bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tacrolimus Exposure in Obese Patients: and A Case–Control Study in Kidney Transplantation
Authors: Robert Vincent , Manos-Sampol Emmanuelle , Manson Thibaut , Robert Thomas , Decourchelle Nicolas , Gruliere Anne-Sophie , Quaranta Sylvie , Moal Valérie , Legris Tristan 
Published: October 2020

Background:
Tacrolimus pharmacokinetics in obese (Ob) patients has been poorly studied. In this article, the authors explored the impact of obesity on tacrolimus exposure in kidney transplant recipients (KTRs) and estimated a more suitable initial dosage in this population.

Methods:
A retrospective, observational, monocentric case–control study was performed in obese KTRs (BMI > 30 kg/m2) who received tacrolimus between 2013 and 2017 (initial dose: 0.15 mg/kg/d) (actual weight). Nonobese (Nob) controls (BMI <30 kg/m2) were matched for age and sex. Weekly centralized monitoring of tacrolimus trough levels was performed by liquid chromatography/mass spectrometry until the third month (M3). Target trough levels were set between 8 and 10 ng/mL. All patients received antilymphocyte globulin, corticosteroids, and mycophenolate mofetil.

Results:
Of the 541 KTRs, 28 tacrolimus-treated Ob patients were included and compared with 28 NOb-matched controls. With a mean of 22 assays/patient, tacrolimus trough levels were higher in Ob patients (mean 9.9 versus 8.7 ng/mL; P = 0.008); the weight-related dose of Tac was lower at M3 (mean 0.10 versus 0.13 mg/kg/d, P < 0.0001). The tacrolimus concentration to dose (C0/D) was higher in the Ob cohort [mean 116 versus 76 (ng/mL)/(mg/kg/d); P = 0.001]. In Ob patients, a mean decrease of −4.6 mg/d in the 3 months after tacrolimus initiation was required (versus −1.12 in NOb; P = 0.001) to remain within the therapeutic range. Obesity, high mycophenolate mofetil daily dose at M3, and CYP3A5 expression were independently associated with higher tacrolimus exposure. Four dose-adaptation strategies were simulated and compared with the study results.

Conclusions:
An initial dose calculation based on either ideal or lean body weight may allow for faster achievement of tacrolimus trough level targets in Ob KTRs, who are at risk of overexposure when tacrolimus is initiated at 0.15 mg/kg/d. A prospective study is required to validate alternative dose calculation strategies in these patients.
Comprehensive Respiratory Muscle Training Improves Pulmonary Function and Respiratory Muscle Strength in Acute Stroke Patients
Authors: Choi Hee Eun , Jo Geun Yeol , Do Hwan Kwon , On Cheol Won 
Published: October 2020

Purpose:
To evaluate the effects of respiratory muscle training (RMT) on pulmonary function, respiratory complications, and stroke-related disabilities in patients with acute stroke.

Methods:
One hundred twenty-two subjects with stroke admitted to the stroke rehabilitation center of Inje Hospital between August 2016 and May 2018 were recruited. After the initial exclusion, the remaining patients were assigned to the RMT group (36 patients) or the standard rehabilitation (SR) group (28 patients who did not undergo RMT). A total of 44 patients completed the study, with 22 patients in each group. The RMT program consisted of air-stacking exercise, manually assisted coughing, inspiratory and expiratory muscle strengthening, cough exercises, and respiratory reeducation. Pulmonary function and respiratory muscle strength were evaluated before commencement and after 1 mo of RMT. The Functional Ambulation Category score, Korean version of the Modified Barthel Index, Shoulder Abduction and Finger Extension score, and handgrip power were assessed. The incidence of pneumonia was also evaluated.

Results:
Both pulmonary function and respiratory muscle strength significantly improved in both groups. However, differences (%) in the RMT group was greater for all parameters of pulmonary function and respiratory muscle strength. Respiratory complications at 1 yr were significantly lower in the RMT group (P = .016).

Conclusion:
Four weeks of comprehensive RMT in patients with acute stroke resulted in significantly greater improvements in both pulmonary function and respiratory muscle strength than SR. Therefore, RMT has the potential to reduce post-stroke respiratory complications.
Telegenetics
Authors: Peterlin Borut 
Published: October 2020

Purpose of review
The aim of the article is to provide an update on recent evidence for utilization and challenges of implementation of telegenetics in the clinical practice.

Recent findings
Implementation of telegenetics in health systems is still limited, below 10%, somewhat higher for cancer genetic counseling. Nevertheless, telegenetic services have been shown useful in the COVID pandemic. Key factors for efficient implementation include a patient-centered approach, engaging the major stakeholders, and incorporating telegenetics into existing health policies. Main barriers remain: limitations to billing and reimbursement, licensure, proper equipment and technical issues, engagement of referring providers and patients, coordination of services with local health providers, and lack of decision-making power. Further rigorous studies are needed to investigate the outcomes of telegenetics and to motivate health policies for change.

Summary
Despite continuous evidence of the benefits of telegenetics, its use in health systems remains limited. Further, larger, prospective, randomized, long-term studies are needed to address the outcomes.
Enabling factors contributing to the implementation of telegenetics are patient-centeredness, the involvement of major stakeholders, and aligning telegenetics with the existing national health policies.
Examining the Longitudinal Predictive Relationship Between HIV Treatment Outcomes and Pre-exposure Prophylaxis Use by Serodiscordant Male Couples
Authors: Jin Harry , Biello Katie , Garofalo Robert , Lurie Mark , Sullivan Patrick S. , Stephenson Rob , Mimiaga Matthew J. 
Published: October 2020

Background:
Men who have sex with men are disproportionately burdened by HIV/AIDS, and the advent of pre-exposure prophylaxis (PrEP) has provided an effective strategy to reduce the risk of HIV transmission. Research has shown that improving one partner's health-promoting behaviors increases the likelihood that their partner adopts healthier behaviors. We examined the longitudinal relationship between favorable HIV treatment outcomes with current PrEP use among HIV serodiscordant male partners.

Setting:
Data are from Project Stronger Together, a randomized controlled trial that recruited serodiscordant male couples from Atlanta, GA; Boston, MA; and Chicago, IL.

Methods:
Serodiscordant couples completed assessments at baseline, 6, 12, 18, and 24 months. We analyzed longitudinal data from 120 HIV serodiscordant male partners to assess the relationship between the HIV-negative partner's current PrEP use and their HIV-positive partner's current ART use, ART adherence, and viral load using generalized estimating equation models.

Results:
Fewer than half of the HIV-negative partners were on PrEP at baseline and nearly two-thirds of their HIV-positive partners were virally suppressed. HIV-negative male partners who had partners with an undetectable viral load had greater odds of being a current PrEP user than HIV-negative partners with partners with a detectable viral load.

Conclusion:
Our study highlights the need to develop dyad-level interventions to improve HIV medication use/adherence by HIV serodiscordant male couples. Our findings also suggest that dyad-level interventions may be able to leverage our understanding of how partners can influence each other's health-promoting behaviors to develop programs that improve health outcomes for both partners.
Tracking the introduction and spread of SARS-CoV-2 in coastal Kenya
Authors: Githinji George , de Laurent Zaydah R. , Mohammed Khadija Said , Omuoyo Donwilliams O. , Macharia Peter M. , Morobe John M. , Otieno Edward , Kinyanjui Samson M. , Agweyu Ambrose , Maitha Eric , Kitole Ben , Suleiman Thani , Mwakinangu Mohamed , Nyambu John , Otieno John , Salim Barke , Kasera Kadondi , Kiiru John , Aman Rashid , Barasa Edwine , Warimwe George , Bejon Philip , Tsofa Benjamin , Ochola-Oyier Lynette Isabella , Nokes D. James , Agoti Charles N. 
Published: October 2020

AbstractWe generated 274 SARS-CoV-2 genomes from samples collected during the early phase of the Kenyan pandemic. Phylogenetic analysis identified 8 global lineages and at least 76 independent SARS-CoV-2 introductions into Kenyan coast. The dominant B.1 lineage (European origin) accounted for 82.1% of the cases. Lineages A, B and B.4 were detected from screened individuals at the Kenya-Tanzania border or returning travellers but did not lead to established transmission. Though multiple lineages were introduced in coastal Kenya within three months following the initial confirmed case, none showed extensive local expansion other than cases characterised by lineage B.1, which accounted for 45 of the 76 introductions. We conclude that the international points of entry were important conduits of SARS-CoV-2 importations. We speculate that early public health responses prevented many introductions leading to established transmission, but nevertheless a few undetected introductions were sufficient to give rise to an established epidemic.
Factors associated with initiation of bone-health medication among older adults in primary care in Ireland
Authors: Walsh Mary E. , Nerdrum Mari , Fahey Tom , Moriarty Frank 
Published: October 2020

ABSTRACTBackgroundAdults at high risk of fragility fracture should be offered pharmacological treatment when not contraindicated, however under-treatment is common.ObjectiveThis study aimed to investigate factors associated with bone-health medication initiation in older patients attending primary care.DesignRetrospective cohort study.Setting44 general practices in Ireland from 2011-2017.SubjectsAdults aged ≥65 years who were naïve to bone-health medication for 12 months.MethodsOverall fracture-risk (based on QFracture) and individual fracture-risk factors were described for patients initiated and not initiated onto medication and compared using generalised linear model regression with Poisson distribution.ResultsOf 36,799 patients (51 % female, mean age 75.4 (SD=8.4)) included, 8% (n=2,992) were observed to initiate on bone-health medication during the study. One fifth of all patients (n=8,193) had osteoporosis or had high fracture-risk but only 21% of them (n=1,687) initiated on medication. Female sex, older age, state-funded health cover and osteoporosis were associated with initiation. Independently of osteoporosis and co-variates, high 5-year QFracture risk for hip (IRR=1.33 (95% CI=1.17-1.50), p<0.01) and all fractures (IRR=1.30 (95% CI=1.17-1.44), p<0.01) were associated with medication initiation. Previous fracture, rheumatoid arthritis, and corticosteroid use were associated with initiation, while liver, kidney, cardiovascular disease, diabetes and oestrogen-only hormone replacement therapy showed an inverse association.ConclusionsBone-health medication initiation is targeted at patients at higher fracture-risk but much potential under-treatment remains, particularly in those >80 years and with co-morbidities. This may reflect clinical uncertainty in older multimorbid patients, and further research should explore decision-making in preventive bone medication prescribing.Key pointsDuring this study, 23% of women and 11% of men defined as high-risk of fracture were newly initiated on bone-health medication.Rates of potential under-treatment were highest in patients over 80 years old.Fracture history, corticosteroid use, and rheumatoid arthritis were independently associated with medication initiation.Patients with diabetes, and liver, kidney, or cardiovascular disease were less likely to be initiated on medication.Clinical guidelines should provide advice on risk-benefit decisions in osteoporosis treatment where co-morbidities are present.
Linked surveillance and genetic data uncovers programmatically relevant geographic scale of Guinea worm transmission in Chad
Authors: Ribado Jessica V. , Li Nancy , Thiele Elizabeth , Lyons Hil , Cotton James A. , Weiss Adam , Ouakou Philippe Tchindebet , Moundai Tchonfienet , Zirimwabagabo Hubert , Guagliardo Sarah Anne J. , Chabot-Couture Guillaume , Proctor Joshua L. 
Published: October 2020

AbstractBackgroundGuinea worm (Dracunculus medinensis) was detected in Chad in 2010 after a supposed ten year absence, posing a challenge to the global eradication effort. Initiation of a village-based surveillance system in 2012 revealed a substantial number of dogs infected with Guinea worm, raising questions about paratenic hosts and cross-species transmission.Methodology/Principal FindingsWe coupled genomic and surveillance data from 2012-2018 cases to investigate the modes of transmission between hosts and the geographic connectivity for genetically similar worm populations. Eighty-six variants across three loci on the mitochondrial genome identified 41 genetically distinct worm genotypes. Spatiotemporal modeling reveals genetically identical worms are within a median range of 18.6 kilometers of each other, but largely within approximately 50 kilometers. Genetically identical worms vary in their degree of spatial clustering, suggesting there may be different factors that favor or constrain transmission. Each worm is surrounded by five to ten genetically distinct worms within a 50 kilometer radius. In an independent population, we show that more variants revealed in whole mitochondrial genome data improved the discrimination between worm pairs.Conclusions/SignificanceIn the largest study linking genetic and surveillance data to date of Guinea worm cases in Chad, we show genetic similarity and modeling can contribute to understanding local transmission. The overlap of genetically distinct worms in quantitatively identified transmission ranges highlights the necessity for genomic tools to link cases. The improved discrimination between worm pairs from variants identified across the complete mitochondrial genome indicates expanding genomic markers could link cases at a finer scale. These results suggest that scaling up genomic surveillance for Guinea worm may provide additional value for programmatic decision-making critical for monitoring cases and intervention efficacy to achieve elimination.
Structural brain imaging predicts individual-level task activation maps using deep learning
Authors: Ellis David G. , Aizenberg Michele R. 
Published: October 2020

AbstractAccurate individual functional mapping of task activations is a potential tool for biomarker discovery and is critically important for clinical care. While structural imaging does not directly map task activation, we hypothesized that structural imaging contains information that can accurately predict variations in task activation between individuals. To this end, we trained a convolutional neural network to use structural imaging (T1-weighted, T2-weighted, and diffusion tensor imaging) to predict 47 different functional MRI task activation volumes across seven task domains. The U-Net model was trained on 654 subjects and then subsequently tested on 122 unrelated subjects. The predicted activation maps correlated more strongly with their actual maps than with the maps of the other test subjects. An ablation study revealed that a model using the shape of the cortex alone or the shape of the subcortical matter alone was sufficient to predict individual-level differences in task activation maps, but a model using the shape of the whole brain resulted in markedly decreased performance. The ablation study also showed that the additional information provided by the T2-weighted and diffusion tensor imaging strengthened the predictions as compared to using the T1-weighted imaging alone. These results indicate that structural imaging contains information that is predictive of inter-subject variability in task activation mapping and cortical folding patterns as well as microstructural features may be a key component to linking brain structure to brain function.
Trans-acting genetic variation affects the expression of adjacent genes
Authors: Van Dyke Krisna , Mekonnen Gemechu , Myers Chad L. , Albert Frank W. 
Published: October 2020

AbstractGene expression differences among individuals are shaped by trans-acting expression quantitative trait loci (eQTLs). Most trans-eQTLs map to hotspot locations that influence many genes. The molecular mechanisms perturbed by hotspots are often assumed to involve “vertical” cascades of effects in pathways that can ultimately affect the expression of thousands of genes. Here, we report that trans-eQTLs can affect the expression of adjacent genes via “horizontal” mechanisms that extend along a chromosome. Genes affected by trans-eQTL hotspots in the yeast Saccharomyces cerevisiae were more likely to be located next to each other than expected by chance. These paired hotspot effects tended to occur at adjacent genes that show coexpression in response to genetic and environmental perturbations. Physical proximity and shared chromatin state, in addition to regulation of adjacent genes by similar transcription factors, were independently associated with paired hotspot effects. The effects of trans-eQTLs can spread among neighboring genes even when these genes do not share a common function. This phenomenon could result in unexpected connections between regulatory genetic variation and phenotypes.
In vivo human whole-brain Connectom diffusion MRI dataset at 760 μm isotropic resolution
Authors: Wang Fuyixue , Dong Zijing , Tian Qiyuan , Liao Congyu , Fan Qiuyun , Hoge W. Scott , Keil Boris , Polimeni Jonathan R. , Wald Lawrence L. , Huang Susie Y. , Setsompop Kawin 
Published: October 2020

AbstractWe present a whole-brain in vivo diffusion MRI (dMRI) dataset acquired at 760 μm isotropic resolution and sampled at 1260 q-space points across 9 two-hour sessions on a single healthy subject. The creation of this benchmark dataset is possible through the synergistic use of advanced acquisition hardware and software including the high-gradient-strength Connectom scanner, a custom-built 64-channel phased-array coil, a personalized motion-robust head stabilizer, a recently developed SNR-efficient dMRI acquisition method, and parallel imaging reconstruction with advanced ghost reduction algorithm. With its unprecedented resolution, SNR and image quality, we envision that this dataset will have a broad range of investigational, educational, and clinical applications that will advance the understanding of human brain structures and connectivity. This comprehensive dataset can also be used as a test bed for new modeling, sub-sampling strategies, denoising and processing algorithms, potentially providing a common testing platform for further development of in vivo high resolution dMRI techniques. Whole brain anatomical T1-weighted and T2-weighted images at submillimeter scale along with field maps are also made available.
The landscape of metabolic pathway dependencies in cancer cell lines
Authors: Joly James H. , Chew Brandon T.L. , Graham Nicholas A. 
Published: October 2020

AbstractThe metabolic reprogramming of cancer cells creates metabolic vulnerabilities that can be therapeutically targeted. However, our understanding of metabolic dependencies and the pathway crosstalk that creates these vulnerabilities in cancer cells remains incomplete. Here, by integrating gene expression data with genetic loss-of-function and pharmacological screening data from hundreds of cancer cell lines, we identified metabolic vulnerabilities at the level of pathways rather than individual genes. This approach revealed that metabolic pathway dependencies are highly context-specific such that cancer cells are vulnerable to inhibition of one metabolic pathway only when activity of another metabolic pathway is altered. Notably, we also found that the no single metabolic pathway was universally essential, suggesting that cancer cells are not invariably dependent on any metabolic pathway. In addition, we confirmed that cell culture medium is a major confounding factor for the analysis of metabolic pathway vulnerabilities. Nevertheless, we found robust associations between metabolic pathway activity and sensitivity to clinically approved drugs that were independent of cell culture medium. Lastly, we used parallel integration of pharmacological and genetic dependency data to confidently identify metabolic pathway vulnerabilities. Taken together, this study serves as a comprehensive characterization of the landscape of metabolic pathway vulnerabilities in cancer cell lines.Author SummaryCancer cells rewire their metabolism, which creates targetable metabolic vulnerabilities. Previous analyses of metabolic vulnerabilities in cancer cells have been limited to the analysis ofindividualgenes or metabolites. However, metabolicpathwaysexhibit significant cross talk and compensation for one another. We developed a computational method to answer the question: when a metabolic pathway’s activity is high, which other metabolic pathways become more essential or less essential? By integrating genetic screen data with drug response data from FDA approved drugs, we identified cancer cell line dependence on metabolicpathwaysas opposed to individualgenes. For example, we found that identifying key regulators of metabolic pathways, such as the Pentose Phosphate Pathway, may serve as a biomarker to identify which patients may benefit from antifolate chemotherapies (e.g. methotrexate, 5-fluorouracil). The efforts outlined here serve as the first characterization of the landscape of metabolic pathway vulnerabilities in cancer cell lines. Our results demonstrate the benefit of analyzing dependencies on metabolic pathways as opposed to metabolic genes.
A potential impact of physical distancing on physical and mental health. A rapid narrative umbrella review of meta-analyses on the link between social isolation and health
Authors: Morina Nexhmedin , Kip Ahlke , Hoppen Thole H. , Priebe Stefan , Meyer Thomas 
Published: October 2020

AbstractBackgroundThe imperative for physical distancing during the coronavirus disease 2019 (COVID-19) pandemic may deteriorate physical and mental health. We aimed at summarizing the strength of evidence in the published literature on the association of social isolation and loneliness with physical and mental health.MethodsWe conducted a systematic search in April 2020 to identify meta-analyses using the Medline, PsycINFO, and Web of Science databases. The search strategy included terms of social isolation, loneliness, living alone, and meta-analysis. Eligible meta-analyses needed to report any sort of association between an indicator of social isolation and any physical or mental health outcome. The findings were summarized in a narrative synthesis.ResultsTwenty-five meta-analyses met our criteria, of which 10 focused on physical health and 15 on mental health outcomes. A total of more than 3 million individuals had participated in the 692 primary studies. The results suggest that social isolation is associated with chronic physical symptoms, frailty, coronary heart disease, malnutrition, hospital readmission, reduced vaccine uptake, early mortality, depression, social anxiety, psychosis, cognitive impairment in later life, and suicidal ideation.ConclusionsThe existing evidence clearly indicates that social isolation is associated with a range of poor physical and mental health outcomes. A potential negative impact on these outcomes needs to be considered in future decisions on physical distancing measures.Strengths and limitations of this studyThis rapid umbrella review focuses on a timely and societally relevant issue.The systematic literature search was conducted in three major databases from inception up to April 2020 warranting an extensive and up-to-date overview on relevant meta-analyses in the field.Quality of included meta-analyses was rated with a standardized measure.Different indicators of social isolation were included.The utilized method did not allow for a quantitative comparison of associations with health outcomes.