bluuebunny/crossref_metadata_2025_split huggingface dataset:
Introducing Novel Molecular-based Method for Quantification of Homologous Recombination Efficiency
Authors: Dibbasey Mustapha , Gaymes Terry 
Published: January 2021

AbstractBackgroundHomologous recombination (HR) pathway is a DNA double-stranded breaks repair pathway well-known for its high level of accuracy. Low HR pathway efficiency clinically known as homologous recombination deficiency (HRD) was identified in some cancers such as breast and ovarian cancers and studies have reported the sensitivity of HRD cancer cells to DNA repair inhibitors such as Olaparib. However, current techniques including immunofluorescence-based technique are qualitative-based, hence lack sensitivity to determine the functionality of HR pathway. Additionally, some of the techniques including gene expression arrays require expression study of wide range genes involve in HR pathway, which is not cost-effective. The aim of the study is to optimise a PCR-based assay (Norgen’s Homologous Recombination kit) that can be employed to quantitate HR efficiency in cells, which accurately reflects the functional status of HR pathway.Methods and FindingsThe kit has two test plasmids (dl-1 and dl-2) with partial deletions in the LacZ gene and the plasmids are generated from modification of pUC19. HR-proficient (HeLa and AsPC-1) and HR-deficient (CAPAN-1 cells) cancer cell lines were transfected with the two plasmids to generate functional LacZ gene (i.e. recombinant product). The recombinant product was quantified by real-time PCR. Although recombinant product was generated in all the cell lines, our real-time PCR demonstrated a high quantity of recombinant product in HeLa cell line whilst low quantity in CAPAN-1 and AsPC-1 cell lines. The quantity of recombinant product generated and quantified reflects HR pathway efficiency.ConclusionOverall, the results have provided some evidence that the PCR-based kit can be suitably employed for quantification of HR efficiency provided appropriate transfection method and reagent are used. However, further study is required to confirm HR efficiency status of AsPC-1 cells to ascertain the low HR efficiency detected by the kit in these cells.
2-kupl: mapping-free variant detection from DNA-seq data of matched samples
Authors: Wang Yunfeng , Xue Haoliang , Pourcel Christine , Du Yang , Gautheret Daniel 
Published: January 2021

AbstractThe detection of genome variants, including point mutations, indels and structural variants, is a fundamental and challenging computational problem. We address here the problem of variant detection between two deep-sequencing (DNA-seq) samples, such as two human samples from an individual patient, or two samples from distinct bacterial strains. The preferred strategy in such a case is to align each sample to a common reference genome, collect all variants and compare these variants between samples. Such mapping-based protocols have several limitations. DNA sequences with large indels, aggregated mutations and structural variants are hard to map to the reference. Furthermore, DNA sequences cannot be mapped reliably to genomic low complexity regions and repeats. Herein, we introduce 2-kupl, a k-mer based, mapping-free protocol to detect variants between two DNA-seq samples. On simulated and actual data, 2-kupl achieves a higher precision than other mapping-free protocols. Applying 2-kupl to prostate cancer whole exome data, we identify a number of candidate variants in hard-to-map regions and propose potential novel recurrent variants in this disease.
Covid-19 respiratory protection: the filtration efficiency assessment of decontaminated FFP2 masks responding to associated shortages
Authors: Benboubker M. , Oumokhtar B. , Hmami F. , Mabrouk K. El , Alami L.EL , Arhoune B. , Belahsen M F. , Aboutajeddine A. 
Published: January 2021

AbstractDuring the Covid-19 pandemic, healthcare workers were extremely vulnerable to infection with the virus and needed continuous protection. One of the most effective and widely used means of protection was the FFP2 respirator. Unfortunately, this crisis created a shortage of these masks, prompting hospitals to explore opportunities to reuse them after decontamination.An approach for assessing the filtration efficiency of decontaminated FFP2 masks has been proposed and applied to evaluate the possibilities of their safe reuse. The decontamination processes adopted are those based on moist heat or hydrogen peroxide. The approach introduces efficiency measures that define the filtration and protection capacity of the masks, which characterize both chemical and structural changes, and encompasses many techniques including scanning electron microscopy (SEM), Fourier transforms infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA). The test protocol was applied to mask samples that had endured different decontamination cycles and the results of their efficiency measures were compared to brand-new masks’ performances.The main result was that chemical and structural characterization of the decontaminated masks have shown no substantial change or deformation of their filter media structures. Indeed, the respiratory resistance test has shown that the results of both the FFP2 masks that have undergone a hydrogen peroxide disinfection cycle or a steam autoclave cycle remained constant with a small variation of 10 Pa from the EN149 standard. The chemical characterization, on the other hand, has shown that the filter media of the decontaminated masks remains unchanged, with no detectable chemical derivatives in its constituents.
The Association between Early Country-level Testing Capacity and Later COVID-19 Mortality Outcomes
Authors: Kannoth Sneha , Kandula Sasikiran , Shaman Jeffrey 
Published: January 2021

ABSTRACTBackgroundThe COVID-19 pandemic has overrun hospital systems while exacerbating economic hardship and food insecurity on a global scale. In an effort to understand how early action to find and control the virus is associated with cumulative outcomes, we explored how country-level testing capacity affects later COVID-19 mortality.MethodsWe used the Our World in Data database to explore testing and mortality records in 27 countries from December 31, 2019 to September 30, 2020; we applied ordinary-least squares regression with clustering on country to determine the association between early COVID-19 testing capacity (cumulative tests per case) and later COVID-19 mortality (time to specified mortality thresholds), adjusting for country-level confounders, including median age, GDP, hospital bed capacity, population density, and non-pharmaceutical interventions.ResultsHigher early testing implementation, as indicated by more cumulative tests per case when mortality was still low, was associated with longer accrual time for higher per capita deaths. For instance, a higher cumulative number of tests administered per case at the time of 6 deaths per million persons was positively predictive of a longer time to reach 15 deaths per million, after adjustment for all confounders (β=0.659;P=0.001).ConclusionsCountries that developed stronger COVID-19 testing capacity at early timepoints, as measured by tests administered per case identified, experienced a slower increase of deaths per capita. Thus, this study operationalizes the value of testing and provides empirical evidence that stronger testing capacity at early timepoints is associated with reduced mortality and better pandemic control.
Cumulative effects of particulate matter pollution and meteorological variables on the risk of influenza-like illness in Bialystok, Poland
Authors: Toczylowski Kacper , Wietlicka-Piszcz Magdalena , Grabowska Magdalena , Sulik Artur 
Published: January 2021

AbstractThe cold season is usually accompanied by an increased incidence of respiratory infections and increased air pollution from combustion sources. As we are facing the growing numbers of COVID-19 cases caused by the novel SARS-CoV-2 coronavirus, an understanding of the impact of air pollutants and meteorological variables on the incidence of respiratory infections is crucial. The influenza-like illness (ILI) incidence might be used as a close proxy for the circulation of influenza viruses. Recently, SARS-CoV-2 has also been detected in patients with ILI. Using distributed lag nonlinear models, we analyzed the association between ILI, meteorological variables and particulate matter concentration in Bialystok, Poland, from 2013-2019. We found an exponential relation between cumulative PM2.5 pollution and the incidence of ILI that remained significant after adjusting for air temperatures and a long-term trend. Pollution had the greatest effect during the same week, but the risk of ILI was increased for the four following weeks. The risk of ILI was also increased by low air temperatures, low absolute humidity, and high wind speed. Altogether, our results show that all measures implemented to decrease PM2.5 concentrations would be beneficial to reduce the transmission of SARS-CoV-2 and other respiratory infections.Capsule summaryLow/medium high concentrations of particulate matter pollution increase the risk of influenza-like illness. The effect is independent from air temperatures and lasts for the four following weeks.
Endothelial cell-activating antibodies in COVID-19
Authors: Shi Hui , Zuo Yu , Navaz Sherwin , Harbaugh Alyssa , Hoy Claire K. , Gandhi Alex A. , Sule Gautam , Yalavarthi Srilakshmi , Gockman Kelsey , Madison Jacqueline A. , Wang Jintao , Zuo Melanie , Shi Yue , Maile Michael D. , Knight Jason S. , Kanthi Yogendra 
Published: January 2021

ABSTRACTObjectiveWhile endothelial dysfunction has been implicated in the widespread thrombo-inflammatory complications of coronavirus disease-19 (COVID-19), the upstream mediators of endotheliopathy remain for the most part cryptic. Our aim was to identify circulating factors contributing to endothelial cell activation and dysfunction in COVID-19.MethodsHuman endothelial cells were cultured in the presence of serum or plasma from 244 patients hospitalized with COVID-19 and plasma from 100 patients with non-COVID sepsis. Cell adhesion molecules (E-selectin, VCAM-1, and ICAM-1) were quantified by in-cell ELISA.ResultsSerum and plasma from patients with COVID-19 increased surface expression of cell adhesion molecules. Furthermore, levels of soluble ICAM-1 and E-selectin were elevated in patient serum and tracked with disease severity. The presence of circulating antiphospholipid antibodies was a strong marker of the ability of COVID-19 serum to activate endothelium. Depletion of total IgG from antiphospholipid antibody-positive serum markedly restrained upregulation of cell adhesion molecules. Conversely, supplementation of control serum with patient IgG was sufficient to trigger endothelial activation.ConclusionThese data are the first to suggest that some patients with COVID-19 have potentially diverse antibodies that drive endotheliopathy, adding important context regarding thrombo-inflammatory effects of autoantibodies in severe COVID-19.
Does non-invasive vagus nerve stimulation affect heart rate variability? A living and interactive Bayesian meta-analysis
Authors: Wolf Vinzent , Kühnel Anne , Teckentrup Vanessa , Koenig Julian , Kroemer Nils B. 
Published: January 2021

AbstractNon-invasive brain stimulation techniques, such as transcutaneous auricular vagus nerve stimulation (taVNS), have considerable potential for clinical use. Beneficial effects of taVNS have been demonstrated on symptoms in patients with mental or neurological disorders as well as transdiagnostic dimensions, including mood and motivation. However, since taVNS research is still an emerging field, the underlying neurophysiological processes are not yet fully understood, and the replicability of findings on biomarkers of taVNS effects has been questioned. Here, we perform a living Bayesian random effects meta-analysis to synthesize the current evidence concerning the effects of taVNS on heart rate variability (HRV), a candidate biomarker that has, so far, received most attention in the field. To keep the synthesis of evidence transparent and up to date as new studies are being published, we developed a Shiny web app that regularly incorporates new results and enables users to modify study selection criteria to evaluate the robustness of the inference across potential confounds. Our analysis focuses on 17 single-blind studies comparing taVNS versus sham in healthy participants. These newly synthesized results provide strong evidence for the null hypothesis (g= 0.011,CIshortest= [−0.103, 0.125],BF01= 25.587), indicating that acute taVNS does not alter HRV compared to sham. To conclude, based on a synthesis of the available evidence to date, there is no support for the hypothesis that HRV is a robust biomarker for acute taVNS. By increasing transparency and timeliness, we believe that the concept of living meta-analyses can lead to transformational benefits in emerging fields such as non-invasive brain stimulation.
Kinetic analysis of ASIC1a delineates conformational signaling from proton-sensing domains to the channel gate
Authors: Vullo Sabrina , Ambrosio Nicolas , Kucera Jan P. , Bignucolo Olivier , Kellenberger Stephan 
Published: January 2021

AbstractAcid-sensing ion channels (ASICs) are neuronal Na+channels that are activated by a drop in pH. Their established physiological and pathological roles, involving fear behaviors, learning, pain sensation and neurodegeneration after stroke, make them promising targets for future drugs. Currently, the ASIC activation mechanism is not understood. Here we used voltage-clamp fluorometry (VCF) combined with fluorophore-quencher pairing to determine the kinetics and direction of movements. Molecular dynamics simulations were used to further evaluate VCF-predicted movements. We show that conformational changes with the speed of channel activation occur close to the gate and in more distant extracellular sites, where they may be driven by local protonation events. Further, we provide evidence for fast conformational changes in a pathway linking protonation sites to the channel pore, in which an extracellular interdomain loop interacts via aromatic residue interactions with the upper end of a transmembrane helix and would thereby open the gate.
Brain networks are decoupled from external stimuli during internal cognition
Authors: Cohen Dror , Nakai Tomoya , Nishimoto Shinji 
Published: January 2021

AbstractOur cognition can be directed to external stimuli or to internal information. While there are many different forms of internal cognition (mind-wandering, recall, imagery etc.), their essential feature is independence from the immediate sensory input. This is thought to be reflected in the decoupling of brain networks from the external stimuli, but a quantitative investigation of this remains outstanding. Here we present a conceptual and analysis framework that links stimulus responses to connectivity between brain networks. This allows us to quantify the coupling of brain networks to the external stimuli. We tested this framework by presenting subjects with an audiovisual stimulus and instructing them to either attend to the stimulus (external task) or engage in mental imagery, recall or arithmetic (internal tasks) while measuring the evoked brain activity using functional MRI. We found that stimulus responses were generally attenuated for the internal tasks, though they increased in a subset of tasks and brain networks. However, using our new measure of coupling, we showed that brain networks became increasingly decoupled from the stimulus, even in the subset of tasks and brain networks in which stimulus responses increased. These results quantitatively demonstrate that during internal cognition brain networks are decoupled from external stimuli, opening the door for a fundamental and quantitative understanding of internal cognition.
Resolving when (and where) the Thylacine went extinct
Authors: Brook Barry W. , Sleightholme Stephen R. , Campbell Cameron R. , Jarić Ivan , Buettel Jessie C. 
Published: January 2021

AbstractLike the Dodo and Passenger Pigeon before it, the predatory marsupial Thylacine (Thylacinus cynocephalus), or ‘Tasmanian tiger’, has become an iconic symbol of human-caused extinction. The last captive animal died in 1936, but even today reports of the Thylacine’s possible ongoing survival in remote regions of Tasmania are newsworthy and capture the public’s imagination. Extirpated from mainland Australia in the mid-Holocene, the large island of Tasmania became the species’ final stronghold. Following European settlement in the 1800s, the Thylacine was heavily persecuted and pushed to the margins of its range, although many sightings were reported thereafter—even well beyond the 1930s. To gain a new depth of insight into the extinction of the Thylacine, we assembled an exhaustive database of 1,237 observational records from Tasmania (from 1910 onwards), quantified their uncertainty, and charted the patterns these revealed. We also developed a new method to visualize the species’ 20th-century spatio-temporal dynamics, to map potential post-bounty refugia and pinpoint the most-likely location of the final persisting subpopulation. A direct reading of the high-quality records (confirmed kills and captures, in combination with sightings by past Thylacine hunters and trappers, wildlife professionals and experienced bushmen) implies a most-likely extinction date within four decades following the last capture (i.e., 1940s to 1970s). However, uncertainty modelling of the entire sighting record, where each observation is assigned a probability and the whole dataset is then subject to a sensitivity analysis, suggests that extinction might have been as recent as the late 1980s to early 2000s, with a small chance of persistence in the remote south-western wilderness areas. Beyond the intrinsically fascinating problem of reconstructing the final fate of the Thylacine, the new spatio-temporal mapping of extirpation developed herein would also be useful for conservation prioritization and search efforts for other rare taxa of uncertain status.
Azithromycin Plus Zinc Sulfate Rapidly and Synergistically Suppresses IκBα-Mediated In Vitro Human Airway Cell ACE2 Expression for SARS-CoV-2 Entry
Authors: Chang Chia-Wei , Lee Ming-Cheng , Lin Bor-Ru , Lu Yen-Pei , Hsu Yih-Jen , Chuang Chun-Yu , Huang Tsung-Tao , Chen Yin-Kai 
Published: January 2021

AbstractLarge-scale efforts have been persistently undertaken for medical prophylaxis and treatment of COVID-19 disasters worldwide. A variety of novel viral spike protein-targeted vaccine preparations have recently been clinically distributed based on accelerated approval. We revisited the early but inconclusive clinical interest in the combination of azithromycin and zinc sulfate repurposing with safety advantages. In vitro proof of concept was provided for rapid and synergistic suppression of ACE2 expression following treatments in human airway cells, Calu-3 and H322M. The two representative ACE2-expressing human airway cells indicate the upper and lower respiratory tracts. Prophylactic and early therapeutic roles of azithromycin combined with zinc are proposed for virus cellular entry prevention potential bridging to effective antibody production.
An all-solid-state heterojunction oxide transistor for the rapid detection of biomolecules and SARS-CoV-2 spike S1 protein
Authors: Lin Yen-Hung , Han Yang , Sharma Abhinav , AlGhamdi Wejdan S. , Liu Chien-Hao , Chang Tzu-Hsuan , Xiao Xi-Wen , Seitkhan Akmaral , Mottram Alexander D. , Pattanasattayavong Pichaya , Faber Hendrik , Heeney Martin , Anthopoulos Thomas D. 
Published: January 2021

AbstractSolid-state transistor sensors that can detect biomolecules in real time are highly attractive for emerging bioanalytical applications. However, combining cost-effective manufacturing with high sensitivity, specificity and fast sensing response, remains challenging. Here we develop low-temperature solution-processed In2O3/ZnO heterojunction transistors featuring a geometrically engineered tri-channel architecture for rapid real-time detection of different biomolecules. The sensor combines a high electron mobility channel, attributed to the quasi-two-dimensional electron gas (q2DEG) at the buried In2O3/ZnO heterointerface, in close proximity to a sensing surface featuring tethered analyte receptors. The unusual tri-channel design enables strong coupling between the buried q2DEG and the minute electronic perturbations occurring during receptor-analyte interactions allowing for robust, real-time detection of biomolecules down to attomolar (aM) concentrations. By functionalizing the tri-channel surface with SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) antibody receptors, we demonstrate real-time detection of the SARS-CoV-2 spike S1 protein down to attomolar concentrations in under two minutes.
Polycomb suppresses a female gene regulatory network to ensure testicular differentiation
Authors: Maezawa So , Yukawa Masashi , Hasegawa Kazuteru , Sugiyama Ryo , Hu Mengwen , Vidal Miguel , Koseki Haruhiko , Barski Artem , DeFalco Tony , Namekawa Satoshi H. 
Published: January 2021

AbstractGonadal sex determination is controlled by the support cells of testes and ovaries. In testes, the epigenetic mechanism that maintains cellular memory to suppress female sexual differentiation remains unknown. Here, we show that Polycomb suppresses a female gene regulatory network in Sertoli cells, the specific support cells for postnatal testes. Through genetic ablation, we removed Polycomb repressive complex 1 (PRC1) from embryonic Sertoli cells after sex determination. PRC1-depleted postnatal Sertoli cells exhibited defective proliferation and cell death, leading to the degeneration of adult testes. In adult Sertoli cells, PRC1 suppressed the specific, critical genes required for granulosa cells, the support cells of ovaries, thereby inactivating the female gene regulatory network. The underlying chromatin of female genes was coated with Polycomb-mediated repressive modifications: PRC1-mediated H2AK119ub and PRC2-mediated H3K27me3. Taken together, we identify a critical mechanism centered on Polycomb that maintains the male fate in adult testes.
Temporal dynamics of SARS-CoV-2 mutation accumulation within and across infected hosts
Authors: Valesano Andrew L. , Rumfelt Kalee E. , Dimcheff Derek E. , Blair Christopher N. , Fitzsimmons William J. , Petrie Joshua G. , Martin Emily T. , Lauring Adam S. 
Published: January 2021

AbstractAnalysis of SARS-CoV-2 genetic diversity within infected hosts can provide insight into the generation and spread of new viral variants and may enable high resolution inference of transmission chains. However, little is known about temporal aspects of SARS-CoV-2 intrahost diversity and the extent to which shared diversity reflects convergent evolution as opposed to transmission linkage. Here we use high depth of coverage sequencing to identify within-host genetic variants in 325 specimens from hospitalized COVID-19 patients and infected employees at a single medical center. We validated our variant calling by sequencing defined RNA mixtures and identified a viral load threshold that minimizes false positives. By leveraging clinical metadata, we found that intrahost diversity is low and does not vary by time from symptom onset. This suggests that variants will only rarely rise to appreciable frequency prior to transmission. Although there was generally little shared variation across the sequenced cohort, we identified intrahost variants shared across individuals who were unlikely to be related by transmission. These variants did not precede a rise in frequency in global consensus genomes, suggesting that intrahost variants may have limited utility for predicting future lineages. These results provide important context for sequence-based inference in SARS-CoV-2 evolution and epidemiology.