bluuebunny/crossref_metadata_2025_split huggingface dataset:
Repurposing The Dark Genome. III - Intronic Proteins
Authors: Garg Mohit , Dhar Pawan K. 
Published: June 2023

AbstractBased on the expression patterns, genomes are viewed as a collection of protein-coding, RNA-coding, and non-expressing DNA sequences. Unlike most prokaryotes, eukaryotic gene expression comes with an additional step called alternative splicing. During the maturation process, different combinations of exons are spliced out and joined together resulting in the formation of mRNA isoforms. After removal from pre-mRNA, introns may be degraded by cellular exonucleases or form long non-coding RNAs (lncRNAs), or temporarily retained in the nucleus for regulating gene expression. We asked: Do introns have an unutilized potential for encoding proteins? If introns had an opportunity of getting translated, what kind of peptides or proteins, would they make? This study is based on the hypothesis of making functional proteins from leftover introns and is an extension of the original work of making functional proteins from theE. coliintergenic sequences (Dhar et al., 2009). Here full-length introns were computationally translated into proteins to study their potential structural, physicochemical, functional, and cellular location properties. Experimental validation is underway for a detailed understanding of the biology of intronic proteins. A synthetic intronic protein repository would provide an opportunity to design first-in-the-class molecules toward functional endpoints.
Paradoxical effects of Zim3, a CRISPRi effector, on human iPSC-cardiomyocyte electrophysiology
Authors: Han Julie L. , Heinson Yuli W. , Pozo Maria R. , Li Weizhen , Entcheva Emilia 
Published: June 2023

AbstractWe show that Zim3, when used as Zim3-KRAB-dCas9 effector in interference CRISPR, without any guide RNAs, paradoxically upregulates key cardiac ion channel genes in human induced pluripotent stem-cell-derived cardiomyocytes, iPSC-CMs, responsible for healthy resting membrane potential, repolarization of the action potential and electrical transmission of signals. These were found to yield expected functional enhancements consistent with a more mature iPSC-CM phenotype, with potentially desirable properties.
High recallability of memory B cells requires ZFP318-dependent transcriptional regulation of mitochondrial function
Authors: Wang Yifeng , Shao Wen , Liu Xin , Liang Qingtai , Lei Jiaqi , Shi Wenjuan , Mei Miao , Li Ying , Tan Xu , Yu Guocan , Yu Li , Zhang Linqi , Qi Hai 
Published: June 2023

AbstractExpression of the transcriptional regulator ZFP318 is induced in germinal center (GC)- exiting memory B cell precursors and memory B cells (MBCs). Using a conditional ZFP318 fluorescence reporter that also enables ablation of ZFP318-expressing cells, we found that ZFP318-expressing MBCs were highly enriched with GC-derived cells. Although ZFP318-expressing MBCs constituted only a minority of the antigen-specific MBC compartment, their ablation severely impaired recall responses. Deletion of Zfp318 did not alter the magnitude of primary responses but markedly reduced MBC participation in recall. CD40 ligation promoted Zfp318 expression, whereas B-cell receptor (BCR) signaling was inhibitory. Enforced ZFP318 expression enhanced recall performance of MBCs that otherwise responded poorly. ZFP318-deficient MBCs expressed less mitochondrial genes, had structurally compromised mitochondria, and were susceptible to reactivation-induced cell death. The abundance of ZFP318-expressing MBCs, instead of the number of antigen-specific MBCs, correlated with the potency of prime-boost vaccination. Therefore, ZFP318 controls the MBC recallability and represents a quality checkpoint of humoral immune memory.
Community occurrence of metapneumovirus, influenza A, and respiratory syncytial virus (RSV) inferred from wastewater solids during the winter 2022-2023 tripledemic
Authors: Boehm Alexandria B. , Wolfe Marlene K. , White Bradley , Hughes Bridgette , Duong Dorothea , Bidwell Amanda 
Published: June 2023

AbstractWastewater monitoring can provide insights into respiratory disease occurrence in communities that contribute to the wastewater system. Using daily measurements of RNA of influenza A (IAV), respiratory syncytial virus (RSV), and human metapneumovirus (HMPV), as well as SARS-CoV-2 in wastewater solids from eight publicly owned treatment works in the Greater San Francisco Bay Area of California between July 2022 until early May 2023, we identify a “tripledemic” when concentrations of IAV, RSV, and SARS-CoV-2 peaked at approximately the same time. HMPV was also widely circulating. We designed novel hydrolysis probe RT-PCR assays for different IAV subtype makers to discern that the dominant circulating IAV subtype was H3N2. We show that wastewater data can be used to identify onset and offset of wastewater disease occurrence events that can provide insight into disease epidemiology and timely, localized information to inform hospital staffing and clinical decision making to respond to circulating viruses. Whereas RSV and IAV wastewater events were mostly regionally coherent, HMPV events displayed localized occurrence patterns.
Epidemiology of chronic pain and opioid use in primary care – a scoping review of big data research
Authors: Lin Junlin , Zhu Hongdian , Murray Greg , Wang Audrey P 
Published: June 2023

AbstractObjectiveRecent research addressing the opioid use and misuse crisis in patients with chronic non-cancer pain in primary care has focused on traditional cohort studies underpinned by survey data. The advent of electronic health records creates a ‘big data’ opportunity for improving our understanding of the epidemiology of chronic non-cancer pain in primary care and opioid use and misuse. This scoping review aimed to map the chronic non-cancer pain patient population in primary care using big data research, investigating the patient characteristics and opioid prescription patterns.MethodsSearches of primary electronic databases and grey literature, including OVID, CINAHL, and Scopus, were performed from January 1, 2010 to December 2, 2022. The search strategy was restricted to the English language.ResultsA total of 1,057 records from databases and 515 records from grey literature were considered. Of these, only three articles met the eligibility criteria, and two articles of these reported an estimated chronic pain prevalence of 3.82% and 10.3% in the primary care setting. Chronic pain patients that presented to primary care providers were predominately female, and common comorbidities were anxiety and depression. An estimated 30% of chronic pain patients used opioids for treatment sourced from general practitioners and family practitioners.ConclusionThe use of big data remains underutilized for investigating the epidemiology of chronic pain and opioid use in primary care. This review calls for a greater focus on pain informatics with big data to improve the accuracy of future clinical chronic pain epidemiology studies.
Geographic differences in population rates of interventional treatment for prostate cancer in Australia
Authors: Cameron Jessica K , Chandrasiri Upeksha , Millar Jeremy , Aitken Joanne F , Cramb Susanna , Dunn Jeff , Frydenberg Mark , Rashid Prem , Mengersen Kerrie , Chambers Suzanne K , Baade Peter D , Smith David P 
Published: June 2023

AbstractBackgroundTreatment decisions for men diagnosed with prostate cancer depend on a range of clinical and patient characteristics such as disease stage, age, general health, risk of side effects and access. Associations between treatment patterns and area-level factors such as remoteness and socioeconomic disadvantage have been observed in many countries but have not been investigated in Australia.MethodsHospital separations data for interventional treatments for prostate cancer (radical prostatectomy, low dose rate and high dose rate brachytherapy) were modelled using spatial models, generalised linear mixed models, maximised excess events tests andk-means statistical clustering.ResultsGeographic differences in population rates of interventional treatments were found (p<0.001). Separation rates for radical prostatectomy were lower in remote areas (12.2 per 10 000 person-years compared with 15.0-15.9 in regional and major city areas). Rates for all treatments decreased with increasing socioeconomic disadvantage (radical prostatectomy 19.1 /10 000 person-years in the most advantaged areas compared with 12.9 in the most disadvantaged areas). Three groups of similar areas were identified: those with higher rates of radical prostatectomy, those with higher rates of low dose brachytherapy, and those with low interventional treatment rates but higher rates of excess deaths. The most disadvantaged areas and remote areas tended to be in the latter group.ConclusionsThe geographic differences in treatment rates may partly reflect differences in patients’ physical and financial access to treatments. Treatment rates also depend on diagnosis rates and thus reflect variation in investigation rates for prostate cancer and presentation of disease. Spatial variation in interventional treatments may aid identification of areas of under-treatment or over-treatment.
Altitude-dependent agro-ecologies impact the microbiome diversity of scavenging indigenous chicken in Ethiopia
Authors: Glendinning Laura , Jia Xinzheng , Kebede Adebabay , Oyola Samuel O. , Park Jong-Eun , Park Woncheoul , Assiri Abdulwahab , Holm Jacob Bak , Kristiansen Karsten , Han Jianlin , Hanotte Olivier 
Published: June 2023

AbstractScavenging indigenous village chickens play a vital role in sub-Saharan Africa, sustaining the livelihood of millions of farmers. These chickens are exposed to vastly different environments and feeds compared to commercial chickens. In this study, we analysed the caecal microbiota of 243 Ethiopian village chickens living in different altitude-dependent agro-ecologies. Differences in bacterial diversity were significantly correlated with differences in specific climate factors, topsoil characteristics, and supplemental diets provided by farmers. Microbiota clustered into 3 enterotypes, with one particularly enriched at high altitudes. We assembled 9,977 taxonomically and functionally diverse metagenome-assembled genomes, the vast majority of which were not found in a dataset of previously published chicken microbes, or in the Genome Taxonomy Database. The wide functional and taxonomic diversity of these microbes highlights their importance in the local adaptation of indigenous poultry, and the significant impacts of environmental factors on the microbiota argues for further discoveries in other agro-ecologies.
Targeting Ras signaling excitability in cancer cells through combined inhibition of FAK and PI3K
Authors: Chen Chao-Cheng , Wang Suyang , Yang Jr-Ming , Huang Chuan-Hsiang 
Published: June 2023

AbstractThe Ras/PI3K/ERK signaling network is frequently mutated in various human cancers including cervical cancer and pancreatic cancer. Previous studies showed that the Ras/PI3K/ERK signaling network displays features of excitable systems including propagation of activity waves, all-or-none responses, and refractoriness. Oncogenic mutations lead to enhanced excitability of the network. A positive feedback loop between Ras, PI3K, the cytoskeleton, and FAK was identified as a driver of excitability. In this study, we investigated the effectiveness of targeting signaling excitability by inhibiting both FAK and PI3K in cervical and pancreatic cancer cells. We found that the combination of FAK and PI3K inhibitors synergistically suppressed the growth of select cervical and pancreatic cancer cell lines through increased apoptosis and decreased mitosis. In particular, FAK inhibition caused downregulation of PI3K and ERK signaling in cervical cancer but not pancreatic cancer cells. Interestingly, PI3K inhibitors activated multiple receptor tyrosine kinases (RTKs), including insulin receptor and IGF-1R in cervical cancer cells, as well as EGFR, Her2, Her3, Axl, and EphA2 in pancreatic cancer cells. Our results highlight the potential of combining FAK and PI3K inhibition for treating cervical and pancreatic cancer, although appropriate biomarkers for drug sensitivity are needed, and concurrent targeting of RTKs may be required for resistant cells.
Natural thermal stress-hardening of corals through cold temperature pulses in the Thai Andaman Sea
Authors: Wall Marlene , Doering Talisa , Pohl Nina , Putchim Lalita , Ratanawongwan Tipwimon , Roik Anna 
Published: June 2023

AbstractThermal variability can render corals stress resistant through a phenomenon coined as “stress-hardening induced by environmental priming”. Fluctuations that involve high temperature peaks have been commonly investigated, however, the effects of a stress-hardening stimulus generated by cold-water pulses has rarely been studied. Offshore island reefs in the Andaman Sea offer an ideal natural setting to study these effects, as cooling water of internal waves induce strong variability with peak intensity in January to June and absence in August to November. While western island shores are exposed to this stimulus, eastern shores remain sheltered. This study examined (1) whether corals from exposed reefs were more heat stress resistant compared to stimulus-sheltered conspecifics and (2) whether this trait can last in the absence of the stimulus. We quantified the thermal stress resistance in two ecologically important coral species,Pocilloporasp. andPoritessp., from the two island shores, during the two seasons. Coral bleaching intensity and photosynthetic efficiency of algal symbionts were measured as response variables after a short-term heat stress assay (24-48 h, 34 °C) to assess thermal stress resistance. Stress responses of all stimulus-exposed corals were either undetectable (during the season of stimulus presence) or very weak (during stimulus absence), while corals from the stimulus-sheltered shore responded strongly to heat stress irrespective of the season. Hence, thermal resistance was overall greater in corals originating from the stimulus-exposed shore, but it was slightly diminished during the season of stimulus absence, emphasizing the relevance of stimulus recurrence in maintaining the resistance trait. We exemplify that the stimulus of fluctuating low temperature pulses successfully induced stress-hardening in corals. This suggests that priming stimuli do not necessarily need to transgress certain upper thermal thresholds, but can also touch on lower thresholds to be effective. Even more, we argue that cooling pulses might represent a safer stress-hardening regime, since warming-stress accumulation can be avoided. More research is required to obtain a better understanding of environmental priming, but current findings should encourage the development of artificial stress-hardening approaches to enhance coral resistance in reef restoration efforts.
Shotgun metagenomic analysis of the skin mucus bacteriome of the common carp (Cyprinus carpio)
Authors: Papp Márton , Tóth Adrienn Gréta , Nagy Sára Ágnes , Erdélyi Károly , Maróti Gergely , Cox Niamh , Czikk László , Katics Máté , Békési László , Solymosi Norbert 
Published: June 2023

ABSTRACTThe skin mucus bacteriome of fish plays an important role in the health of their hosts. Despite the economic importance of the common carp (Cyprinus carpio), research on its skin bacteriome composition is still missing. To date, most studies on the composition of fish skin bacteriome have used amplicon sequencing, despite the limitations associated with this method. In our study, a shotgun metagenomic approach was applied to characterize the external mucus bacteriome of 8 carp specimens from two different ponds on a fish farm in Hungary. Besides the carp samples, water was also sequenced from the two corresponding ponds. Each carp skin sample was dominated by the phylumProteobacteria, followed byActinobacteria, Bacteroidota, Firmicutes, CyanobacteriaandPlanctomycetota. Additionally, we have found strong concordance between the water and carp skin mucus samples, despite most studies describing an opposite relationship. Furthermore, shotgun metagenomics allowed us to apply functional annotation to the metagenomes, which revealed several metabolic functions. We present, to our knowledge, the first description of the common carp (Cyprinus carpio) skin mucus bacteriome. Even though our results showed a high level of host genome contamination, we could still provide valuable insight into the external bacterial community of this species. The presented data can provide a basis for future metagenome studies of carp or other fish species.
Semi-automated curation and manual addition of sequences to build reliable and extensive reference databases for ITS2 vascular plant DNA (meta-)barcoding
Authors: Quaresma Andreia , Yadró Garcia Carlos Ariel , Rufino José , Honrado Mónica , Amaral Joana , Brodschneider Robert , Brusbardis Valters , Gratzer Kristina , Hatjina Fani , Kilpinen Ole , Pietropaoli Marco , Roessink Ivo , van der Steen Jozef , Vejsnæs Flemming , Pinto M. Alice , Keller Alexander 
Published: June 2023

AbstractWith the breakthrough of DNA (meta)-barcoding, it soon became clear that one of the most critical steps for accurate taxonomic identification is to have an accurate DNA reference database for the DNA barcode marker of choice. Therefore, developing such a database has been a long-term ambition, especially in the Viridiplantae kingdom. Typically, reference databases are constructed from marker sequences downloaded from general public databases, which can carry taxonomic and other relevant errors. Herein, we constructed a curated (i) global database, (ii) European crop database, and (iii) 27 databases for the EU countries for the ITS2 barcoding marker of vascular plants. To that end, we first developed a pipeline script that entails (i) an automated curation stage comprising five filters, (ii) manual taxonomic correction for misclassified taxa, and (iii) manual addition of newly sequenced species. The pipeline allows easy updating of the curated global database. With this approach, 13% of the sequences, corresponding to 7% of species, originally imported from GenBank were discarded. Further, 259 sequences were newly added to the curated global database, which now comprises 307,977 sequences of 111,382 plant species.
Rapid molecular species identification of mammalian scat samples using nanopore adaptive sampling
Authors: Frank Lexi E. , Lindsey Laramie L. , Kipp Evan J. , Faulk Christopher , Stone Suzanne , Roerick Tanya M. , Moore Seth A. , Wolf Tiffany M. , Larsen Peter A. 
Published: June 2023

AbstractAccurate species identification is essential to mammalogy. Despite this necessity, rapid and accurate identification of cryptic, understudied, and elusive mammals remains challenging. Traditional barcoding of mitochondrial genes is standard for molecular identification but requires time-consuming wet-lab methodologies. Recent bioinformatic advancements for nanopore sequencing data offer exciting opportunities for non-invasive and field-based identification of mammals. Nanopore adaptive sampling (NAS), a PCR-free method, selectively sequences regions of DNA according to user-specified reference databases. Here, we utilized NAS to enrich mammalian mitochondrial genome sequencing to identify species. Fecal DNA extractions were sequenced from nine mammals, several collected in collaboration with Minnesota Tribal Nations, to demonstrate utility for NAS-barcoding of non-invasive samples. By mapping to the entire National Center for Biotechnology Information (NCBI) mammalian mitochondrial reference genome database and bioinformatically analyzing highly similar matches, we successfully produced species identifications for all of our fecal samples. Eight of nine species identifications matched previous PCR or animal/fecal morphological identifications. For the ninth species, our genetic data indicate a misidentification stemming from the original study. Our approach has a range of applications, particularly field-based wildlife research, conservation, disease surveillance, and monitoring of wildlife trade. Of importance to Minnesota tribes is invasive species monitoring, detections, and confirmation as climate impacts causes changes in biodiversity and shifts in species distributions. The rapid assessment techniques described here will be useful as new introductions and range expansions of native and invasive species may first be detected by the presence of signs such as scat rather than direct observations and will be helpful for chronically understaffed tribal natural resources agencies.
cudaMMC - GPU-enhanced Multiscale Monte Carlo Chromatin 3D Modelling
Authors: Wlasnowolski Michał , Grabowski Paweł , Roszczyk Damian , Kaczmarski Krzysztof , Plewczynski Dariusz 
Published: June 2023

AbstractMotivationInvestigating the 3D structure of chromatin provides new insights into transcriptional regulation. With the advancements in 3C new-sequencing techniques such as ChiA-PET and Hi-C, there has been a substantial increase in the volume of collected data, necessitating faster algorithms for chromatin spatial modelling. This study presents the cudaMMC method, which utilises the Simulated Annealing Monte Carlo approach extended by GPU-accelerated computing to generate ensembles of chromatin 3D structures efficiently.ResultsThecudaMMCcalculations demonstrate significantly faster performance and lower (better) model scores compared to our previous method on the same workstation.cudaMMCsubstantially reduces the computation time required for generating ensembles of large chromatin models, making it an invaluable tool for studying chromatin spatial conformation.AvailabilityOpen-source software and manual and sample data are freely available onhttps://github.com/SFGLab/cudaMMCContactDariusz.Plewczynski@pw.edu.pl
Improving modelling for epidemic responses: reflections from members of the UK infectious disease modelling community on their experiences during the COVID-19 pandemic
Authors: Sherratt Katharine , Carnegie Anna C. , Kucharski Adam , Cori Anne , Pearson Carl A. B. , Jarvis Christopher I. , Overton Christopher , Weston Dale , Hill Edward M. , Knock Edward , Fearon Elizabeth , Nightingale Emily , Hellewell Joel , Edmunds W. John , Arenas Julián Villabona , Prem Kiesha , Pi Li , Baguelin Marc , Kendall Michelle , Ferguson Neil , Davies Nicholas , Eggo Rosalind M. , van Elsland Sabine , Russell Timothy , Funk Sebastian , Liu Yang , Abbott Sam 
Published: June 2023

AbstractThe COVID-19 pandemic both relied and placed significant burdens on the experts involved from research and public health sectors. The sustained high pressure of a pandemic on responders, such as healthcare workers, can lead to lasting psychological impacts including acute stress disorder, post-traumatic stress disorder, burnout, and moral injury, which can impact individual wellbeing and productivity. As members of the infectious disease modelling community, we convened a reflective workshop to understand the professional and personal impacts of response work on our community and to propose recommendations for future epidemic responses. The attendees represented a range of career stages, institutions, and disciplines. This piece was collectively produced by those present at the session based on our collective experiences. Key issues we identified at the workshop were lack of institutional support, insecure contracts, unequal credit and recognition, and mental health impacts. Our recommendations include rewarding impactful work, fostering academia-public health collaboration, decreasing dependence on key individuals by developing teams, increasing transparency in decision-making, and implementing sustainable work practices. Despite limitations in representation, this workshop provided valuable insights into the UK COVID-19 modelling experience and guidance for future public health crises. Recognising and addressing the issues highlighted is crucial, in our view, for ensuring the effectiveness of epidemic response work in the future.