bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Optimized Circular Polymerase Extension Reaction-based Method for Functional Analysis of SARS-CoV-2
Authors: Liu GuanQun , Gack Michaela U. 
Published: November 2022

SUMMARYReverse genetics systems have been crucial for studying specific viral genes and their relevance in the virus lifecycle, and become important tools for the rational attenuation of viruses and thereby for vaccine design. Recent rapid progress has been made in the establishment of reverse genetics systems for functional analysis of SARS-CoV-2, a coronavirus that causes the ongoing COVID-19 pandemic that has resulted in detrimental public health and economic burden. Among the different reverse genetics approaches, CPER (circular polymerase extension reaction) has become one of the leading methodologies to generate recombinant SARS-CoV-2 infectious clones due to its accuracy, efficiency, and flexibility. Here, we report an optimized CPER methodology which, through the use of a modified linker plasmid and by performing DNA nick ligation and direct transfection of permissive cells, overcomes certain intrinsic limitations of the ‘traditional’ CPER approaches for SARS-CoV-2, allowing for efficient virus rescue. This optimized CPER system may facilitate research studies to assess the contribution of SARS-CoV-2 genes and individual motifs or residues to virus replication, pathogenesis and immune escape, and may also be adapted to other viruses.
Gambling Disorder: Simultaneous Measurement of Screening Scales in Multiple Regions of Japan
Authors: Noda Tatsuya , Kido Moritoshi , Ito Chieko 
Published: November 2022

AbstractBackground and ObjectivesGambling disorder is defined as persistent and recurrent problematic gambling behavior leading to clinically significant impairment or distress in DSM-5 diagnostic criteria. According to the DSM-5, the past-year prevalence rate of gambling disorder is about 0.2%-0.3% in the general population, and the lifetime prevalence is about 0.4%-1.0%. Japan currently has no casinos, but three integrated resorts (IRs), including casinos, are scheduled to open in the late 2020s. In abroad, there have been studies on the effect of casinos on the prevalence of gambling in a region, but similar empirical studies do not exist in Japan. There are a lot of surveys being conducted in many areas, but the different screening tests used make it difficult to compare the results. However, comparisons between screening tests are less common. The first objective of this study is to measure the prevalence of gambling disorder in areas where IRs are planned to open and control areas. The second objective is to identify relationships among screening tests and examine differences between measures by administering multiple screening tests for gambling disorder to the same subjects.Materials and methodsThis survey was a self-administered, online survey of 2000 people in Japan, ranging in age from 20 to 69 conducted in 2021. We administered 4 gambling disorder screening tests (SOGS, PGSI, LieBet Screen,DSM-5). Experience rates for each of 8 gambles were measured. Percentage above cut-off score (PAC) was calculated and compared by gender and region for 4 tests.ResultsAmong the eight gambling activities, the lottery had the largest experience rate at 58.5%, PACHINKO was second at 42.2%, and there were no major regional disparities. In each of the 4 screening tests, PAC was greater in males, and regional differences were found in SOGS and DSM-5. The distribution of PAC for different cut-off scores for each test is illustrated in a “dango chart” for comparison.DiscussionThis study indicates PACs for 4 gambling disorder screening tests in planned and non-IR areas, and this will be a baseline survey to measure the impact of opening an IR. Although our results will contain some biases likely due to methodological factors, by continuing to use the same measurement method, our research project will be able to reach its ultimate goal of observing changes in the applicable rate before and after the opening of the IR. In addition, this study administered several gambling disorder screening tests to the same subjects in the same region and illustrated them in a chart format named the dango chart. This visualized the changes in the applicable person rate when the cut-off scores of the screening tests were changed (within-test comparisons) and the differences in the distribution of the applicable person rate across tests (between-test comparisons). We think that the dango chart is a useful presentation method for comparing several different tests.
Sex differences in associations betweenAPOE ε2and longitudinal cognitive decline
Authors: Wood Madeline E. , Xiong Lisa Y. , Wong Yuen Yan , Buckley Rachel F. , Swardfager Walter , Masellis Mario , Lim Andrew S. P. , Nichols Emma , Joie Renaud La , Casaletto Kaitlin B. , Kumar Raj G. , Dams-O’Connor Kristen , Palta Priya , George Kristen M. , Satizabal Claudia L. , Barnes Lisa L. , Schneider Julie A. , Binet Alexa Pichette , Villeneuve Sylvia , Pa Judy , Brickman Adam M. , Black Sandra E. , Rabin Jennifer S. ,   the ADNI and Prevent-AD Research Groups
Published: November 2022

AbstractINTRODUCTIONWe examined whether sex modifies the association betweenAPOEε2and cognitive decline across two independent samples.METHODSWe used observational data from non-Hispanic White (NHW) and non-Hispanic Black (NHB) cognitively unimpaired adults. Linear mixed models examined interactive associations ofAPOEgenotype (ε2or ε4carrier vs. ε3/ε3) and sex on cognitive decline in NHW and NHB participants separately.RESULTSIn both Sample 1 (N=9,766) and Sample 2 (N=915), sex modified the association betweenAPOEε2and cognitive decline in NHW participants. Specifically, relative toAPOEε3/ε3, APOEε2protected against cognitive decline in men but not women. AmongAPOEε2carriers, men had slower decline than women. AmongAPOEε3/ε3carriers, cognitive trajectories did not differ between sexes. There were no sex-specific associations ofAPOEε2 with cognitive decline in NHB participants (N=2,010).DISCUSSIONIn NHW adults,APOEε2may selectively protect men against cognitive decline.
Unappreciated Subcontinental Admixture in Europeans and European Americans: Implications for Genetic Epidemiology Studies
Authors: Gouveia Mateus H. , Bentley Amy R. , Tarazona-Santos Eduardo , Bustamante Carlos D. , Adeyemo Adebowale A. , Rotimi Charles N. , Shriner Daniel 
Published: November 2022

ABSTRACTEuropean-ancestry populations are recognized as stratified but not as admixed, implying that residual confounding by locus-specific ancestry can affect studies of association, polygenic adaptation, and polygenic risk scores. We integrated individual-level genome-wide data from~19,000 European-ancestry individuals across 79 European populations and five European American cohorts. We generated a new reference panel that captures ancestral diversity missed by both the 1000 Genomes and Human Genome Diversity Projects. Both Europeans and European-Americans are admixed at subcontinental level, with admixture dates differing among subgroups of European Americans. After adjustment for both genome-wide and locus-specific ancestry, associations between a highly differentiated variant inLCT(rs4988235) and height or LDL-cholesterol were confirmed to be false positives whereas the association betweenLCTand body mass index was genuine. We provide formal evidence of subcontinental admixture in individuals with European ancestry, which, if not properly accounted for, can produce spurious results in genetic epidemiology studies.
NanoPack2: Population scale evaluation of long-read sequencing data
Authors: De Coster Wouter , Rademakers Rosa 
Published: November 2022

AbstractSummaryIncreases in the cohort size in long-read sequencing projects necessitate more efficient software for quality assessment and processing of sequencing data from Oxford Nanopore Technologies and Pacific Biosciences. Here we describe novel tools for summarizing experiments, filtering datasets and visualizing phased alignments results, as well as updates to the NanoPack software suite.Availability and implementationCramino, chopper, and phasius are written in Rust and available as executable binaries without requiring installation or managing dependencies. NanoPlot and NanoComp are written in Python3. Links to the separate tools and their documentation can be found athttps://github.com/wdecoster/nanopack. All tools are compatible with Linux, Mac OS, and the MS Windows 10 Subsystem for Linux and are released under the MIT license. The repositories include test data, and the tools are continuously tested using GitHub Actions.Contactwouter.decoster@uantwerpen.vib.be
Bimodal stimulation for the reduction of tinnitus using vibration on the skin
Authors: Perrotta Michael V. , Kohler Izzy , Eagleman David M. 
Published: November 2022

AbstractTinnitus (ringing in the ears) affects 1 in 10 adults in the United States, often with damaging psychological consequences. Currently, there exists no cure for most forms of tinnitus. Recently, bimodal stimulation – the pairing of sounds with haptic stimulation – has shown efficacy in reducing the symptoms of tinnitus. Previous bimodal stimulation approaches have used electrical shocks on the tongue, a technique that requires daily in-person sessions at an audiologist’s office. We here show that excellent results can be achieved wearing a wristband with multiple vibratory motors. Tones are played and the wristband correspondingly vibrates the wrist of the user at different spatial locations depending on the frequency of the tone. We compared the experimental group with a control group who listened to the tones but did not wear the wristband. The tone frequencies were centered on each user’s tinnitus frequency and the tones were randomized both in frequency and duration. 45 participants with Tinnitus Functional Index (TFI) scores of 25 and above were tested. Results show a significantly greater reduction in TFI scores for the experimental group compared to the control. Importantly, with higher baseline severity we find larger differences between the experimental and control groups, revealing greater symptom improvement for those with severe tinnitus. The therapeutic approach of combining sounds with spatially- and temporally-correlated vibrations on the wrist is found to be a simple, time-efficient, and effective procedure to lessen the symptoms of tinnitus.
Zebrafish embryos are more efficient and robust than zebrafish larvae in evaluating human norovirus infectivity
Authors: Tan Malcolm Turk Hsern , Gong Zhiyuan , Li Dan 
Published: November 2022

ABSTRACTThis study reports an essential improvement of the method for replication of human norovirus (hNoV) with the use of zebrafish (Danio rerio) embryos. With three globally prevalent hNoV genotypes and P-types GII.2[P16], GII.4[P16], and GII.17[P31], we demonstrated that this tool had high efficiency and robustness, and enabled continuous virus passaging. This tool is versatile in being applied in hNoV related research. In pathogenesis study, the zebrafish embryo generated hNoVs showed clear binding patterns to human histo-blood group antigens (HBGAs) in human saliva by a simple saliva-binding reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In disinfection study, it was shown that a dose of 6 mJ/cm2UV254was able induce > 2-log reduction in hNoV infectivity for all three hNoV strains tested, suggesting that hNoVs were more UV susceptible than multiple enteric viruses and commonly used hNoV surrogates as tested before.IMPORTANCEHNoVs are a leading cause of gastroenteritis outbreaks worldwide. The zebrafish embryo tool as developed in this study serves as an efficient way to generate viruses with high titers and clean background and a straightforward platform to evaluate hNoV inactivation efficacies. It is expected that this tool will not only benefit epidemiological research of hNoV but also be used to generate hNoV inactivation parameters which are highly needed by the water treatment and food industry.
Age-related differences in colon and rectal cancer survival: An analysis of United States SEER-18 data
Authors: Pilleron Sophie , Withrow Diana , Nicholson Brian D , Morris Eva JA 
Published: November 2022

AbstractAge-related differences in colon and rectal cancer survival have been observed, even after accounting for differences in background mortality. To determine to what extent stage, tumour site, or histology could contribute to these differences, we estimated 1-year relative survival (RS) age stratified by these factors. Colon and rectal cancer cases diagnosed between 2012 and 2016 and followed up until 2017 were retrieved from 18 United States Surveillance Epidemiology and End Results cancer registries. For colon cancer, 1-year RS ranged from 87.8% [95% Confidence Interval: 87.5-88.2] in the 50–64-year-old age group to 62.3% [61.3-63.3] in the 85–99-year-old age group and for rectal cancer ranged from 92.3% [91.8-82.7] to 65.0% [62.3-67.5]. With respect to stage, absolute differences in RS between 50–64-year-old and 75–84-year-old in RS increased with increasing stage (from 6 [5-7] %-points in localized disease to 27 [25-29] %-points in distant disease) and were the highest for cancers of unknown stage (>28%-points). With respect to topography, age-related differences in survival were smallest for those in right-sided colon (8 [7-9] %-points) and largest for tumours of the colon without topography further specified (25 [21-29] %-points). While age-related differences in survival varied by histology and tumour site, the overall age-related differences in survival could not be explained by differences in distribution of these factors by age, consistent with a hypothesis that stage at diagnosis or treatment are more likely drivers. Incorporating data on geriatric conditions such as frailty and comorbidity would support further understanding of the age gap in colon and rectal cancer survival.
Characterizing the interactions between influenza and respiratory syncytial viruses and their implications for epidemic control
Authors: Kramer Sarah C. , Pirikahu Sarah , Casalegno Jean-Sébastien , Domenech de Cellès Matthieu 
Published: November 2022

AbstractPathogen-pathogen interactions represent a critical but little-understood feature of infectious disease dynamics. In particular, experimental evidence suggests that influenza virus and respiratory syncytial virus (RSV) compete with each other, such that infection with one confers temporary protection against the other. However, such interactions are challenging to study using common epidemiologic methods. Here, we use a mathematical modeling approach, in conjunction with detailed surveillance data from Hong Kong and Canada, to infer the strength and duration of the interaction between influenza and RSV. Based on our estimates, we further utilize our model to evaluate the potential conflicting effects of live attenuated influenza vaccines (LAIV) on RSV burden. We find evidence of a moderate to strong, negative, bidirectional interaction, such that infection with either virus yields 40-100% protection against infection with the other for one to five months. Assuming that LAIV reduces RSV susceptibility in a similar manner, we predict that the impact of such a vaccine at the population level would likely depend greatly on underlying viral circulation patterns. More broadly, we highlight the utility of mathematical models as a tool to characterize pathogen-pathogen interactions.
A Functional Sensor-to-Segment Orientation Method to Reduce the Effects of Varied Sensor Placement: Implications for IMU Best Practices
Authors: Mihy Julien A. , Wagatsuma Mayumi , Cain Stephen M. , Hafer Jocelyn F. 
Published: November 2022

AbstractTo collect reliable data, it is important to determine how inertial measurement unit (IMU) sensor placement affects measurements of segment motion and to establish best practices for sensor placement and orientation procedures. We aimed to determine the extent to which a functional orientation method minimizes the effect of variations in sensor placement on IMU-derived segment excursions. Twenty healthy adults walked overground in a lab. Three IMUs were placed per segment on the pelvis, thigh, shank, and foot. Differences in estimated segment angular excursions between sensor placements were compared between an assumed sensor-to-segment orientation and two versions of a walking-based functional sensor-to-segment orientation. For time series data, differences in angular excursion between sensor placements were reduced from 60% of the gait cycle (assumed orientation) to 44% of the gait cycle (functional orientation) for the pelvis; from 31% (assumed) to 28% (functional) of the gait cycle for the thigh; and from 84% (assumed) to 0% (functional) of the gait cycle for the shank. Mean angular excursion RMSDs between sensor placements were <5° for most comparisons for the functionally oriented data. Functional orientation did not minimize inter-sensor placement effects when one sensor was located on a region with high soft tissue artifact (e.g., anterior thigh). Functional orientation reduced inter-sensor differences in segment excursion for the shank and foot and between-subject variance in inter-sensor differences for all segments. Functional orientation minimizes the effect of variations in IMU sensor placement, but care should be taken to select sensor placements that minimize soft-tissue artifact.
Selective whole-genome sequencing ofPlasmodiumparasites directly from blood samples by Nanopore adaptive sampling
Authors: De Meulenaere Katlijn , Cuypers Wim L. , Rosanas-Urgell Anna , Laukens Kris , Cuypers Bart 
Published: November 2022

AbstractBackgroundWhole-genome sequencing (WGS) is becoming an increasingly popular tool to study the population genetics and drug resistance ofPlasmodiumspp. However, the predominance of human DNA in a malaria patient blood sample requires time-consuming lab procedures to filter out human DNA or enrichPlasmodiumDNA. Here, we investigated the potential of adaptive sampling to enrich forPlasmodiumDNA while sequencing unenriched patient blood samples on a minION device.ResultsTo compare adaptive sampling versus regular sequencing, a dilution series consisting of 0% up to 100%P. falciparumDNA in human DNA was sequenced. Half of the flowcell channels were run in adaptive sampling mode, enriching for theP. falciparumreference genome, resulting in a 3.2 fold enrichment ofP. falciparumbases on average. Samples with a lower concentration of parasite DNA had a higher enrichment potential. We confirmed these findings by sequencing twoP. falciparumpatient blood samples with common levels of parasitaemia (0.1% and 0.2%). The estimated enrichment was 3.9 and 5.8, which was sufficient to cover at least 97% of theP. falciparumreference genome at a median depth of 20 (highest parasitaemia) or 5 (lowest parasitaemia). A comparison of 38 drug resistance variants (WHO) obtained via adaptive sequencing or Sanger sequencing showed a high concordance between the two methods, suggesting that the obtained sequencing data is of sufficient quality to address common clinical research questions for patients with parasitaemias of 0.1% and higher.ConclusionsOur results demonstrate that adaptive Nanopore sequencing has the potential to replace more time-consumingPlasmodium-enrichment protocols and sequence directly from patient blood, given further improvements in cost-efficiency.
A novel and simple heat-based method eliminates the highly detrimental effect of xylene deparaffinization on acid-fast stains
Authors: Marinho Pedro F. , Vieira Soraia L. , Carvalho Tânia G. , Peleteiro Maria C. , Hanscheid Thomas 
Published: November 2022

AbstractObjectivesHistopathology is an important method for the diagnosis of extrapulmonary tuberculosis, yet tissue sections are often negative for mycobacteria after acid-fast-staining (AFS). This study investigated the mechanism of AFS and the detrimental effect of histological processing, in particular xylene deparaffinization, on AFS staining and mycobacterial detection.MethodsThe target of the fluorescent Auramine O (AuO) AFS was investigated using triple staining with DNA and RNA specific dyes. The effect of xylene deparaffinization on acid-fastness of mycobacteria in cultures or tissue sections was studied using AuO fluorescence as a quantitative marker. The xylene method was compared to a novel, solvent-free projected-hot-air-deparaffinization (PHAD).ResultsColocalization of AuO with DNA/RNA stains suggests that intracellular nucleic acids are the true target of AFS, producing highly specific patterns. Xylene reduces mycobacterial fluorescence significantly (p<0,0001, moderate effect size:r= 0.33). PHAD yielded significantly higher fluorescence than xylene deparaffinization in tissues (p<0.0001, large effect size:r= 0.85).ConclusionsAuO can be applied for nucleic-acid-staining of mycobacteria in tissues producing typical beaded patterns. AFS depends crucially on the integrity of the mycobacterial cell-wall, which seems to be damaged by xylene. A solvent-free tissue deparaffinization method has the potential to increase mycobacterial detection significantly.Key PointsAcid-fast-stains for mycobacterial detection have a notoriously poor yield, due to misconceptions of the underlying staining principle, but mainly because of the possible detrimental effect of xylene.The yield of acid-fast-stains for mycobacterial detection in histology, including fluorescent stains, can be significantly increased by eliminating solvents (xylene) in the deparaffinization step.Acid-fast-stains depend on bacterial integrity because they target nucleic acids. A simple hot air deparaffinization is significantly superior to xylene, avoiding damage to the lipid-rich cell wall.
PTEN deficiency exposes a requirement for an ARF GTPase module in integrin-dependent invasion in ovarian cancer
Authors: Nikolatou Konstantina , Sandilands Emma , Román-Fernández Alvaro , Cumming Erin M. , Freckmann Eva , Lilla Sergio , Buetow Lori , McGarry Lynn , Neilson Matthew , Shaw Robin , Strachan David , Miller Crispin , Huang Danny T. , McNeish Iain A. , Norman James C. , Zanivan Sara , Bryant David M. 
Published: November 2022

AbstractDysregulation of the PI3K/AKT pathway is a common occurrence in ovarian carcinomas. Loss of the tumour suppressorPTENin high-grade serous ovarian carcinoma (HGSOC) is associated with a patient subgroup with poor prognosis. The cellular mechanisms of howPTENloss contributes to HGSOC are largely unknown. We utilise long-term time-lapse imaging of HGSOC spheroids coupled to a machine learning approach to classify the phenotype ofPTENloss.PTENdeficiency does not affect proliferation but rather induces PI(3,4,5)P3-rich and -dependent membrane protrusions into the extracellular matrix (ECM), resulting in a collective invasion phenotype. We identify the small GTPase ARF6 as a crucial vulnerability uponPTENloss. Through a functional proteomic CRISPR screen of ARF6 interactors, we identify the ARF GTPase-activating protein (GAP) AGAP1 and the ECM receptor β1-integrin (ITGB1) as key ARF6 interactors regulating thePTENloss-associated invasion phenotype. ARF6 functions to promote invasion by controlling the recycling of internalised, active β1-integrin complexes to maintain invasive activity into the ECM. The expression of the ARF6-centred complex in HGSOC patients is inversely associated with outcome, allowing identification of patient groups with improved versus poor outcome. ARF6 may represent a new therapeutic vulnerability inPTEN- depleted HGSOC tumours.