bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modelling NHS 111 demand for primary care services: a discrete event simulation
Authors: Pilbery Richard , Smith Madeleine , Green Jonathan , Chalk Daniel , O’Keeffe Colin 
Published: May 2023

AbstractBackgroundAlmost half of the 16,650,745 calls to NHS 111 each year are triaged to a primary care disposition. However, there is evidence that contact with a primary care service occurs in less than 50% of cases and triage time frames are frequently not met. This can result in increased utilisation of other healthcare services.This feasibility study aimed to modelin-silicothe current healthcare system for patients triaged to a primary care disposition and determine the effect of reconfiguring the system to ensure a timely primary care service contact.MethodsData from the Connected Yorkshire research database were used to develop a model and Discrete Event Simulation in Python, using the SimPy package. This included all 111 calls made in 2021 by callers registered with a Bradford GP who were triaged to a primary care disposition, and their subsequent healthcare system access during the following 72 hours.We simulated 100 runs of one year of 111 calls and calculated the mean difference and 95% confidence intervals in primary care contacts, emergency ambulance (999) calls and avoidable ED attendances.ResultsThe simulation of the current system estimated that there would be 39,283 (95%CI 39,237–39,328) primary care contacts, 2,042 (95%CI 2,032–2,051) 999 calls and 1,120 (95%CI 1,114–1,127) avoidable ED attendances. Modifying the model to ensure a timely primary care response resulted in a mean increase in primary care contacts of 37,748 (95%CI 37,667–37,829), a mean reduction in 999 calls of -449 (95%CI -461– -436) and a mean reduction in avoidable ED attendance of -26 (95%CI -35– -17).ConclusionIn this simulated study, ensuring timely contact with a primary care service would lead to a significant reduction in 999 and 111 calls, and ED attendances (although not avoidable ED attendance). However, this is likely to be impractical given the need to almost double current primary care service provision. Further economic and qualitative research is needed to determine whether this intervention would be cost effective and acceptable to both patients and primary care clinicians.
Classification of colon cancer patients into Consensus Molecular Subtypes using Support Vector Machines
Authors: Kochan Necla , Dayanc Barıs Emre 
Published: May 2023

AbstractObjectiveThe molecular heterogeneity of colon cancer has made classification of tumors a requirement for effective treatment. One of the approaches for molecular subtyping of colon cancer patients is the Consensus Molecular Subtypes (CMS) developed by the Colorectal Cancer Subtyping Consortium (CRCSC). CMS-specific RNA-Seq dependent classification approaches are recent with relatively low sensitivity and specificity. In this study, we aimed to classify patients into CMS groups using RNA-seq profiles.MethodsWe first identified subtype specific and survival associated genes using Fuzzy C-Means (FCM) algorithm and log-rank test. Then we classified patients using Support Vector Machines with Backward Elimination methodology.ResultsWe optimized RNA-seq based classification using 25 genes with minimum classification error rate. Here we report the classification performance using precision, sensitivity, specificity, false discovery rate and balanced accuracy metrics.ConclusionWe present the gene list for colon cancer classification with minimum classification error rates. We observed the lowest sensitivity but highest specificity with CMS3-associated genes, which is significant due to low number of patients in the clinic for this group.
Rare variants of the glucagon-like peptide-1 receptor (GLP1R) gene are overrepresented in a severe obesity cohort and associated with type 2 diabetes in the UK Biobank
Authors: Handley Dale , Almansoori Sumaya , Sato Mitra S. , Amin Hasnat , Alsters Suzanne , Chahal Harvinder , Purkayastha Sanjay , Murphy Kevin G. , van Haelst Mieke , le Roux Carel W , Tan Tricia , Walters Robin G , Drenos Fotios , Blakemore Alexandra I 
Published: May 2023

AbstractIntroductionGlucagon-like peptide 1 (GLP1) agonists are highly effective agents for the treatment of obesity and type 2 diabetes (T2D). GLP-1 is also implicated in outcomes of bariatric surgery, including appetite changes and T2D remission. Rare, potentially deleterious mutations in the glucagon-like peptide 1 receptor gene (GLP1R) may, therefore, have important implications for pathogenesis of obesity and T2D, and for response to therapeutic interventions.MethodsA custom Axion genotyping array, including 117 rare predicted-deleteriousGLP1Rmutations (MAF<0.01 in gnomAD, CADD-PHRED m >= 15), was used to screen 1714 unrelated adults with BMI >35 kg/m2from the PMMO study. We also examined the UK Biobank (UKB) exome sequence dataset for rare, predicted-deleteriousGLP1Rvariants and tested their effects on weight and glycaemia-related traits.ResultsThirty-four PMMO participants carried one of the 117GLP1Rvariants screened (11 might have been expected using the sum of their gnomAD control MAFs). These 8 variants were associated with T2D in the UKB and subsequent gene-level analysis of the UKB exome sequence dataset (629/39,274 carriers) confirmed that rareGLP1Rvariants are associated with increased risk of T2D (OR=1.58), as well as with higher HbA1c levels (p= 0.039). Furthermore, our data highlight a potential interaction of these variants with body mass index.ConclusionRare, potentially deleteriousGLP1Rmutations is associated with increased T2D risk, as well as higher HbA1c in UKB participants without diabetes. Future studies should examine the implications ofGLP1Rmutations for response to GLP1 agonist treatment and explore the observed interactions with obesity in T2D risk, including in larger cohorts with obesity.
The SENTINEL study of differentiated service delivery models for HIV treatment in Malawi, South Africa, and Zambia: research protocol for a prospective cohort study
Authors: Pascoe Sophie , Huber Amy , Mokhele Idah , Lekodeba Nkgomeleng , Ntjikelane Vinolia , Sande Linda , Tcherini Timothy , Haimbe Prudence , Rosen Sydney ,   the AMBIT SENTINEL study team
Published: May 2023

AbstractBackgroundMany countries in sub-Saharan Africa are rapidly scaling up “differentiated service delivery” (DSD) models for HIV treatment to improve the quality of care, increase access, reduce costs, and support the continued expansion and sustainability of antiretroviral therapy (ART) programs. Although there is some published evidence about the health outcomes of patients in DSD models, little is known about their impacts on healthcare providers’ job satisfaction, patients’ quality of life, costs to providers or patients, or how DSD models affect resource allocation at the facility level.MethodsSENTINEL is a multi-year observational study that will collect detailed data about DSD models for ART delivery and related services from 12 healthcare facilities in Malawi, 24 in South Africa, and 12 in Zambia. The first round of SENTINEL included a patient survey, provider survey, provider time-and-motion observations, and facility resource use inventory. A survey of clients testing for HIV and a supplement to the facility resource use component to describe service delivery integration will be added for the second round. The patient survey will ask up to 10 patients enrolled in each DSD model at each study site about their experiences in HIV care and in DSD models, costs incurred seeking treatment, and preferences for HIV service delivery. The provider survey will ask up to 10 providers per site about the impact of DSD models on their positions and clinics. The time-and-motion component will directly observe the time use of a sample of providers implementing DSD models. Finally, the resource utilization component will collect facility-level data about DSD model availability and enrollment and the human and other resources needed to implement them. SENTINEL is planned to include four or more approximately annual rounds of data collection between 2021 and 2026.DiscussionAs national DSD programs for HIV treatment mature, it is important to understand how individual healthcare facilities are interpreting and implementing national guidelines and how healthcare workers and clients are adapting to new models of service delivery. SENTINEL will help policy makers and program managers understand the benefits and costs of differentiated service delivery and improve resource allocation going forward.
Imputation Accuracy Across Global Human Populations
Authors: Cahoon Jordan L. , Rui Xinyue , Tang Echo , Simons Christopher , Langie Jalen , Chen Minhui , Lo Ying-Chu , Chiang Charleston W. K. 
Published: May 2023

AbstractGenotype imputation is now fundamental for genome-wide association studies but lacks fairness due to the underrepresentation of populations with non-European ancestries. The state-of-the-art imputation reference panel released by the Trans-Omics for Precision Medicine (TOPMed) initiative contains a substantial number of admixed African-ancestry and Hispanic/Latino samples to impute these populations with nearly the same accuracy as European-ancestry cohorts. However, imputation for populations primarily residing outside of North America may still fall short in performance due to persisting underrepresentation. To illustrate this point, we curated genome-wide array data from 23 publications published between 2008 to 2021. In total, we imputed over 43k individuals across 123 populations around the world. We identified a number of populations where imputation accuracy paled in comparison to that of European-ancestry populations. For instance, the mean imputation r-squared (Rsq) for 1-5% alleles in Saudi Arabians (N=1061), Vietnamese (N=1264), Thai (N=2435), and Papua New Guineans (N=776) were 0.79, 0.78, 0.76, and 0.62, respectively. In contrast, the mean Rsq ranged from 0.90 to 0.93 for comparable European populations matched in sample size and SNP content. Outside of Africa and Latin America, Rsq appeared to decrease as genetic distances to European reference increased, as predicted. Further analysis using sequencing data as ground truth suggested that imputation software may over-estimate imputation accuracy for non-European populations than European populations, suggesting further disparity between populations. Using 1496 whole genome sequenced individuals from Taiwan Biobank as a reference, we also assessed a strategy to improve imputation for non-European populations with meta-imputation, which can combine results from TOPMed with smaller population-specific reference panels. We found that meta-imputation in this design did not improve Rsq genome-wide. Taken together, our analysis suggests that with the current size of alternative reference panels, meta-imputation alone cannot improve imputation efficacy for underrepresented cohorts and we must ultimately strive to increase diversity and size to promote equity within genetics research.
pH-responsive upconversion mesoporous silica nanospheres for combined multimodal diagnostic imaging and targeted photodynamic and photothermal cancer therapy
Authors: Palanikumar L. , Kalmouni Mona , Houhou Tatiana , Abdullah Osama , Ali Liaqat , Pasricha Renu , Thomas Sneha , Afzal Ahmed J. , Barrera Francisco N. , Magzoub Mazin 
Published: May 2023

ABSTRACTPhotodynamic therapy (PDT) and photothermal therapy (PTT) have garnered considerable interest as non-invasive cancer treatment modalities. However, these approaches remain limited by low solubility, poor stability and inefficient targeting of many common photosensitizers (PSs) and photothermal agents (PTAs). To overcome these limitations, we have designed biocompatible and biodegradable tumor-targeted upconversion nanospheres with imaging capabilities. The multifunctional nanospheres consist of a sodium yttrium fluoride core doped with lanthanides (ytterbium, erbium and gadolinium) and bismuth selenide (NaYF4:Yb/Er/Gd,Bi2Se3) within a mesoporous silica shell that encapsulates a PS, Chlorin e6 (Ce6), in its pores. NaYF4:Yb/Er converts deeply penetrating near-infrared (NIR) light to visible light, which excites the Ce6 to generate cytotoxic reactive oxygen species (ROS), while the PTA Bi2Se3efficiently converts absorbed NIR light to heat. Additionally, Gd enables magnetic resonance imaging (MRI) of the nanospheres. The mesoporous silica shell is coated with lipid/polyethylene glycol (DPPC/cholesterol/DSPE-PEG) to ensure retention of the encapsulated Ce6 and minimize interactions with serum proteins and macrophages that impede tumor targeting. Finally, the coat is functionalized with the acidity-triggered rational membrane (ATRAM) peptide, which promotes specific and efficient internalization into cancer cells within the mildly acidic tumor microenvironment. Following uptake by cancer cellsin vitro, NIR laser irradiation of the nanospheres caused substantial cytotoxicity due to ROS production and hyperthermia. The nanospheres facilitated tumor MRI and thermal imaging, and exhibited potent NIR laser light-induced antitumor effectsin vivovia combined PDT and PTT, with no observable toxicity to healthy tissue, thereby substantially prolonging survival. Our results demonstrate that the ATRAM-functionalized, lipid/PEG-coated upconversion mesoporous silica nanospheres (ALUMSNs) offer multimodal diagnostic imaging and targeted combinatorial cancer therapy.
Extinct and extant termites reveal the fidelity of behavior fossilization in amber
Authors: Mizumoto Nobuaki , Hellemans Simon , Engel Michael S , Bourguignon Thomas , Buček Aleš 
Published: May 2023

AbstractFossils encompassing multiple individuals provide rare direct evidence of behavioral interactions among extinct organisms. However, the fossilization process can alter the spatial relationship between individuals and hinder behavioral reconstruction. Here, we report a Baltic amber inclusion preserving a female-male pair of the extinct termite speciesElectrotermes affinis. The head-to-abdomen contact in the fossilized pair resembles the tandem courtship behavior of extant termites, although their parallel body alignment differs from the linear alignment typical of tandem runs. To solve this inconsistency, we simulated the first stage of amber formation, the immobilization of captured organisms, by exposing living termite tandems to sticky surfaces. We found that the posture of the fossilized pair matches trapped tandems and differs from untrapped tandems. Thus, the fossilized pair likely is a tandem running pair, representing the first direct evidence of the mating behavior of extinct termites. Furthermore, by comparing the positions of partners on a sticky surface and in the amber inclusion, we estimated to 67% the probability that the leader role in the fossilized tandem was performed by a male. Our results demonstrate that past behavioral interactions can be reconstructed despite the spatial distortion of body poses during fossilization. Our taphonomic approach clarifies how certain behaviors can be inferred from fossil occurrences.
Synchrony of Bird Migration with Avian Influenza Global Spread; Implications for Vulnerable Bird Orders
Authors: Yang Qiqi , Wang Ben , Lemey Phillipe , Dong Lu , Mu Tong , Wiebe R. Alex , Guo Fengyi , Trovão Nídia Sequeira , Park Sang Woo , Lewis Nicola , Tsui Joseph , Bajaj Sumali , Cheng Yachang , Yang Luojun , Haba Yuki , Li Bingying , Zhang Guogang , Pybus Oliver G. , Tian Huaiyu , Grenfell Bryan 
Published: May 2023

AbstractHighly pathogenic avian influenza virus (HPAIV) A H5 clade 2.3.4.4 has caused worldwide outbreaks in domestic poultry, occasional spillover to humans, and increasing deaths of diverse species of wild birds since 2014. Wild bird migration is currently acknowledged as an important ecological process contributing to the global dispersal of HPAIV H5. However, it is unclearhow seasonal bird migration facilitates global virus dispersal, andwhich avian species are exposed to HPAI H5 clade 2.3.4.4 viruses and where. To shed light on ongoing global outbreaks, we sought to explore these questions through phylodynamic analyses based on empirical data of bird movement tracking and virus genome sequences. First, based on viral phylogeography and bird migration networks, we demonstrate that seasonal bird migration can explain salient features of the global dispersal of clade 2.3.4.4. Second, we detect synchrony between the seasonality of bird annual cycle phases and virus lineage movements. We reveal the differing vulnerable bird orders at geographical origins and destinations of HPAIV H5 lineage movements. Notably, we highlight the potential importance of relatively under-discussed Suliformes and Ciconiiformes, in addition to Anseriformes and Charadriiformes, in virus lineage movements. Our study provides a phylodynamic framework that links the bird movement ecology and genomic epidemiology of avian influenza; it highlights the importance of integrating bird behaviour and life history in avian influenza studies.
treespat:an R package for spatial tree diversity analysis
Authors: Chianucci F. , Puletti N. , Cesaretti L. 
Published: May 2023

AbstractForest structure is a key element in understanding functionality and resilience of forest ecosystems. Analyses of forest structure and diversity have traditionally employed non-spatial measures, due to the simplicity of such approach. However, spatial structure can provide a deeper understanding of tree patterns, but widespread use of a spatially-explicit approach has been often limited by the complexity of theoretical equations and formulas, and the lack of freely distributed tools to calculate such spatial indices. To fill this gap we created the R packagetreespat, which allows to calculate some of the most diffuse stand-level spatial diversity indices. The document describes theory, basic definition and example application for using thetreespatpackage.Abstract Figure
Uncertainty in the mating strategy causes bias and inaccuracy in estimates of genetic parameters in honeybees
Authors: Kistler Tristan , Brascamp Evert W. , Basso Benjamin , Bijma Piter , Phocas Florence 
Published: May 2023

AbstractBackgroundWith the increased number of honeybee breeding plans worldwide, records from queens with diversified mating strategies need to be considered. Breeding queens might be inseminated with drones produced by a single drone-producing queen (DPQ), or by a group of sister-DPQs. Often, only the dam of DPQ(s) is reported in the pedigree. Furthermore, datasets might include colony phenotypes from DPQs that were open mated in different locations. Using simulation, we investigated the impact of the mating strategy on estimates of genetic parameters and breeding values, when the DPQs were treated in different ways in the statistical evaluation model. We quantify the bias and standard error of estimates when breeding queens are mated to a single or a group of DPQs, assuming that this information is either known or not. We also investigated two alternative strategies to accommodate phenotypes of open-mated DPQs in the genetic evaluation, adding either a dummy pseudo sire in the pedigree, or a non-genetic effect to the statistical evaluation model to account for the origin of the DPQs’ mates.ResultsWhen breeding queens were inseminated with semen from drones of a single DPQ and this was known, estimates of genetic parameters and genetic trends were more precise. If they were inseminated using drones from a single or a group of DPQs, and this information was not known, erroneous assumptions led to considerable bias in the estimates. For colony phenotypes of open-mated DPQs, adding a dummy pseudo sire in the pedigree for each mating location led to considerable overestimation of genetic variances, while correcting for the mating area by adding a non-genetic effect in the evaluation model gave unbiased estimates.ConclusionsKnowing only the dam of the DPQ(s) in the mating may lead to erroneous assumptions on how DPQs were used and cause severe biases in estimates of genetic parameters and genetic trends. Therefore, keeping track in the pedigree of which DPQ(s), and not only which dam of DPQ(s) are used, is recommended. Records from DPQ colonies with queens open mated to a heterogeneous drone population can be integrated by adding non-genetic effects to the statistical evaluation model.
Direct mass spectrometry-based detection and antibody sequencing of Monoclonal Gammopathy of Undetermined Significance from patient serum – a case study
Authors: Peng Weiwei , den Boer Maurits A. , Tamara Sem , Mokiem Nadia J. , van der Lans Sjors P.A. , Schulte Douwe , Haas Pieter-Jan , Minnema Monique C. , Rooijakkers Suzan H.M. , van Zuilen Arjan D. , Heck Albert J.R. , Snijder Joost 
Published: May 2023

AbstractMonoclonal gammopathy of undetermined significance (MGUS) is a plasma cell disorder, characterized by the presence of a predominant monoclonal antibody (i.e., M-protein) in serum, without clinical symptoms. Here we present a case study in which we detect MGUS by liquid-chromatography coupled with mass spectrometry (LC-MS) profiling of IgG1 in human serum. We detected a Fab-glycosylated M-protein and determined the full heavy and light chain sequences by bottom-up proteomics techniques using multiple proteases, further validated by top-down LC-MS. Moreover, the composition and location of the Fab-glycan could be determined in CDR1 of the heavy chain. The outlined approach adds to an expanding mass spectrometry-based toolkit to characterize monoclonal gammopathies such as MGUS and multiple myeloma, with fine molecular detail. The ability to detect monoclonal gammopathies and determine M-protein sequences straight from blood samples by mass spectrometry provides new opportunities to understand the molecular mechanisms of such diseases.
Recovery from anhydrobiosis in the tardigradeParamacrobiotus experimentalis: better to be young than old and in a group than alone
Authors: Nagwani Amit Kumar , Melosik Iwona , Kaczmarek Łukasz , Kmita Hanna 
Published: May 2023

AbstractDesiccation-tolerant organisms can survive dehydration in a state of anhydrobiosis. Tardigrades can recover from anhydrobiosis at any life stage and are considered among the toughest animals on Earth. However, the factors that influence recovery from anhydrobiosis are not well understood. The study aimed to evaluate the effect of sex, age, the presence of other individuals and the combination of the number and duration of anhydrobiosis episodes on the recovery ofParamacrobiotus experimentalis. The activity of 1,200 individuals for up to 48 hours after rehydration was evaluated using ANOVA. Age was the main factor influencing return to activity, followed by the combination of number and duration of anhydrobiosis episodes, influence of the presence of other individuals, and sex. More individuals returned to activity after repeated short than repeated long anhydrobiosis episodes and older individuals were less likely to recover than younger individuals. In addition, when compared to single animals, the presence of other individuals resulted in higher number of active animals after dehydration and rehydration. The effect of sex was significant, but there was no general tendency for one sex to recover from anhydrobiosis better than the other one. The results contribute to a better understanding of the anhydrobiosis ability ofPam. experimentalisand provide background for full explanation of molecular, cellular and environmental mechanisms of anhydrobiosis.