bluuebunny/crossref_metadata_2025_split huggingface dataset:
GnRHa protects the ovarian reserve by reducing endoplasmic reticulum stress during cyclophosphamide-based chemotherapy
Authors: Li Xiaolin , Liu Sixuan , Chen Xuan , Huang Run , Ma Lisi , Weng Huaiyu , Yu Yang , Zong Xiangyun 
Published: October 2021

AbstractChemotherapy-induced ovarian dysfunction is a serious adverse effect in premenopausal patients with cancer. Gonadotrophin-releasing hormone analogs (GnRHa) protect ovarian function, but its molecular mechanisms have not yet been determined. In this study, we attempted to determine the previously unknown molecular mechanism by which such protection occurs. Serum anti-Müllerian hormone (AMH) levels were tested in tumor-bearing nude mice, a series of exploratory experiments were conducted. We discovered that GnRHa protects granulosa cells from chemotherapeutic toxicity in vivo and in vitro. We also showed that CTX-induced endoplasmic reticulum stress inhibits the secretion of AMH, and treatment with GnRHa relieves ER stress and the subsequent unfolded-protein response by modulating mTOR signaling to induce autophagy. The results of mechanistic studies indicated that GnRHa-modulated mTOR signaling to induce autophagy, which alleviated CTX-induced ER stress and promoted the secretion of AMH.
Haplotyping-based preimplantation genetic testing reveals parent-of-origin specific mechanisms of aneuploidy formation
Authors: Tšuiko Olga , Vanneste Michiel , Melotte Cindy , Ding Jia , Debrock Sophie , Masset Heleen , Peters Maire , Salumets Andres , De Leener Anne , Pirard Céline , Kluyskens Candice , Hostens Katleen , van de Vijver Arne , Peeraer Karen , Denayer Ellen , Vermeesch Joris Robert , Dimitriadou Eftychia 
Published: October 2021

AbstractChromosome instability is inherent to human IVF embryos, but the full spectrum and developmental fate of chromosome anomalies remain uncharacterized. Using haplotyping-based preimplantation genetic testing for monogenic diseases (PGT-M), we mapped the parental and mechanistic origin of common and rare genomic abnormalities in 2300 cleavage stage and 361 trophectoderm biopsies. We show that while single whole chromosome aneuploidy arises due to chromosome-specific meiotic errors in the oocyte, segmental imbalances predominantly affect paternal chromosomes, implicating sperm DNA damage in segmental aneuploidy formation. We also show that postzygotic aneuploidy affects multiple chromosomes across the genome and does not discriminate between parental homologs. In addition, 6% of cleavage stage embryos demonstrated signatures of tripolar cell division with excessive chromosome loss, however hypodiploid blastomeres can be excluded from further embryo development. This observation supports the selective-pressure hypothesis in embryos. Finally, considering that ploidy violations may constitute a significant proportion of non-viable embryos, using haplotyping-based approach to map these events might further improve IVF success rate.
Single-cell epigenomics reveals mechanisms of human cortical development
Authors: Ziffra Ryan S. , Kim Chang N. , Ross Jayden M. , Wilfert Amy , Turner Tychele N. , Haeussler Maximilian , Casella Alex M. , Przytycki Pawel F. , Keough Kathleen C. , Shin David , Bogdanoff Derek , Kreimer Anat , Pollard Katherine S. , Ament Seth A. , Eichler Evan E. , Ahituv Nadav , Nowakowski Tomasz J. 
Published: October 2021

AbstractDuring mammalian development, differences in chromatin state coincide with cellular differentiation and reflect changes in the gene regulatory landscape1. In the developing brain, cell fate specification and topographic identity are important for defining cell identity2 and confer selective vulnerabilities to neurodevelopmental disorders3. Here, to identify cell-type-specific chromatin accessibility patterns in the developing human brain, we used a single-cell assay for transposase accessibility by sequencing (scATAC-seq) in primary tissue samples from the human forebrain. We applied unbiased analyses to identify genomic loci that undergo extensive cell-type- and brain-region-specific changes in accessibility during neurogenesis, and an integrative analysis to predict cell-type-specific candidate regulatory elements. We found that cerebral organoids recapitulate most putative cell-type-specific enhancer accessibility patterns but lack many cell-type-specific open chromatin regions that are found in vivo. Systematic comparison of chromatin accessibility across brain regions revealed unexpected diversity among neural progenitor cells in the cerebral cortex and implicated retinoic acid signalling in the specification of neuronal lineage identity in the prefrontal cortex. Together, our results reveal the important contribution of chromatin state to the emerging patterns of cell type diversity and cell fate specification and provide a blueprint for evaluating the fidelity and robustness of cerebral organoids as a model for cortical development.
Epigenomic diversity of cortical projection neurons in the mouse brain
Authors: Zhang Zhuzhu , Zhou Jingtian , Tan Pengcheng , Pang Yan , Rivkin Angeline C. , Kirchgessner Megan A. , Williams Elora , Lee Cheng-Ta , Liu Hanqing , Franklin Alexis D. , Miyazaki Paula Assakura , Bartlett Anna , Aldridge Andrew I. , Vu Minh , Boggeman Lara , Fitzpatrick Conor , Nery Joseph R. , Castanon Rosa G. , Rashid Mohammad , Jacobs Matthew W. , Ito-Cole Tony , O’Connor Carolyn , Pinto-Duartec António , Dominguez Bertha , Smith Jared B. , Niu Sheng-Yong , Lee Kuo-Fen , Jin Xin , Mukamel Eran A. , Behrens M. Margarita , Ecker Joseph R. , Callaway Edward M. 
Published: October 2021

AbstractNeuronal cell types are classically defined by their molecular properties, anatomy and functions. Although recent advances in single-cell genomics have led to high-resolution molecular characterization of cell type diversity in the brain1, neuronal cell types are often studied out of the context of their anatomical properties. To improve our understanding of the relationship between molecular and anatomical features that define cortical neurons, here we combined retrograde labelling with single-nucleus DNA methylation sequencing to link neural epigenomic properties to projections. We examined 11,827 single neocortical neurons from 63 cortico-cortical and cortico-subcortical long-distance projections. Our results showed unique epigenetic signatures of projection neurons that correspond to their laminar and regional location and projection patterns. On the basis of their epigenomes, intra-telencephalic cells that project to different cortical targets could be further distinguished, and some layer 5 neurons that project to extra-telencephalic targets (L5 ET) formed separate clusters that aligned with their axonal projections. Such separation varied between cortical areas, which suggests that there are area-specific differences in L5 ET subtypes, which were further validated by anatomical studies. Notably, a population of cortico-cortical projection neurons clustered with L5 ET rather than intra-telencephalic neurons, which suggests that a population of L5 ET cortical neurons projects to both targets. We verified the existence of these neurons by dual retrograde labelling and anterograde tracing of cortico-cortical projection neurons, which revealed axon terminals in extra-telencephalic targets including the thalamus, superior colliculus and pons. These findings highlight the power of single-cell epigenomic approaches to connect the molecular properties of neurons with their anatomical and projection properties.
Anti-SARS-CoV-2 receptor-binding domain antibody evolution after mRNA vaccination
Authors: Cho Alice , Muecksch Frauke , Schaefer-Babajew Dennis , Wang Zijun , Finkin Shlomo , Gaebler Christian , Ramos Victor , Cipolla Melissa , Mendoza Pilar , Agudelo Marianna , Bednarski Eva , DaSilva Justin , Shimeliovich Irina , Dizon Juan , Daga Mridushi , Millard Katrina G. , Turroja Martina , Schmidt Fabian , Zhang Fengwen , Tanfous Tarek Ben , Jankovic Mila , Oliveria Thiago Y. , Gazumyan Anna , Caskey Marina , Bieniasz Paul D. , Hatziioannou Theodora , Nussenzweig Michel C. 
Published: October 2021

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection produces B cell responses that continue to evolve for at least a year. During that time, memory B cells express increasingly broad and potent antibodies that are resistant to mutations found in variants of concern1. As a result, vaccination of coronavirus disease 2019 (COVID-19) convalescent individuals with currently available mRNA vaccines produces high levels of plasma neutralizing activity against all variants tested1,2. Here we examine memory B cell evolution five months after vaccination with either Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) mRNA vaccine in a cohort of SARS-CoV-2-naive individuals. Between prime and boost, memory B cells produce antibodies that evolve increased neutralizing activity, but there is no further increase in potency or breadth thereafter. Instead, memory B cells that emerge five months after vaccination of naive individuals express antibodies that are similar to those that dominate the initial response. While individual memory antibodies selected over time by natural infection have greater potency and breadth than antibodies elicited by vaccination, the overall neutralizing potency of plasma is greater following vaccination. These results suggest that boosting vaccinated individuals with currently available mRNA vaccines will increase plasma neutralizing activity but may not produce antibodies with equivalent breadth to those obtained by vaccinating convalescent individuals.
An independently validated, portable algorithm for the rapid identification of COPD patients using electronic health records
Authors: Chu Su H. , Wan Emily S. , Cho Michael H. , Goryachev Sergey , Gainer Vivian , Linneman James , Scotty Erica J. , Hebbring Scott J. , Murphy Shawn , Lasky-Su Jessica , Weiss Scott T. , Smoller Jordan W. , Karlson Elizabeth 
Published: October 2021

AbstractElectronic health records (EHR) provide an unprecedented opportunity to conduct large, cost-efficient, population-based studies. However, the studies of heterogeneous diseases, such as chronic obstructive pulmonary disease (COPD), often require labor-intensive clinical review and testing, limiting widespread use of these important resources. To develop a generalizable and efficient method for accurate identification of large COPD cohorts in EHRs, a COPD datamart was developed from 3420 participants meeting inclusion criteria in the Mass General Brigham Biobank. Training and test sets were selected and labeled with gold-standard COPD classifications obtained from chart review by pulmonologists. Multiple classes of algorithms were built utilizing both structured (e.g. ICD codes) and unstructured (e.g. medical notes) data via elastic net regression. Models explicitly including and excluding spirometry features were compared. External validation of the final algorithm was conducted in an independent biobank with a different EHR system. The final COPD classification model demonstrated excellent positive predictive value (PPV; 91.7%), sensitivity (71.7%), and specificity (94.4%). This algorithm performed well not only within the MGBB, but also demonstrated similar or improved classification performance in an independent biobank (PPV 93.5%, sensitivity 61.4%, specificity 90%). Ancillary comparisons showed that the classification model built including a binary feature for FEV1/FVC produced substantially higher sensitivity than those excluding. This study fills a gap in COPD research involving population-based EHRs, providing an important resource for the rapid, automated classification of COPD cases that is both cost-efficient and requires minimal information from unstructured medical records.
A proof of concept for machine learning-based virtual knapping using neural networks
Authors: Orellana Figueroa Jordy Didier , Reeves Jonathan Scott , McPherron Shannon P. , Tennie Claudio 
Published: October 2021

AbstractPrehistoric stone tools are an important source of evidence for the study of human behavioural and cognitive evolution. Archaeologists use insights from the experimental replication of lithics to understand phenomena such as the behaviours and cognitive capacities required to manufacture them. However, such experiments can require large amounts of time and raw materials, and achieving sufficient control of key variables can be difficult. A computer program able to accurately simulate stone tool production would make lithic experimentation faster, more accessible, reproducible, less biased, and may lead to reliable insights into the factors that structure the archaeological record. We present here a proof of concept for a machine learning-based virtual knapping framework capable of quickly and accurately predicting flake removals from 3D cores using a conditional adversarial neural network (CGAN). We programmatically generated a testing dataset of standardised 3D cores with flakes knapped from them. After training, the CGAN accurately predicted the length, volume, width, and shape of these flake removals using the intact core surface information alone. This demonstrates the feasibility of machine learning for investigating lithic production virtually. With a larger training sample and validation against archaeological data, virtual knapping could enable fast, cheap, and highly-reproducible virtual lithic experimentation.
Avian influenza transmission risk along live poultry trading networks in Bangladesh
Authors: Moyen Natalie , Hoque Md. Ahasanul , Mahmud Rashed , Hasan Mahmudul , Sarkar Sudipta , Biswas Paritosh Kumar , Mehedi Hossain , Henning Joerg , Mangtani Punam , Flora Meerjady Sabrina , Rahman Mahmudur , Debnath Nitish C. , Giasuddin Mohammad , Barnett Tony , Pfeiffer Dirk U. , Fournié Guillaume 
Published: October 2021

AbstractLive animal markets are known hotspots of zoonotic disease emergence. To mitigate those risks, we need to understand how networks shaped by trading practices influence disease spread. Yet, those practices are rarely recorded in high-risk settings. Through a large cross-sectional study, we assessed the potential impact of live poultry trading networks’ structures on avian influenza transmission dynamics in Bangladesh. Networks promoted mixing between chickens sourced from different farming systems and geographical locations, fostering co-circulation of viral strains of diverse origins in markets. Viral transmission models suggested that the observed rise in viral prevalence from farms to markets was unlikely explained by intra-market transmission alone, but substantially influenced by transmission occurring in upstream network nodes. Disease control interventions should therefore alter the entire network structures. However, as networks differed between chicken types and city supplied, standardised interventions are unlikely to be effective, and should be tailored to local structural characteristics.
Contamination-resistant, rapid emulsion-based isothermal nucleic acid amplification with Mie-scatter inspired light scatter analysis for bacterial identification
Authors: Day Alexander S. , Ulep Tiffany-Heather , Budiman Elizabeth , Dieckhaus Laurel , Safavinia Babak , Hertenstein Tyler , Yoon Jeong-Yeol 
Published: October 2021

AbstractAn emulsion loop-mediated isothermal amplification (eLAMP) platform was developed to reduce the impact that contamination has on assay performance. Ongoing LAMP reactions within the emulsion droplets cause a decrease in interfacial tension, causing a decrease in droplet size, which results in decreased light scatter intensity due to Mie theory. Light scatter intensity was monitored via spectrophotometers and fiber optic cables placed at 30° and 60°. Light scatter intensities collected at 3 min, 30° were able to statistically differentiate 103 and 106 CFU/µL initial Escherichia coli O157:H7 concentrations compared to NTC (0 CFU/µL), while the intensity at 60° were able to statistically differentiate 106 CFU/µL initial concentrations and NTC. Control experiments were conducted to validate nucleic acid detection versus bacterial adsorption, finding that the light scatter intensities change is due specifically to ongoing LAMP amplification. After inducing contamination of bulk LAMP reagents, specificity lowered to 0% with conventional LAMP, while the eLAMP platform showed 87.5% specificity. We have demonstrated the use of angle-dependent light scatter intensity as a means of real-time monitoring of an emulsion LAMP platform and fabricated a smartphone-based monitoring system that showed similar trends as spectrophotometer light scatter data, validating the technology for a field deployable platform.
Vaccination intentions generate racial disparities in the societal persistence of COVID-19
Authors: Wang Yanchao , Ristea Alina , Amiri Mehrnaz , Dooley Dan , Gibbons Sage , Grabowski Hannah , Hargraves J. Lee , Kovacevic Nikola , Roman Anthony , Schutt Russell K. , Gao Jianxi , Wang Qi , O’Brien Daniel T. 
Published: October 2021

AbstractWe combined survey, mobility, and infections data in greater Boston, MA to simulate the effects of racial disparities in the inclination to become vaccinated on continued infection rates and the attainment of herd immunity. The simulation projected marked inequities, with communities of color experiencing infection rates 3 times higher than predominantly White communities and reaching herd immunity 45 days later on average. Persuasion of individuals uncertain about vaccination was crucial to preventing the worst inequities but could only narrow them so far because 1/5th of Black and Latinx individuals said that they would never vaccinate. The results point to a need for well-crafted, compassionate messaging that reaches out to those most resistant to the vaccine.
Exploration of efficient electron acceptors for organic solar cells: rational design of indacenodithiophene based non-fullerene compounds
Authors: Khalid Muhammad , Khan Muhammad Usman , -Razia Eisha-tul , Shafiq Zahid , Alam Mohammed Mujahid , Imran Muhammad , Akram Muhammad Safwan 
Published: October 2021

AbstractThe global need for renewable sources of energy has compelled researchers to explore new sources and improve the efficiency of the existing technologies. Solar energy is considered to be one of the best options to resolve climate and energy crises because of its long-term stability and pollution free energy production. Herein, we have synthesized a small acceptor compound (TPDR) and have utilized for rational designing of non-fullerene chromophores (TPD1–TPD6) using end-capped manipulation in A2–A1–D–A1–A2 configuration. The quantum chemical study (DFT/TD-DFT) was used to characterize the effect of end group redistribution through frontier molecular orbital (FMO), optical absorption, reorganization energy, open circuit voltage (Voc), photovoltaic properties and intermolecular charge transfer for the designed compounds. FMO data exhibited that TPD5 had the least ΔE (1.71 eV) with highest maximum absorption (λmax) among all compounds due to the four cyano groups as the end-capped acceptor moieties. The reorganization energies of TPD1–TPD6 hinted at credible electron transportation due to the lower values of λe than λh. Furthermore, open circuit voltage (Voc) values showed similar amplitude for all compounds including parent chromophore, except TPD4 and TPD5 compounds. These designed compounds with unique end group acceptors have the potential to be used as novel fabrication materials for energy devices.
Reliably quantifying the evolving worldwide dynamic state of the COVID-19 outbreak from death records, clinical parametrization, and demographic data
Authors: Vilar Jose M. G. , Saiz Leonor 
Published: October 2021

AbstractThe dynamic characterization of the COVID-19 outbreak is critical to implement effective actions for its control and eradication but the information available at a global scale is not sufficiently reliable to be used directly. Here, we develop a quantitative approach to reliably quantify its temporal evolution and controllability through the integration of multiple data sources, including death records, clinical parametrization of the disease, and demographic data, and we explicitly apply it to countries worldwide, covering 97.4% of the human population, and to states within the United States (US). The validation of the approach shows that it can accurately reproduce the available prevalence data and that it can precisely infer the timing of nonpharmaceutical interventions. The results of the analysis identified general patterns of recession, stabilization, and resurgence. The diversity of dynamic behaviors of the outbreak across countries is paralleled by those of states and territories in the US, converging to remarkably similar global states in both cases. Our results offer precise insights into the dynamics of the outbreak and an efficient avenue for the estimation of the prevalence rates over time.
Identification of biomarkers of brown adipose tissue aging highlights the role of dysfunctional energy and nucleotide metabolism pathways
Authors: Mancini Carola , Gohlke Sabrina , Garcia-Carrizo Francisco , Zagoriy Vyacheslav , Stephanowitz Heike , Schulz Tim J. 
Published: October 2021

AbstractBrown adipose tissue function declines during aging and may contribute to the onset of metabolic disorders such as diabetes and obesity. Only limited understanding of the mechanisms leading to the metabolic impairment of brown adipocytes during aging exists. To this end, interscapular brown adipose tissue samples were collected from young and aged mice for quantification of differential gene expression and metabolite levels. To identify potential processes involved in brown adipocyte dysfunction, metabolite concentrations were correlated to aging and significantly changed candidates were subsequently integrated with a non-targeted proteomic dataset and gene expression analyses. Our results include novel age-dependent correlations of polar intermediates in brown adipose tissue. Identified metabolites clustered around three biochemical processes, specifically energy metabolism, nucleotide metabolism and vitamin metabolism. One mechanism of brown adipose tissue dysfunction may be linked to mast cell activity, and we identify increased histamine levels in aged brown fat as a potential biomarker. In addition, alterations of genes involved in synthesis and degradation of many metabolites were mainly observed in the mature brown adipocyte fraction as opposed to the stromal vascular fraction. These findings may provide novel insights on the molecular mechanisms contributing to the impaired thermogenesis of brown adipocytes during aging.