bluuebunny/crossref_metadata_2025 huggingface dataset:
Seroprevalence of Measles, Mumps, Rubella, and Varicella-Zoster Virus and Seroresponse to the Vaccinations in Adult Solid Organ Transplant Candidates
Authors: Javaid Hana , Prasad Pooja , De Golovine Aleksandra , Hasbun Rodrigo , Jyothula Soma , Machicao Victor , Bynon John S. , Ostrosky Luis , Nigo Masayuki
Published: June 2023

Background.

Updating live vaccines such as measles, mumps, rubella, and varicella (MMRV) is an important step in preparing patients for solid organ transplant (SOT) to prevent morbidity from these preventable diseases. However, data for this approach are scarce. Thus, we aimed to describe the seroprevalence of MMRV and the efficacy of the vaccines in our transplant center.

Methods.

Pre-SOT candidates >18 y of age were retrospectively retrieved from SOT database in Memorial Hermann Hospital Texas Medical Center. MMRV serologies are routinely screened at the time of pretransplant evaluation. We divided patients into 2 groups: MMRV-positive group versus MMRV-negative group, patients with positive all MMRV serologies and with negative immunity to at least 1 dose of MMRV, respectively.

Results.

A total of 1213 patients were identified. Three hundred ninety-four patients (32.4%) did not have immunity to at least 1 dose of MMRV. Multivariate analysis was conducted. Older age (odds ratio [OR]: 1.04) and liver transplant candidates (OR: 1.71) were associated with seropositivity. Previous history of SOT (OR: 0.54) and pancreas/kidney transplant candidates (OR: 0.24) were associated with seronegativity. Among 394 MMRV seronegative patients, 60 patients received 1 dose of MMR vaccine and 14 patients received 1 dose of varicella-zoster virus vaccine without severe adverse events. A total of 35% (13/37) of patients who had follow-up serologies did not have a serological response.

Conclusions.

A significant number of pre-SOT candidates were not immune to at least 1 dose of MMRV. This highlights the importance of MMRV screening and vaccinations pre-SOT. Postvaccination serological confirmation should be performed to evaluate the necessity for a second dose.
Body mass index does not decline during winter for the sedentary marine gastropod
Crepidula fornicata
Authors: Franklin Amanda M. , Rivera Alberto , Robbins Justin , Pechenik Jan A.
Published: June 2023

Seasonal extremes in environmental conditions can substantially limit the growth and reproduction of animals. Sedentary marine animals are particularly susceptible to winter food limitation since they cannot relocate to more favourable conditions. In several temperate-zone bivalve species, substantial winter tissue mass declines have been documented; however, no comparable studies have been conducted on intertidal gastropods. Here, we investigate whether the suspension-feeding intertidal gastropod
Crepidula fornicata
also loses substantial tissue mass during the winter. We calculated body mass index (BMI) for individuals collected in New England at different times of year for 7 years to determine whether BMI declines through winter or varies seasonally. Remarkably,
C. fornicata
body mass did not decline significantly during winter months; indeed, a relatively poorer body condition was associated with higher seawater temperature, higher air temperature and higher chlorophyll concentration. In a laboratory experiment, we found that
C. fornicata
adults that were not fed for three weeks at 6°C (local winter seawater temperature) showed no detectable declines in BMI compared to field-collected individuals. Future studies should document energy budgets of
C. fornicata
and other sedentary marine animals at low winter seawater temperatures, and the impact of short-term elevated temperatures on those energy budgets.
Comparative analysis of clinical breakpoints (CB), normalised resistance interpretation (NRI), and epidemiological cut-offs (ECOFFS), in interpreting antimicrobial resistance of E. coli isolates originating from poultry in different farm types in Tanzania.
Authors: Maganga Ruth , Sindiyo Emmanuel , Musyoki Victor Moses , Shirima Gabriel , Mmbaga Blandina T.
Published: June 2023

Existing breakpoint guidelines are not optimal for interpreting antimicrobial resistance data from animal studies and low-income countries, and therefore their utility for analysing such data is limited. There is need to integrate diverse data sets, such as those from low-income populations and animals, to improve data interpretation. There is very limited research on the relative merits of clinical breakpoints, epidemiological cut-offs, and normalised resistance interpretation breakpoints in interpreting microbiological data, particularly in animal studies and studies from low-income countries. The aim of this study was to compare antimicrobial resistance in E. coli isolates using ECOFFS, CLSI, and NRI breakpoints. A total of 69 non-repetitive poultry isolates were selected for investigation based on lactose fermentation on MacConkey agar and subsequent identification and confirmation as E. coli using chromogenic agar and uidA Polymerase Chain Reaction. Kirby Bauer disc diffusion technique was used for susceptibility testing. For each antimicrobial agent, inhibition zone diameters were measured, and ECOFFs, CLSI, and NRI bespoke breakpoints used for resistance interpretation. According to the interpretation of all breakpoints except ECOFFs, tetracycline resistance was significantly higher (TET) (67.8% – 69.5%), than ciprofloxacin (CIPRO) (18.6%– 32.2%), imipenem (IMI) (3.4% – 35%), and ceftazidime (CEF) (1.7% – 45.8%). Prevalence estimates of antimicrobial resistance (AMR) using CLSI and NRI bespoke breakpoints did not differ for CEF (1.7% CB and 1.7% COWT), IMI (3.4% CB and 4.0% COWT) and TET (67.8% CB and 69.5% COWT). However, with ECOFFs, antimicrobial resistance estimates for CEF, IMI, and CIP were significantly higher (45.8%, 35.6%, and 64.4%, respectively; P < 0.01). Across all the three breakpoints, resistance to ciprofloxacin varied significantly (32.2% CB, 64.4% ECOFFs, and 18.6% COWT). Antimicrobial resistance interpretation is influenced by the breakpoint used, necesscitating further standardisation, especially for microbiological breakpoints, in order to harmonise outputs. The AMR ECOFFs estimates in the present study were significantly higher compared to CLSI and NRI.
Evaluation of a new dengue 3 controlled human infection model for use in the evaluation of candidate dengue vaccines
Authors: Pierce KK , Whitehead SS , Diehl SA , Naro G , Carmolli MC , He H , Tibery CM , Sabundayo BP , Kirkpatrick BD , Durbin AP
Published: June 2023

All four serotypes of dengue virus (DENV) cause the full spectrum of disease. Therefore, vaccines must protect against all serotypes. To evaluate candidate vaccines, a human challenge model of dengue serotype 3 (rDEN30Δ30) was developed. All challenge virus recipients safely met the primary endpoint of viremia and secondary endpoints of rash and seroconversion to DENV-3.
Night-time neuronal activation of Cluster N in a North American songbird
Authors: Rudolf Jennifer , Philipello Natalie , Fleihan Tamara , Dickman J. David , Delmore Kira E.
Published: June 2023

Night-migrating songbirds utilize the Earth’s magnetic field to help navigate to and from their breeding sites each year. A region of the avian forebrain called Cluster N has been shown to be activated during night migratory behavior and it has been implicated in processing geomagnetic information. Previous studies with night-migratory European songbirds have shown that neuronal activity at Cluster N is higher at night than during the day. Comparable work in North American migrants has only been performed in one species of swallows, so extension of examination for Cluster N in other migratory birds is needed. In addition, it is unclear if Cluster N activation is lateralized and the full extent of its boundaries in the forebrain have yet to be described. We used sensory-driven gene expression based on ZENK and the Swainson’s thrush, a night-migratory North American songbird, to fill these knowledge gaps. We found elevated levels of gene expression in night-vs. day-active thrushes and no evidence for lateralization in this region. We further examined the anatomical extent of neural activation in the forebrain using 3D reconstruction topology. Our findings demonstrate that Swainson’s thrushes possess an extensive bilateral night-activated Cluster N region in the forebrain similar to other European avian species, suggesting that Cluster N is highly conserved in nocturnal migrants.
DS4DH at MEDIQA-Chat 2023: Leveraging SVM and GPT-3 Prompt Engineering for Medical Dialogue Classification and Summarization
Authors: Zhang Boya , Mishra Rahul , Teodoro Douglas
Published: June 2023

This paper presents the results of the Data Science for Digital Health (DS4DH) group in the MEDIQA-Chat Tasks at ACL-ClinicalNLP 2023. Our study combines the power of a classical machine learning method, Support Vector Machine, for classifying medical dialogues, along with the implementation of oneshot prompts using GPT-3.5. We employ dialogues and summaries from the same category as prompts to generate summaries for novel dialogues. Our findings exceed the average benchmark score, offering a robust reference for assessing performance in this field.
Intra-lineage microevolution ofWolbachialeads to the emergence of new cytoplasmic incompatibility patterns
Authors: Namias Alice , Ngaku Annais , Makoundou Patrick , Unal Sandra , Sicard Mathieu , Weill Mylène
Published: June 2023

Mosquitoes of theCulex pipienscomplex are worldwide vectors of arbovirus, filarial nematode, and avian malaria agents. In these hosts, the endosymbiotic bacteriaWolbachiainduce cytoplasmic incompatibility (CI), that is, reduced embryo viability in so-called incompatible crosses.WolbachiainfectingCulex pipiens(wPip) cause CI patterns of unparalleled complexity, associated with the amplification and diversification ofcidAandcidBgenes, with up to six different gene copies described in a singlewPip genome. By repeating crosses betweenCulexisofemale lines over 17 years, we documented the emergence of a new compatibility type. Using a new sequencing method adapted to multigene families to acquirecidgenes, we showed that somewPip genomes lost specificcidAgene copies, thus giving rise to several sub-lineages segregating in the same cage. By linking phenotypic changes to their underlying genotypic bases, we showed that gene copies that are key for CI phenotypes originated from recombinations, not point mutations. We revealed how new CI patterns could emerge as part of a two-step process: first, local changes take place in the CI repertoires while maintaining compatibility with the surrounding mosquitoes, and then migration and secondary contact occur with the incompatible lines.
Intraspecific scaling of home range size and its bioenergetic dependence
Authors: Byrnes Evan E. , Hounslow Jenna L. , Heim Vital , White Clemency E. , Smukall Matthew J. , Beatty Stephen J. , Gleiss Adrian C.
Published: June 2023

Home range size and metabolic rate of animals are expected to scale with body mass at similar rates; with home ranges expanding to meet increased metabolic requirements. This expectation has widely been tested using lab-derived estimates of basal metabolic rate as proxies for field energy requirements, however, it is unclear if existing theory aligns with patterns of home range scaling observed in the field. Here, we conduct the first direct field test of the relationship between home range and metabolic rate allometry. Using acoustic telemetry, we simultaneously measured the individual home range size and field metabolic rate of lemon sharks(Negaprion brevirostris)spanning one order of magnitude in body mass. Although scaling rates of field metabolic rate were consistent with standard metabolic rate, home range size scaled at shallower rates than metabolic rates. This is evidence for strong top-down controls on home range scaling rates, likely a result of predation pressure placing constraints on home range expansions. Consequently, direct resource competition can lead to decreased home range scaling rates. We highlight inconsistencies with theory on the effects of population density and competition on home range scaling and propose that the influence of diverse types of competition should be examined.
Autoencoder Model for Translating Omics Signatures
Authors: Meimetis Nikolaos , Pullen Krista M. , Zhu Daniel Y. , Nilsson Avlant , Hoang Trong Nghia , Magliacane Sara , Lauffenburger Douglas A.
Published: June 2023

The development of effective therapeutics and vaccines for human diseases requires a systematic understanding of human biology. While animal and in vitro culture models have successfully elucidated the molecular mechanisms of diseases in many studies, they yet fail to adequately recapitulate human biology as evidenced by the predominant likelihood of failure in clinical trials. To address this broadly important problem, we developed AutoTransOP, a neural network autoencoder framework to map omics profiles from designated species or cellular contexts into a global latent space, from which germane information can be mapped between different contexts. This approach performs as well or better than extant machine learning methods and can identify animal/culture-specific molecular features predictive of other contexts, without requiring homology matching. For an especially challenging test case, we successfully apply our framework to a set of inter-species vaccine serology studies, where no 1-1 mapping between human and non-human primate features exists.
Modelling the probability of meeting IUCN Red List criteria to support reassessments
Authors: Henry Etienne Georges , Santini Luca , Butchart Stuart , Gonzalez-Suarez Manuela , Lucas Pablo Miguel , Benitez-Lopez Ana , Mancini Giordano , Jung Martin , Cardoso Pedro , Zizka Alexander , Meyer Carsten , Akcakaya H. Resit , Berryman Alex , Cazalis Victor , Di Marco Moreno
Published: June 2023

Comparative extinction risk analysis - which predicts species extinction risk from correlation with traits or geographical characteristics - has gained research attention as a promising tool to support extinction risk assessment in the IUCN Red List of Threatened Species. However, its uptake has been very limited so far, possibly because these models only predict a species’ Red List category, without indicating which Red List criteria may be triggered by which such approaches cannot easily be used in Red List assessments. We overcome this implementation gap by developing models that predict the probability of species meeting individual Red List criteria. Using data on the world’s birds, we evaluated the predictive performance of our criterion-specific models and compared it with the typical criterion-blind modelling approach. We compiled data on biological traits (e.g., range size, clutch size) and external drivers (e.g., change in canopy cover) often associated with extinction risk. For each specific criterion, we modelled the relationship between extinction risk predictors and species’ Red List category under that criterion using ordinal regression models. We found criterion-specific models were better at predicting threatened species compared to a criterion-blind model (higher sensitivity), but less good at predicting not threatened species (lower specificity). As expected, different covariates were important for predicting threat status under different criteria, for example change in annual temperature was important to predict criteria related to population trends, while clutch size was important for criteria related to restricted area of occupancy or small population size. Our criteria-specific method can support Red List assessors by producing outputs that identify species likely to meet specific criteria, and which are the most important predictors: these species can be prioritised for re-evaluation. We expect this new approach to increase the uptake of extinction risk models in Red List assessments, bridging a long-standing research-implementation gap.
Twilight length alters growth and flowering time in Arabidopsis via LHY/CCA1
Authors: Mehta Devang , Scandola Sabine , Kennedy Curtis , Lummer Christina , Rodriguez Gallo Maria Camila , Grubb Lauren E. , Tan Maryalle , Scarpella Enrico , Uhrig R. Glen
Published: June 2023

The plant circadian clock governs growth and development by syncing biological processes to periodic environmental changes. Decades of research has shown how the clock enables plants to respond to two environmental variables that change at different latitudes and over different seasons: photoperiod and temperature. However, a third variable, twilight length, has so far gone unstudied. The duration of twilight changes across the planet, lengthening with latitude and changing across seasons, and yet most circadian experiments are performed in lab environments with no twilight. Here, using controlled growth setups, we show that twilight length impacts plant growth and changes flowering time via the LHY/CCA1 morning module of the Arabidopsis circadian clock. Using a series of progressively truncated no-twilight photoperiods, we also found that plants are more sensitive to twilight length compared to equivalent changes in solely photoperiod. Further, transcriptome and proteome analyses indicated that twilight length alters the regulation of proteins involved in reactive oxygen species metabolism, photosynthesis, and carbon metabolism. Genetic analyses also implicated a twilight sensing pathway from phytochromes D and E, the morning elements of the circadian clock and modulating flowering time through theGI-FTpathway. Overall, our findings call for more nuanced models of daylength perception in plants and posit that twilight length is an important determinant of plant growth, development, and circadian function.
PlotS: web-based application for data visualization and analysis
Authors: Jajo Ringyao , Kansal Shivani , Balyan Sonia , Raghuvanshi Saurabh
Published: June 2023

Background

Data visualisation technique has greatly improved as technology has advanced. While representing the data through graph, it has made the underlying data structure become more transparent and interpretable. However, the informational scope of freely available generic visualisation tools is still limited since they only support descriptive statistics as well as no metainformation can be incorporated. Additionally, there is a need to promote the use of accepted scientific standards when performing and reporting statistical analysis.

Result

PlotS is a visualization centric web-based application that allows the integration of statistical analysis into a single workflow. The current version has eight types of graphs (bar, box, density, frequency polygon, histogram, line, scatter and violin plot) and four statistical methods (T-test, ANOVA, Wilcoxon test and Krushkal-Wallis test). It is an interactive application that provide many useful customization options for data analysis-focused visualization. It support incorporation of metainformation in the graph and multivariate data analysis by adding layer with or without secondary y-axis, side graphs, inset graph or through faceting. It can handle variety of data formats with or without replicates and inferential statistical analysis can be incorporated in the graph. Necessary statistical results are explicitly displayed for inferences and reporting.

Conclusion

PlotS is freely available athttps://plots-application.shinyapps.io/plots/. We hope it will be a useful tool for data visualisation and analysis that will also encourage the widespread use of proper statistical methods in research and teaching.
CHPF boosts proliferation and invasion of clear cell renal cell carcinoma
Authors: Zhang Yaoyu , Li Xiaowei , Ran Shu , Zhao Youguang , Huang Yuanshun , Zhou Tingting , Wang Qiwu , Liu Jiwen , Zhang Qimin , Li Xiaodong , Leng Taiping , Luo Yihang , Li Shadan
Published: June 2023

Background

Clear cell renal cell carcinoma (ccRCC) is a malignant tumor most commonly seen in the urinary system, featuring quick progression, invasive behavior, frequent recrudesce, and bad prognosis, whereas Chondroitin polymerizing factor (CHPF) is an essential glycosyl transferase of biosynthesis involved chondroitin sulphate. But the relationship between the two has not been fully understood so far. The present research will probe into the relationship between CHPF and ccRCC.

Methods

Explore the CHPF expression level in renal ccRCC tissues through bioinformatics analysis of The Cancer Genome Atlas (TCGA) and the real-time quantitative polymerase chain reaction detection system (qPCR); acquire relevant clinical data from the TCGA data-base and use Kaplan-Meier survival analysis to verify the relevance of CHPF expression to the clinical prognosis of ccRCC patients; then, effectively silence CHPF in ccRCC 786-O cells by a lentivirus-mediated approach; next, observe the effects of CHPF on tumor cell proliferation, cell cycle progression, and apoptosis.

Results

In ccRCC tissues, CHPF expression has been significantly upregulated; the higher expression, the shorter survival of ccRCC patients. CHPF downregulation in the 786-O cell can effectively hold back the proliferation, apoptosis and cycle of cancer cells.

Conclusion

Based on the above results, we arrive at a conclusion that CHPF expression contributes markedly to the development of human ccRCC cells. Therefore, CHPF may act as a potential prognostic marker of ccRCC and provide a new target for ccRCC treatment.

Simple Summary

Chondroitin polymerizing factor (CHPF) is an important glycosyltransferase involved in the biosynthesis of chondroitin sulfate, which is thought to have some pro-carcinogenic effects. However, the role and mechanism of CHPF in clear cell renal cell carcinoma (ccRCC) have not been reported. The aim of this study was to investigate the relationship between CHPF and ccRCC. In this study, we found that CHPF was highly expressed in ccRCC and knocking out CHPF can greatly inhibit the proliferation and cell cycle progression of ccRCC and accelerate its apoptosis, suggesting that CHPF can predict the prognosis of ccRCC and a potential target for treatment.
Plasmodium falciparumtransmission in the highlands of Ethiopia is driven by closely related and clonal parasites
Authors: Holzschuh Aurel , Ewnetu Yalemwork , Carlier Lise , Lerch Anita , Gerlovina Inna , Baker Sarah Cate , Yewhalaw Delenasaw , Haileselassie Werissaw , Berhane Nega , Lemma Wossenseged , Koepfli Cristian
Published: June 2023

Malaria cases are frequently recorded in the Ethiopian highlands even at altitudes above 2,000 m. The epidemiology of malaria in the Ethiopian highlands, and in particular the role of importation by human migration from the highly endemic lowlands is not well understood. We characterized the parasite population structure and genetic relatedness by sequencing 159P. falciparumsamples from Gondar and an additional 28 samples from Ziway using a highly multiplexed droplet digital PCR (ddPCR)-based amplicon deep sequencing method targeting 35 microhaplotypes and drug resistance loci. Diversity was moderate (mean HE: 0.54), and infection complexity was low (74.9% single clone infections). A significant percentage of infections shared genomic haplotypes, even across transmission seasons, indicating persistent local and focal transmission. Multiple clusters of clonal or near-clonal infections were identified, highlighting the overall high genetic relatedness. Frequently, infections from travelers were the earliest observed cases, suggesting that parasites may have been imported and then transmitted locally. We observed population structure between Gondar and Ziway, although some haplotypes were shared between sites. 31.1% of infections carriedpfhrp2deletions and 84.4%pfhrp3deletions, and 28.7%pfhrp2/pfhrp3double deletions. Parasites withpfhrp2/3deletions and wild-type parasites were genetically distinct. Mutations associated with resistance to sulfadoxine-pyrimethamine and lumefantrine were observed at near-fixation, but no mutations inpfk13were found. In conclusion, genomic data corroborates local transmission and the importance of intensified control in the Ethiopian highlands.
Alteration of DNMT1/DNMT3A by eribulin elicits global DNA methylation changes with potential therapeutic implications for triple-negative breast cancer
Authors: Bagheri Meisam , Lee Min Kyung , Muller Kristen E. , Miller Todd W. , Pattabiraman Diwakar R. , Christensen Brock C.
Published: June 2023

Triple-negative breast cancer (TNBC) is an aggressive disease subtype with limited treatment options. Eribulin is a chemotherapeutic approved for the treatment of advanced breast cancer that has been shown to elicit epigenetic changes. We investigated the effect of eribulin treatment on genome-scale DNA methylation patterns in TNBC cells. Following repeated treatment, The results showed that eribulin-induced changes in DNA methylation patterns evident in persister cells. Eribulin also affected the binding of transcription factors to genomic ZEB1 binding sites and regulated several cellular pathways, including ERBB and VEGF signaling and cell adhesion. Eribulin also altered the expression of epigenetic modifiers including DNMT1, TET1, and DNMT3A/B in persister cells. Data from primary human TNBC tumors supported these findings: DNMT1 and DNMT3A levels were altered by eribulin treatment in human primary TNBC tumors. Our results suggest that eribulin modulates DNA methylation patterns in TNBC cells by altering the expression of epigenetic modifiers. These findings have clinical implications for using eribulin as a therapeutic agent.
RBD-based high affinity ACE2 antagonist limits SARS-CoV-2 replication in upper and lower airways
Authors: Gagne Matthew , Flynn Barbara J. , Honeycutt Christopher Cole , Flebbe Dillon R. , Andrew Shayne F. , Provost Samantha J. , McCormick Lauren , Van Ry Alex , McCarthy Elizabeth , Todd John-Paul M. , Bao Saran , Teng I-Ting , Marciano Shir , Rudich Yinon , Li Chunlin , Pessaint Laurent , Dodson Alan , Cook Anthony , Lewis Mark G. , Andersen Hanne , Zahradník Jiří , Nason Martha C. , Foulds Kathryn E. , Kwong Peter D. , Roederer Mario , Schreiber Gideon , Seder Robert A. , Douek Daniel C.
Published: June 2023

SARS-CoV-2 has the capacity to evolve mutations to escape vaccine-and infection-acquired immunity and antiviral drugs. A variant-agnostic therapeutic agent that protects against severe disease without putting selective pressure on the virus would thus be a valuable biomedical tool. Here, we challenged rhesus macaques with SARS-CoV-2 Delta and simultaneously treated them with aerosolized RBD-62, a protein developed through multiple rounds ofin vitroevolution of SARS-CoV-2 RBD to acquire 1000-fold enhanced ACE2 binding affinity. RBD-62 treatment gave equivalent protection in upper and lower airways, a phenomenon not previously observed with clinically approved vaccines. Importantly, RBD-62 did not block the development of memory responses to Delta and did not elicit anti-drug immunity. These data provide proof-of-concept that RBD-62 can prevent severe disease from a highly virulent variant.
Microbiome Features Associated with Performance Measures in Non-Athletic and Athletic Individuals
Authors: Humińska-Lisowska Kinga , Zielińska Kinga , Mieszkowski Jan , Sawczyn Monika Michałowska- , Cięszczyk Paweł , Łabaj Paweł P , Wasąg Bartosz , Frączek Barbara , Grzywacz Anna , Kochanowicz Andrzej , Kosciolek Tomasz
Published: June 2023

The influence of human gut microbiota on health and disease is now well established. Therefore, it is not surprising that microbiome research has found applications within the sports community, hoping to improve health and optimize performance. Every comparison study found new species or pathways that were more enriched in elites than in sedentary controls. In addition, sport-specific and performance-level-specific microbiome features have been identified. However, the results remain inconclusive and indicate the need for further assessment. In our study, we conducted two interventions, anaerobic (Wingate Anaerobic Tests (WAnTs)) and aerobic (Bruce Treadmill Test), on fit non-athletic but physically active controls and athletic strength (training professional sports which increase anaerobic efforts such as weightlifting, powerlifting, and bodybuilding) and endurance (training professional sports which increase aerobic efforts such as race walking, long-distance running, or ski running) individuals to compare sport-specific and training-specific responses. While we did not identify any differences in alpha and beta diversity or significant differential abundance of microbiome components at baseline, we noted that one-third of the species identified were unique to either group. Longitudinal analysis of samples (pre- and post-intervention) revealed an abundance ofAlistipes communisin the strength group during the WAnT intervention and 88 species with notable differences between groups during the Bruce Test intervention. SparCC recognizedBifidobacterium longumandBifidobacterium adolescentis, short-chain fatty acid producers with probiotic properties, as species strongly associated with VO2max. Ultimately, we identified several taxa with different baseline abundances and longitudinal changes when comparing individuals based on their VO2max, average power, and maximal power parameters. Our results confirmed the health status of the individuals involved in the study, based on previous assumptions about microbiome health. Furthermore, our findings indicate that microbiome features are associated with better performance measures previously identified in elite athletes.
Repurposing The Dark Genome. III - Intronic Proteins
Authors: Garg Mohit , Dhar Pawan K.
Published: June 2023

Based 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

We 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

Expression 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

Wastewater 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

Objective

Recent 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.

Methods

Searches 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.

Results

A 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.

Conclusion

The 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

Background

Treatment 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.

Methods

Hospital 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.

Results

Geographic 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.

Conclusions

The 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

Scavenging 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

The 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

Thermal 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

The 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

With 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.