bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined radiotherapy and chemotherapy versus radiotherapy alone in elderly patients with nasopharyngeal carcinoma
Authors: Lu Yan , Hua Jianfeng , Yan Fengqin , Jiang Chuner , Piao Yongfeng , Ye Zhimin , Fu Zhenfu , Jiang Haitao , Wang Fangzheng , Jiang Yangming 
Published: August 2021

Abstract
Currently, the impact of chemotherapy (CT) on survival outcomes in elderly patients with nasopharyngeal carcinoma (NPC) receiving radiation therapy (RT) remains controversial. This retrospective study aims to investigate survival outcomes in a cohort of elderly NPC patients receiving RT alone or together with CT.
Clinical data on 529 NPC patients aged 65 years and older extracted from the Surveillance, Epidemiology, and End Results registry (2004–2015) was collected and retrospectively reviewed. In this cohort, 74 patients were treated with RT alone and 455 individuals received RT and CT. We used propensity score matching with a 1:3 ratio to identify correlations between patients based on 6 different variables. Kaplan–Meier analysis was used to evaluate overall (OS) and cancer-specific survival (CSS). The differences in OS and CSS between the 2 treatment groups were compared using the Log-rank test and Cox proportional hazards models.
The estimated 5-year OS and CSS rates for all patients were 49.5% and 59.3%, respectively. The combination of RT and CT provided longer OS than RT alone (53.7% vs 36.9%, P = .002), while no significant difference was observed in CSS (61.8% vs 51.7%, P = .074) between the 2 groups. Moreover, multivariate analysis demonstrated that the combination of CT and RT correlated favorably with OS and CSS. Subgroup analyses showed that the combination of RT and CT correlated better with both OS and CSS in patients with stage T3 or N2 or stage III.
Among NPC patients aged 65 years and older, treatment with RT and CT provided longer OS than RT alone. Furthermore, the combination of RT and CT showed a better correlation with OS and CSS in NPC patients with stage T3 or N2 or stage III.
The genomic and transcriptional landscape of primary central nervous system lymphoma
Authors: Radke Josefine , Ishaque Naveed , Koll Randi , Gu Zuguang , Schumann Elisa , Sieverling Lina , Uhrig Sebastian , Hübschmann Daniel , Toprak Umut H. , López Cristina , Hostench Xavier Pastor , Borgoni Simone , Juraeva Dilafruz , Pritsch Fabienne , Paramasivam Nagarajan , Balasubramanian Gnana Prakash , Schlesner Matthias , Sahay Shashwat , Pehl Debora , Radbruch Helena , Osterloh Anja , Korfel Agnieszka , Misch Martin , Onken Julia , Faust Katharina , Vajkoczy Peter , Moskopp Dag , Wang Yawen , Jödicke Andreas , Trümper Lorenz , Anagnostopoulos Ioannis , Lenze Dido , Hummel Michael , Schmitt Clemens A. , Wiestler Otmar D. , Wolf Stephan , Unterberg Andreas , Eils Roland , Herold-Mende Christel , Brors Benedikt ,   ICGC MMML-Seq Consortium, Siebert Reiner , Wiemann Stefan , Heppner Frank L. 
Published: August 2021

AbstractPrimary lymphomas of the central nervous system (PCNSL) are mainly diffuse large B-cell lymphomas (DLBCLs) confined to the central nervous system (CNS). Despite extensive research, the molecular alterations leading to PCNSL have not been fully elucidated. In order to provide a comprehensive description of the genomic and transcriptional landscape of PCNSL, we here performed whole-genome and transcriptome sequencing and integrative analysis of 51 lymphomas presenting in the CNS, including 42 EBV-negative PCNSL, 6 secondary CNS lymphomas (SCNSL) and 3 EBV+ CNSL and matched controls. The results were compared to an independent validation cohort of 31 FFPE CNSL specimens (PCNSL, n = 19; SCNSL, n = 9; EBV+ CNSL, n = 3) as well as 39 FL and 36 systemic DLBCL cases outside the CNS. Somatic genomic alterations in PCNSL mainly affect the JAK-STAT, NFkB, and B-cell receptor signaling pathways, with hallmark recurrent mutations includingMYD88L265P (67%) andCD79B(63%),CDKN2Adeletions (83%) and also non-coding RNA genes such asMALAT1(70%),NEAT(60%), andMIR142(80%). Kataegis events, which affected 15 of 50 identified driver genes and 21 of the top 50 mutated ncRNAs, played a decisive role in shaping the mutational repertoire of PCNSL. Compared to systemic DLBCL, PCNSLs exhibited significantly more focal deletions in 6p21 targeting the HLA-D locus that encodes for MHC class II molecules as a potential mechanism of immune evasion. Mutational signatures correlating with DNA replication and mitosis (SBS1, ID1 and ID2) were significantly enriched in PCNSL (SBS1:p= 0.0027, ID1/ID2:p< 1×10−4). Furthermore,TERTgene expression was significantly higher in PCNSL compared to ABC-DLBCL (p= 0.027). Although PCNSL share many genetic alterations with systemic ABC-DLBCL in the same signaling pathways, transcriptome analysis clearly distinguished both into distinct molecular subtypes. EBV+ CNSL cases may be distinguished by lack of recurrent mutational hotspots apart from IG andHLA-DRBloci.
A Comparison of Aerosol Mitigation Strategies and Aerosol Persistence in Dental Environments
Authors: Choudhary Shruti , Durkin Michael J. , Stoeckel Daniel C. , Steinkamp Heidi M. , Thornhill Martin H. , Lockhart Peter B. , Babcock Hilary M. , Kwon Jennie H. , Liang Stephen Y. , Biswas Pratim 
Published: August 2021

AbstractObjectivesTo determine the impact of various aerosol mitigation interventions and establish duration of aerosol persistence in a variety of dental clinic configurations.MethodsWe performed aerosol measurement studies in endodontic, orthodontic, periodontic, pediatric, and general dentistry clinics. We used an optical aerosol spectrometer and wearable particulate matter sensors to measure real-time aerosol concentration from the vantage point of the dentist during routine care in a variety of clinic configurations (e.g, open bay, single room, partitioned operatories). We compared the impact of aerosol mitigation strategies [ventilation and high-volume evacuation (HVE)] and prevalence of particulate matter in the dental clinic environment before, during and after high-speed drilling, slow speed drilling and ultrasonic scaling procedures.ResultsConical and ISOVAC® HVE were superior to standard tip evacuation for aerosol-generating procedures. When aerosols were detected in the environment, they were rapidly dispersed within minutes of completing the aerosol-generating procedure. Few aerosols were detected in dental clinics – regardless of configuration – when conical and ISOVAC® HVE were used.ConclusionsDentists should consider using conical or ISOVAC® HVE rather than standard tip evacuators to reduce aerosols generated during routine clinical practice. Furthermore, when such effective aerosol mitigation strategies are employed, dentists need not leave dental chairs fallow between patients as aerosols are rapidly dispersed.Clinical SignificanceISOVAC® HVE is highly effective in reducing aerosol emissions, with adequate ventilation and HVE use, dental fallow time can be reduced to 5 minutes.
In-depth analysis of Bacillus anthracis 16S rRNA genes and transcripts reveals intra- and intergenomic diversity and facilitates anthrax detection
Authors: Braun Peter , Zimmermann Fee , Walter Mathias C. , Mantel Sonja , Aistleitner Karin , Stürz Inga , Grass Gregor , Stoecker Kilian 
Published: August 2021

AbstractAnalysis of 16S ribosomal RNA (rRNA) genes provides a central means of taxonomic classification of bacterial species. Based on presumed sequence identity among species of the Bacillus cereus sensu lato group, the 16S rRNA genes of B. anthracis have been considered unsuitable for diagnosis of the anthrax pathogen. With the recent identification of a single nucleotide polymorphism in some 16S rRNA gene copies, specific identification of B. anthracis becomes feasible. Here, we designed and evaluated a set of in situ-, in vitro- and in silico-assays to assess the yet unknown 16S-state of B. anthracis from different perspectives. Using a combination of digital PCR, fluorescence in situ hybridization, long-read genome sequencing and bioinformatics we were able to detect and quantify a unique 16S rRNA gene allele of B. anthracis (16S-BA-allele). This allele was found in all available B.anthracis genomes and may facilitate differentiation of the pathogen from any close relative. Bioinformatics analysis of 959 B. anthracis genome data-sets inferred that abundances and genomic arrangements of the 16S-BA-allele and the entire rRNA operon copy-numbers differ considerably between strains. Expression ratios of 16S-BA-alleles were proportional to the respective genomic allele copy-numbers. The findings and experimental tools presented here provide detailed insights into the intra- and intergenomic diversity of 16S rRNA genes and may pave the way for improved identification of B. anthracis and other pathogens with diverse rRNA operons.
Population normalisation in wastewater-based epidemiology for improved understanding of SARS-CoV-2 prevalence: A multi-site study
Authors: Sweetapple Chris , Wade Matthew J. , Grimsley Jasmine M. S. , Bunce Joshua T. , Melville-Shreeve Peter , Chen Albert S. 
Published: August 2021

ABSTRACTThis paper aims to determine whether population normalisation significantly alters the SARS-CoV-2 trends revealed by wastewater-based epidemiology, and whether it is beneficial and/or necessary to provide an understanding of prevalence from wastewater SARS-CoV-2 concentrations. It uses wastewater SARS-CoV-2 data collected from 394 sampling sites, and implements normalisation based on concentrations of a) ammoniacal nitrogen, and b) orthophosphate. Wastewater SARS-CoV-2 metrics are evaluated at a site and aggregated level against three indicators prevalence, based on positivity rates from the Office for National Statistics Coronavirus Infection Survey and test results reported by NHS Test and Trace. Normalisation is shown to have little impact on the overall trends in the wastewater SARS-CoV-2 data on average. However, significant variability between the impact of population normalisation at different sites, which is not evident from previous WBE studies focussed on a single site, is also revealed. Critically, it is demonstrated that while the impact of normalisation on SARS-CoV-2 trends is small on average, it is not reasonable to conclude that it is always insignificant. When averaged across many sites, normalisation strengthens the correlation between wastewater SARS-CoV-2 data and indicators of prevalence; however, confidence in the improvement is low. Lastly, it is noted that most data were collected during periods of national lockdown and/or local restrictions, and thus the impacts and benefits of population normalisation are expected to be higher when normal travel habits resume.
Increased brain atrophy over 3 years in stroke survivors is linked to early post-stroke cognitive impairment
Authors: Brodtmann Amy , Werden Emilio , Khlif Mohamed Salah , Bird Laura J. , Egorova Natalia , Veldsman Michele , Pardoe Heath , Jackson Graeme , Bradshaw Jennifer , Darby David , Cumming Toby , Churilov Leonid , Donnan Geoffrey 
Published: August 2021

ABSTRACTBackgroundStroke survivors are at high risk of dementia, associated with increasing age and vascular burden and with pre-existing cognitive impairment, older age. Brain atrophy patterns are recognised as signatures of neurodegenerative conditions, but the natural history of brain atrophy after stroke remains poorly described. We sought to determine whether stroke survivors who were cognitively normal at time of stroke had greater total brain (TBV) and hippocampal volume (HV) loss over 3 years than controls. We examined whether stroke survivors who were cognitively impaired (CI) at 3 months following their stroke had greater brain volume loss than cognitively normal (CN) stroke participants.MethodsCognition And Neocortical Volume After Stroke (CANVAS) study is a multi-centre cohort study of first-ever or recurrent adult ischaemic stroke participants compared to age- and sex-matched community controls. Participants were followed with MRI and cognitive assessments over 3 years and were free of a history of cognitive impairment or decline at inclusion. Our primary outcome measure was TBV change between 3 months and 3 years; secondary outcomes were TBV and HV change comparing CI and CN participants. We investigated associations between group status and brain volume change using a baseline-volume adjusted linear regression model with robust standard error.ResultsNinety-three stroke (26 women, 66.7±12 years) and 39 control participants (15 women, 68.7±7 years) were available at 3 years. TBV loss in stroke patients was greater than controls: stroke mean (M)=20.3cm3±SD14.8cm3; controls M=14.2cm3±SD13.2cm3; (adjusted mean difference 7.88 95%CI [2.84,12.91] p-value=0.002). TBV decline was greater in those stroke participants who were cognitively impaired (M=30.7cm3; SD=14.2cm3) at 3 months (M=19.6cm3; SD=13.8cm3); (adjusted mean difference 10.42; 95%CI [3.04,17.80], p-value=0.006). No statistically significant differences in HV change were observed.ConclusionsIschaemic stroke survivors exhibit greater neurodegeneration compared to stroke-free controls. Brain atrophy is greater in stroke participants who were cognitively impaired people early after their stroke. Early cognitive impairment may predict greater subsequent atrophy, reflecting the combined impacts of stroke and vascular brain burden. Atrophy rates could serve as a useful biomarker for trials testing interventions to reduce post-stroke cognitive impairment.
Association of Systemic Immune-inflammation Index With Short-Term Mortality of Congestive Heart Failure: A Retrospective Cohort Study
Authors: Tang Yiyang , Zeng Xiaofang , Feng Yilu , Chen Qin , Liu Zhenghui , Luo Hui , Zha Lihuang , Yu Zaixin 
Published: August 2021

AbstractPurposeThe present study aimed to clarify the potential predictive significance of Systemic immune-inflammation index (SII) in assessing the poor prognosis of critically ill patients with congestive heart failure (CHF).MethodsDetailed clinical data were extracted from the Multiparameter Intelligent Monitoring in Intensive Care III database after gaining access and building the local platform. The 30- and 90-day and hospital all-cause mortalities of the patient was the primary outcome, and the readmission rate and the occurrence of major cardiovascular adverse events (MACEs) were the secondary outcomes. the Cox proportional hazard model and Logistic regression analysis were selected to reveal the relationship between SII level and the research outcome. Further, the propensity score matching (PSM) analysis was performed to improve the reliability of results by reducing the imbalance across groups.ResultsThere were a total of 4606 subjects who passed the screening process and entered the subsequent analysis. Multivariate regression analysis showed that after adjusting for possible confounders, including age, heart rate, and albumin, etc., the high level of SII was independently associated with 30- and 90-day and hospital mortalities (tertile 3 versus tertile 1: HR, 95% CIs: 1.23, 1.04-1.45; 1.21, 1.06-1.39; 1.26, 1.05-1.50) and the incidence of MACEs (tertile 3 versus tertile 1: OR, 95% CI: 1.39, 1.12-1.73) in critically ill patients with CHF, but no significant correlation was found between SII and the readmission rate. Consistently, patients with high SII level still presented a significantly higher short-term mortality than patients with low SII in the PSM subset.ConclusionIn critically ill patients with CHF, high level of SII could effectively predict high 30- and 90-day and hospital mortalities, as well as the high risk of occurrence of MACEs.
Thekpc-13’UTR facilitates dendritic transport and translation of mRNAs for dendrite arborization of a mechanosensory neuron important for male courtship
Authors: Shih Mushaine , Zou Yan , Ferreira Tarsis , Suzuki Nobuko , Kim Eunseo , Chuang Chiou-Fen , Chang Chieh 
Published: August 2021

SummaryA recently reported Schizophrenia-associated genetic variant in the 3’UTR of the human furin gene, a homolog ofC. elegans kpc-1, highlights an important role of the furin 3’UTR in neuronal development(1). We isolate threekpc-1mutants that display abnormal dendrite arborization in PVD neurons and defective male mating behaviors. We show that thekpc-13’UTR participates in dendrite branching and self-avoidance. Thekpc-13’UTR facilitates mRNA localization to branching points and contact points between sibling dendrites and promotes local protein synthesis. We identify a secondary structural motif in thekpc-13’UTR required for dendrite self-avoidance. Animals withdma-1receptor over-expression exhibit similar dendrite branching and self-avoidance defects that are suppressed withkpc-1over-expression. Our results support a model in which KPC-1 proteins are synthesized at branching points and contact points to locally down-regulate DMA-1 receptors to promote dendrite branching and self-avoidance of a mechanosensory neuron important for male courtship.
Deep learning model of somatic hypermutation reveals importance of sequence context beyond targeting of AID and Polη hotspots
Authors: Tang Catherine , Krantsevich Artem , MacCarthy Thomas 
Published: August 2021

SummaryB-cells undergo somatic hypermutation (SHM) of the Immunoglobulin (Ig) variable region to generate high-affinity antibodies. SHM relies on the activity of activation-induced deaminase (AID), which mutates C>U preferentially targeting WRC(W=A/T, R=A/G) hotspots. Downstream mutations at WAPolymerase η hotspots contribute further mutations. Computational models of SHM can describe the probability of mutations essential for vaccine responses. Previous studies using short subsequences (k-mers) failed to explain divergent mutability for the samek-mer. We developed the DeepSHM (Deep learning on SHM) model usingk-mers of size 5-21, improving accuracy over previous models. Interpretation of DeepSHM identified an extended DWRCT (D=A/G/T) motif with particularly high mutability. Increased mutability was further associated with lower surrounding G content. Our model also discovered a conserved AGYCTGGGGG (Y=C/T) motif within FW1 of IGHV3 family genes with unusually high T>G substitution rates. Thus, a wider sequence context increases predictive power and identifies novel features that drive mutational targeting.
A rear-engine drives adherent tissue migration in vivo
Authors: Yamaguchi Naoya , Zhang Ziyi , Schneider Teseo , Wang Biran , Panozzo Daniele , Knaut Holger 
Published: August 2021

AbstractDuring animal embryogenesis, homeostasis and disease, tissues push and pull on their surroundings to move forward. Although the force-generating machinery is known, it is unknown how tissues exert physical stresses on their substrate to generate motion in vivo. Here, we identify the force transmission machinery, the substrate, and the stresses that a tissue, the zebrafish posterior lateral line primordium, generates during its migration. We find that the primordium couples actin flow through integrins to the basement membrane for forward movement. Talin/integrin-mediated coupling is required for efficient migration and its loss is partly compensated for by increased actin flow. Using Embryogram, an approach to measure stresses in vivo, we show that the primordium’s rear exerts high stresses, indicating that this tissue pushes itself forward with its back. This unexpected strategy likely also underlies the motion of other tissues in animals
NanoNet: Rapid end-to-end nanobody modeling by deep learning at sub angstrom resolution
Authors: Cohen Tomer , Halfon Matan , Schneidman-Duhovny Dina 
Published: August 2021

AbstractAntibodies are a rapidly growing class of therapeutics. Recently, single domain camelid VHH antibodies, and their recognition nanobody domain (Nb) appeared as a cost-effective highly stable alternative to full-length antibodies. There is a growing need for high-throughput epitope mapping based on accurate structural modeling of the variable domains that share a common fold and differ in the Complementarity Determining Regions (CDRs). We develop a deep learning end-to-end model, NanoNet, that given a sequence directly produces the 3D coordinates of the Cɑ atoms of the entire VH domain. For the Nb test set, NanoNet achieves 1.7Å overall average RMSD and 3.0Å average RMSD for the most variable CDR3 loops. The accuracy for antibody VH domains is even higher: overall average RMSD < 1Å and 2.2Å RMSD for CDR3. NanoNet runtimes allow generation of ~1M nanobody structures in less than an hour on a standard CPU computer enabling high-throughput structure modeling.
The impact of eye closure on anticipatory alpha activity in a tactile discrimination task
Authors: ElShafei Hesham A. , Orlemann Corinne , Haegens Saskia 
Published: August 2021

AbstractOne of the very first observations made regarding alpha oscillations (8–14 Hz), is that they increase in power over posterior areas when awake participants close their eyes. Recent work, especially in the context of (spatial) attention, suggests that alpha activity reflects a mechanism of functional inhibition. However, it remains unclear how eye closure impacts anticipatory alpha modulation observed in attention paradigms, and how this affects subsequent behavioral performance. Here, we recorded magnetoencephalography (MEG) in 33 human participants performing a tactile discrimination task with their eyes open vs. closed. We replicated the hallmarks of previous somatosensory spatial attention studies: alpha lateralization across the somatosensory cortices as well as alpha increase over posterior regions. Furthermore, we found that eye closure leads to (i) reduced task performance, (ii) widespread increase in alpha power, and (iii) reduced anticipatory visual alpha modulation (iv) with no effect on somatosensory alpha lateralization. Regardless of whether participants had their eyes open or closed, increased posterior alpha power and somatosensory alpha lateralization improved their performance. Thus, we provide evidence that eye closure does not alter the impact of anticipatory alpha modulations on behavioral performance. We propose there is an optimal posterior alpha level for somatosensory task performance, which can be achieved through a combination of eye closure and top-down anticipatory attention.Significance StatementAlpha oscillations are dominant when awake participants have their eyes closed. Furthermore, alpha is known to modulate with anticipatory attention, and has been ascribed a role of active functional inhibition. Surprisingly, the link between anticipatory alpha and eye closure remains unclear. Here we collected MEG data while human participants performed a tactile discrimination task either with their eyes open or closed. Eye closure led to a widespread increase in alpha power, and affected anticipatory visual alpha modulation but not somatosensory alpha lateralization. Importantly, eye closure did not affect the correlation between alpha and task performance. Our findings provide novel insights into how eye closure impacts anticipatory alpha modulation, and how optimal alpha levels for task performance can be achieved differently.