bluuebunny/crossref_metadata_2025_split huggingface dataset:
Premature Atrial Stimulation Accentuates Conduction Abnormalities in Cardiac Surgery Patients that Develop Postoperative Atrial Fibrillation
Authors: Khan Muhammad S. , Lange Matthias , Ranjan Ravi , Sharma Vikas , Glotzbach Jason P. , Selzman Craig , Dosdall Derek J. 
Published: August 2021

ABSTRACTBACKGROUNDpostoperative atrial fibrillation (POAF) is a common cardiac surgery complication that is associated with increased complications and negative outcomes, but the association between presurgical atrial conduction abnormalities and POAF has not been investigated clinically during premature atrial S1S2 stimulation. This clinical study sought to examine whether intraoperative premature atrial stimulation reveals increased areas of slowed and/or blocked conduction in patients that develop POAF.METHODSHigh-density intraoperative epicardial left atrial mapping was conducted in 20 cardiac surgery patients with no prior history of atrial fibrillation (AF). In 20 patients, 6 (30%) developed POAF. A flexible-array of 240-electrodes was placed on the posterior left atrial wall in between the pulmonary veins. Activation maps were generated for sinus and premature atrial S1S2 stimulated beats. The area of conduction block (CB), conduction delay (CD) and the combination of both (CDCB) for conduction velocity <0.1, 0.1≤x<0.2 and <0.2 m/s, respectively were quantified.RESULTSFor a premature atrial S2 beat with shortest cycle length captured, conduction velocity maps revealed a significantly higher area for CD (13.19±6.59 versus 6.06±4.22 mm2, p=0.028) and CDCB (17.36±8.75 versus 7.41±6.39 mm2, p=0.034), and a trend toward a larger area for CB (4.17±3.66 versus 1.34±2.86 mm2, p=0.063) in patients who developed POAF in comparison to those that remained in the sinus. Sinus and S1 paced beats did not show substantial differences in abnormal conduction areas between patients with and without POAF.CONCLUSIONIn comparison to sinus and S1 beats, premature atrial S2 beats accentuate conduction abnormalities in cardiac surgery patients that developed POAF.
COVID-19 Infection risk posed by drinking alcohol at restaurants or bars in Japan
Authors: Kurita Junko , Sugawara Tamie , Ohkusa Yasushi 
Published: August 2021

AbstractBackgroundOn April 25, 2021, the third state of emergency was declared in Japan. Drinking alcohol at restaurants and bars was banned.ObjectWe used published data to evaluate drinking ban effects.MethodWe bootstrapped the data and evaluated the risk ratio for drinking compared with non-drinking during group dining with similar frequency and numbers of participants.ResultsThe 99% lower bound of the bootstrapped distribution of the risk ratio was less than one. Therefore the null hypothesis, that incidence in the two styles of group dining were the same, cannot be rejected.Discussion and ConclusionResults constitute no clear evidence indicating a risk of drinking alcohol in groups. However, further analyses using collected data are necessary. Moreover, risks posed by the number of group diners or their dining frequency must be evaluated.
The Effect of Image Resolution on Automated Classification of Chest X-rays
Authors: Haque Md Inzamam Ul , Dubey Abhishek K. , Hinkle Jacob D. 
Published: August 2021

AbstractDeep learning models have received much attention lately for their ability to achieve expert-level performance on the accurate automated analysis of chest X-rays. Although publicly available chest X-ray datasets include high resolution images, most models are trained on reduced size images due to limitations on GPU memory and training time. As compute capability continues to advance, it will become feasible to train large convolutional neural networks on high-resolution images. To verify that this will lead to increased performance, we perform a systematic evaluation to measure the effect of input chest X-ray image resolution on accuracy. This study is based on the publicly available MIMIC-CXR-JPG dataset, comprising 377,110 high resolution chest X-ray images, and provided with 14 labels to the corresponding free-text radiology reports. Our original hypothesis that increased resolution would lead to higher accuracy held true for some but not all of the tasks. We find, interestingly, that tasks that require a large receptive field are better suited to downscaled input images, and we verify this qualitatively by inspecting effective receptive fields and class activation maps of trained models. Finally, we show that stacking an ensemble across resolutions outperforms each individual learner at all input resolutions while providing interpretable scale weights, suggesting that multi-scale features are crucially important to information extraction from high-resolution chest X-rays.
Wastewater based surveillance system to detect SARS-CoV-2 genetic material for countries with on-site sanitation facilities: an experience from Bangladesh
Authors: Jakariya Md. , Ahmed Firoz , Islam Md. Aminul , Ahmed Tanvir , Marzan Abdullah Al , Hossain Maqsud , Reza Hasan Mahmud , Bhattacharya Prosun , Hossain Ahmed , Nahla Turasa , Bahadur Newaz Mohammed , Hasan Mohammad Nayeem , Islam Md. Tahmidul , Hossen Md. Foysal , Didar-ul-Alam Md. , Mow Nowrin , Jahan Hasin 
Published: August 2021

AbstractThe presence of SARS-CoV-2 genetic materials in wastewater has become a matter of grave for many countries of the world. Wastewater based epidemiology, in this context, emerged as an important tool in developed countries where proper sewage system is available. Due to the recent shift in the spread of the infection from urban to rural areas, it is now equally important to develop a similar mechanism for rural areas as well. Considering the urgency of the issue a study was conducted in 14 districts of Bangladesh and a total of 238 sewage samples were collected in two different periods from December 2020 to January 2021. We are the first to propose a surveillance system for both urban and rural areas where a proper sewage system is absent. Based on RT-PCR analysis of the water samples, in more than 92% of cases, we found the presence of the SARS-COV-2 gene (ORF1ab, N, and Internal Control-IC). The trend of Ct value varies for different study locations. The spread of genetic material for on-site (Δm = 0.0749) sanitation system was found more prominent than that of off-site sewage system (Δm = 0.0219); which indicated the shift of genetic material from urban to rural areas. Wastewater samples were also measured for physicochemical parameters, including pH (6.30 - 12.50) and temperature (22.10 - 32.60) ºC. The highest viral titer of 1975 copy/mL in sewage sample was observed in a sample collected from the isolation ward of the SARS-COV-2 hospital. Additionally, a correlation was found between bacterial load and SARS-CoV-2 genetic materials. The results indicated the association of increased Ct values with decreasing number of patients and vice versa. The findings reported in this paper contributed to the field of wastewater-based epidemiology dealing with SARS-COV-2 surveillance for developing countries where proper sewage system is absent and highlighting some of the challenges associated with this approach in such settings.HighlightsDevelopment of wastewater-based surveillance system based on on-site sanitation system for developing countries.Association of different environmental parameters with the presence of SARS CoV-2 genetic material in wastewater.Prediction of the viral concentration of sewage system using viral load and copy number parameter.Graphical Abstract
Assessment of label-free quantification and missing value imputation for proteomics in non-human primates
Authors: Hamid Zeeshan , Zimmerman Kip D. , Guillen-Ahlers Hector , Li Cun , Nathanielsz Peter , Cox Laura A. , Olivier Michael 
Published: August 2021

AbstractIntroductionReliable and effective label-free quantification (LFQ) analyses are dependent not only on the method of data acquisition in the mass spectrometer, but also on the downstream data processing, including software tools, query database, data normalization and imputation. In non-human primates (NHP), LFQ is challenging because the query databases for NHP are limited since the genomes of these species are not comprehensively annotated. This invariably results in limited discovery of proteins and associated Post Translational Modifications (PTMs) and a higher fraction of missing data points. While identification of fewer proteins and PTMs due to database limitations can negatively impact uncovering important and meaningful biological information, missing data also limits downstream analyses (e.g., multivariate analyses), decreases statistical power, biases statistical inference, and makes biological interpretation of the data more challenging. In this study we attempted to address both issues: first, we used the MetaMorphues proteomics search engine to counter the limits of NHP query databases and maximize the discovery of proteins and associated PTMs, and second, we evaluated different imputation methods for accurate data inference.ResultsUsing the MetaMorpheus proteomics search engine we obtained quantitative data for 1,622 proteins and 10,634 peptides including 58 different PTMs (biological, metal and artifacts) across a diverse age range of NHP brain frontal cortex. However, among the 1,622 proteins identified, only 293 proteins were quantified across all samples with no missing values, emphasizing the importance of implementing an accurate and statiscaly valid imputation method to fill in missing data. In our imputation analysis we demonstrate that Single Imputation methods that borrow information from correlated proteins such as Generalized Ridge Regression (GRR), Random Forest (RF), local least squares (LLS), and a Bayesian Principal Component Analysis methods (BPCA), are able to estimate missing protein abundance values with great accuracy.ConclusionsOverall, this study offers a detailed comparative analysis of LFQ data generated in NHP and proposes strategies for improved LFQ in NHP proteomics data.
Species hybridisation and clonal expansion as a new fungicide resistance evolutionary mechanism in Pyrenophora teres spp
Authors: Turo Chala , Mair Wesley , Martin Anke , Ellwood Simon , Oliver Richard , Lopez-Ruiz Francisco 
Published: August 2021

ABSTRACTThe barley net blotch diseases are caused by two fungal species of the Pyrenophora genus. Specifically, spot form net blotch is caused by P. teres f. sp. maculata (Ptm) whereas net form net blotch is caused by P. teres f. sp. teres (Ptt). Ptt and Ptm show high genetic diversity in the field due to intraspecific sexual recombination and hybridisation of the two species although the latter is considered rare. Here we present occurrence of a natural Ptt/Ptm hybrid with azole fungicides resistance and its implication to barley disease management in Australia. We collected and sequenced a hybrid, 3 Ptm and 10 Ptt isolates and performed recombination analyses in the intergenic and whole genome level. Eleven out of 12 chromosomes showed significant (P < 0.05) recombination events in the intergenic regions while variable recombination rate showed significant recombination across all the chromosomes. Locus specific analyses of Cyp51A1 gene showed at least four recombination breakpoints including a point mutation that alter target protein function. This point mutation did not found in Ptt and Ptm collected prior to 2013 and 2017, respectively. Further genotyping of fourteen Ptt, 48 HR Ptm, fifteen Ptm and two P. teres isolates from barley grass using Diversity Arrays Technology markers showed that all HR Ptm isolates were clonal and not clustered with Ptt or Ptm. The result confirms occurrence of natural recombination between Ptt and Ptm in Western Australia and the HR Ptm is likely acquired azole fungicide resistance through recombination and underwent recent rapid selective sweep likely within the last decade. The use of available fungicide resistance management tactics are essential to minimise and restrict further dissemination of these adaptive HR Ptm isolates.
Non-linear frequency-dependence of neurovascular coupling in the cerebellar cortex implies vasodilation-vasoconstriction competition
Authors: Gagliano Giuseppe , Monteverdi Anita , Casali Stefano , Laforenza Umberto , Gandini Wheeler-Kingshott Claudia A.M. , D’Angelo Egidio , Mapelli Lisa 
Published: August 2021

AbstractNeurovascular coupling (NVC) is the process associating local cerebral blood flow (CBF) to neuronal activity (NA). Although NVC provides the basis for the blood-oxygen-level-dependent (BOLD) effect used in functional MRI (fMRI), the relationship between NVC and NA is still unclear. Since recent studies reported cerebellar non-linearities in BOLD signals during motor tasks execution, we investigated the NVC/NA relationship using a range of input frequencies in acute mouse cerebellar slices of vermis and hemisphere. The capillary diameter increased in response to mossy fiber activation in the 6-300Hz range, with a marked inflection around 50Hz (vermis) and 100Hz (hemisphere). The corresponding NA was recorded using high-density multi-electrode arrays and correlated to capillary dynamics through a computational model dissecting the main components of granular layer activity. Here, NVC is known to involve a balance between the NMDAR-NO pathway driving vasodilation and the mGluRs-20HETE pathway driving vasoconstriction. Simulations showed that the NMDAR-mediated component of NA was sufficient to explain the time-course of the capillary dilation but not its non-linear frequency-dependence, suggesting that the mGluRs-20HETE pathway plays a role at intermediate frequencies. These parallel control pathways imply a vasodilation-vasoconstriction competition hypothesis that could adapt local hemodynamics at the microscale bearing implications for fMRI signals interpretation.
Engineering adoptive T cell therapy to co-opt Fas ligand-mediated death signaling in ovarian cancer enhances therapeutic efficacy
Authors: Anderson Kristin G. , Oda Shannon K. , Bates Breanna M. , Burnett Madison G. , Suarez Magdalia Rodgers , Ruskin Susan L. , Greenberg Philip D. 
Published: August 2021

AbstractBackgroundIn the U.S., more than 50% of ovarian cancer patients die within 5 years of diagnosis, highlighting the need for innovations such as engineered T cell therapies. Mesothelin (Msln) is an attractive immunotherapy target for this cancer, as it is overexpressed by the tumor and contributes to malignant and invasive phenotypes, making antigen loss disadvantageous to the tumor. We previously showed that adoptively transferred T cells engineered to be Msln-specific (TCR1045) preferentially accumulate within established ovarian tumors, delay tumor growth and significantly prolong survival in the ID8VEGF mouse model. However, T cell persistence and anti-tumor activity were not sustained, and we and others have previously detected FasL in the tumor vasculature and the tumor microenvironment (TME) of human and murine ovarian cancers, which can induce apoptosis in infiltrating lymphocytes expressing Fas receptor (Fas).MethodsTo concurrently overcome this mechanism for potential immune evasion and enhance T cell responses, we generated an immunomodulatory fusion protein (IFP) containing the Fas extracellular binding domain fused to a 4-1BB co-stimulatory domain, rather than the natural death domain. T cells engineered to express TCR1045 alone or in combination with the IFP were transferred into ID8VEGF-tumor bearing mice and evaluated for persistence, proliferation, anti-tumor cytokine production, and therapeutic efficacy.ResultsRelative to T cells modified only to express TCR1045, T cells engineered to express both TCR1045 and a Fas IFP preferentially persisted in the TME of tumor-bearing mice due to improved T cell proliferation and survival. Moreover, adoptive immunotherapy with IFP+ T cells significantly prolonged survival in tumor-bearing mice, relative to TCR1045 T cells lacking the IFP.ConclusionsFas/FasL signaling can mediate T cell death in the ovarian cancer microenvironment, as well as induce activation-induced cell death, an apoptotic mechanism responsible for regulating T cell expansion. Upregulation of FasL by tumor cells and tumor vasculature represents a mechanism for protecting growing tumors from attack by tumor-infiltrating lymphocytes. As many solid tumors overexpress FasL, an IFP that converts the Fas-mediated death signal into pro-survival and proliferative signals may provide an opportunity to enhance engineered adoptive T cell therapy against many malignancies.
Intraspecific interaction of host plant influences local distribution of specialist herbivores through metabolic alterations in leaves
Authors: Ohsaki Haruna , Miyagi Atsuko , Kawai-Yamada Maki , Yamawo Akira 
Published: August 2021

AbstractRecent studies suggest that changes in leaf traits due to interactions between plants affect the resource utilisation and distribution of herbivores. However, this has not yet been confirmed experimentally. Here, we investigated the effects of phenotypic plasticity in leaf traits of Rumex obtusifolius (host plant) in response to the intra- and interspecific interaction on distribution of two leaf beetles, Gastrophysa atrocyanea (specialist herbivore) and Galerucella grisescens (generalist herbivore).We investigated the local population density of R. obtusifolius plants and the presence of leaf beetles on the plants at five study sites. Leaf chemicals (condensed tannins and total phenolics) were compared between aggregated and solitary R. obtusifolius plants. To clarify the effects of the interaction environment of R. obtusifolius plants on their leaf traits and resource utilisation by leaf beetles, we conducted cultivation and preference experiments. Leaf chemicals (chlorophylls, organic acids, primary metabolites, condensed tannins and total phenolics) and preferences of adult leaf beetles were compared between intraspecific, interspecific plant interaction, or no-interaction treatments. Finally, we evaluated the effects of interaction between R. obtusifolius on leaf beetle distribution in mesocosm experiments.In the field, the presence of the specialist leaf beetle, G. atrocyanea, was positively correlated with the local population density (rosette overlap ratio) of R. obtusifolius plants; however, no correlation was observed in the case of the generalist leaf beetle, G. grisescens. In the cultivation experiment, plants in the intraspecific interaction treatment increased their leaf contents of condensed tannins and total phenolics, and G. atrocyanea consumed more of these leaves than leaves in other treatments. Similar results were observed in the field. In the mesocosm experiment, larger numbers of G. atrocyanea were distributed on R. obtusifolius plants exposed to below-ground intraspecific interaction than on plants not exposed to intraspecific interaction.Our results provide experimental evidence that leaf-trait changes in response to intraspecific interaction between host plants influence specialist herbivore distribution. This highlights the need to integrate plant–plant interactions into our understanding of plant–animal interactions.
Unique signals of clinal and seasonal allele frequency change at eQTLs in Drosophila melanogaster
Authors: Yu Yang , Bergland Alan O. 
Published: August 2021

AbstractPopulations of short-lived organisms can respond to spatial and temporal environmental heterogeneity through local adaptation. Local adaptation can be reflected on both phenotypic and genetic levels, and it has been documented in many organisms. Although some complex fitness-related phenotypes have been shown to vary across latitudinal clines and seasons in similar ways in Drosophila melanogaster populations, we lack a general understanding of the genetic architecture of local adaptation across space and time. To address this problem, we examined patterns of allele frequency change across latitudinal clines and between seasons at previously reported expression quantitative trait loci (eQTLs). We divided eQTLs into groups by utilizing differential expression profiles of fly populations collected across a latitudinal cline or exposed to different environmental conditions. We also examined clinal and seasonal patterns of allele frequency change at eQTLs grouped by tissues. In general, we find that clinally varying polymorphisms are enriched for eQTLs, and that these eQTLs change in frequency in predictable ways across the cline and in response to starvation tolerance. The enrichment of eQTL among seasonally varying polymorphisms is more subtle, and the direction of allele frequency change at eQTL appears to be somewhat idiosyncratic. Taken together, we suggest that clinal adaptation at eQTLs is distinct than that of seasonal adaptation.
NusG links transcription and translation in Escherichia coli extracts
Authors: Bailey Elizabeth J. , Gottesman Max E. , Gonzalez Ruben L. 
Published: August 2021

AbstractIn bacteria, transcription is coupled to, and can be regulated by, translation. Although recent structural studies suggest that the N-utilization substance G (NusG) transcription factor can serve as a direct, physical link between the transcribing RNA polymerase (RNAP) and the lead ribosome, mechanistic studies investigating the potential role of NusG in mediating transcription-translation coupling are lacking. Here, we report development of a cellular extract- and reporter gene-based, in vitro biochemical system that supports transcription-translation coupling as well as the use of this system to study the role of NusG in coupling. Our findings show that NusG is required for coupling and that the enhanced gene expression that results from coupling is dependent on the ability of NusG to directly interact with the lead ribosome. Moreover, we provide strong evidence that NusG-dependent coupling enhances gene expression through a mechanism in which the lead ribosome that is tethered to the RNAP by NusG suppresses spontaneous backtracking of the RNAP on its DNA template that would otherwise inhibit transcription.
The human TRPA1 intrinsic cold and heat sensitivity involves separate channel structures beyond the N-ARD domain
Authors: Moparthi Lavanya , Sinica Viktor , Filipovic Milos , Vlachova Viktorie , Zygmunt Peter M. 
Published: August 2021

AbstractThe human TRPA1 (hTRPA1) is an intrinsic thermosensitive ion channel responding to both cold and heat, depending on the redox environment. Here, we have studied purified hTRPA1 truncated proteins to gain further insight into the temperature gating of hTRPA1. We found in patch-clamp bilayer recordings that Δ1-688 hTRPA1, without the N-terminal ankyrin repeat domain (N-ARD), was more sensitive to cold and heat, whereas Δ1-854 hTRPA1 that is also lacking the S1-S4 voltage sensing-like domain (VSLD) gained sensitivity to cold but lost its heat sensitivity. The thiol reducing agent TCEP abolished the temperature sensitivity of both Δ1-688 hTRPA1 and Δ1-854 hTRPA1. Cold and heat activity of Δ1-688 hTRPA1 and Δ1-854 hTRPA1 were associated with different structural conformational changes as revealed by intrinsic tryptophan fluorescence measurements. Heat evoked major structural rearrangement of the VSLD as well as the C-terminus domain distal to the transmembrane pore domain S5-S6 (CTD), whereas cold only caused minor conformational changes. As shown for Δ1-854 hTRPA1, a sudden drop in tryptophan fluorescence occurred within 25-20°C indicating a transition between heat and cold conformations of the CTD, and thus it is proposed that the CTD contains a bidirectional temperature switch priming hTRPA1 for either cold or heat. In whole-cell patch clamp electrophysiology experiments, replacement of the cysteines 865, 1021 and 1025 with alanine modulated the cold sensitivity of hTRPA1 when heterologously expressed in HEK293T cells. It is proposed that the hTRPA1 CTD harbors cold and heat sensitive domains allosterically coupled to the S5-S6 pore region and the VSLD, respectively.