bluuebunny/crossref_metadata_2025_split huggingface dataset:
Screening strategies for the detection of anal high-grade squamous intraepithelial lesions in women living with HIV
Authors: Chiao Elizabeth Y. , Lensing Shelly Y. , Wiley Dorothy J. , Deshmukh Ashish A. , Lee Jeannette , Darragh Teresa M. , Einstein Mark H. , Jay Naomi , Berry-Lawhorn John Michael , Palefsky Joel M. , Wilkin Timothy , Barroso Luis F. , Cranston Ross D. , Levine Rebecca , Guiot Humberto M. , French Audrey L. , Citron Deborah , Rezaei Masoumeh Katayoon , Goldstone Stephen E. , Stier Elizabeth A. 
Published: September 2020

Objective:
HIV-infected women (WLHIV) have more than 10-fold higher risk for squamous cell cancer of the anus. Experts suggest cytology-based strategies developed for cervical cancer screening may prevent anal cancer by detecting anal cytologic or histological high-grade squamous intraepithelial lesion (hHSIL) for treatment. Currently, there is no consensus on anal-hHSIL screening strategies for WLHIV.

Design:
Between 2014 and 2016, 276 WLHIV were recruited at 12 US AIDS Malignancy Consortium clinical trials sites to evaluate hHSIL prevalence and (test) screening strategies.

Methods:
Participants completed detailed questionnaire, underwent anal assessments including high-risk human papillomavirus (hrHPV) testing using hrHPV-Hybrid Capture 2 (HC2) and hrHPV-APTIMA, anal cytology, and concurrent high-resolution anoscopy. Screening test characteristics for predicting hHSIL validated by central review of histologic diagnosis were estimated sensitivity, specificity, positive predictive value, and false-omission rate. Paired analyses compared sensitivity and specificity for hrHPV single tests to anal cytology alone.

Results:
83% (229/276) of enrolled WLHIV had complete anal assessment data and were included in this analysis. Mean age was 50, 62% black and 60 (26%) had hHSIL. Anal cyotology (>atypical squamous cells of undetermined significance), hrHPV-HC2, and hrHPV-APTIMA sensitivity estimates were similarly high (83, 77, and 75%, respectively, P values > 0.2). Specificity was higher for both hrHPV-APTIMA and hrHPV-HC2 compared with anal cytology (67 vs. 50%, P < 0.001) and (61 vs. 50%, P = 0.020), respectively.

Conclusion:
Anal hrHPV testing demonstrated similar sensitivity for anal cytology (>atypical squamous cells of undetermined significance) to predict anal hHSIL. Among tests with similar sensitivity, the specificity was significantly higher for hrHPV-APTIMA and hrHPV-HC2. Thus, anal hrHPV testing may be an important alternative strategy to anal cytology for anal hHSIL screening among WLHIV.
Computational design of two new soluble epoxide hydrolase (sEH) inhibitors
Authors: Liem Jennifer , Adhikari Sambid , Huang Peishan , Siegel Justin B. 
Published: September 2020

ABSTRACTInhibitors of soluble epoxide hydrolase (sEH) enzymes have shown great potential for the treatment of neuropathic pain. However, current sEH inhibitors have poor physicochemical properties and has not been proven to be safe for human treatments yet. New inhibitor designs could have the potential to improve current drugs’ efficacy, and so in this work, chemical intuition and bioisosteric replacement were used to computationally design two novel sEH inhibitors. These new candidates showed good pharmacokinetic properties and presented better docking scores compared to a known sEH inhibitor, t-TUCB, used in the treatment of pain in horses. Homology analysis revealed thatMus musculusmay not be suitable organism for preclinical trials studies of these novel inhibitors.
Restricted constrictors: Space use and habitat selection of native Burmese pythons in Northeast Thailand
Authors: Smith Samantha Nicole , Jones Max Dolton , Marshall Benjamin Michael , Waengsothorn Surachit , Gale George A. , Strine Colin Thomas 
Published: September 2020

AbstractAnimal movement and resource use are tightly linked. Investigating these links to understand how animals utilize space and select habitats is especially relevant in areas that have been affected by habitat fragmentation and agricultural conversion. We set out to explore the space use and habitat selection of Burmese pythons (Python bivittatus) in a patchy land use matrix dominated by agricultural crops and human settlements. We used radio telemetry to record daily locations of seven Burmese pythons over the course of our study period of approximately 22 months. We created dynamic Brownian Bridge Movement Models (dBBMMs) for all individuals, using occurrence distributions to estimate extent of movements and motion variance to reveal temporal patterns. Then we used integrated step selection functions to determine whether individual movements were associated with particular landscape features (aquatic agriculture, forest, roads, settlements, terrestrial agriculture, water), and whether there were consistent associations at the population level. Our dBBMM estimates suggested that Burmese pythons made use of small areas (98.97 ± 35.42 ha), with low mean individual motion variance characterized by infrequent moves and long periods at a single location. At both the individual and population level, Burmese pythons in the agricultural matrix were associated with aquatic environments. Only one individual showed a strong avoidance for human settlements which is troublesome from a human-wildlife conflict angle, especially as Burmese pythons have been observed entering human settlements and consuming livestock in our study site. Our study is one of the first to contribute to the knowledge of Burmese python ecology in their native range as the majority of studies have focused on invasive populations.
STAMPede: A Precision Oncology Catalogue of Solid Tumors
Authors: Chen Jessica W. , Kalantarian Haik , Kunder Christian A. , Zehnder James L. , Stehr Henning , Costa Helio A. 
Published: September 2020

ABSTRACTMolecular profiling of tumor specimens is a key contributor in the application of precision medicine toward patient care in oncology. The presence of genetic mutational data may provide insight into the etiology of the cancer and inform about the available therapeutic options for patients diagnosed with various cancer types. However, the ability to centrally organize, structure, and visualize this genetic data can be hindered by the lack of necessary computational infrastructure. Here we present a somatic tumor data visualization portal titled STAMPede that utilizes tumor sequencing data from an in-house solid tumor oncology sequencing panel at Stanford Health Care. STAMPede is intended to provide Stanford healthcare providers and clinical researchers an easy to navigate web-based portal to query and display gene-, variant-, and cancer-level summary statistics.
Cryo-EM of a viral RNA and RNA-protein complex reveals how structural dynamics and novel tRNA mimicry combine to hijack host machinery
Authors: Bonilla Steve L. , Sherlock Madeline E. , MacFadden Andrea , Kieft Jeffrey S. 
Published: September 2020

AbstractViruses require multifunctional structured RNAs to hijack their host’s biochemistry, but their mechanisms can be obscured by the difficulty of solving conformationally dynamic RNA structures. Using cryo-EM, we visualized the structure of the mysterious viral tRNA-like structure (TLS) from brome mosaic virus (BMV), which affects replication, translation, and genome encapsidation. Structures in isolation and bound to tyrosyl-tRNA synthetase (TyrRS) show that this ∼55 kDa purported tRNA mimic undergoes large conformational rearrangements to bind TyrRS in a form that differs dramatically from tRNA. Our studies reveal how viral RNAs can use a combination of static and dynamic RNA structures to bind host machinery through highly noncanonical interactions and highlights the utility of cryo-EM for visualizing small conformationally dynamic structured RNAs.
Pain-related opioidergic and dopaminergic neurotransmission: Dual Meta-Analyses of PET Radioligand Studies
Authors: Garcia Sergio Guerra , Spadoni Andrea , Mitchell Jennifer , Strigo Irina A. 
Published: September 2020

AbstractMolecular mechanisms of the interaction between pain and reward associated with pain relief processes in the human brain are still incompletely understood. This is partially due to the invasive nature of the available techniques to visualize and measure metabolic activity. Positron Emission Tomography (PET) radioligand studies using radioactive substances are still the only available modality to date that allows for the investigation of the molecular mechanisms in the human brain. For pain and reward studies, the most commonly studied PET radiotracers are [11C]-carfentanil (CFN) and [11C]- or [18F]-diprenorphine (DPN), which bind to opioid receptors, and [11C]-raclopride (RAC) and [18F]-fallypride (FAL) tracers, which bind to dopamine receptors. The current meta-analysis looks at 15 pain-related studies using opioid radioligands and 8 studies using dopamine radioligands in an effort to consolidate the available data into the most likely activated regions. Our primary goal was to identify regions of shared opioid/dopamine neurotransmission during pain-related experiences. SDM analysis of previously published voxel coordinate data showed that opioidergic activations were strongest in the bilateral caudate, thalamus, right putamen, cingulate gyrus, midbrain, inferior frontal gyrus, and left superior temporal gyrus. The dopaminergic studies showed that the bilateral caudate, thalamus, right putamen, cingulate gyrus, and left putamen had the highest activations. We were able to see a clear overlap between opioid and dopamine activations in a majority of the regions during pain-related processing, though there were some unique areas of dopaminergic activation such as the left putamen. Regions unique to opioidergic activation include the midbrain, inferior frontal gyrus, and left superior temporal gyrus. By investigating the regions of dopaminergic and opioidergic activation, we can potentially provide more targeted treatment to these sets of receptors in patients with pain conditions. These findings could eventually assist in the development of more targeted medication in order to help treat pain conditions and simultaneously prevent physical dependency.
Maternal diabetes induces senescence and neural tube defects sensitive to the senomorphic Rapamycin
Authors: Xu Cheng , Shen Wei-Bin , Reece E. Albert , Hasuwa Hidetoshi , Harman Christopher , Kaushal Sunjay , Yang Peixin 
Published: September 2020

ABSTRACTNeural tube defects (NTDs) are the second most common structural birth defects. Senescence, a state of permanent cell cyle arrest, only occurs after neural tube closure. Maternal diabetes-induced NTDs, severe diabetic complications leading to infant mortality or lifelong morbidity, may be linked to premature senescence. Here we report that premature senescence occurs in the mouse neuroepithelium and disrupts neurulation, leading to NTDs in diabetic pregnancy. Premature senescence and NTDs were abolished by deleting the transcription factorFoxo3a, themiR-200cgene, the cell cycle inhibitorsp21orp27, or by transgenic expression of the dominant-negative FoxO3a mutant or by the senomorphic rapamycin. Double transgenic expression of p21 and p27 mimicked maternal diabetes in inducing premature neuroepithelium senescence and NTDs. These findings integrate transcription- and epigenome-regulated miRNAs and cell cycle regulators in premature neruoepithelium senescence, and provide a mechanistic basis for targeting premature senescence and NTDs using senomorphs.
Metabolic effects of the schizophrenia-associated 3q29 deletion are sex-specific and uncoupled from behavioral phenotypes
Authors: Pollak Rebecca M , Purcell Ryan H , Rutkowski Timothy P , Malone Tamika , Pachura Kimberly J , Bassell Gary J , Epstein Michael P , Dawson Paul A , Smith Matthew R , Jones Dean P , Zwick Michael E ,   the Emory 3q29 Project, Warren Stephen T , Caspary Tamara , Weinshenker David , Mulle Jennifer G 
Published: September 2020

SUMMARYThe 1.6 Mb 3q29 deletion is associated with developmental and psychiatric phenotypes. Reduced birthweight and a high prevalence of feeding disorders in patients suggest underlying metabolic dysregulation. We investigated 3q29 deletion-induced metabolic changes using the B6.Del16+/Bdh1-Tfrcmouse model. We found that B6.Del16+/Bdh1-Tfrcanimals preferentially use dietary lipids as an energy source. Untargeted metabolomics showed a strong sex-dependent effect of the 3q29 deletion on fat metabolism. A high-fat diet (HFD) partially rescued the 3q29 deletion-associated weight deficit in females, but not males. Untargeted metabolomics after HFD revealed persistent fat metabolism alterations in females. The HFD did not affect B6.Del16+/Bdh1-Tfrcbehavioral phenotypes, suggesting that 3q29 deletion-associated metabolic and behavioral outcomes are uncoupled. Our data indicate a HFD intervention in 3q29 deletion syndrome may improve weight phenotypes without exacerbating behavioral manifestations. Our study also highlights the importance of assessing sex in metabolic studies and suggests mechanisms underlying 3q29 deletion-associated metabolic phenotypes are sex-specific.
Carbamazepine Causes Changes in Maternal Reproductive Performance and Fetal Growth Retardation in Rats
Authors: Nunes Marina , de Sousa Felipe Duarte Coelho , Andretta Rhaiza Roberta , Miraglia Sandra Maria , de Oliva Samara Urban 
Published: September 2020

ABSTRACTPurposeCarbamazepine (CBZ) is widely used in the treatment of trigeminal neuralgia, affective disorders, and mainly as an anticonvulsant, specially by fertile women, due to their need to continuously use CBZ during pregnancy and the lactation period. CBZ crosses the placenta barrier and may impair pregnancy and the embryonic development. The aim of this study was to determine the effect of CBZ on maternal reproductive outcome, besides fetal growth and development in Wistar rats.MethodsRat dams received CBZ (20mg/Kg/day) or propylene glycol (vehicle) via intraperitoneal (i.p.) injection throughout the gestational period. On the 19thday of gestation, the ovary and uterine contents were examined, and the placenta and fetuses were analyzed.ResultsThe CBZ exposure during pregnancy caused a reduction in fetal weight, fetal weight classification, and crown-rump distance. CBZ also decreased the implantation index, average number of corpora lutea, fetal weights and crown-rump length and increased the pre and post-implantation loss rate. The CBZ-exposed fetus also presented external congenital malformations.ConclusionThe results suggest that maternal exposure to CBZ interfered on several maternal reproductive outcomes and can cause severe fetal intrauterine growth restriction (IUGR).
Stochasticity explains differences in the number ofde novomutations between families
Authors: Goldmann Jakob M. , Hampstead Juliet , Wong Wendy S.W. , Wilfert Amy B. , Turner Tychele , Jonker Marianne A. , Bernier Raphael , Huynen Martijn A. , Eichler Evan E. , Veltman Joris A. , Maxwell George L. , Gilissen Christian 
Published: September 2020

AbstractThe number of de novo mutations (DNMs) in the human germline is correlated with parental age at conception, but this explains only part of the observed variation. We investigated whether there is a family-specific contribution to the number of DNMs in offspring. The analysis of DNMs in 111 dizygotic twin pairs did not identify a significant family-specific contribution. This result was corroborated by comparing DNMs of 1669 siblings to those of age-matched unrelated offspring. In addition, by modeling DNM data from 1714 multi-offspring families we estimated that the family specific contribution explains approximately 5.2% of the variation in DNM number. Furthermore, we found no significant difference between the observed number of DNMs and those based on a stochastic Poisson process. We conclude that a family-specific contribution to DNMs is small and that stochasticity explains a large proportion of variation in DNM counts.
Expression of a membrane-targeted fluorescent reporter disrupts auditory hair cell mechanoelectrical transduction and causes profound deafness
Authors: Ballesteros Angela , Fitzgerald Tracy S. , Swartz Kenton J. 
Published: September 2020

AbstractThe reporter mT/mG mice expressing a membrane-targeted fluorescent protein are becoming widely used to study the auditory and vestibular system due to its versatility. Here we show that high expression levels of the fluorescent mtdTomato reporter affect the function of the sensory hair cells and the auditory performance of mT/mG transgenic mice. Auditory brainstem responses and distortion product otoacoustic emissions revealed that adult mT/mG homozygous mice are profoundly deaf, whereas heterozygous mice present high frequency loss. We explore whether this line would be useful for studying and visualizing the membrane of auditory hair cells by airyscan super-resolution confocal microscopy. Membrane localization of the reporter was observed in hair cells of the cochlea, facilitating imaging of both cell bodies and stereocilia bundles without altering cellular architecture or the expression of the integral membrane motor protein prestin. Remarkably, hair cells from mT/mG homozygous mice failed to uptake the FM1-43 dye and to locate TMC1 at the stereocilia, indicating defective mechanoelectrical transduction machinery. Our work emphasizes that precautions must be considered when working with reporter mice and highlights the potential role of the cellular membrane in maintaining functional hair cells and ensuring proper hearing.
A sexual dimorphism in the spatial vision of band-winged grasshoppers
Authors: Duncan Alex B. , Salazar Brae A. , Garcia Sara R. , Brandley Nicholas C. 
Published: September 2020

AbstractVisual acuity (VA) --- a measurement of the fineness or coarseness of vision --- correlates with the size of an animal, with larger species often possessing sharper vision. However, it is unknown whether the same relationship between visual acuity and size holds within a species when individuals differ consistently and substantially in size, such as through a sexual size dimorphism. Here we examine the visual acuity of three species of sexually dimorphic band-winged grasshoppers, in which females are the larger sex (Arphia pseudonietana, Dissosteira carolina, andSpharagemon equale;total n = 98). Using a radius of curvature estimation method, we find that females have ∼21% finer vision in the most acute region and axis of the eye than do males. Further explorations of the eyes of the species showing the greatest size dimorphism (D. carolina) suggest that this VA dimorphism is driven by females having larger eyes with more ommatidia. In contrast to many flying insects where males have finer vision to acquire mates, our study is one of the first to demonstrate a female-biased sexual dimorphism in acuity. Given the number of species in which females are larger than males, our results suggest that differences in VA between the sexes may be more common than currently appreciated.
Orchestrating and sharing large multimodal data for transparent and reproducible research
Authors: Mammoliti Anthony , Smirnov Petr , Nakano Minoru , Safikhani Zhaleh , Eeles Christopher , Seo Heewon , Nair Sisira Kadambat , Mer Arvind S. , Ho Chantal , Beri Gangesh , Kusko Rebecca ,   MAQC Society, Haibe-Kains Benjamin 
Published: September 2020

ABSTRACTReproducibility is essential to open science, as there is limited relevance for findings that can not be reproduced by independent research groups, regardless of its validity. It is therefore crucial for scientists to describe their experiments in sufficient detail so they can be reproduced, scrutinized, challenged, and built upon. However, the intrinsic complexity and continuous growth of biomedical data makes it increasingly difficult to process, analyze, and share with the community in a FAIR (findable, accessible, interoperable, and reusable) manner. To overcome these issues, we created a cloud-based platform called ORCESTRA (orcestra.ca), which provides a flexible framework for the reproducible processing of multimodal biomedical data. It enables processing of clinical, genomic and perturbation profiles of cancer samples through automated processing pipelines that are user-customizable. ORCESTRA creates integrated and fully documented data objects with persistent identifiers (DOI) and manages multiple dataset versions, which can be shared for future studies.
Cell type-selective secretome profiling in vivo
Authors: Wei Wei , Riley Nicholas M. , Yang Andrew C. , Kim Joon T. , Terrell Stephanie M. , Li Veronica L. , Garcia-Contreras Marta , Bertozzi Carolyn R. , Long Jonathan Z. 
Published: September 2020

ABSTRACTSecreted polypeptides are a fundamental biochemical axis of intercellular and endocrine communication. However, a global understanding of composition and dynamics of cellular secretomes in intact mammalian organisms has been lacking. Here, we introduce a proximity biotinylation strategy that enables labeling, detection, and enrichment of secreted polypeptides in a cell type-selective manner in mice. We generate a proteomic atlas of hepatocyte, myocyte, pericyte, and myeloid cell secretomes by direct purification of biotinylated secreted polypeptides from blood. Our secretome atlas validates known cell type-protein pairs, reveals secreted polypeptides that distinguish between cell types, and identifies new cellular sources for classical plasma proteins. Lastly, we uncover a dynamic and previously undescribed nutrient-dependent reprogramming of the hepatocyte secretome characterized by increased unconventional secretion of the cytosolic enzyme BHMT. This secretome profiling strategy enables dynamic and cell-type dissection of the plasma proteome and the secreted polypeptides that mediate intercellular signaling.
A unique multi-synaptic mechanism regulates dopamine release in the nucleus accumbens during adolescence
Authors: Pitts Elizabeth G. , Stowe Taylor A. , Ferris Mark J. 
Published: September 2020

SummaryAdolescence is characterized by changes in reward-related behaviors, social behaviors, and decision making. These behavioral changes are necessary for the transition into adulthood, but they also increase vulnerability to the development of a range of psychiatric disorders. Major reorganization of the dopamine system during adolescence is thought to underlie, in part, the behavioral changes and increased vulnerability. Here, we utilized fast scan cyclic voltammetry to examine differences in regulation of dopamine release in the nucleus accumbens core of adolescent and adult male rats. We found that differences between adolescent and adult stimulated dopamine release is driven by a unique multisynaptic mechanism in early adolescence involving acetylcholine acting at α6-containing nicotinic acetylcholine receptors to mediate inhibition of dopamine via GABA release. These changes in dopamine regulation across adolescence provides a springboard for our understanding of basic brain development and targeted therapy for a range of psychiatric conditions that emerge in adolescence.