bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatitis C subtyping assay failure in UK patients born in Sub-Saharan Africa: implications for global treatment and elimination
Authors: Adeboyejo Kazeem , King Barnabas J. , Tsoleridis Theocharis , Tarr Alexander W. , McLauchlan John , Irving William L. , Ball Jonathan K. , McClure C. Patrick 
Published: December 2021

AbstractThe newly developed direct-acting antivirals (DAAs) have revolutionised the treatment of chronic hepatitis C virus (HCV), where cohort studies have shown that cure rates as high as 98% can be achieved. Whilst genome sequencing has demonstrated that some subtypes of HCV naturally harbour drug resistance associated substitutions (RAS), these have not been considered important as previous molecular epidemiological studies have suggested that such difficult-to-treat subtypes are rare. Therefore, to optimise and streamline molecular detection and sequence-based typing of diverse RAS-containing subtypes, a novel panel of single round PCR assays was applied to HCV derived from 146 individuals, whose likely source of infection was from regions of sub-Saharan Africa (SSA). Partial NS5A and NS5B sequences were obtained from 135 HCV-positive patients born in 19 different countries from SSA but attending clinics in the UK.Virus subtype assignments were determined by pairwise-distance analysis and compared to both diagnostic laboratory assignments and free-to-use online typing tools. We determined that routine clinical diagnostic methods incorrectly subtyped 59.0% of samples, with a further 6.8% incorrectly genotyped. Of five commonly used online tools, Geno2Pheno performed most effectively in determining a subtype in agreement with pairwise distance analysis. Considering the estimated number of HCV infections to have occurred in across Africa, this study provides a simple low-cost pathway to guide regional therapeutic choice and assist global eradication programmes.
Impact of Population Mixing Between a Vaccinated Majority and Unvaccinated Minority on Disease Dynamics: Implications for SARS-CoV-2
Authors: Fisman David N. , Amoako Afia , Tuite Ashleigh R. 
Published: December 2021

AbstractBackgroundThe speed of vaccine development has been a singular achievement during the SARS-CoV-2 pandemic, though uptake has not been universal. Vaccine opponents often frame their opposition in terms of the rights of the unvaccinated. Our objective was to explore the impact of mixing of vaccinated and unvaccinated populations on risk among vaccinated individuals.MethodsWe constructed a simple Susceptible-Infectious-Recovered (SIR) compartmental model of a respiratory infectious disease with two connected sub-populations: vaccinated individuals and unvaccinated individuals. We simulated a spectrum of patterns of mixing between vaccinated and unvaccinated groups that ranged from random mixing to like-with-like mixing (complete assortativity), where individuals preferentially have contact with others with the same vaccination status. We evaluated the dynamics of an epidemic within each subgroup, and in the population as a whole.ResultsThe relative risk of infection was markedly higher among unvaccinated individuals than among vaccinated individuals. However, the contact-adjusted contribution of unvaccinated individuals to infection risk during the epidemic was disproportionate, with unvaccinated individuals contributing to infections among the vaccinated at a rate higher than would have been expected based on contact numbers alone. As assortativity increased, attack rates among the vaccinated decreased, but the contact-adjusted contribution to risk among vaccinated individuals derived from contact with unvaccinated individuals increased.InterpretationWhile risk associated with avoiding vaccination during a virulent pandemic accrues chiefly to the unvaccinated, the choices of unvaccinated individuals impact the health and safety of vaccinated individuals in a manner disproportionate to the fraction of unvaccinated individuals in the population.
Final sizes and durations of new COVID-19 pandemic waves in Poland and Germany predicted by generalized SIR model
Authors: Nesteruk Igor 
Published: December 2021

ABSTRACTNew waves of the COVID-19 pandemic in Europe, which began in the autumn of 2021, are a matter of great concern and the need to immediately predict the epidemic dynamics in order to assess the possible maximum values of new cases, the risk of infection and the number of deaths. The generalized SIR-model and corresponding parameter identification procedure was used to simulate and predict the dynamics of new epidemic waves in Poland and Germany. Results of calculations show that new cases in these countries will not stop to appear in 2022.
COVID-19 vaccine hesitancy in diverse groups in the UK - is the driver economic or cultural in student populations?
Authors: Drobniewski Francis , Kusuma Dian , Broda Agnieszka , Castro-Sánchez Enrique , Ahmad Raheelah 
Published: December 2021

ABSTRACTStudies have identified a greater reluctance for members of the Black, Asian, and minority ethnic communities to be vaccinated against COVID-19 despite a higher probability of greater harm from COVID-19. We conducted an anonymised questionnaire-based study of students (recruiting primarily before first reports of embolic events) at two London universities to identify whether economic or educational levels were primarily responsible for this reluctance: a postgraduate core group (PGCC) n=860 and a pilot study of undergraduate medical and nursing students (n=103). Asian and Black students were 2.0 and 3.2 times (PGCC) less likely to accept the COVID vaccine than White British students. Similar findings were noted in the pilot study students. As students were studying for Masters or PhD degrees and voluntarily paying high fees, educational and economic reasons were unlikely to be the underlying cause, and wider cultural reservations were more likely. Politicians exerted a strong negative influence, suggesting that campaigns should omit politicians.
Efficient control of IL-6, CRP and Ferritin in Covid-19 patients with two variants of Beta-1,3-1,6 glucans in combination, within 15 days in an open-label prospective randomized clinical trial
Authors: Pushkala Subramanian , Seshayyan Sudha , Theranirajan Ethirajan , Sudhakar Doraisamy , Raghavan Kadalraja , Dedeepiya Vidyasagar Devaprasad , Ikewaki Nobunao , Iwasaki Masaru , Preethy Senthilkumar , Abraham Samuel JK 
Published: December 2021

AbstractBackgroundSeveral biomarkers, including C-reactive protein (CRP), ferritin, fibrinogen, D-dimer, and Interleukin-6 (IL-6), are established predictors of disease severity and respiratory failure in COVID-19 patients.ObjectiveIn this randomized clinical study, we evaluated the efficiency of the combination of two variants’ AFO-202 and N-163 strains of Aureobasidium Pullulans produced 1,3-1,6 beta glucans in comparison with the control arm on these biomarkers in COVID-19 patients.MethodsA total of 40 RT-PCR positive Covid-19 patients divided into two groups: i. control (n=22) – Standard treatment; ii. (n =18) – Standard treatment + combination of AFO-202 and N-163 beta glucans for 15 days.ResultsThe treatment group showed decrease in CRP level compared to control. At day 7, CRP reduced to 5.53 ± 8.21 mg/L in the treatment group vs. 4.91 ± 12.54 mg/L in control (p = 0.98) (95% CI: -34.40 to 35.14). By day 15, CRP continued to be decreased at 5.42 ± 10.41 mg/L in the treatment group but it increased to 14.0 ± 37.16 mg/L in control (p = 0.52) (95% CI: -37.65 to 19.40). IL-6 levels significantly decreased in the treatment group on day 7 (p = 0.03) but the difference was not significant by day 15 (p = 0.30). Ferritin levels in the treatment group decreased from 560.58 ± 537.30 ng/mL to 127.51 ± 215.91 ng/mL by day 15, while in control increased (p = 0.98). D-Dimer level decreased in the treatment group by day 15 but was not significantly different from control (p = 0.56).ConclusionThese results suggest that 15-day co-supplementation with AFO-202 and N-163 beta-glucans effectively controlled CRP, ferritin, and IL-6 in COVID-19 patients. Further research is warranted to investigate the potential of this supplement as a treatment adjunct, especially in vulnerable populations facing emerging SARS-CoV-2 variants.
Performances of community pharmacists and community pharmacies during COVID-19 outbreak: a cross-sectional study
Authors: Sadeghinejad Afsaneh , Nikvarz Naemeh 
Published: December 2021

AbstractBackgroundCommunity pharmacists can play an important role in the management of coronavirus disease-19 (COVID-19) outbreak by providing pharmaceutical care and education services. In addition to providing drug-related services, community pharmacies must take measures to reduce the risk of COVID-19 transmission to customers and technicians in pharmacy. Therefore, a study was designed to assess community pharmacists’ performance and community pharmacies’ preparedness during COVID-19 outbreak.Materials & MethodsA cross-sectional study was conducted in Kerman, Iran. A 20-item checklist consisting of nine items assessing the practice of pharmacists regarding use of personal protective equipment (PPE) and education of people about routes of transmission, prophylaxis and treatment of COVID-19 and eleven items evaluating the adherence of pharmacies to principles of reducing the risk of COVID-19 transmission in public places was used.ResultsOf 95 enrolled pharmacists, 55 (57.9%) were female and 78.9% had work experience ≤ 10 years. More than 90% of pharmacists used appropriate PPE and provided information about medications for prevention and treatment of COVID-19 and routs of its transmission to the pharmacy customers. Phone consultation was done by 71.6% of pharmacists. Concerning the preparedness of pharmacies, 92% of personnel used PPE, and hand sanitizers were available in 89.5% of pharmacies. However, a clear sheet was not placed at counters in the majority of pharmacies, and home delivery services were not provided by most pharmacies.ConclusionsThe practice of most community pharmacists was acceptable. However, stricter measures should be taken to diminish the probability of COVID-19 transmission in community pharmacies.
Individualized isometric neuromuscular electrical stimulation training promotes myonuclear accretion in mouse skeletal muscle
Authors: Zavoriti Aliki , Fessard Aurélie , Rahmati Masoud , Del Carmine Peggy , Chazaud Bénédicte , Gondin Julien 
Published: December 2021

AbstractSkeletal muscle is a plastic tissue that adapts to exercise through fusion of muscle stem cells (MuSCs) with myofibers, a physiological process referred to as myonuclear accretion. However, it is still unclear whether myonuclear accretion is driven by increased mechanical loading per se, or occurs, at least in part, in response to exercise-induced muscle injury. Here, we developed a carefully monitored and individualized neuromuscular electrical stimulation (NMES) training protocol of the mouse plantar flexor muscles. Each NMES training session consisted of 80 isometric contractions at a submaximal mechanical intensity corresponding to ~ 15% of maximal tetanic force to avoid muscle damage. NMES trained mice were stimulated for 2 × 3 consecutive days separated by one day of rest, for a total of 6 sessions. Experiments were conducted on C57BL/6J and BALB/c males at 10-12 weeks of age. NMES led to a robust myonuclear accretion and higher MuSC content in gastrocnemius muscle of both mouse lines, without overt signs of muscle damage/regeneration or muscle hypertrophy or force improvement. This new mouse model of myonuclear accretion relying on the main function of skeletal muscles, i.e., force production in response to electrical stimuli, will be of utmost interest to further understand the role of MuSCs in skeletal muscle adaptations.
Loss of Activity-Induced Mitochondrial ATP Production Underlies the Synaptic Defects in a Drosophila model of ALS
Authors: Karagas Nicholas E. , Tan Kai Li , Bellen Hugo J. , Venkatachalam Kartik , Wong Ching-On 
Published: December 2021

AbstractMutations in the gene encoding VAPB (vesicle-associated membrane protein B) cause a familial form of Amyotrophic Lateral Sclerosis (ALS). Expression of an ALS-related variant of vapb (vapbP58S) in Drosophila motor neurons results in morphological changes at the larval neuromuscular junction (NMJ) characterized by the appearance of fewer, but larger, presynaptic boutons. Although diminished microtubule stability is known to underlie these morphological changes, a mechanism for the loss of presynaptic microtubules has been lacking. Here, we demonstrate the suppression of vapbP58S- induced changes in NMJ morphology by either the loss of ER Ca2+ release channels or the inhibition Ca2+/calmodulin (CaM)-activated kinase II (CaMKII). These data suggest a model in which decreased stability of presynaptic microtubules at vapbP58S NMJs result from hyperactivation of CaMKII due to elevated cytosolic [Ca2+]. We attribute the Ca2+ dyshomeostasis to delayed extrusion of cytosolic Ca2+ stemming from a paucity of activity-induced mitochondrial ATP production coupled with elevated rates of ATP consumption. Taken together, our data point to bioenergetic dysfunction as the root cause for the synaptic defects in vapbP58S-expressing Drosophila motor neurons.Significance StatementRates of ATP production and consumption are tightly synchronized in healthy neurons. Whether this synchrony is lost in models of neurodegenerative diseases remains poorly understood. Here, we find that expression of a gene encoding an ALS-causing variant of an ER membrane protein, VAPB, decouples mitochondrial ATP production from neuronal activity. Due to a combination of diminished ATP production and elevated ATP consumption — established outcomes in ALS neurons — the levels of ATP in vapbP58S neurons are unable to keep up with the bioenergetic burden of depolarization. The resulting paucity of ATP and attendant decrease in the activity of Ca2+ ATPases results in diminished extrusion of cytosolic Ca2+ in vapbP58S-expressing motor neurons. The accumulation of residual Ca2+ in vapbP58S-expressing neurons underlies paired-pulse facilitation of synaptic vesicle release, and the changes in bouton development at the NMJ. In summary, our findings point to bioenergetic dysfunction due to the loss of activity-induced ATP production as being the cause of the synaptic defects observed in a Drosophila model of ALS.
A framework for research into continental ancestry groups of the UK Biobank
Authors: Constantinescu Andrei-Emil , Mitchell Ruth E. , Zheng Jie , Bull Caroline J. , Timpson Nicholas J. , Amulic Borko , Vincent Emma E. , Hughes David A. 
Published: December 2021

AbstractBackgroundThe UK Biobank is a large prospective cohort, based in the United Kingdom, that has deep phenotypic and genomic data on roughly a half a million individuals. Included in this resource are data on approximately 78,000 individuals with “non-white British ancestry”. Whilst most epidemiology studies have focused predominantly on populations of European ancestry, there is an opportunity to contribute to the study of health and disease for a broader segment of the population by making use of the UK Biobank’s “non-white British ancestry” samples. Here we present an empirical description of the continental ancestry and population structure among the individuals in this UK Biobank subset.ResultsReference populations from the 1000 Genomes Project for Africa, Europe, East Asia, and South Asia were used to estimate ancestry for each individual. Those with at least 80% ancestry in one of these four continental ancestry groups were taken forward (N=62,484). Principal component and K-means clustering analyses were used to identify and characterize population structure within each ancestry group. Of the approximately 78,000 individuals in the UK Biobank that are of “non-white British” ancestry, 50,685, 6,653, 2,782, and 2,364 individuals were associated to the European, African, South Asian, and East Asian continental ancestry groups, respectively. Each continental ancestry group exhibits prominent population structure that is consistent with self-reported country of birth data and geography.ConclusionsMethods outlined here provide an avenue to leverage UK Biobank’s deeply phenotyped data allowing researchers to maximise its potential in the study of health and disease in individuals of non-white British ancestry.
Using Piecewise Regression to Identify Biological Phenomena in Biotelemetry Datasets
Authors: Wolfson David W. , Andersen David E. , Fieberg John R. 
Published: December 2021

AbstractTechnological advances in the field of animal tracking have greatly expanded the potential to remotely monitor animals, opening the door to exploring how animals shift their behavior over time or respond to external stimuli. A wide variety of animal-borne sensors can provide information on an animal’s location, movement characteristics, external environmental conditions, and internal physiological status. Here, we demonstrate how piecewise regression can be used to identify the presence and timing of potential shifts in a variety of biological responses using GPS telemetry and other biologging data streams. Different biological latent states can be inferred by partitioning a time-series into multiple segments based on changes in modeled responses (e.g., their mean, variance, trend, degree of autocorrelation) and specifying a unique model structure for each interval. We provide five example applications highlighting a variety of taxonomic species, data streams, timescales, and biological phenomena. These examples include a short-term behavioral response (flee and return) by a trumpeter swan (Cygnus buccinator)immediately following a GPS collar deployment; remote identification of parturition based on movements by a pregnant moose (Alces alces); a physiological response (spike in heart-rate) in a black bear (Ursus americanus) to a stressful stimulus (presence of a drone); a mortality event of a trumpeter swan signaled by changes in collar temperature and Overall Dynamic Body Acceleration; and an unsupervised method for identifying the onset, return, duration, and staging use of sandhill crane (Antigone canadensis) migration. We implement analyses using the mcp package in R, which provides functionality for specifying and fitting a wide variety of user-defined model structures in a Bayesian framework and methods for assessing and comparing models using information criterion and cross-validation measures. This approach uses simple modeling approaches that are accessible to a wide audience and is a straightforward means of assessing a variety of biologically relevant changes in animal behavior.
Scalable, ultra-fast, and low-memory construction of compacted de Bruijn graphs with Cuttlefish 2
Authors: Khan Jamshed , Kokot Marek , Deorowicz Sebastian , Patro Rob 
Published: December 2021

The de Bruijn graph is a key data structure in modern computational genomics, and construction of its compacted variant resides upstream of many genomic analyses. As the quantity of genomic data grows rapidly, this often forms a computational bottleneck.We present Cuttlefish 2, significantly advancing the state-of-the-art for this problem. On a commodity server, it reduces the graph construction time for 661K bacterial genomes, of size 2.58Tbp, from 4.5 days to 17–23 hours; and it constructs the graph for 1.52Tbp white spruce reads in ∼10 hours, while the closest competitor requires 54–58 hours, using considerably more memory.
Protocol for a cluster randomised trial to evaluate a community-level complementary-food safety and hygiene and nutrition intervention in Mali: The MaaCiwara study
Authors: Watson Samuel I , Asamane E , Lilford RJ , Hemming K , Sidibe Cheick , Rego Ryan T. , Bensassi Sami , Diarra Ayouba , Diarra Youssouf , Diop Samba , Gautam Om Prasad , Islam Mohammad Sirajul , Jackson Louise , Jolly Kate , Kayentao Kassoum , Koita Ousmane , Manjang Buba , Tebbs Susan , Gale Nicola , Griffiths Paula , Cairncross Sandy , Toure Ousmane , Manaseki-Holland Semira 
Published: December 2021

ABSTRACTBackgroundDiarrheal disease remains a significant cause of morbidity and mortality among the under-fives in many low- and middle-income countries. Changes to food safety practices and feeding methods around the weaning period, alongside improved nutrition, may significantly reduce the risk of disease and improve development for infants. This article describes a protocol for a cluster randomized trial to evaluate the effectiveness of a multi-faceted community-based educational intervention that aims to improve food safety and hygiene behaviours and enhance child nutrition.MethodsWe will conduct a mixed-methods, parallel cluster randomised controlled trial with baseline measures. 120 clusters comprising small urban and rural communities will be recruited in equal numbers and randomly allocated in a 1:1 ratio to either treatment or control arms. Participants will be mother-child dyads (27 per cluster period) with children aged 6 to 24 months. Data collection will comprise a day of observation and interviews with each participating mother-child pair and will take place at baseline and four and 15 months post-intervention. The primary analysis will estimate the effectiveness of the intervention on changes to complementary food safety and preparation behaviours, food and water contamination, and diarrhoea. Secondary outcomes include maternal autonomy, enteric infection, nutritional content of meals, and child anthropometry. A secondary structural equation analysis will be conducted to examine the causal relationships between the different outcomes.ConclusionsThe trial will provide evidence on the effectiveness of community-based behavioural change and educational interventions designed to reduce the burden of diarrhoeal disease in the under fives, and how effectiveness varies across different contexts.