bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design of a multi-epitope-based vaccine candidate against Bovine Genital Campylobacteriosis using a reverse vaccinology approach
Authors: Silva Marta Filipa , Pereira Gonçalo , Mateus Luísa , da Costa Luís Lopes , Silva Elisabete 
Published: April 2024

Abstract
Background
Bovine Genital Campylobacteriosis (BGC), a worldwide distributed venereal disease caused by Campylobacter fetus subsp. venerealis (Cfv), has a relevant negative economic impact in cattle herds. The control of BGC is hampered by the inexistence of globally available effective vaccines. The present in silico study aimed to develop a multi-epitope vaccine candidate against Cfv through reverse vaccinology.

Results
The analysis of Cfv strain NCTC 10354 proteome allowed the identification of 9 proteins suitable for vaccine development. From these, an outer membrane protein, OmpA, and a flagellar protein, FliK, were selected for prediction of B-cell and T-cell epitopes. The top-ranked epitopes conservancy was assessed in 31 Cfv strains. The selected epitopes were integrated to form a multi-epitope fragment of 241 amino acids, which included 2 epitopes from OmpA and 13 epitopes from FliK linked by GPGPG linkers and connected to the cholera toxin subunit B by an EAAAK linker. The vaccine candidate was predicted to be antigenic, non-toxic, non-allergenic, and soluble upon overexpression. The protein structure was predicted and optimized, and the sequence was successfully cloned in silico into a plasmid vector. Additionally, immunological simulations demonstrated the vaccine candidate’s ability to stimulate an immune response.

Conclusions
This study developed a novel vaccine candidate suitable for further in vitro and in vivo experimental validation, which may become a useful tool for the control of BGC.
Reduced mortality associated with pulmonary embolism response team consultation for intermediate and high-risk pulmonary embolism: a retrospective cohort study
Authors: Gardner Tiffany A. , Fuher Alexandra , Longino August , Sink Eric M. , Jurica James , Park Bryan , Lindquist Jonathan , Bull Todd M. , Hountras Peter 
Published: April 2024

Abstract
Background
The management of acute pulmonary embolism (PE) has become increasingly complex with the expansion of advanced therapeutic options, resulting in the development and widespread adoption of multidisciplinary Pulmonary Embolism Response Teams (PERTs). Much of the literature evaluating the impact of PERTs has been limited by pre- postimplementation study design, leading to confounding by changes in global practice patterns over time, and has yielded mixed results. To address this ambiguity, we conducted a retrospective cohort study to evaluate the impact of the distinct exposures of PERT availability and direct PERT consultation.

Methods
At a single tertiary center, we conducted propensity-matched analyses of hospitalized patients with intermediate or high-risk PE. To assess the impact of PERT availability, we evaluated the changes in 30-day mortality, hospital length of stay (HLOS), time to therapeutic anticoagulation (TAC), in-hospital bleeding complications, and use of advanced therapies between the two years preceding and following PERT implementation. To evaluate the impact of direct PERT consultation, we conducted the same analyses in the post-PERT era, comparing patients who did and did not receive PERT consultation.

Results
Six hundred eighty four patients were included, of which 315 were pre-PERT patients. Of the 367 postPERT patients, 201 received PERT consultation. For patients who received PERT consultation, we observed a significant reduction in 30-day mortality (5% vs 20%, OR 0.38, p = 0.0024), HLOS.
(-5.4 days, p < 0.001), TAC (-0.25 h, p = 0.041), and in-hospital bleeding (OR 0.28, p = 0.011).
These differences were not observed evaluating the impact of PERT presence in pre-vs postimplementation eras.

Conclusions
We observed a significant reduction in 30-day mortality, hospital LOS, TAC, and in-hospital bleeding complications for patients who received PERT consultation without an observed difference in these metrics when comparing the pre- vs post-implementation eras. This suggests the benefits stem from direct PERT involvement rather than the mere existence of PERT. Our data supports that PERT consultation may provide benefit to patients with acute intermediate or high-risk PE and can be achieved without a concomitant increase in advanced therapies.
Structural determinants for activation of the Tau kinase CDK5 by the serotonin receptor 5-HT7R
Authors: Ackmann Jana , Brüge Alina , Gotina Lizaveta , Lim Sungsu , Jahreis Kathrin , Vollbrecht Anna-Lena , Kim Yun Kyung , Pae Ae Nim , Labus Josephine , Ponimaskin Evgeni 
Published: April 2024

Abstract
Background
Multiple neurodegenerative diseases are induced by the formation and deposition of protein aggregates. In particular, the microtubule-associated protein Tau leads to the development of so-called tauopathies characterized by the aggregation of hyperphosphorylated Tau within neurons. We recently showed that the constitutive activity of the serotonin receptor 7 (5-HT7R) is required for Tau hyperphosphorylation and aggregation through activation of the cyclin-dependent kinase 5 (CDK5). We also demonstrated physical interaction between 5-HT7R and CDK5 at the plasma membrane suggesting that the 5-HT7R/CDK5 complex is an integral part of the signaling network involved in Tau-mediated pathology.

Methods
Using biochemical, microscopic, molecular biological, computational and AI-based approaches, we investigated structural requirements for the formation of 5-HT7R/CDK5 complex.

Results
We demonstrated that 5-HT7R domains responsible for coupling to Gs proteins are not involved in receptor interaction with CDK5. We also created a structural model of the 5-HT7R/CDK5 complex and refined the interaction interface. The model predicted two conserved phenylalanine residues, F278 and F281, within the third intracellular loop of 5-HT7R to be potentially important for complex formation. While site-directed mutagenesis of these residues did not influence Gs protein-mediated receptor signaling, replacement of both phenylalanines by alanine residues significantly reduced 5-HT7R/CDK5 interaction and receptor-mediated CDK5 activation, leading to reduced Tau hyperphosphorylation and aggregation. Molecular dynamics simulations of 5-HT7R/CDK5 complex for wild-type and receptor mutants confirmed binding interface stability of the initial model.

Conclusions
Our results provide a structural basis for the development of novel drugs targeting the 5-HT7R/CDK5 interaction interface for the selective treatment of Tau-related disorders, including frontotemporal dementia and Alzheimer’s disease.
Bone health and physical activity in adolescents with juvenile idiopathic arthritis: a cross-sectional case-control study
Authors: Vasil Egi , M. Nesbitt Colleen , Toomey Clodagh , Kuntze Gregor , Esau Shane , A. Emery Carolyn , Gabel Leigh 
Published: April 2024

Abstract
Background
Adolescents with juvenile idiopathic arthritis (JIA) tend to engage in less physical activity than their typically developing peers. Physical activity is essential for bone development and reduced physical activity may detrimentally effect bone health. Thus, we examined differences in total body bone mineral content (BMC) and areal bone mineral density (aBMD) between adolescents with JIA and adolescent controls without JIA. We also examined associations between moderate-to-vigorous physical activity (MVPA), lean mass, and bone outcomes.

Methods
Participants included 21 adolescents with JIA (14 females, 7 males) and 21 sex- and age-matched controls aged 10–20 years. Assessments included: height; weight; triple-single-leg-hop distance (TSLH); MVPA by accelerometry; and total body BMC, aBMD, and lean mass measured using dual X-ray absorptiometry. Height-adjusted z-scores were calculated for BMC and aBMD and used for all analyses. Multiple linear mixed effects models examined group differences in BMC and aBMD, adjusting for sex, maturity, MVPA, TSLH, and lean mass. Participants clusters, based on sex and age (within 18 months), were considered random effects.

Results
Adolescents with JIA had lower total body aBMD z-scores [β (95% CI); -0.58 (-1.10 to -0.07), p = 0.03] and BMC z-scores [-0.47 (-0.91 to -0.03), p = 0.04] compared with controls. Mean daily MVPA was 22.0 min/day lower in adolescents with JIA than controls; however, MVPA was not associated with aBMD [-0.01 (-0.01 to 0.01), p = 0.32] or BMC [0.00 (-0.01 to 0.00), p = 0.39]. Lean mass was positively associated with aBMD [0.05 (0.01 to 0.09) g/cm2, p = 0.03] and BMC [0.06 (0.03 to 0.10) g, p < 0.001].

Conclusion
Adolescents with JIA had lower total body aBMD and BMC compared with sex- and age-matched controls without JIA. Group differences in bone outcomes were not associated with the lower MVPA participation of adolescents with JIA. Despite this, physical activity should still be encouraged as it promotes physical well-being.
A quantitative and qualitative analysis of patient group narratives suggests common biopsychosocial red flags of undiagnosed rare disease
Authors: Al-Attar Mariam , Butterworth Sondra , McKay Lucy 
Published: April 2024

Abstract
Background
The ‘diagnostic odyssey’ is a common challenge faced by patients living with rare diseases and poses a significant burden for patients, their families and carers, and the healthcare system. The diagnosis of rare diseases in clinical settings is challenging, with patients typically experiencing a multitude of unnecessary tests and procedures. To improve diagnosis of rare disease, clinicians require evidence-based guidance on when their patient may be presenting with a rare disease. This study aims to identify common experiences amongst patients with rare diseases, to inform a series of ‘red flags’ that can aid diagnosis of rare diseases in non-specialist settings.
A questionnaire was developed by Medics for Rare Diseases, informed by the experiences of clinicians, rare disease patients and patient advocates, and was shared with UK-based rare disease patient groups. Study participants were engaged via social media platforms, blogs and email newsletters of three umbrella rare disease organisations. The questionnaire, comprising 22 questions, was designed to identify typical experiences relating to physical and psychosocial manifestations and presentation of disease, patient interactions with healthcare providers, and family history.

Results
Questionnaire responses were received from 79 different rare disease patient groups and the common experiences identified were used to inform seven red flags of rare disease: multi-system involvement (3 or more); genetic inheritance pattern; continued presentation throughout childhood and adulthood; difficulties at school, especially relating to absences, difficulty participating in physical education and experiences of bullying or social isolation; multiple specialist referrals; extended period with unexplained symptoms; and misdiagnosis. In light of the red flags identified, recommendations for primary care and education settings have been proposed, focusing on the need for holistic assessment and awareness of both physical and psychosocial factors.

Conclusions
This study identified key commonalities experienced by patients with rare disease across physical and psychosocial domains, in addition to understanding patients’ history and experiences with healthcare providers. These findings could be used to develop a clinical decision‑making tool to support non-specialist practitioners to consider when their patient may have an undiagnosed rare condition, which may minimise the challenges of the ‘diagnostic odyssey’ and improve the patient experience.
Cervicovaginal microbiota: a promising direction for prevention and treatment in cervical cancer
Authors: Shen Jie , Sun Hao , Chu Jing , Gong Xiaodi , Liu Xiaojun 
Published: April 2024

AbstractCervical cancer is a common malignancy in women, with high incidence rate and mortality. Persistent infection of high-risk human papillomavirus (HPV) is the most important risk factor for cervical cancer and precancerous lesions. Cervicovaginal microbiota (CVM) plays an essential role in the defense of HPV infections and prevention of subsequent lesions. Dominance of Lactobacillus is the key of CVM homeostasis, which can be regulated by host, exogenous and endogenous factors. Dysbiosis of CVM, including altered microbial, metabolic, and immune signatures, can contribute to persist HPV infection, leading to cervical cancer. However, there is no evidence of the causality between CVM and cervical cancer, and the underlying mechanism remains unexplored. Considering the close correlation between CVM dysbiosis and persistent HPV infection, this review will overview CVM, its role in cervical cancer development and related mechanisms, and the prospects for therapeutic applications.
Minimum information and guidelines for reporting a multiplexed assay of variant effect
Authors: Claussnitzer Melina , Parikh Victoria N. , Wagner Alex H. , Arbesfeld Jeremy A. , Bult Carol J. , Firth Helen V. , Muffley Lara A. , Nguyen Ba Alex N. , Riehle Kevin , Roth Frederick P. , Tabet Daniel , Bolognesi Benedetta , Glazer Andrew M. , Rubin Alan F. 
Published: April 2024

AbstractMultiplexed assays of variant effect (MAVEs) have emerged as a powerful approach for interrogating thousands of genetic variants in a single experiment. The flexibility and widespread adoption of these techniques across diverse disciplines have led to a heterogeneous mix of data formats and descriptions, which complicates the downstream use of the resulting datasets. To address these issues and promote reproducibility and reuse of MAVE data, we define a set of minimum information standards for MAVE data and metadata and outline a controlled vocabulary aligned with established biomedical ontologies for describing these experimental designs.
Exploring relationship of poor sleeping habits with prenatal stress among pregnant women in Pakistan: a cross-sectional study
Authors: Waqas Ahmed , Siddique Irfan , Ahsen Mehroz , Zubair Muhammad , Naeem Mehak , Memon Aamir Raoof , Naveed Sadiq 
Published: April 2024

AbstractObjectivePregnancy is a complex phenomenon accompanied by biological, physiological and psychosocial changes for a mother. It is also regarded as a stressful life event where a woman’s role, identity and interpersonal relationships are restructured. The present study from Pakistan explores the association of sleep quality and poor sleeping habits with prenatal stress using Pittsburgh Sleep quality Index.ResultsThere were a total of 516 women (mean age = 29.82 years), with more than half reporting poor sleep quality. Ethnically, a majority (395, 76.6%) were natives of the Punjab province while rest were non-natives. A high percentage of respondents reported poor subjective sleep quality (22.1%), sleep latency (44.1%), habitual sleep efficiency (27.5%), sleep disturbance (30.1%), use of medications (7.1%) and daytime dysfunction (29.5%). According to logistic regression analysis, respondents with poor sleep quality were 2.24 (95% CI = 1.55–3.22,P < 0.001) times more likely to have high stress levels (P < 0.001).
Effect of soil contamination and additives on fermentative profile, microbial community and iron bioaccessibility of alfalfa silage
Authors: Jia Tingting , Luo Ying , Wang Lei , Yu Zhu 
Published: April 2024

Abstract
Background
During alfalfa harvesting and preservation, it is important to minimize losses and preserve dry matter and nutrients. Soil contamination of alfalfa forage is a common issue that occurs during the ensiling process. Soil contamination can adversely influence the quality of silage, potentially altering the fermentation process, microbial composition, and iron content.

Results
In this study, different levels of soil (0, 1.5% or 7.5% contamination on a wet basis; silt loam soil) and two types of additives (LP, Lactobacillus plantarum inoculant alone; MLP, combination addition of molasses and Lactobacillus plantarum) were added to alfalfa and subjected to anaerobic fermentation for 45 days to evaluate the iron content as well as the alpha diversity and relative abundance of bacterial and fungal communities. Soil-contaminated alfalfa contained lower levels of LA (14.2–41.8 g kg−1 DM) and higher levels of AN (50.0–156.4 g kg−1 DM) compared to uncontaminated alfalfa. Soil contamination of alfalfa forage increased the abundance of Clostridia, Actinobacteria, and Alphaproteobacteria in silage. The application of LP or MLP in soil-contaminated silage increased the abundance of Lactobacillus and inhibited the growth of Enterococcus faecium, Pediococcus pentosaceus, unclassified_f_Enterobacteriaceae, and Weissella cibaria. In addition, as the level of soil contamination increased, both the total and bioaccessible iron contents in alfalfa silage increased. The dominant bacteria Lactobacillus plantarum exhibited a positive relationship with LA and bioaccessible iron contents and a negative relationship with pH, AN and BA. The dominant fungi Neocosmospora rubicola showed a positive relationship with total iron, BA, AN and pH.

Conclusions
Soil contamination of alfalfa increased the abundance of Clostridia, Actinobacteria, and Alphaproteobacteria and it also increased the total and bioaccessible iron content in silage. The addition of LP and MLP improved the fermentation quality of soil-contaminated silage by increasing LA production and reducing the relative abundance of Enterococcus faecium, Pediococcus pentosaceus, unclassified_f_Enterobacteriaceae, and Weissella cibaria.

Graphical Abstract
Knowledge Translation Task Force for core measures clinical practice guideline: a short report on the process and utilization
Authors: Bland Marghuretta D. , Moore Jennifer L. , Anderl Elizabeth , Eikenberry Megan , McCarthy Arlene , Olivier Geneviève N. , Rice Tracy , Siles Amelia , Zeleznik Hallie , Romney Wendy 
Published: April 2024

Abstract
Background
As part of the 2018 Clinical Practice Guideline (CPG): A Core Set of Outcome Measures for Adults with Neurologic Conditions Undergoing Rehabilitation, a Knowledge Translation (KT) Task Force was convened. The purpose of this short report was to (1) demonstrate the potential impact of a CPG KT Task Force through a practical example of efforts to implement a CPG into neurologic physical therapy practice and (2) describe the process to convene a KT Task Force and develop products (KT Toolkit) to facilitate implementation of the CPG.

Methods
To describe the process used by the KT Task Force to develop and review a KT Toolkit for implementation of the CPG.

Results
Utilizing the Knowledge-To-Action Cycle framework, eight tools were developed as part of the KT Toolkit and are available with open access to the public. Findings indicate that the Core Outcome Measures Homepage, which houses the KT Toolkit, has had greater than 70,000 views since its publication.

Conclusions
This short report serves as an example of the efforts made to implement a CPG into physical therapy practice. The processes to facilitate KT and the tools developed can inform future implementation efforts and underscore the importance of having a KT Task Force to implement a CPG. Moving forward, KT Task Forces should be convened to implement new or revised guidelines.

Trial registration
N/A.
Exploring the co-occurrence of depression, anxiety and insomnia symptoms, diagnoses and treatments in primary care: observational study using UK primary care data
Authors: Nimmons Danielle , Bazo-Alvarez Juan Carlos , Avgerinou Christina , Hayes Joseph , Osborn David , Cooper Claudia , Petersen Irene , Walters Kate 
Published: April 2024

BackgroundDepression, anxiety and insomnia often co-occur. However, there is a lack of research regarding how they cluster and how this is related to medication used to treat them.AimsTo describe the frequencies and associations between depression, anxiety and insomnia, and treatment for these conditions in primary care.MethodA retrospective cohort study using UK electronic primary care records. We included individuals aged between 18 and 99 years old with one or more records suggesting they had a diagnosis, symptom or drug treatment for anxiety, depression or insomnia between 2015 and 2017. We report the conditional probabilities of having different combinations of diagnoses, symptoms and treatments recorded.ResultsThere were 1 325 960 records indicative of depression, anxiety or insomnia, for 739 834 individuals. Depression was the most common condition (n = 106 117 records), and SSRIs were the most commonly prescribed medication (n = 347 751 records). Overall, individuals with a record of anxiety were most likely to have co-occurring symptoms and diagnoses of other mental health conditions. For example, of the individuals with a record of generalised anxiety disorder (GAD), 24% also had a diagnosis of depression. In contrast, only 0.6% of those who had a diagnosis of depression had a diagnosis or symptom of GAD. Prescribing of more than one psychotropic medication within the same year was common. For example, of those who were prescribed an SNRI (serotonin-norepinephrine reuptake inhibitor), 40% were also prescribed an SSRI (selective serotonin reuptake inhibitor).ConclusionsThe conditional probabilities of co-occurring anxiety, depression and insomnia symptoms, diagnoses and treatments are high.
Comparative Anatomic Analysis of Neuronavigated Transmastoid-Infralabyrinthine Approaches for Jugular Fossa Pathologies: Short Anterior Rerouting Versus Nonrerouting and Tailored Nonrerouting Techniques
Authors: Cinibulak Zafer , Martinez Santos Jaime L. , Poggenborg Jörg , Schliwa Stefanie , Ostovar Nima , Keles Abdullah , Baskaya Mustafa K. , Nakamura Makoto 
Published: April 2024

BACKGROUND AND OBJECTIVES:
Access to the jugular fossa pathologies (JFPs) via the transmastoid infralabyrinthine approach (TI-A) using the nonrerouting technique (removing the bone anterior and posterior to the facial nerve while leaving the nerve protected within the fallopian canal) or with the short-rerouting technique (rerouting the mastoid segment of the facial nerve anteriorly) has been described in previous studies. The objective of this study is to compare the access to Fisch class C lesions (JFPs extending or destroying the infralabyrinthine and apical compartment of the temporal bone with or without involving the carotid canal) between the nonrerouting and the short-rerouting techniques. Also, some tailored steps to the nonrerouting technique (NR-T) were outlined to enhance access to the jugular fossa (JF) as an alternative to the short-rerouting technique.

METHODS:
Neuronavigated TI-A was performed using the nonrerouting, tailored nonrerouting, and short-rerouting techniques on both sides of 10 human head specimens. Exposed area, horizontal distance, surgical freedom, and horizontal angle were calculated using vector coordinates for nonrerouting and short-rerouting techniques.

RESULTS:
The short-rerouting technique had significantly higher values than the NR-T (P < .01) for the exposed area (169.1 ± SD 11.5 mm2 vs 151.0 ± SD 12.4 mm2), horizontal distance (15.9 ± SD 0.6 mm vs 10.6 ± SD 0.5 mm2), surgical freedom (19 650.2 ± SD 722.5 mm2 vs 17 233.8 ± SD 631.7 mm2), and horizontal angle (75.2 ± SD 5.1° vs 61.7 ± SD 4.6°). However, adding some tailored steps to the NR-T permitted comparable access to the JF.

CONCLUSION:
Neuronavigated TI-A with the short-rerouting technique permits wider access to the JF compared with the NR-T. However, the tailored NR-T provides comparable access to the JF and may be a better option for class C1 and selected class C2 and C3 JFPs.