated patients with HCM. Of these, 967 had 12-lead ECGs suitable for computerized derivation of VCG parameters, including the spatial mean and peaks QRS-T angles, spatial ventricular gradient (SVG), spatial QRS, QT, and Tpeak-Tend (TpTe) intervals. ECGs were also evaluated using Seattle ECG criteria. Differences between HCM patients and healthy controls as well as between genotype positive versus genotype negative HCM patients were assessed. Results: Spatial peaks (129.3. ±. 26.4 vs.30.5. ±. 24.2 degrees) and spatial mean QRS-T angles (121.8. ±. 38.6 vs. 47.3. ±. 27.6 degrees) were significantly higher in patients with HCM than in controls (P. <. 0.001). The spatial peaks and mean QRS-T angles identified 94% and 84% of HCM patients, respectively, while Seattle criteria identified 70.7% of patients (P. <. 0.001). Genotype positive patients had higher spatial mean QRS-T angles, spatial TpTe (P. <. 0.001 respectively), spatial peaks QRS-T angles (P. =0.017) and lower SVG (P. <. 0.001) than genotype negative patients. Conclusions: ECG-derived spatial QRS-T angles can differentiate patients with HCM from controls and could provide a better tool than traditional Seattle criteria. Clinical usefulness of VCG to differentiate genotype-negative from genotype-positive patients has yet to be established.
|
|
| 25. |
- Cortez, Daniel, et al.
(author)
-
Vectorcardiography identifies patients with electrocardiographically concealed long QT syndrome
- 2017
-
In: Heart Rhythm. - : Elsevier BV. - 1547-5271. ; 14:6, s. 894-899
-
Journal article (peer-reviewed)abstract
- Background Long QT syndrome (LQTS) and genotypic subtypes are associated with distinctive T-wave patterns, arrhythmogenic triggers, and corrected QT (QTc) interval risk associations. Twenty percent of patients with LQTS have normal QTc values, defined as electrographically concealed LQTS (ecLQTS). Vectorcardiography (VCG) has value for sudden cardiac death risk assessment. Objective The purpose of this study was to determine the use of VCG to identify patients with ecLQTS. Methods We performed a retrospective analysis in patients with ecLQTS with resting QTc values <440 ms. Computerized derivation of the spatial mean and peak QRS-T angles, QTpeak, Tpeak-Tend (angle between QRS and T-wave peak amplitudes in 3-dimensional space), and T-wave eigenvalues (TwEVs; amplitudes [in microvolts] for each of the first 4 TwEVs were derived from the 12-lead electrocardiogram) was performed. The results were compared with those for healthy controls. Intergenotype differences were analyzed. Results Of 610 patients with LQTS, 169 patients (28%) had ecLQTS (86 (51%) men; mean age 22 ± 16 years; mean QTc interval 422 ± 14 ms). There were 519 healthy controls (44% men; mean age 19.8 ± 13.8 years) with a mean QTc interval of 426 ± 28 ms. Among VCG parameters, QTpeak and TwEVs significantly differentiated patients with ecLQTS from controls (P ≤.01 for each) as well as differentiated KCNQ1-encoded type 1 LQTS (ecLQT1), KCNH2-encoded type 2 LQTS (ecLQT2), and SCN5A-encoded type 3 LQTS (ecLQT3) from controls (P <.01). ecLQT3 was differentiated from controls and ecLQT1 and ecLQT2 by the fourth TwEV (P <.01 for each). The fourth TwEV differentiated symptomatic patients with ecLQTS from asymptomatic patients with ecLQTS (P <.01). Conclusion ecLQTS can be distinguished from controls using QTpeak. ecLQT3 was best differentiated by the fourth TwEV. VCG may facilitate familial diagnostic anticipation of LQTS status before the completion of mutation-specific genetic testing even with normal resting QTc values.
|
|
| 26. |
- Gei, Maga, et al.
(author)
-
Legume abundance along successional and rainfall gradients in Neotropical forests
- 2018
-
In: Nature Ecology & Evolution. - : Springer Science and Business Media LLC. - 2397-334X. ; 2:7
-
Journal article (peer-reviewed)abstract
- The nutrient demands of regrowing tropical forests are partly satisfied by nitrogen-fixing legume trees, but our understanding of the abundance of those species is biased towards wet tropical regions. Here we show how the abundance of Leguminosae is affected by both recovery from disturbance and large-scale rainfall gradients through a synthesis of forest inventory plots from a network of 42 Neotropical forest chronosequences. During the first three decades of natural forest regeneration, legume basal area is twice as high in dry compared with wet secondary forests. The tremendous ecological success of legumes in recently disturbed, water-limited forests is likely to be related to both their reduced leaflet size and ability to fix N2, which together enhance legume drought tolerance and water-use efficiency. Earth system models should incorporate these large-scale successional and climatic patterns of legume dominance to provide more accurate estimates of the maximum potential for natural nitrogen fixation across tropical forests.
|
|
| 27. |
|
|
| 28. |
|
|
| 29. |
|
|
| 30. |
|
|
| 31. |
|
|
| 32. |
|
|
| 33. |
- Rodriguez-Cortez, VC, et al.
(author)
-
Monozygotic twins discordant for common variable immunodeficiency reveal impaired DNA demethylation during naïve-to-memory B-cell transition
- 2015
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6, s. 7335-
-
Journal article (peer-reviewed)abstract
- Common variable immunodeficiency (CVID), the most frequent primary immunodeficiency characterized by loss of B-cell function, depends partly on genetic defects, and epigenetic changes are thought to contribute to its aetiology. Here we perform a high-throughput DNA methylation analysis of this disorder using a pair of CVID-discordant MZ twins and show predominant gain of DNA methylation in CVID B cells with respect to those from the healthy sibling in critical B lymphocyte genes, such as PIK3CD, BCL2L1, RPS6KB2, TCF3 and KCNN4. Individual analysis confirms hypermethylation of these genes. Analysis in naive, unswitched and switched memory B cells in a CVID patient cohort shows impaired ability to demethylate and upregulate these genes in transitioning from naive to memory cells in CVID. Our results not only indicate a role for epigenetic alterations in CVID but also identify relevant DNA methylation changes in B cells that could explain the clinical manifestations of CVID individuals.
|
|
| 34. |
- Adlemo, Anders, et al.
(author)
-
Hybrid education : A critical review into challenges and opportunities
- 2023
-
In: Proceedings of the International CDIO Conference. - : Norges teknisk-naturvitenskapelige universitet. - 9788230361863 ; , s. 857-865
-
Conference paper (peer-reviewed)abstract
- Hybrid education is a complex combination of simultaneous face-to-face and online teaching. This model of teaching comes with a wide range of benefits, primarily being able to offer the same content to a wider audience. Hybrid education became an effective form of teaching during the COVID-19 pandemic. In these post pandemic years, the benefit of hybrid education can still be utilized, allowing for improved flexibility in teaching schedules, engaging students in interactive learning, bringing online students closer to the teacher and face-to-face students, and offering education to students who could not otherwise participate. However, with all the benefits of hybrid education, there are some significant challenges which restrict the implementation or hinder the full potential of hybrid education. Some key challenges are student engagement from the online students with the teacher as well as with other students, technological requirements, physical classroom set-up, education of the teachers, and time investment in re-structuring courses. In this article, we review the challenges of hybrid education, strategies to address these challenges focusing on implementation and effectiveness, as well as evaluating student feedback from students at Jönköping University that have been a part of hybrid education.
|
|
| 35. |
|
|
| 36. |
- Agramont, J, et al.
(author)
-
Fecal Pollution Drives Antibiotic Resistance and Class 1 Integron Abundance in Aquatic Environments of the Bolivian Andes Impacted by Mining and Wastewater
- 2020
-
In: Microorganisms. - : MDPI AG. - 2076-2607. ; 8:8
-
Journal article (peer-reviewed)abstract
- An increased abundance of antibiotic resistance genes (ARGs) in aquatic environments has been linked to environmental pollution. Mining polluted sites with high concentration of metals could favor the in situ coselection of ARGs, whereas wastewater discharges release fecal antibiotic resistant bacteria in the environment. To study the effect of human fecal contamination and mining pollution, water and sediment samples affected by mining activities and sewage discharges were collected from three lakes in Bolivia, the pristine Andean lake Pata Khota, the Milluni Chico lake directly impacted by acid mine drainage, and the Uru-Uru lake located close to Oruro city and highly polluted by mining activities and human wastewater discharges. Physicochemical parameters, including metal composition, were analyzed in water and sediment samples. ARGs were screened for and verified by quantitative polymerase chain reaction (PCR) together with the mobile element class 1 integron (intl1), as well as crAssphage, a marker of human fecal pollution. The gene intl1 was positively correlated with sul1, sul2, tetA, and blaOXA-2. CrAssphage was only detected in the Uru-Uru lake, and its tributaries and significantly higher abundance of ARGs were found in these sites. Multivariate analysis showed that crAssphage abundance, electrical conductivity, and pH were positively correlated with higher levels of intl1 and ARGs. Taken together, our results suggest that fecal pollution is the major driver of higher levels of ARGs and intl1 in environments contaminated by wastewater and mining activities.
|
|
| 37. |
- Bootpetch, TC, et al.
(author)
-
Multi-omic studies on missense PLG variants in families with otitis media
- 2020
-
In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 15035-
-
Journal article (peer-reviewed)abstract
- Otitis media (OM), a very common disease in young children, can result in hearing loss. In order to potentially replicate previously reported associations between OM and PLG, exome and Sanger sequencing, RNA-sequencing of saliva and middle ear samples, 16S rRNA sequencing, molecular modeling, and statistical analyses including transmission disequilibrium tests (TDT) were performed in a multi-ethnic cohort of 718 families and simplex cases with OM. We identified four rare PLG variants c.112A > G (p.Lys38Glu), c.782G > A (p.Arg261His), c.1481C > T (p.Ala494Val) and c.2045 T > A (p.Ile682Asn), and one common variant c.1414G > A (p.Asp472Asn). However TDT analyses for these PLG variants did not demonstrate association with OM in 314 families. Additionally PLG expression is very low or absent in normal or diseased middle ear in mouse and human, and salivary expression and microbial α-diversity were non-significant in c.1414G > A (p.Asp472Asn) carriers. Based on molecular modeling, the novel rare variants particularly c.782G > A (p.Arg261His) and c.2045 T > A (p.Ile682Asn) were predicted to affect protein structure. Exploration of other potential disease mechanisms will help elucidate how PLG contributes to OM susceptibility in humans. Our results underline the importance of following up findings from genome-wide association through replication studies, preferably using multi-omic datasets.
|
|
| 38. |
- Chazdon, Robin L., et al.
(author)
-
Carbon sequestration potential of second-growth forest regeneration in the Latin American tropics
- 2016
-
In: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 2:5
-
Journal article (peer-reviewed)abstract
- Regrowth of tropical secondary forests following complete or nearly complete removal of forest vegetation actively stores carbon in aboveground biomass, partially counterbalancing carbon emissions from deforestation, forest degradation, burning of fossil fuels, and other anthropogenic sources. We estimate the age and spatial extent of lowland second-growth forests in the Latin American tropics and model their potential aboveground carbon accumulation over four decades. Our model shows that, in 2008, second-growth forests (1 to 60 years old) covered 2.4 million km2 of land (28.1% of the total study area). Over 40 years, these lands can potentially accumulate a total aboveground carbon stock of 8.48 Pg C (petagrams of carbon) in aboveground biomass via low-cost natural regeneration or assisted regeneration, corresponding to a total CO2 sequestration of 31.09 Pg CO2. This total is equivalent to carbon emissions from fossil fuel use and industrial processes in all of Latin America and the Caribbean from 1993 to 2014. Ten countries account for 95% of this carbon storage potential, led by Brazil, Colombia, Mexico, and Venezuela. We model future land-use scenarios to guide national carbon mitigation policies. Permitting natural regeneration on 40% of lowland pastures potentially stores an additional 2.0 Pg C over 40 years. Our study provides information and maps to guide national-level forest-based carbon mitigation plans on the basis of estimated rates of natural regeneration and pasture abandonment. Coupled with avoided deforestation and sustainable forest management, natural regeneration of second-growth forests provides a low-cost mechanism that yields a high carbon sequestration potential with multiple benefits for biodiversity and ecosystem services.
|
|
| 39. |
|
|
| 40. |
|
|
| 41. |
- Frank, DN, et al.
(author)
-
Otitis media susceptibility and shifts in the head and neck microbiome due to SPINK5 variants
- 2021
-
In: Journal of medical genetics. - : BMJ. - 1468-6244 .- 0022-2593. ; 58:7, s. 442-452
-
Journal article (peer-reviewed)abstract
- Otitis media (OM) susceptibility has significant heritability; however, the role of rare variants in OM is mostly unknown. Our goal is to identify novel rare variants that confer OM susceptibility.MethodsWe performed exome and Sanger sequencing of >1000 DNA samples from 551 multiethnic families with OM and unrelated individuals, RNA-sequencing and microbiome sequencing and analyses of swabs from the outer ear, middle ear, nasopharynx and oral cavity. We also examined protein localisation and gene expression in infected and healthy middle ear tissues.ResultsA large, intermarried pedigree that includes 81 OM-affected and 53 unaffected individuals cosegregates two known rare A2ML1 variants, a common FUT2 variant and a rare, novel pathogenic variant c.1682A>G (p.Glu561Gly) within SPINK5 (LOD=4.09). Carriage of the SPINK5 missense variant resulted in increased relative abundance of Microbacteriaceae in the middle ear, along with occurrence of Microbacteriaceae in the outer ear and oral cavity but not the nasopharynx. Eight additional novel SPINK5 variants were identified in 12 families and individuals with OM. A role for SPINK5 in OM susceptibility is further supported by lower RNA counts in variant carriers, strong SPINK5 localisation in outer ear skin, faint localisation to middle ear mucosa and eardrum and increased SPINK5 expression in human cholesteatoma.ConclusionSPINK5 variants confer susceptibility to non-syndromic OM. These variants potentially contribute to middle ear pathology through breakdown of mucosal and epithelial barriers, immunodeficiency such as poor vaccination response, alteration of head and neck microbiota and facilitation of entry of opportunistic pathogens into the middle ear.
|
|
| 42. |
- Kaneberg, Elvira Ruiz, et al.
(author)
-
Hydrogen technology for supply chain sustainability : The Mexican transportation impacts on society
- 2022
-
In: International journal of hydrogen energy. - : Elsevier. - 0360-3199 .- 1879-3487. ; 47:70, s. 29999-30011
-
Journal article (peer-reviewed)abstract
- This study sheds light on the Hydrogen technology in transportation for reaching the sustainability goals of societies, illustrated by the case of Mexico. In terms of the affected supply chains the study explores how the packaging and distribution of a fuel-saving tool that allows the adoption of hydrogen as complementary energy for maritime transportation to improve economic and environmental performance in Mexico. This exploratory study performs interviews, observations, simulations, and tests involving producers, suppliers, and users at 26 ports in Mexico. The study shows that environmental and economic performance are related to key processes in Supply Chain Management (SCM) in which packaging and distribution are critical for achieving logistics and transportation sustainability goals. Reusable packaging and the distribution of a fuel-saving tool can help decrease costs -, of transport, and downstream/upstream processes in SCM while at the same time increasing the environmental performance.
|
|
| 43. |
|
|
| 44. |
- Raj, Satish R, et al.
(author)
-
Postural orthostatic tachycardia syndrome (POTS) : Priorities for POTS care and research from a 2019 National Institutes of Health Expert Consensus Meeting - Part 2
- 2021
-
In: Autonomic Neuroscience: Basic & Clinical. - : Elsevier BV. - 1872-7484. ; 235
-
Journal article (peer-reviewed)abstract
- The National Institutes of Health hosted a workshop in 2019 to build consensus around the current state of understanding of the pathophysiology of postural orthostatic tachycardia syndrome (POTS) and to identify knowledge gaps that must be addressed to enhance clinical care of POTS patients through research. This second (of two) articles summarizes current knowledge gaps, and outlines the clinical and research priorities for POTS. POTS is a complex, multi-system, chronic disorder of the autonomic nervous system characterized by orthostatic intolerance and orthostatic tachycardia without hypotension. Patients often experience a host of other related disabling symptoms. The functional and economic impacts of this disorder are significant. The pathophysiology remains incompletely understood. Beyond the significant gaps in understanding the disorder itself, there is a paucity of evidence to guide treatment which can contribute to suboptimal care for this patient population. The vast majority of physicians have minimal to no familiarity or training in the assessment and management of POTS. Funding for POTS research remains very low relative to the size of the patient population and impact of the syndrome. In addition to efforts to improve awareness and physician education, an investment in research infrastructure including the development of standardized disease-specific evaluation tools and outcome measures is needed to facilitate effective collaborative research. A national POTS research consortium could facilitate well-controlled multidisciplinary clinical research studies and therapeutic trials. These priorities will require a substantial increase in the number of research investigators and the amount of research funding in this area.
|
|
| 45. |
- Rogers, Miranda, et al.
(author)
-
Genetically proxied impaired GIPR signaling and risk of 6 cancers
- 2023
-
In: iScience. - 2589-0042. ; 26:6
-
Journal article (peer-reviewed)abstract
- Preclinical and genetic studies suggest that impaired glucose-dependent insulinotropic polypeptide receptor (GIPR) signaling worsens glycemic control. The relationship between GIPR signaling and the risk of cancers influenced by impaired glucose homeostasis is unclear. We examined the association of a variant in GIPR, rs1800437 (E354Q), shown to impair long-term GIPR signaling and lower circulating glucose-dependent insulinotropic peptide concentrations, with risk of 6 cancers influenced by impaired glucose homeostasis (breast, colorectal, endometrial, lung, pancreatic, and renal) in up to 235,698 cases and 333,932 controls. Each copy of E354Q was associated with a higher risk of overall and luminal A-like breast cancer and this association was consistent in replication and colocalization analyses. E354Q was also associated with higher postprandial glucose concentrations but diminished insulin secretion and lower testosterone concentrations. Our human genetics analysis suggests an adverse effect of the GIPR E354Q variant on breast cancer risk, supporting further evaluation of GIPR signaling in breast cancer prevention.
|
|
| 46. |
- Rosengren, Anna, et al.
(author)
-
Collegial learning during the pandemic : Realized activities and lessons learnt
- 2022
-
In: Proceedings of the 18th International CDIO Conference. - Reykjavík : Reykjavík University. - 9789935965561 ; , s. 385-395
-
Conference paper (peer-reviewed)abstract
- The pandemic has forced teaching as well as as the Software Development industry, to be performed remotely. The educational institutions are therefore facing the situation of training and steering the students in, not only complex work, but also in remote-based work and it processes. Specific challenges here relate to project work with larger groups of developers, with testing, and integration of technical components for complete solutions, but the psychosocial factors come into play as well. This paper considers the situation that has arisen as a consequence of the pandemic and regards how project-based courses should be adapted to ‘The New Normal’. In focus is a course in Software Engineering, where a large-scaled project shall be developed remotely. Representatives from IT-companies act at the course remote, and at specific occurrences. The course is observed by the teachers to see its outcome, as well as different aspects on attitudes towards future remote work. Interviews and surveys regarding attitudes of students, as well as involved company representatives are presented, where the focus is on process, productivity, work environment, interest in remote work, as well as social aspects. The main findings, based on the surveys, motivates hybrid solutions for university courses, to meet the corresponding companies’ way of future working style.
|
|
| 47. |
- Roswall, Pernilla, et al.
(author)
-
Microenvironmental control of breast cancer subtype elicited through paracrine platelet-derived growth factor-CC signaling
- 2018
-
In: Nature Medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 24, s. 463-473
-
Journal article (peer-reviewed)abstract
- Breast tumors of the basal-like, hormone receptor-negative subtype remain an unmet clinical challenge, as there is high rate of recurrence and poor survival in patients following treatment. Coevolution of the malignant mammary epithelium and its underlying stroma instigates cancer-associated fibroblasts (CAFs) to support most, if not all, hallmarks of cancer progression. Here we delineate a previously unappreciated role for CAFs as determinants of the molecular subtype of breast cancer. We identified paracrine crosstalk between cancer cells expressing platelet-derived growth factor (PDGF)-CC and CAFs expressing the cognate receptors in human basal-like mammary carcinomas. Genetic or pharmacological intervention of PDGF-CC activity in mouse models of cancer resulted in conversion of basal-like breast cancers into a hormone receptor-positive state that enhanced sensitivity to endocrine therapy in previously resistant tumors. We conclude that specification of breast cancer to the basal-like subtype is under microenvironmental control and is therapeutically actionable.
|
|
| 48. |
- Shah, MY, et al.
(author)
-
Cancer-associated rs6983267 SNP and its accompanying long noncoding RNA CCAT2 induce myeloid malignancies via unique SNP-specific RNA mutations
- 2018
-
In: Genome research. - : Cold Spring Harbor Laboratory. - 1549-5469 .- 1088-9051. ; 28:4, s. 432-447
-
Journal article (peer-reviewed)abstract
- The cancer-risk-associated rs6983267 single nucleotide polymorphism (SNP) and the accompanying long noncoding RNA CCAT2 in the highly amplified 8q24.21 region have been implicated in cancer predisposition, although causality has not been established. Here, using allele-specific CCAT2 transgenic mice, we demonstrate that CCAT2 overexpression leads to spontaneous myeloid malignancies. We further identified that CCAT2 is overexpressed in bone marrow and peripheral blood of myelodysplastic/myeloproliferative neoplasms (MDS/MPN) patients. CCAT2 induces global deregulation of gene expression by down-regulating EZH2 in vitro and in vivo in an allele-specific manner. We also identified a novel non-APOBEC, non-ADAR, RNA editing at the SNP locus in MDS/MPN patients and CCAT2-transgenic mice. The RNA transcribed from the SNP locus in malignant hematopoietic cells have different allelic composition from the corresponding genomic DNA, a phenomenon rarely observed in normal cells. Our findings provide fundamental insights into the functional role of rs6983267 SNP and CCAT2 in myeloid malignancies.
|
|
| 49. |
- Vernino, Steven, et al.
(author)
-
Postural orthostatic tachycardia syndrome (POTS) : State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1
- 2021
-
In: Autonomic Neuroscience: Basic and Clinical. - : Elsevier BV. - 1566-0702. ; 235
-
Journal article (peer-reviewed)abstract
- Postural orthostatic tachycardia syndrome (POTS) is a chronic and often disabling disorder characterized by orthostatic intolerance with excessive heart rate increase without hypotension during upright posture. Patients often experience a constellation of other typical symptoms including fatigue, exercise intolerance and gastrointestinal distress. A typical patient with POTS is a female of child-bearing age, who often first displays symptoms in adolescence. The onset of POTS may be precipitated by immunological stressors such as a viral infection. A variety of pathophysiologies are involved in the abnormal postural tachycardia response; however, the pathophysiology of the syndrome is incompletely understood and undoubtedly multifaceted. Clinicians and researchers focused on POTS convened at the National Institutes of Health in July 2019 to discuss the current state of understanding of the pathophysiology of POTS and to identify priorities for POTS research. This article, the first of two articles summarizing the information discussed at this meeting, summarizes the current understanding of this disorder and best practices for clinical care. The evaluation of a patient with suspected POTS should seek to establish the diagnosis, identify co-morbid conditions, and exclude conditions that could cause or mimic the syndrome. Once diagnosed, management typically begins with patient education and non-pharmacologic treatment options. Various medications are often used to address specific symptoms, but there are currently no FDA-approved medications for the treatment of POTS, and evidence for many of the medications used to treat POTS is not robust.
|
|
| 50. |
- Vico, Giulia, et al.
(author)
-
Climatic, ecophysiological, and phenological controls on plant ecohydrological strategies in seasonally dry ecosystems
- 2015
-
In: Ecohydrology. - : Wiley. - 1936-0584 .- 1936-0592. ; 8:4, s. 660-681
-
Research review (peer-reviewed)abstract
- Large areas in the tropics and at mid-latitudes experience pronounced seasonality and inter-annual variability in rainfall and hence water availability. Despite the importance of these seasonally dry ecosystems (SDEs) for the global carbon cycling and in providing ecosystem services, a unifying ecohydrological framework to interpret the effects of climatic variability on SDEs is still lacking. A synthesis of existing data about plant functional adaptations in SDEs, covering some 400 species, shows that leaf phenological variations, rather than physiological traits, provide the dominant control on plant-water-carbon interactions. Motivated by this result, the combined implications of leaf phenology and climatic variability on plant water use strategies are here explored with a minimalist model of the coupled soil water and plant carbon balances. The analyses are extended to five locations with different hydroclimatic forcing, spanning seasonally dry tropical climates (without temperature seasonality) and Mediterranean climates (exhibiting out of phase seasonal patterns of rainfall and temperature). The most beneficial leaf phenology in terms of carbon uptake depends on the climatic regime: evergreen species are favoured by short dry seasons or access to persistent water stores, whereas high inter-annual variability of rainy season duration favours the coexistence of multiple drought-deciduous phenological strategies. We conclude that drought-deciduousness may provide a competitive advantage in face of predicted declines in rainfall totals, while reduced seasonality and access to deep water stores may favour evergreen species. This article has been contributed to by US Government employees and their work is in the public domain in the USA.
|
|
