bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Association Between Human Immunodeficiency Virus and Bacterial Vaginosis and Metronidazole Treatment Failure for Trichomonas vaginalis
Authors: Frechtling Dan , Chopra Shubam , Ratnayake Aneeka , Kissinger Patricia J. 
Published: November 2023

Background

Trichomonas vaginalis (TV) is a common sexually transmitted infection. High rates of repeated infections have been observed, particularly among women living with human immunodeficiency virus (HIV). Trichomonas vaginalis frequently cooccurs with bacterial vaginosis (BV). The purpose of this study was to determine if coinfections with TV, BV, and HIV could lead to differential treatment failure outcomes.

Methods
Data were pooled from 2 prior randomized control trials comparing 2 g oral single-dose versus 500-mg twice daily oral 7-day dose metronidazole for the treatment of TV in HIV infected and HIV uninfected women. Trichomonas vaginalis rates 1-month postcompletion of treatment were compared by arm, HIV and BV status after removing those who had sexual reexposure, and/or did not complete their treatment.

Results
Data for 795 subjects were included in the study, of which 76 (9.6%) experienced treatment failure. In the final multivariable model, which included treatment dose, HIV status, and BV status, odds of treatment failure infection in the 7-day dose group were lower than the odds in the single dose group (odds ratio, 040; 95% confidence interval, 0.23–0.68). Treatment failure was lower in the multidose arm compared with single dose for both HIV-infected (4.0% vs 10.3%; P = 0.0568) and HIV-uninfected (7.3% vs 15.4%; P = 0.0037). Neither HIV nor BV was associated with higher treatment failure.

Conclusions
Human immunodeficiency virus infection and BV status did not significantly alter the rate of repeat infection for either single dose or 7-day dose metronidazole. Among all women, 7-day metronidazole lowered the odds of treatment failure.
DystoGen Compendium: A comprehensive resource of ACMG annotated movement disorder associated genetic variants
Authors: Saikia Bhaskar Jyoti , Gaharwar Utkarsh , Poojary Mukta , Mhaske Aditi , Paul Sangita , Kumar Mukesh , Sharma Srishti , Pandhare Kavita , Rastogi Shivanshi , Karal Medhavi , Rophina Mercy , Scaria Vinod , BK Binukumar 
Published: November 2023

AbstractPurposeIn recent years, the advent of high throughput sequencing techniques has led to the identification of a number of genetic variants across different genes that are associated with movement disorders. However, the under-appreciation of the variant spectrum in movement disorders and the lack of consolidated and systematic evidence-based annotation of these variants has long undermined the true potential of genomic approaches to expedite precision medicine.MethodsWe manually curated the genetic variants from a panel of 118 genes that have been associated with monogenic causes of movement disorders and systematically annotated them according to ACMG & AMP (American College of Medical Genetics and the Association of Molecular Pathologists) guidelines.ResultsData integration after systematic classification of variants according to ACMG & AMP guidelines showed 5118 pathogenic/likely pathogenic variants accounting for 18.03% of the total unique variants being annotated. This data and annotations are available in a comprehensive online compendium DystoGen.ConclusionTo the best of our knowledge, this is the most comprehensive compendium of genetic variants in movement disorders annotated as per the ACMG & AMP guidelines for pathogenicity. The compendium indexes 28377 variants along with a wide array of information including the geographical origin of the variant, global distribution, and population allele frequency. The resource has been made available in the URLhttps://clingen.igib.res.in/dystogen/.
Early-life immune activation is a vulnerability factor for adult epileptogenesis in neurofibromatosis type 1
Authors: Faidi Rania , Reid Aylin Y 
Published: November 2023

AbstractIntroductionPatients with Neurofibromatosis type 1 (NF1), the most common neurocutaneous disorder, can develop several neurological manifestations that include cognitive impairments and epilepsy over their lifetime. It is unclear why certain patients with NF1 develop these conditions while others do not. Early-life immune activation promotes later-life seizure susceptibility, neurocognitive impairments, and leads to spontaneous seizures in some animal models of neurodevelopmental disorders, but the central nervous system immune profile and the enduring consequences of early-life immune activation on the developmental trajectory of the brain in NF1 have not yet been explored. We tested the hypothesis that early-life immune activation promotes the development of spatial memory impairments and epileptogenesis in a mouse model of NF1.MethodsMale wild-type (WT) andNf1+/-mice received systemic lipopolysaccharide (LPS) or saline at post-natal day 10 and were assessed in adulthood for learning and memory deficits in the Barnes maze and underwent EEG recordings to look for spontaneous epileptiform abnormalities and susceptibility to challenge with pentylenetetrazole (PTZ).ResultsWhereas early-life immune activation by a single injection of LPS acutely elicited a comparable brain cytokine signature in WT andNf1+/-mice, it promoted spontaneous seizure activity in adulthood only in theNf1+/-mice. Early-life immune activation affected susceptibility to PTZ-induced seizures similarly in both WT andNf1+/-mice. There was no effect on spatial learning and memory regardless of mouse genotype.DiscussionOur findings suggestsecond-hitenvironmental events such as early-life immune activation may promote epileptogenesis in theNf1+/-mouse and may be a risk-factor for NF1-associated epilepsy.
Land, carbon and biodiversity data for supply chain impact calculations
Authors: Gassert Francis , Stela Biel , Palao Elena , Harfoot Mike 
Published: November 2023

AbstractMonitoring, halting and reversing land conversion is fundamental to meeting international biodiversity and climate targets, and agriculture is the major driver of land conversion. We present an open access set of global data for calculating land use change impacts of agricultural supply chains. These data, originally prepared for the LandGriffon service, include indicators of deforestation, conversion of natural ecosystems, greenhouse gas emissions, and loss of intact or high integrity ecosystems following international standards and guidelines for reporting and target setting in the agriculture, forestry, and land use sector. In order to assign impacts to agricultural production, we prepare data using a spatial adaptation of the statistical Land Use Change (sLUC) accounting approach distributing impact to human activities across the local area using a 50km radius. The results are high resolution global maps of impact per hectare of land occupation. These can then be combined with land footprint data, cropland extent, or productivity maps to calculate land use change related impacts for specific crop volumes sourced from specific regions. Carbon and deforestation results are validated against FAO statistics at the national level.
Confounding Fuels Misinterpretation in Human Genetics
Authors: Benning John W. , Carlson Jedidiah , Smith Olivia S. , Shaw Ruth G. , Harpak Arbel 
Published: November 2023

AbstractThe scientific literature has seen a resurgence of interest in genetic influences on human behavior and socioeconomic outcomes. Such studies face the central difficulty of distinguishing possible causal influences, in particular genetic and non-genetic ones. When confounding between possible influences is not rigorously addressed, it invites over- and misinterpretation of data. We illustrate the breadth of this problem through a discussion of the literature and a reanalysis of two examples. Clark (2023) suggested that patterns of similarity in social status between relatives indicate that social status is largely determined by one’s DNA. We show that the paper’s conclusions are based on the conflation of genetic and non-genetic transmission, such as wealth, within families. Song & Zhang (2024) posited that genetic variants underlying bisexual behavior are maintained in the population because they also affect risk-taking behavior, thereby conferring an evolutionary fitness advantage through increased sexual promiscuity. In this case, too, we show that possible explanations cannot be distinguished, but only one is chosen and presented as a conclusion. We discuss how issues of confounding apply more broadly to studies that claim to establish genetic underpinnings to human behavior and societal outcomes.
Unveiling Driver Modules in Lung Cancer: A Clustering-Based Gene-Gene Interaction Network Analysis
Authors: Taheri Golnaz , Szalai Marcell , Habibi Mahnaz , Papapetrou Panagiotis 
Published: November 2023

AbstractLung cancer, which is the leading cause of cancer-related death worldwide and is characterized by genetic changes and hetero-geneity, presents a significant treatment challenge. Existing approaches utilizing Machine Learning (ML) techniques for identifying driver modules lack specificity, particularly for lung cancer. This study addresses this limitation by proposing a novel method that combines gene-gene interaction network construction with ML-based clustering to identify lung cancer-specific driver modules. The methodology involves mapping biological processes to genes and constructing a weighted gene-gene interaction network to identify correlations within gene clusters. A clustering algorithm is then applied to identify potential cancer-driver modules, focusing on biologically relevant modules that contribute to lung cancer development. The results highlight the effectiveness and robustness of the clustering approach, identifying 110 unique clusters ranging in size from 4 to 10. These clusters surpass evaluation requirements and demonstrate significant relevance to critical cancer-related pathways. The identified driver modules hold promise for influencing future approaches to lung cancer diagnosis, prognosis, and treatment. This research expands our understanding of lung cancer and sets the stage for further investigations and potential clinical advancements.
Small-molecule binding and sensing with a designed protein family
Authors: Lee Gyu Rie , Pellock Samuel J. , Norn Christoffer , Tischer Doug , Dauparas Justas , Anischenko Ivan , Mercer Jaron A. M. , Kang Alex , Bera Asim , Nguyen Hannah , Goreshnik Inna , Vafeados Dionne , Roullier Nicole , Han Hannah L. , Coventry Brian , Haddox Hugh K. , Liu David R. , Yeh Andy Hsien-Wei , Baker David 
Published: November 2023

AbstractDespite transformative advances in protein design with deep learning, the design of small-molecule–binding proteins and sensors for arbitrary ligands remains a grand challenge. Here we combine deep learning and physics-based methods to generate a family of proteins with diverse and designable pocket geometries, which we employ to computationally design binders for six chemically and structurally distinct small-molecule targets. Biophysical characterization of the designed binders revealed nanomolar to low micromolar binding affinities and atomic-level design accuracy. The bound ligands are exposed at one edge of the binding pocket, enabling thede novodesign of chemically induced dimerization (CID) systems; we take advantage of this to create a biosensor with nanomolar sensitivity for cortisol. Our approach provides a general method to design proteins that bind and sense small molecules for a wide range of analytical, environmental, and biomedical applications.
Uromonitor®: Clinical Validation and Performance Assessment of a Urinary Biomarker for Recurrence Surveillance in Non-Muscle Invasive Bladder Cancer Patients
Authors: Ramos Pedro , Brás João Paulo , Dias Carolina , Bessa-Gonçalves Mafalda , Prazeres Hugo , Botelho Francisco , Silva João , Silva Carlos , Pacheco-Figueiredo Luís 
Published: November 2023

ABSTRACTIntroductionBladder cancer (BC) remains the most common malignancy of the urinary tract, with non-muscle invasive BC (NMIBC) representing the vast majority of bladder cancer patients. The current standard of care (SOC) follow-up in NMIBC patients demands an intensive schedule and requires costly and burdensome methods, driving the development of alternative, non-invasive, cost-effective methods that may complement or serve as substitutes to cystoscopy and cytology. Uromonitor® is a urine biomarker test that detects hotspot mutations in three genes (TERT, FGFR3, andKRAS) for the evaluation of disease recurrence. The aim of the current study was to assess its performance comparing it to the current SOC methods.Materials and MethodsA total of 528 NMIBC surveillances from 439 individual patients were enrolled from December 2021 to June 2023. All subjects underwent SOC methods and provided an urine sample before undergoing cystoscopy for Uromonitor® analysis. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for recurrence and compared to the gold-standard cystoscopy plus trans-urethral resection (TURBT) pathology.ResultsUromonitor® displayed a sensitivity of 87.2%, with only 6 recurrences failing to be detected by the urinary biomarker test, a specificity of 99.2%, a positive predictive value (PPV) of 93.2% and a negative predictive value (NPV) of 98.8%. Cystoscopy showed a total of 22 (31,88%) false positives not confirmed by TURBT, while Uromonitor® presented only 3 positive tests where no suspected lesions were found in cystoscopy. Sensitivity, specificity and NPV values for Uromonitor® also remained high across all NMIBC grades and stages.ConclusionIn the present study, we confirmed that the Uromonitor® biomarker test represents a reliable tool in the detection of NMIBC recurrence in patients undergoing routine surveillance, regardless of stage and grade. It offers either an alternative or a complement to the current SOC methods, providing rapid results and a non-invasive option, potentially improving patients’ quality of life and helping reduce the economic burden of NMIBC follow-up. To our knowledge, this is the largest single-center study assessing Uromonitor®’s performance and thus validating its usefulness in clinical practice.
COMPARISON BETWEEN SANGER, ILLUMINA AND NANOPORE SEQUENCING EVIDENCING INTRA-HOST VARIATION OF FELINE LEUKEMIA VIRUS THAT INFECTS DOMESTIC CATS
Authors: Castillo-Aliaga Cristobal , Blanchard Adam Mark , Castro-Seriche Susana , Hidalgo-Hermoso Ezequiel , Jerez-Morales Alonso , Loose Matthew W , Tarlinton Rachael E 
Published: November 2023

ABSTRACTKnowledge of Feline Leukemia Virus (FeLV) sequence variation has mainly been developed using Sanger sequencing methods. However, advances in next generation sequencing methods and their broad use in laboratories has been changing our understanding of viral genetics. FeLV sequencing has specific complications with the presence of both exogenous (exFeLV) and endogenous (enFeLV) virus with frequent recombination between them, limiting sequencing approaches. Here we report an FeLV-A and FeLV-B amplicon-based comparison between Sanger, Illumina, and Oxford Nanopore sequencing methods in Chilean domestic cats. We analysed the hypervariable envelope gene, where a higher number of variants as well as recombination with endogenous strains occurs. We detected multiple variants and viral quasispecies infecting the cats. We compared these three methods to evaluate the advantages and disadvantages between them. Although the Sanger method is highly reliable, it showed a high fail rate (many amplicons did not produce useable sequence) and the sequences obtained showed artificial sequence clustering when compared with the NGS methods. Illumina sequencing showed a lower error rate but could not discriminate between exogenous and endogenous viruses. Finally, Oxford Nanopore (MinION) sequencing could successfully detect low-abundance sequences and discriminate between FeLV-A and FeLV-B sequences, although its higher error-rate requires caution in interpretation of the results. Our results indicate advantages and disadvantages for each method, with the purpose of sequencing needing to be considered in the choice of method. Results of large viral phylogenetic trees combing sequences derived from mixed sequencing methods, such as those combining historical and contemporary sequencing need to be considered with some caution as artificial clustering by sequencing method may occur.
Human promoter directionality is determined by transcriptional initiation and the opposing activities of INTS11 and CDK9
Authors: Eaton Joshua D , Board Jessica , Davidson Lee , Estell Chris , West Steven 
Published: November 2023

ABSTRACTRNA polymerase II (RNAPII) transcription initiates bidirectionally at many human protein-coding genes. Sense transcription usually dominates and leads to messenger RNA production, whereas antisense transcription rapidly terminates. The basis for this directionality is not fully understood. Here, we show that sense transcriptional initiation is more efficient than in the antisense direction, which establishes initial directionality. After transcription begins, the opposing functions of Integrator (INTS11) and cyclin-dependent kinase 9 (CDK9) maintain directionality. Specifically, INTS11 terminates antisense transcription, whereas sense transcription is protected from INTS11-dependent attenuation by CDK9 activity. Strikingly, INTS11 attenuates transcription in both directions upon CDK9 inhibition, and the engineered recruitment of CDK9 desensitises transcription to INTS11. Therefore, the preferential initiation of sense transcription and the opposing activities of CDK9 and INTS11 explain mammalian promoter directionality.
Rab27 in tick extracellular vesicle biogenesis and infection
Authors: Butler L. Rainer , Singh Nisha , Marnin Liron , Valencia Luisa M. , O’Neal Anya J. , Cabrera Paz Francy E. , Shaw Dana K. , Oliva Chavez Adela S. , Pedra Joao H.F. 
Published: November 2023

AbstractBackgroundThe blacklegged tick,Ixodes scapularis, transmits most vector-borne diseases in the United States. It vectors seven pathogens of public health relevance, including the emerging human pathogenAnaplasma phagocytophilum. Nevertheless, it remains critically understudied when compared to other arthropod vectors.I. scapularisreleases a variety of molecules that assist in the modulation of host responses. Recently, it was found that extracellular vesicles (EVs) carry several of these molecules and may impact microbial transmission to the mammalian host. EV biogenesis has been studied in mammalian systems and is relatively well understood, but the molecular players important for the formation and secretion of EVs in arthropods of public health relevance remain elusive. RabGTPases are among the major molecular players in mammalian EV biogenesis. They influence membrane identity and vesicle budding, uncoating, and motility.MethodsUsing BLAST, anin-silicopathway for EV biogenesis in ticks was re-constructed. We identified Rab27 for further study. EVs were collected from ISE6 tick cells after knocking downrab27to examine its role in tick EV biogenesis.I. scapularisnymphs were injected with small interfering RNAs to knock downrab27then fed on naïve andA. phagocytophiluminfected mice to explore the importance ofrab27in tick feeding and bacterial acquisition.ResultsOur BLAST analysis identified several of the proteins involved in EV biogenesis in ticks, including Rab27. We show that silencingrab27inI. scapularisimpacts tick fitness. Additionally, ticks acquire lessA. phagocytophilumafterrab27silencing. Experiments in the tick ISE6 cell line show that silencing ofrab27causes a distinct range profile of tick EVs, indicating that Rab27 is needed to regulate EV biogenesis.ConclusionsRab27 is needed for successful tick feeding and may be important for acquiringA. phagocytophilumduring a blood meal. Additionally, silencingrab27in tick cells results in a shift of extracellular vesicle size. Overall, we have observed that Rab27 plays a key role in tick EV biogenesis and the tripartite interactions among the vector, the mammalian host, and a microbe it encounters.
Learning about what is most important: incorporating values into the design of learning experiences
Authors: Campana Kathleen , Kociubuk Jacqueline , Mills J. Elizabeth , Martin Michelle H. 
Published: November 2023

Purpose
The purpose of this study was to bring library practitioners and researchers together to develop two co-designed tools for helping library practitioners gain a more holistic understanding of families in underserved groups and identify their values with the goal of developing more relevant learning experiences for them. The co-designed tools were then tested with Master’s of Library and Information Science (MLIS) students at two universities, whose feedback yielded several valuable findings and informed revisions to the tools.

Design/methodology/approach
A participatory, design-based approach was used throughout the study, both with engaging library practitioners in the co-design of different tools and processes introduced in the Toolkit, and to help MLIS students and library practitioners test the tools and provide feedback on the tool revisions.

Findings
Students indicated that the tools helped them develop a deeper understanding of underserved groups and their values and gave the students the time and space to reflect on their understanding of the socio-cultural and value contexts of their communities and the values they hold.

Originality/value
This study can help libraries more effectively design strengths-based learning experiences that are meaningful and relevant to underserved groups and their values, particularly for children and families from underserved communities.
Resource sustainability in the water, energy and food nexus: role of technological innovation
Authors: David Love Opeyemi , Nwulu Nnamdi Ikechi , Aigbavboa Clinton Ohis , Adepoju Omoseni Oyindamola 
Published: November 2023

Purpose
This paper aims to examine the role of technological Innovation in ensuring resource sustainability in the water, energy and food (WEF) nexus, as there exists a shortage of statistical research on the extent of the influence of technological Innovation on the WEF nexus.

Design/methodology/approach
The study used a quantitative research method, using a well-structured questionnaire to collect data from management staff in the WEF departments in South Africa. The collected data were analyzed by using mean score ranking, exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) for structural equation modelling (SEM).

Findings
The findings show that the technological process of technological innovation is significant for resource sustainability. The result also showed that technological innovations directly and statistically significantly affect WEF nexus. The EFA resulted in three components of WEF nexus product innovation, WEF nexus process innovation and WEF nexus novel innovations. Furthermore, the CFA and SEM analysis reveals that six technological innovation indicators influence the sustainability of the nexus: smart water metering technology, smart metering technology, food quality monitoring technology, agricultural technology solutions, new technological design and eco-friendly WEF products.

Originality/value
The sustainability of these three inevitable resources for man’s survival is dependent on technological innovations, and this study has shown the major categories of innovations needed, thus establishing a pathway for engineering design.