bluuebunny/crossref_metadata_2025_split huggingface dataset:
The way of SARS-CoV-2 vaccine development: success and challenges
Authors: Dong Yetian , Dai Tong , Wang Bin , Zhang Lei , Zeng Ling-hui , Huang Jun , Yan Haiyan , Zhang Long , Zhou Fangfang 
Published: November 2021

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). To halt the pandemic, multiple SARS-CoV-2 vaccines have been developed and several have been allowed for emergency use and rollout worldwide. With novel SARS-CoV-2 variants emerging and circulating widely, whether the original vaccines that were designed based on the wild-type SARS-CoV-2 were effective against these variants has been a contentious discussion. Moreover, some studies revealed the long-term changes of immune responses post SARS-CoV-2 infection or vaccination and the factors that might impact the vaccine-induced immunity. Thus, in this review, we have summarized the influence of mutational hotspots on the vaccine efficacy and characteristics of variants of interest and concern. We have also discussed the reasons that might result in discrepancies in the efficacy of different vaccines estimated in different trials. Furthermore, we provided an overview of the duration of immune responses after natural infection or vaccination and shed light on the factors that may affect the immunity induced by the vaccines, such as special disease conditions, sex, and pre-existing immunity, with the aim of aiding in combating COVID-19 and distributing SARS-CoV-2 vaccines under the prevalence of diverse SARS-CoV-2 variants.
An atlas of inter- and intra-tumor heterogeneity of apoptosis competency in colorectal cancer tissue at single-cell resolution
Authors: Lindner Andreas Ulrich , Salvucci Manuela , McDonough Elizabeth , Cho Sanghee , Stachtea Xanthi , O’Connell Emer P. , Corwin Alex D. , Santamaria-Pang Alberto , Carberry Steven , Fichtner Michael , Van Schaeybroeck Sandra , Laurent-Puig Pierre , Burke John P. , McNamara Deborah A. , Lawler Mark , Sood Anup , Graf John F. , Rehm Markus , Dunne Philip D. , Longley Daniel B. , Ginty Fiona , Prehn Jochen H. M. 
Published: November 2021

AbstractCancer cells’ ability to inhibit apoptosis is key to malignant transformation and limits response to therapy. Here, we performed multiplexed immunofluorescence analysis on tissue microarrays with 373 cores from 168 patients, segmentation of 2.4 million individual cells, and quantification of 18 cell lineage and apoptosis proteins. We identified an enrichment for BCL2 in immune, and BAK, SMAC, and XIAP in cancer cells. Ordinary differential equation-based modeling of apoptosis sensitivity at single-cell resolution was conducted and an atlas of inter- and intra-tumor heterogeneity in apoptosis susceptibility generated. Systems modeling at single-cell resolution identified an enhanced sensitivity of cancer cells to mitochondrial permeabilization and executioner caspase activation compared to immune and stromal cells, but showed significant inter- and intra-tumor heterogeneity.
Tumor-associated macrophages (TAMs) depend on MMP1 for their cancer-promoting role
Authors: Yu Junhui , Xu Zhengshui , Guo Jing , Yang Kui , Zheng Jianbao , Sun Xuejun 
Published: November 2021

AbstractThe complex interaction between tumor-associated macrophages (TAMs) and tumor cells through several soluble factors and signaling is essential for colorectal cancer (CRC) progression. However, the molecular mechanism involved remains elusive. In this study, we demonstrated that MMP1 derived from TAMs markedly facilitated colon cancer cell proliferation via accelerating cell cycle transition from G0/G1 to S and G2/M phase. Moreover, exogenous MMP1 activated cdc25a/CDK4-cyclin D1 and p21/cdc2-cyclin B1 complexes through altering c-Myc and ETV4. Mechanistic studies indicated that inhibition of PAR1 or blockage of MAPK/Erk signaling eliminated the proliferation induced by exogenous MMP1 in vitro and in vivo. In addition, ETV4 could bind to the promoter of MMP1 and activate MMP1 transcription, which confirmed the MMP1/ETV4/MMP1 positive feedback. Altogether, our study identified a cytokine paracrine manner between colon cancer cells and TAMs. MMP1/PAR1/Erk1/2/ETV4 positive feedback loop may represent to be a therapeutic target and prognostic marker in CRC.
A novel SARS-CoV-2 related coronavirus in bats from Cambodia
Authors: Delaune Deborah , Hul Vibol , Karlsson Erik A. , Hassanin Alexandre , Ou Tey Putita , Baidaliuk Artem , Gámbaro Fabiana , Prot Matthieu , Tu Vuong Tan , Chea Sokha , Keatts Lucy , Mazet Jonna , Johnson Christine K. , Buchy Philippe , Dussart Philippe , Goldstein Tracey , Simon-Lorière Etienne , Duong Veasna 
Published: November 2021

AbstractKnowledge of the origin and reservoir of the coronavirus responsible for the ongoing COVID-19 pandemic is still fragmentary. To date, the closest relatives to SARS-CoV-2 have been detected in Rhinolophus bats sampled in the Yunnan province, China. Here we describe the identification of SARS-CoV-2 related coronaviruses in two Rhinolophus shameli bats sampled in Cambodia in 2010. Metagenomic sequencing identifies nearly identical viruses sharing 92.6% nucleotide identity with SARS-CoV-2. Most genomic regions are closely related to SARS-CoV-2, with the exception of a region of the spike, which is not compatible with human ACE2-mediated entry. The discovery of these viruses in a bat species not found in China indicates that SARS-CoV-2 related viruses have a much wider geographic distribution than previously reported, and suggests that Southeast Asia represents a key area to consider for future surveillance for coronaviruses.
Single-molecule imaging with cell-derived nanovesicles reveals early binding dynamics at a cyclic nucleotide-gated ion channel
Authors: Patel Vishal R. , Salinas Arturo M. , Qi Darong , Gupta Shipra , Sidote David J. , Goldschen-Ohm Marcel P. 
Published: November 2021

AbstractLigand binding to membrane proteins is critical for many biological signaling processes. However, individual binding events are rarely directly observed, and their asynchronous dynamics are occluded in ensemble-averaged measures. For membrane proteins, single-molecule approaches that resolve these dynamics are challenged by dysfunction in non-native lipid environments, lack of access to intracellular sites, and costly sample preparation. Here, we introduce an approach combining cell-derived nanovesicles, microfluidics, and single-molecule fluorescence colocalization microscopy to track individual binding events at a cyclic nucleotide-gated TAX-4 ion channel critical for sensory transduction. Our observations reveal dynamics of both nucleotide binding and a subsequent conformational change likely preceding pore opening. Kinetic modeling suggests that binding of the second ligand is either independent of the first ligand or exhibits up to ~10-fold positive binding cooperativity. This approach is broadly applicable to studies of binding dynamics for proteins with extracellular or intracellular domains in native cell membrane.
MPK3- and MPK6-mediated VLN3 phosphorylation regulates actin dynamics during stomatal immunity in Arabidopsis
Authors: Zou Minxia , Guo Mengmeng , Zhou Zhaoyang , Wang Bingxiao , Pan Qing , Li Jiajing , Zhou Jian-Min , Li Jiejie 
Published: November 2021

AbstractUpon perception of pathogens, plants can rapidly close their stomata to restrict pathogen entry into internal tissue, leading to stomatal immunity as one aspect of innate immune responses. The actin cytoskeleton is required for plant defense against microbial invaders. However, the precise functions of host actin during plant immunity remain largely unknown. Here, we report that Arabidopsis villin3 (VLN3) is critical for plant resistance to bacteria by regulating stomatal immunity. Our in vitro and in vivo phosphorylation assays show that VLN3 is a physiological substrate of two pathogen-responsive mitogen-activated protein kinases, MPK3/6. Quantitative analyses of actin dynamics and genetic studies reveal that VLN3 phosphorylation by MPK3/6 modulates actin remodeling to activate stomatal defense in Arabidopsis.
Whole genome and exome sequencing reference datasets from a multi-center and cross-platform benchmark study
Authors: Zhao Yongmei , Fang Li Tai , Shen Tsai-wei , Choudhari Sulbha , Talsania Keyur , Chen Xiongfong , Shetty Jyoti , Kriga Yuliya , Tran Bao , Zhu Bin , Chen Zhong , Chen Wanqiu , Wang Charles , Jaeger Erich , Meerzaman Daoud , Lu Charles , Idler Kenneth , Ren Luyao , Zheng Yuanting , Shi Leming , Petitjean Virginie , Sultan Marc , Hung Tiffany , Peters Eric , Drabek Jiri , Vojta Petr , Maestro Roberta , Gasparotto Daniela , Kõks Sulev , Reimann Ene , Scherer Andreas , Nordlund Jessica , Liljedahl Ulrika , Foox Jonathan , Mason Christopher E. , Xiao Chunlin , Hong Huixiao , Xiao Wenming 
Published: November 2021

AbstractWith the rapid advancement of sequencing technologies, next generation sequencing (NGS) analysis has been widely applied in cancer genomics research. More recently, NGS has been adopted in clinical oncology to advance personalized medicine. Clinical applications of precision oncology require accurate tests that can distinguish tumor-specific mutations from artifacts introduced during NGS processes or data analysis. Therefore, there is an urgent need to develop best practices in cancer mutation detection using NGS and the need for standard reference data sets for systematically measuring accuracy and reproducibility across platforms and methods. Within the SEQC2 consortium context, we established paired tumor-normal reference samples and generated whole-genome (WGS) and whole-exome sequencing (WES) data using sixteen library protocols, seven sequencing platforms at six different centers. We systematically interrogated somatic mutations in the reference samples to identify factors affecting detection reproducibility and accuracy in cancer genomes. These large cross-platform/site WGS and WES datasets using well-characterized reference samples will represent a powerful resource for benchmarking NGS technologies, bioinformatics pipelines, and for the cancer genomics studies.
Impaired remapping of social relationships in older adults
Authors: Oltmer Jan , Wolbers Thomas , Kuehn Esther 
Published: November 2021

AbstractSocial relationships are a central aspect of our everyday life, yet our ability to change established social relationships is an under-investigated topic. Here, we use the concept of cognitive mapping to investigate the plasticity of social relationships in younger and older adults. We describe social relationships within a ‘social space’, defined as a two-dimensional grid composed of the axis ‘power’ and ‘affiliation’, and investigate it using a 3D virtual environment with interacting avatars. We show that participants remap dimensions in ‘social space’ when avatars show conflicting behavior compared to consistent behavior and that, while older adults show similar updating behavior than younger adults, they show a distinct reduction in remapping social space. Our data provide first evidence that older adults show more rigid social behavior when avatars change their behavior in the dimensions of power and affiliation, which may explain age-related social behavior differences in everyday life.
DeepFake electrocardiograms using generative adversarial networks are the beginning of the end for privacy issues in medicine
Authors: Thambawita Vajira , Isaksen Jonas L. , Hicks Steven A. , Ghouse Jonas , Ahlberg Gustav , Linneberg Allan , Grarup Niels , Ellervik Christina , Olesen Morten Salling , Hansen Torben , Graff Claus , Holstein-Rathlou Niels-Henrik , Strümke Inga , Hammer Hugo L. , Maleckar Mary M. , Halvorsen Pål , Riegler Michael A. , Kanters Jørgen K. 
Published: November 2021

AbstractRecent global developments underscore the prominent role big data have in modern medical science. But privacy issues constitute a prevalent problem for collecting and sharing data between researchers. However, synthetic data generated to represent real data carrying similar information and distribution may alleviate the privacy issue. In this study, we present generative adversarial networks (GANs) capable of generating realistic synthetic DeepFake 10-s 12-lead electrocardiograms (ECGs). We have developed and compared two methods, named WaveGAN* and Pulse2Pulse. We trained the GANs with 7,233 real normal ECGs to produce 121,977 DeepFake normal ECGs. By verifying the ECGs using a commercial ECG interpretation program (MUSE 12SL, GE Healthcare), we demonstrate that the Pulse2Pulse GAN was superior to the WaveGAN* to produce realistic ECGs. ECG intervals and amplitudes were similar between the DeepFake and real ECGs. Although these synthetic ECGs mimic the dataset used for creation, the ECGs are not linked to any individuals and may thus be used freely. The synthetic dataset will be available as open access for researchers at OSF.io and the DeepFake generator available at the Python Package Index (PyPI) for generating synthetic ECGs. In conclusion, we were able to generate realistic synthetic ECGs using generative adversarial neural networks on normal ECGs from two population studies, thereby addressing the relevant privacy issues in medical datasets.
Recurrence monitoring for ovarian cancer using a cell phone-integrated paper device to measure the ovarian cancer biomarker HE4/CRE ratio in urine
Authors: Kight Emily C. , Hussain Iftak , Bowden Audrey K. , Haselton Frederick R. 
Published: November 2021

AbstractOvarian cancer has a poor cure rate and rates of relapse are high. Current recurrence detection is limited by non-specific methods such as blood testing and ultrasound. Based on reports that human epididymis four (HE4) / creatinine (CRE) ratios found in urine are elevated in ovarian cancers, we have developed a paper-based device that combines lateral flow technology and cell phone analysis to quantitatively measure HE4/CRE. Surrogate samples were used to test the performance over clinically expected HE4/CRE ratios. For HE4/CRE ratios of 2 to 47, the percent error was found to be 16.0% on average whether measured by a flatbed scanner or cell phone. There was not a significant difference between the results from the cell phone or scanner. Based on published studies, error in this method was less than the difference required to detect recurrence. This promising new tool, with further development, could be used at home or in low-resource settings to provide timely detection of ovarian cancer recurrence.
CYP11B1 variants influence skeletal maturation via alternative splicing
Authors: Grgic Olja , Gazzara Matthew R. , Chesi Alessandra , Medina-Gomez Carolina , Cousminer Diana L. , Mitchell Jonathan A. , Prijatelj Vid , de Vries Jard , Shevroja Enisa , McCormack Shana E. , Kalkwarf Heidi J. , Lappe Joan M. , Gilsanz Vicente , Oberfield Sharon E. , Shepherd John A. , Kelly Andrea , Mahboubi Soroosh , Faucz Fabio R. , Feelders Richard A. , de Jong Frank H. , Uitterlinden Andre G. , Visser Jenny A. , Ghanem Louis R. , Wolvius Eppo B. , Hofland Leo J. , Stratakis Constantine A. , Zemel Babette S. , Barash Yoseph , Grant Struan F. A. , Rivadeneira Fernando 
Published: November 2021

AbstractWe performed genome-wide association study meta-analysis to identify genetic determinants of skeletal age (SA) deviating in multiple growth disorders. The joint meta-analysis (N = 4557) in two multiethnic cohorts of school-aged children identified one locus, CYP11B1 (expression confined to the adrenal gland), robustly associated with SA (rs6471570-A; β = 0.14; P = 6.2 × 10−12). rs6410 (a synonymous variant in the first exon of CYP11B1 in high LD with rs6471570), was prioritized for functional follow-up being second most significant and the one closest to the first intron-exon boundary. In 208 adrenal RNA-seq samples from GTEx, C-allele of rs6410 was associated with intron 3 retention (P = 8.11 × 10−40), exon 4 inclusion (P = 4.29 × 10−34), and decreased exon 3 and 5 splicing (P = 7.85 × 10−43), replicated using RT-PCR in 15 adrenal samples. As CYP11B1 encodes 11-β-hydroxylase, involved in adrenal glucocorticoid and mineralocorticoid biosynthesis, our findings highlight the role of adrenal steroidogenesis in SA in healthy children, suggesting alternative splicing as a likely underlying mechanism.
Two energy barriers and a transient intermediate state determine the unfolding and folding dynamics of cold shock protein
Authors: Hong Haiyan , Guo Zilong , Sun Hao , Yu Ping , Su Huanhuan , Ma Xuening , Chen Hu 
Published: November 2021

AbstractCold shock protein (Csp) is a typical two-state folding model protein which has been widely studied by biochemistry and single molecule techniques. Recently two-state property of Csp was confirmed by atomic force microscopy (AFM) through direct pulling measurement, while several long-lifetime intermediate states were found by force-clamp AFM. We systematically studied force-dependent folding and unfolding dynamics of Csp using magnetic tweezers with intrinsic constant force capability. Here we report that Csp mostly folds and unfolds with a single step over force range from 5 pN to 50 pN, and the unfolding rates show different force sensitivities at forces below and above ~8 pN, which determines a free energy landscape with two barriers and a transient intermediate state between them along one transition pathway. Our results provide a new insight on protein folding mechanism of two-state proteins.
Enhanced in-plane ferroelectricity, antiferroelectricity, and unconventional 2D emergent fermions in quadruple-layer XSbO2 (X = Li, Na)
Authors: Guan Shan , Zhang GuangBiao , Liu Chang 
Published: November 2021

The electrically tunable in-plane multiple spontaneous polarization and various 2D emergent fermions in quadruple-layer XSbO2 (X = Li, Na)
Detection of subtype-specific breast cancer surface protein biomarkers via a novel transcriptomics approach
Authors: Mercatelli Daniele , Formaggio Francesco , Caprini Marco , Holding Andrew , Giorgi Federico M. 
Published: November 2021

Abstract
Background: Cell-surface proteins have been widely used as diagnostic and prognostic markers in cancer research and as targets for the development of anticancer agents. So far, very few attempts have been made to characterize the surfaceome of patients with breast cancer, particularly in relation with the current molecular breast cancer (BRCA) classification. In this view, we developed a new computational method to infer cell-surface protein activities from transcriptomics data, termed ‘SURFACER’.
Methods: Gene expression data from GTEx were used to build a normal breast network model as input to infer differential cell-surface proteins activity in BRCA tissue samples retrieved from TCGA versus normal samples. Data were stratified according to the PAM50 transcriptional subtypes (Luminal A, Luminal B, HER2 and Basal), while unsupervised clustering techniques were applied to define BRCA subtypes according to cell-surface proteins activity.
Results: Our approach led to the identification of 213 PAM50 subtypes-specific deregulated surface genes and the definition of five BRCA subtypes, whose prognostic value was assessed by survival analysis, identifying a cell-surface activity configuration at increased risk. The value of the SURFACER method in BRCA genotyping was tested by evaluating the performance of 11 different machine learning classification algorithms.
Conclusions: BRCA patients can be stratified into five surface activity-specific groups having the potential to identify subtype-specific actionable targets to design tailored targeted therapies or for diagnostic purposes. SURFACER-defined subtypes show also a prognostic value, identifying surface-activity profiles at higher risk.
Speech-Language Pathologist Perspectives of the Implementation of Telepractice-Delivered Stuttering Treatment for School-Age Children
Authors: Erickson Shane , Bridgman Kate , Furlong Lisa , Stark Hannah 
Published: November 2021

Purpose:
The impact of stuttering can be significant, and effective treatment is critical. Despite evidence supporting direct treatment approaches for school-age children who stutter, a complex set of barriers can prevent access at school. One potential solution is telepractice. To date, however, there is no published evidence regarding the use of telepractice to deliver the Lidcombe Program within a school setting.

Method:
In this pilot study, a telepractice service was established and the perspectives of the five treating speech-language pathologists (SLPs) were evaluated before, during, and after the trial through focus groups and recorded telesupervision sessions.

Results:
An inductive and reflexive thematic analysis identified four main themes: (a) Understanding and managing technology is critical; (b) logistical considerations can be time-consuming and challenging; (c) preparation and support are essential; and (d) family engagement, acceptance, and independence with telepractice services can be facilitated by external support and coaching. Initially, the SLPs shared feelings of uncertainty, fear, and apprehension. Yet, despite this concern, the SLPs ultimately reported that telepractice can play an important role in their service.

Conclusions:
In order to maximize the potential value of telepractice, SLPs require training and support to (a) manage the technology and troubleshoot problems that invariably arise, (b) have the opportunity to watch demonstrations of the technology, and (c) clearly explain the roles, responsibilities, and expectations of the parent engaging in treatment. These findings have particular relevance now, as schools and support services navigate a COVID-safe delivery model for the indefinite future.
J-PLUS: Spectral evolution of white dwarfs by PDF analysis
Authors: López-Sanjuan C. , Tremblay P.-E. , Ederoclite A. , Vázquez Ramió H. , Carrasco J. M. , Varela J. , Cenarro A. J. , Marín-Franch A. , Civera T. , Daflon S. , Gänsicke B. T. , Gentile Fusillo N. P. , Jiménez-Esteban F. M. , Alcaniz J. , Angulo R. E. , Cristóbal-Hornillos D. , Dupke R. A. , Hernández-Monteagudo C. , Moles M. , Sodré L. 
Published: November 2021

Aims.We estimated the spectral evolution of white dwarfs with effective temperature using the Javalambre Photometric Local Universe Survey (J-PLUS) second data release (DR2), which provides 12 photometric optical passbands over 2176 deg2.Methods.We analyzed 5926 white dwarfs withr ≤ 19.5 mag in common between a white dwarf catalog defined fromGaiaEDR3 and J-PLUS DR2. We performed a Bayesian analysis by comparing the observed J-PLUS photometry with theoretical models of hydrogen- and helium-dominated atmospheres. We estimated the probability distribution functions for effective temperature (Teff), surface gravity, parallax, and composition; and the probability of having a H-dominated atmosphere (pH) for each source. We applied a prior in parallax, usingGaiaEDR3 measurements as a reference, and derived a self-consistent prior for the atmospheric composition as a function ofTeff.Results.We described the fraction of white dwarfs with a He-dominated atmosphere (fHe) with a linear function of the effective temperature at 5000 < Teff < 30 000 K. We findfHe = 0.24 ± 0.01 atTeff = 10 000 K, a change rate along the cooling sequence of 0.14 ± 0.02 per 10 kK, and a minimum He-dominated fraction of 0.08 ± 0.02 at the high-temperature end. We tested the obtainedpHby comparison with spectroscopic classifications, finding that it is reliable. We estimated the mass distribution for the 351 sources with distanced < 100 pc, massM > 0.45M⊙, andTeff > 6000 K. The result for H-dominated white dwarfs agrees with previous studies, with a dominantM = 0.59M⊙peak and the presence of an excess atM ∼ 0.8M⊙. This high-mass excess is absent in the He-dominated distribution, which presents a single peak.Conclusions.The J-PLUS optical data provide a reliable statistical classification of white dwarfs into H- and He-dominated atmospheres. We find a 21 ± 3% increase in the fraction of He-dominated white dwarfs fromTeff = 20 000 K toTeff = 5000 K.