bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brief Report: Switching From TDF to TAF in HIV/HBV-Coinfected Individuals With Renal Dysfunction—A Prospective Cohort Study
Authors: Surial Bernard , Béguelin Charles , Chave Jean-Philippe , Stöckle Marcel , Boillat-Blanco Noémie , Doco-Lecompte Thanh , Bernasconi Enos , Fehr Jan , Günthard Huldrych F. , Schmid Patrick , Walti Laura N. , Furrer Hansjakob , Rauch Andri , Wandeler Gilles ,   and the Swiss HIV Cohort Study
Published: July 2020

Background:
Whereas tenofovir disoproxil fumarate (TDF) can lead to renal adverse events, tenofovir alafenamide (TAF) has a more favorable renal safety profile. However, the impact of replacing TDF with TAF on renal function and liver parameters among HIV/hepatitis B virus (HBV)-coinfected individuals with renal dysfunction remains unclear.

Methods:
We included all participants from the Swiss HIV Cohort Study with an HIV/HBV coinfection who switched from TDF to TAF and had an estimated glomerular filtration rate (eGFR) <90 mL/min/1.73 m2 and a suppressed HIV viral load (<200 cp/mL). We assessed changes in eGFR, urine protein-to-creatinine ratio, and alanine aminotransferase (ALT) after 1 year using mixed-effect models with interrupted time series.

Results:
Among 106 participants (15.1% women, median age 53 years), eGFR was 60–89 mL/min/1.73 m2 in 84 (79.2%) and <60 mL/min/1.73 m2 in 22 (20.8%) individuals at the time of switch. One year after the switch from TDF to TAF, individuals with an eGFR between 60 and 89 mL/min/1.73 m2 experienced increases in eGFR of 3.2 mL/min/1.73 m2 (95% confidence interval [CI] 1.2 to 5.2), whereas those with an eGFR <60 mL/min/1.73 m2 experienced improvements of 6.2 mL/min/1.73 m2 (95% CI 2.4 to 10.0). Urine protein-to-creatinine ratio decreased overall (−6.3 mg/mmol, 95% CI −10.0 to −2.7), and ALT levels declined in patients with elevated baseline levels (−11.8 IU/L, 95% CI −17.3 to −6.4) 1 year after replacing TDF with TAF.

Conclusions:
Switching from TDF to TAF among HIV/HBV-coinfected individuals with renal impairment led to improvements in eGFR, a decline in proteinuria, and to ALT normalization in those with elevated ALT levels.
Recent advances in diagnosis and management of irritable bowel syndrome
Authors: Van den Houte Karen , Colomier Esther , Schol Jolien , Carbone Florencia , Tack Jan 
Published: July 2020

Purpose of review
This review summarizes recent progress in the diagnosis and management of irritable bowel syndrome, with a focus on dietary and microbiota aspects.

Recent findings
From a pathophysiological point of view, IBS is a multifactorial condition with both peripheral (transit) as central (visceral hypersensitivity, anxiety, depression) contribution in a cumulative fashion to the symptom pattern and severity. More recently, the focus has shifted to diet and microbiota. The number of dietary options that can be used for IBS and the understanding of determinants of their efficacy is rapidly increasing. Several studies have confirmed the efficacy of the low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet. Sucrose-isomaltase deficiency has emerged as pathogenetic mechanisms in a subset of patients, who do not respond to low FODMAP diet but may respond to starch and sucrose elimination. Herbal remedies, probiotics and secretagogues have been the topic of additional treatment trials. The efficacy of fecal microbiota transplantation in IBS is variable across studies, but donor selection is emerging as a critical factor.

Summary
Irritable bowel syndrome has evolved into a disorder of interaction between dietary factors and gut microbiota, with impact on bowel symptoms as well as extra-intestinal, central, symptoms. Dietary adjustments and treatments targeting the gut microbiota are areas of active research and clinical progress.
Renal carcinoma is associated with increased risk of coronavirus infections
Authors: Tripathi Satyendra C , Deshmukh Vishwajit , Creighton Chad J. , Patil Ashlesh 
Published: July 2020

AbstractThe current pandemic COVID-19 has affected most severely to the people with old age, or with comorbidities such as hypertension, diabetes mellitus, chronic kidney disease, COPD, and cancers. Cancer patients are twice more likely to contract the disease because of the malignancy or treatment-related immunosuppression; hence identification of the vulnerable population among these patients is essential. It is speculated that along with ACE2, other auxiliary proteins (DPP4, ANPEP, ENPEP, TMPRSS2) might facilitate the entry of coronaviruses in the host cells. We took a bioinformatics approach to analyze the gene and protein expression data of these coronavirus receptors in human normal and cancer tissues of multiple organs. Here, we demonstrated an extensive RNA and protein expression profiling analysis of these receptors across solid tumors and normal tissues. We found that among all, renal tumor and normal tissues exhibited increased levels of ACE2, DPP4, ANPEP, and ENPEP. Our results revealed that TMPRSS2 may not be the co-receptor for coronavirus in renal carcinoma patients. The receptors’ expression levels were variable in different tumor stage, molecular and immune subtypes of renal carcinoma. In clear cell renal cell carcinomas, coronavirus receptors were associated with high immune infiltration, markers of immunosuppression, and T cell exhaustion. Our study indicates that CoV receptors may play an important role in modulating the immune infiltrate and hence cellular immunity in renal carcinoma. As our current knowledge of pathogenic mechanisms will improve, it may help us in designing focused therapeutic approaches.
Associations between state-level healthcare access and COVID-19 case trajectories in the United States
Authors: Liu Shelley H. , Liu Bian , Norbury Agnes , Li Yan 
Published: July 2020

AbstractIntroductionWe conducted an ecological study to determine if state-level healthcare access is associated with trajectories of daily reported COVID-19 cases in the United States. Our focus is on trajectories of daily reported COVID-19 cases, rather than cumulative cases, as trajectories help us identify trends in how the pandemic naturally develops over time, and study the shapes of the curve in different states.MethodsWe analyzed data on daily reported confirmed and probable COVID-19 cases from January 21 to June 16, 2020 in 50 states, adjusted for the population size of each state. Cluster analysis for time-series data was used to split the states into clusters that have distinct trajectories of daily cases. Differences in socio-demographic characteristics and healthcare access between clusters were tested. Adjusted models were used to determine if healthcare access is associated with reporting a high trajectory of COVID-19 cases.ResultsTwo clusters of states were identified. One cluster had a high trajectory of population- adjusted COVID-19 cases, and comprised of 19 states, including New York and New Jersey. The other cluster of states (n=31) had a low trajectory of population-adjusted COVID-19 cases.There were significantly more Black residents (p=0.027) and more nursing facility residents (p=0.001) in states reporting high trajectory of COVID-19 cases. States reporting a high trajectory of COVID-19 cases also had fewer uninsured persons (p=0.005), fewer persons who reported having to forgo medical care due to cost (p=0.016), more registered physicians (p=0.002) and more nurses (p=0.03), higher health spending per capita (p=0.01), fewer residents in Health Professional Shortage Areas per 100,000 population (p=0.027), and higher adoption of Medicaid Expansion (p=0.05).In adjusted models, a higher proportion of uninsured persons (OR: 0.51 [0.25-0.85]; p=0.032), higher proportion of patients who had to forgo medical care due to cost (OR: 0.55 [0.28-0.95]; p=0.048), and no adoption of Medicaid expansion (OR: 0.05 [0 – 0.59]; p=0.04), were associated with reporting a low trajectory of COVID-19 cases.ConclusionOur findings from adjusted models suggest that healthcare access can partially explain variations in COVID-19 case trajectories by state.
Combination Treatment Optimization Using a Pan-Cancer Pathway Model
Authors: Schmucker Robin , Farina Gabriele , Faeder James , Fröhlich Fabian , Saglam Ali Sinan , Sandholm Tuomas 
Published: July 2020

AbstractThe design of efficient combination therapies is a difficult key challenge in the treatment of complex diseases such as cancers. The large heterogeneity of cancers and the large number of available drugs renders exhaustivein vivoor evenin vitroinvestigation of possible treatments impractical. In recent years, sophisti-cated mechanistic, ordinary differential equation-based pathways models that can predict treatment responses at amolecularlevel have been developed. However, surprisingly little effort has been put into leveraging these models to find novel therapies. In this paper we use for the first time, to our knowledge, a large-scale state-of-the-art pan-cancer signaling pathway model to identify potentially novel combination therapies to treat individual cancer cell lines from various tissues (e.g., minimizing proliferation while keeping dosage low to avoid adverse side effects) and populations of cancer cell lines (e.g., minimizing the maximum or average proliferation across the cell lines while keeping dosage low). We also show how our method can be used to optimize the mixtures and dosages used insequentialtreatment plans—that is, optimized sequences of potentially different drug combinations—providing additional benefits. In order to solve the treatment optimization problems, we combine the Covariance Matrix Adaptation Evolution Strategy (CMA-ES) algorithm with a significantly more scalable sampling scheme for truncated Gaussian distributions, based on a Hamiltonian Monte-Carlo method. These optimization techniques are independent of the signaling pathway model, and can thus be used for other signaling pathway models also, provided that a suitable predictive model is available.
Calumenin contributes to epithelial-mesenchymal transition and predicts poor survival in glioma
Authors: Yang Ying , Wang Jin , Xu Shihai , Shi Fei , Shan Aijun 
Published: July 2020

AbstractCalumenin (CALU) has been reported to be associated with invasiveness and metastasis in some malignancies. However, in glioma, the role of CALU remains unclear. In the current study, we aimed to unveil its role in glioma based on transcriptome level. Clinical and transcriptome data of 998 glioma patients, including 301 from CGGA mRNA microarray dataset and 697 from TCGA RNA sequencing dataset, were downloaded and analyzed. R language was used to perform statistical analyses and generate figures. In glioma, CALU expression seemed to be positively associated with WHO grade system, and was enriched in IDH wildtype, mesenchymal and classical subtype. Genes that tightly correlated with CALU were screened and annotated with Gene Ontology, and it turned out that, these genes were highly enriched in cell/biological adhesion, response to wounding, and extracellular matrix/structure organization, all of which were strongly correlated with the epithelial-mesenchymal transition (EMT) phenotype. Subsequent GSEA analysis further validated the profound involvement of CALU in EMT. To get further understanding of the association between EMT and CALU, GSVA analysis was performed to identify the EMT signaling pathways that CALU might involve. CALU expression was found to be positively correlated with TGFβ, PI3K/AKT, and hypoxia pathway. Furthermore, Pearson correlation indicated that CALU played synergistically with EMT key markers, including N-cadherin, vimentin, snail, slug and TWIST1, in both CGGA and TCGA dataset. Kaplan-Meier curves and Cox regression analyses showed that higher CALU predicted a worse survival for patients, and the prognostic value was independent of WHO grade and age. In conclusion, CALU was correlated with more malignant phenotypes in glioma. Moreover, CALU seemed to serve as a pro-EMT molecular target and could contribute to predict prognosis independently for glioma patients.
Predicting alcohol use from genome-wide polygenic scores, environmental factors, and their interactions in young adulthood
Authors: Kandaswamy Radhika , Allegrini Andrea , Nancarrow Alexandra F. , Cave Sophie Nicole , Plomin Robert , von Stumm Sophie 
Published: July 2020

AbstractAlcohol use during emerging adulthood is associated with adverse life outcomes but its risk factors are not well known. Here, we predicted alcohol use in 3,153 young adults aged 22 years from (a) genome-wide polygenic scores (GPS) based on genome-wide association studies for the target phenotypes number of drinks per week and Alcohol Use Disorders Identification Test scores, (b) 30 environmental factors, and (c) their interactions (i.e., GxE effects). Data was collected from 1994 to 2018 as a part of the UK Twins Early Development Study. GPS accounted for up to 1.9% of the variance in alcohol use (i.e., Alcohol Use Disorders Identification Test score), while the 30 measures of environmental factors together accounted for 21.1%. The 30 GPS-environment interactions did not explain any additional variance and none of the interaction terms exceeded the significance threshold after correcting for multiple testing. Our findings suggest that GPS and environmental factors have primarily direct, additive effects rather than interacting systematically.
Multilevel community assembly of the tadpole gut microbiome
Authors: Correa Decio T. , Rodriguez David , Emer Carine , Saenz Daniel , Adams Cory K. , Schiesari Luis , Matz Mikhail , Leibold Mathew A. 
Published: July 2020

AbstractThe assembly of local communities is likely to reflect the effects of local environmental factors associated with filters that act at larger spatial scales. Dissecting these multiscale effects remains a timely challenge that is particularly important for host-associated microbiomes. We investigated the relative roles of local selection (due to host species identity) and regional effects (due to water body identity) on the community structure of bacteria in the gut of tadpoles from three biogeographic areas and used graph theory and metanetwork approaches to explore and illustrate the distribution of bacteria across different ponds. The pond of origin, which represents a regional species pool of bacteria, was in general more important in shaping the gut microbiome of tadpoles than host species identity. The resulting metanetworks are modular and indicate relatively few species of bacteria occurring in more than one pond. Thus, each pond represents a relatively distinct species pool of bacteria available for community assembly of the tadpole microbiomes. Our findings indicate that microbiome community assembly in amphibian larvae, as in many other communities, is a multiscale process with important regional effects that constrain how local (i.e. host-dependent) filters act to influence microbiome community composition.
DNNBrain: a unifying toolbox for mapping deep neural networks and brains
Authors: Chen Xiayu , Zhou Ming , Gong Zhengxin , Xu Wei , Liu Xingyu , Huang Taicheng , Zhen Zonglei , Liu Jia 
Published: July 2020

ABSTRACTDeep neural networks (DNNs) have attained human-level performance on dozens of challenging tasks through an end-to-end deep learning strategy. Deep learning gives rise to data representations with multiple levels of abstraction; however, it does not explicitly provide any insights into the internal operations of DNNs. Its success appeals to neuroscientists not only to apply DNNs to model biological neural systems, but also to adopt concepts and methods from cognitive neuroscience to understand the internal representations of DNNs. Although general deep learning frameworks such as PyTorch and TensorFlow could be used to allow such cross-disciplinary studies, the use of these frameworks typically requires high-level programming expertise and comprehensive mathematical knowledge. A toolbox specifically designed for cognitive neuroscientists to map DNNs and brains is urgently needed. Here, we present DNNBrain, a Python-based toolbox designed for exploring internal representations in both DNNs and the brain. By integrating DNN software packages and well-established brain imaging tools, DNNBrain provides application programming and command line interfaces for a variety of research scenarios, such as extracting DNN activation, probing DNN representations, mapping DNN representations onto the brain, and visualizing DNN representations. We expect that our toolbox will accelerate scientific research in applying DNNs to model biological neural systems and utilizing paradigms of cognitive neuroscience to unveil the black box of DNNs.
Enablingin vivoAnalysis Via Nanoparticle-mediated Intracellular Assay Probe Delivery: Using RAS as the Prototype
Authors: Chen Fengqian , Liu Qi , Hilliard Terrell , Wang Tingzeng , Dong Ziye , Li Wei , Liang Hongjun , Gao Weimin , Huang Leaf , Wang Degeng 
Published: July 2020

AbstractMany experimental protocols must be executedin vitrodue to a lack of cell-permeable analysis probes. For instance, the cellular signaling moderator RAS proteins alternate between the active GTP-binding and the inactive GDP-binding states. Though many GTP analogs can serve as probes for RAS activity analysis, their cell impermeability rendersin vivoanalysis impossible. On the other hand, the lipid/calcium/phosphate (LCP) nanoparticle has enabled efficient intracellular delivery of a nucleotide analog as a chemotherapy agent. Thus, using RAS analysis and LCP nanoparticle as the prototype, we tackled the cell-impermeability issue via nanoparticle-mediated intracellular delivery of the analysis probe. Briefly, BODIPY-FT-GTP-γ-S, a GTP analog that becomes fluorescent only upon protein binding, was chosen as the analysis probe, so that GTP binding can be quantified by fluorescent activity. BODIPY-FT-GTP-γ-S-loaded LCP-nanoparticle was synthesized for efficient intracellular BODIPY-FT-GTP-γ-S delivery. Binding of the delivered BODIPY-FT-GTP-γ-S to the RAS proteins were consistent with previously reported observations; the RAS GTP binding activity was reduced in serum-starved cells; and a transient activation peak of the binding activity was observed upon subsequent serum reactivation of the cells. In a word, nanoparticle-mediated probe delivery enabled anin vivoRAS analysis method. The approach should be applicable to a wide variety of analysis protocols.
Rats and the COVID-19 pandemic: Early data on the global emergence of rats in response to social distancing
Authors: Parsons Michael H. , Kiyokawa Yasushi , Richardson Jonathan L. , Stryjek Rafal , Byers Kaylee A. , Himsworth Chelsea G. , Corrigan Robert M. , Deutsch Michael A , Ootaki Masato , Tanikawa Tsutomu , Parsons Faith E. , Munshi-South Jason 
Published: July 2020

AbstractFollowing widespread closures of food-related businesses due to efforts to curtail the spread of SARS-CoV-2, public health authorities reported increased sightings of rats in close vicinity of people. Because rats vector a number of pathogens transmissible to people, changes in their behavior has consequences for human health risks. To determine the extent of how stay-at-home measures influenced patterns of rat sightings we: 1) examined the number of rat-related public service requests before and during the period of lockdown in New York City (NYC) and Tokyo, Japan; 2) examined reports made in proximity to closed food service establishments in NYC; and 3) surveyed pest control companies in the United States, Canada, Japan, and Poland. During the month following lockdown, the overall number of reports decreased by 30% in NYC, while increasing 24% in Tokyo. However, new hotspots of 311 calls were observed in proximity of closed food service establishments in NYC; and there was a consistent positive association between kernel density estimates of food service establishments and location of 311 calls (r = 0.33 to 0.45). Similarly, more reports were observed in the restaurant-dense eastern side of Tokyo. Changes in clientele for pest control companies varied geographically, with 37% of pest-management companies surveyed in North America reporting 50-100% of their post-lockdown rat-related requests coming from new clients. In Warsaw, where there are no clusters of restaurants in densely-populated areas, there were no changes. In Tokyo, there were no changes in clients. We conclude that changes in public service calls are region-specific and localized, with increases in rat sightings more likely near restaurant-dense regions. Pest control companies surveyed in North America either lost much of their business or shifted clientele from old to new locations. We discuss possible mitigation measures including ramping up pest control during re-opening of food-related establishments and the need for citywide rodent surveillance and disease monitoring.
Change points in the spread of COVID-19 question the effectiveness of nonpharmaceutical interventions in Germany
Authors: Wieland Thomas 
Published: July 2020

AbstractAimsNonpharmaceutical interventions against the spread of SARS-CoV-2 in Germany included the cancellation of mass events (from March 8), closures of schools and child day care facilities (from March 16) as well as a “lockdown” (from March 23). This study attempts to assess the effectiveness of these interventions in terms of revealing their impact on infections over time.MethodsDates of infections were estimated from official German case data by incorporating the incubation period and an empirical reporting delay. Exponential growth models for infections and reproduction numbers were estimated and investigated with respect to change points in the time series.ResultsA significant decline of daily and cumulative infections as well as reproduction numbers is found at March 8 (CI [7, 9]), March 10 (CI [9, 11] and March 3 (CI [2, 4]), respectively. Further declines and stabilizations are found in the end of March. There is also a change point in new infections at April 19 (CI [18, 20]), but daily infections still show a negative growth. From March 19 (CI [18, 20]), the reproduction numbers fluctuate on a level below one.ConclusionsThe decline of infections in early March 2020 can be attributed to relatively small interventions and voluntary behavioural changes. Additional effects of later interventions cannot be detected clearly. Liberalizations of measures did not induce a re-increase of infections. Thus, the effectiveness of most German interventions remains questionable. Moreover, assessing of interventions is impeded by the estimation of true infection dates and the influence of test volume.
The human oral phageome is highly diverse and rich in jumbo phages
Authors: Carr Victoria R. , Shkoporov Andrey , Gomez-Cabrero David , Mullany Peter , Hill Colin , Moyes David L. 
Published: July 2020

AbstractUntil recently, the contribution of bacteriophages to the composition and function of the human microbiome has been largely overlooked. Recent developments in discovering novel bacteriophages from human metagenomes have been mostly focused on the gut. Here we profile and compare the phageome of 633 human oral sites and 221 paired gut phageomes acquired from countries worldwide. Phageome profiles are specific to oral sites and the gut across individuals, with the largest separation between the oral cavity and the gut. The differences in phage genotypes is bolstered by distinct phage host compositions between these sites. The greatest diversity of phages is found on the tongue and in dental plaque. Notably, 37 unique circular jumbo phage genomes were identified in oral sites, particularly on the dorsum of the tongue, whilst none were found in the gut. Oral sites provide conducive environments, such as robust biofilms, that can harbour genetically diverse phages.