bluuebunny/crossref_metadata_2025 huggingface dataset:
Pitch Types and Their Influence on Elbow Varus Torque and Spin Rate in Professional Baseball Pitchers
Authors: Hodakowski Alexander J. , Dowling Brittany , Streepy John T. , Olmanson Bjorn , Schmitt Logan , Richard Marc J. , Verma Nikhil N. , Garrigues Grant E.
Published: January 2025

Background:

Elbow injuries are prevalent among professional baseball pitchers as nearly 25% undergo ulnar collateral ligament reconstruction. Pitch type, ball velocity, and spin rate have been previously hypothesized to influence elbow varus torque and subsequent risk of injury, but existing research is inconclusive.

Purpose:

To examine elbow varus torque, cumulative torque, and loading rate within professional pitchers throwing fastball, curveball, change-up, and slider pitches, as well as to identify potential influences of ball spin on the elbow.

Study Design:

Descriptive laboratory study.

Methods:

A total of 31 professional pitchers (mean height, 189.0 ± 5.7 cm; mean weight, 91.7 ± 8.2 kg) were analyzed using motion capture (480 Hz) and TrackMan while throwing a full bullpen of pitches consisting of fastballs, curveballs, change-ups, and sliders. Elbow varus torque, loading rate, cumulative torque, and spin rate were calculated and analyzed using linear regression to establish within-player and mixed-effects models to establish between-player differences in pitch types.

Results:

Analyzed by individual pitcher, fastballs exhibited significantly higher mean ball velocity and elbow varus torque (40.4 ± 0.6 m/s; 90.1 ± 3.5 N·m) (all P < .001) and peak elbow varus torque compared with curveballs (33.4 ± 0.6 m/s; 87.5 ± 2.7 N·m), change-ups (36.4 ± 0.6 m/s; 81.3 ± 2.4 N·m), and sliders (36.2 ± 0.7 m/s; 87.7 ± 2.7 N·m). Fastball pitches had a significantly greater cumulative elbow varus torque and loading rate compared to all pitch types within a pitcher ( P < .001). Despite the lower peak elbow varus torque and loading rate, the change-up pitch had the second highest cumulative torque. Curveballs were found to have the lowest cumulative elbow varus torque. No significant relationship was found between spin rates and elbow varus torque across pitch types.

Conclusion:

Fastballs produced the greatest ball velocity, peak elbow varus torque, loading rate, and cumulative torque among the 4 pitch types analyzed in professional pitchers. Although spin rate has become a popular topic in modern pitching strategies and analyses, this study found no significant relationship between spin rate and elbow varus torque across pitch types, suggesting that spin rate alone may not be a reliable predictor of elbow torque or injury.

Clinical Relevance:

These findings suggest that pitch type, rather than spin rate, should be considered when assessing risk of elbow injuries in professional pitchers.
Reconfiguration of the Capitalist World-System: From Oligarchy to Fascism
Authors: Demirel Ege
Published: January 2025

There has been an organic crisis in terms of governing the world-system. The United States and its vassal states (e.g. the European Union countries, the Commonwealth countries, and Japan) have been struggling to maintain the status quo of the capitalist world-system. Under these circumstances, it appears that the bourgeoisie of the core may have attempted to introduce a new project to preserve the status quo, which can be identified as fascism. For many years, there has been a liberal democracy, which is essentially an oligarchy. However, over the years, liberal democracy has deteriorated and failed to respond to the needs of the bourgeoisie of the core. This has led to the possibility of fascism being considered as a solution to the structural/systemic crisis of the capitalist world-system. Given these developments, it has been analyzed the situation of fascism in the 21st century in terms of the capitalist world-system in this study.
Mandibular Reconstruction With a Patient-Specific Implant Following Surgical Excision of an Acanthomatous Ameloblastoma in a Dog
Authors: Sampaio Erica , Perry Andrew , Freeman Alix
Published: January 2025

Canine acanthomatous ameloblastoma (CAA) is an invasive benign epithelial odontogenic tumour most commonly affecting the mandible of large breed dogs. To the author's knowledge, this report describes the first computer-aided design patient-specific implant (PSI) that has been placed for a critical sized bone defect in mandibular reconstruction of a dog in the UK. The aim was to restore mandibular stability using a regenerative approach combining a titanium locking plate and compression-resistant matrix infused with recombinant human bone morphogenetic protein-2 (rhBMP-2) to bridge the 85 mm mandibular defect created by a segmental mandibulectomy. A 7-year-old neutered crossbreed dog with a focal 60 × 45 × 30 mm3 mildly ulcerated mass on the left mandible was presented. Histopathology confirmed a CAA. A left segmental mandibulectomy was followed by a delayed (secondary) reconstructive surgery. The porous titanium scaffold was manufactured from the first computed tomography (CT) scan and was designed with a channel to be filled with a compression-resistant osteoconductive resorbable sponge material infused with an osteoinductive solution containing rhBMP-2. Follow-up CT scans were performed on the day of the second surgery, and 4 and 12 months after the second surgery. Filling the porous titanium scaffold with an osteoconductive strip mixed with rhBMP-2 promoted bone remodeling and stimulated partial osseous integration of the implant; however there was no evidence of complete osteosynthesis bridging the bone defect as initially expected. Twelve months after reconstruction, dorsal longitudinal implant exposure necessitated PSI explantation. This study reflects a recent surgical therapeutic approach that can be utilised to reconstruct mandibles. PSIs can help reduce the known postoperative complications inherent to large gap mandibulectomies. Therefore, their use has the potential to improve patient welfare by restoring mandibular and temporomandibular joint (TMJ) stability, preventing mandibular drift, improving prehension, and reducing the risk of secondary TMJ degenerative disease and pain. It is likely that some implant design refinement is required to achieve better success rates for these challenging cases.
What Time Will It Be? A Comprehensive Literature Review on Daylight Saving Time
Authors: Neumann Philipp , von Blanckenburg Korbinian
Published: January 2025

Daylight saving time (DST) affects millions of people in various everyday situations and is a common topic of debate in legislative parliaments around the world. This paper presents a literature review on the effects of the clock change and DST on electricity usage, health, crime rates, road safety, and economic aspects. This addresses a gap in current literature reviews, as there is a lack of linked analyses considering these research fields. We show that there are partial positive effects on crime rates and road safety generally that result from the delay in ambient light availability. This contrasts with the clearly negative effects on health and the economic aspects, which are mainly driven by the disturbed circadian rhythm and the resulting sleep problems. Furthermore, we find that the initial idea of DST to save electricity will probably no longer apply and may even lead to increased usage. This literature review provides a basis for future research and promotes interdisciplinary research by summarizing current findings in a cross-disciplinary manner and identifying research gaps and opportunities. Furthermore, the findings may guide policy-making discussions and decisions.
Advanced fault diagnostics in rotating machinery: A deep learning approach using octave theory of dynamic vibration signals
Authors: Zhang Dawei , Shao Shuai , Zhao Xuan , Zhou Chenyu , Liu Dan , Xu Peijuan , Kong Lingchen
Published: January 2025

In engineering practice, the diagnosis of rotating machinery faults often faces numerous challenges, including noise interference and changes in operating conditions, which pose new difficulties for deep learning methods lacking prior knowledge. In response to this issue, this paper proposes a rotating machinery fault diagnosis method (OCML) based on octave, convolutional neural networks, and MOGRIFIER LSTM. This method can simply and effectively achieve noise reduction, feature extraction, and classification. Firstly, through octave analysis, noise and redundant information can be conveniently and effectively filtered out, enhancing the signal feature representation. Secondly, the designed CNN-MOGRIFIER LSTM model can effectively capture local features and temporal dependencies in the data and has good information interaction capabilities. Experiments on the CWRU dataset and the permanent magnet synchronous motor fault dataset demonstrate that the proposed method exhibits good diagnostic performance across different fault scenarios and different operating conditions. Furthermore, compared to other rotating machinery fault diagnosis methods, the proposed OCML method performs better in terms of diagnostic accuracy and stability. These results collectively confirm the good generalization of the proposed method.
Clinical outcomes among COVID-19 patients initiated on molnupiravir in Denmark – A national registry study
Authors: Larsen Carsten S , Westergaard Caroline L , Stærke Nina B , Arnet Urs , Liu Gui , Kantsø Line R , Kjellberg Jakob
Published: January 2025

Background

Molnupiravir (MOV) is an orally bioavailable ribonucleoside with antiviral activity against all tested SARS-CoV-2 variants. We describe the demographic, clinical, and treatment characteristics of non-hospitalized Danish patients treated with MOV and their clinical outcomes following MOV initiation.

Method

Among all adults (>18 years) who received MOV between 16 December 2021 and 30 April 2022 in an outpatient setting in Denmark, we summarized their demographic and clinical characteristics at baseline and post-MOV outcomes using descriptive statistics. Outcomes were emergent hospitalization and all-cause mortality during the 28 days after MOV initiation. We estimated the odds ratios (OR) of outcomes by time from positive test to treatment using logistic regression.

Results

We identified 3691 MOV-treated patients, of whom 45.8% were male and mean age was 70.1 years. Most patients (76.2%) initiated MOV within 0–2 days after a positive SARS-CoV-2 test and 16.8% within 3–5 days. Over a 28-day period, rates for all-cause, respiratory- or COVID-19-related, and COVID-19-related hospitalization were 4.8%, 2.6% and 1.5%, respectively. All-cause mortality was 1.6%. Initiation of MOV 3–5 days after a positive SARS-CoV-2 test compared to 1–2 days was associated with an increased risk of all-cause (OR 1.85, 95% CI 1.29–2.67) and respiratory or COVID-19-related (OR 1.78, 95% CI 1.07–2.94) hospitalization, and all-cause mortality (OR 2.90, 95% CI 1.64–5.15).

Conclusion

MOV was primarily prescribed to vaccinated elderly persons with multiple comorbidities. The all-cause hospitalization and mortality rates in this population were low. Early initiation of MOV reduced the risk of hospitalization and death compared with late initiation.
Exploring predementia: Understanding the characteristics of subjective cognitive decline plus from India
Authors: S Monisha , Roy Dwaiti , Menon Anjana J , G Sandhya , Gupta Anant , Basavaraju Nimisha , Singh Sadhana , Sundarakumar Jonas S , Kommaddi Reddy , Issac Thomas Gregor
Published: January 2025

Background

Subjective cognitive decline (SCD) is the early predementia syndrome. that occurs even before the development of objective cognitive decline. SCD plus refers to an additional set of criteria that increases the likelihood of developing mild cognitive impairment and further progressing to Alzheimer's disease (AD). Studying the progression of SCD-plus participants will help in understanding the importance of diagnosing this condition at an early stage and delaying its onset.

Objective

The present tries to examine neurocognitive changes in individuals who met the criteria of SCD-plus patients. The study also investigated the imaging correlates of these individuals in both cohorts.

Methods

This study included 94 participants from Srinivaspura Aging, Neuro Senescence, and COGnition (SANSCOG) and Tata Longitudinal Study of Aging (TLSA) cohorts who satisfy the criteria of SCD plus. Mann-Whitney U test was used to compare the SCD plus participants and healthy controls. Regression analysis was performed to find the association between SCD plus and cognition.

Results

The SCD-plus group performed poorer than the healthy group in episodic memory delayed recall (p = 0.049), name face recognition (p = 0.023), and letter fluency (p = 0.004) tasks. The generalized linear model revealed that the SCD-plus group had lower left cerebellar cortex (p = 0.010) and right inferior occipital cortex (p = 0.016) volumes than the healthy control group.

Conclusions

The participants in the SCD-plus group performed poorly on memory and language-related tasks, and the volumes of the associated brain regions decreased. This study suggested that the SCD-plus group had characteristics similar to AD group and can help in identifying AD at the earliest.
SGLT2 inhibition, circulating biomarkers, and Alzheimer's disease: A Mendelian randomization study
Authors: Yang Hao , Ning Yuye , Chen Meilin , Jia Jianping
Published: January 2025

Background

Sodium-glucose cotransporter 2 (SGLT2) inhibitors is a novel category of medications for diabetes, exhibiting neuroprotective potential. However, evidence regarding whether the use of SGLT2 inhibitors effectively reduces the risk of Alzheimer's disease (AD) remains unclear.

Objective

Our study employed Mendelian randomization (MR) analysis to investigate potential causal relationships between SGLT2 inhibition, metabolites, and AD.

Methods

In our research, we used a two-sample MR method to explore the link between SGLT2 inhibitor use and AD, addressing both its late-onset and early-onset forms. Furthermore, we executed a two-step MR analysis to explore how circulating metabolites, primarily endogenous in nature due to SGLT2 inhibition, mediate the relationship between SGLT2 inhibition and AD. The genetic instruments for SGLT2 inhibition were pinpointed through their association with SLC5A2 gene expression and the decreased glycated hemoglobin (HbA1c) levels.

Results

Genetic analysis indicated that SGLT2 inhibition, which effectively reduces HbA1c by enhancing renal glucose excretion and improving glycemic control, was associated with a lower likelihood of developing AD for every 1 SD decrease in HbA1c (OR = 0.48, [0.36, 0.63], p < 0.001). Our MR analysis revealed that SGLT2 inhibition significantly affected 27 of the 123 metabolites examined, adhering to a Bonferroni correction threshold (p < 4.06 × 10-4). Among these 27 significant metabolites, citrate was also associated with AD, showing a significant association (0.81 [0.79, 0.83], p < 0.001).

Conclusions

The study provides strong evidence linking SGLT2 inhibition with a lower AD risk, highlighting citrate's potential mediating role for subsequent clinical research.
Modulation of mitochondrial functions contributes to the protection of lamotrigine against Alzheimer's disease
Authors: Fu Xin-Xin , Wei Bin , Huang Zhi-Hang , Duan Rui , Deng Yang , E Yan , Wang Shi-Yao , Chen Shuai-Yu , Zhang Ying-Dong , Jiang Teng
Published: January 2025

Background

Our previous studies have established that the broad-spectrum anti-epileptic drug lamotrigine (LTG) confers protection against cognitive impairments, synapse and nerve cell damage, as well as characteristic neuropathologies in APP/PS1 mice, a mouse model of Alzheimer's disease (AD). However, the precise molecular mechanisms responsible for this protective effect induced by LTG remain largely elusive.

Objective

In this study, we aimed to investigate the mechanisms underlying the beneficial effects of LTG against AD.

Methods

Five-month-old APP/PS1 mice were treated with 30 mg/kg of LTG daily for three consecutive months. Subsequently, high-throughput ribosome profiling sequencing was conducted to identify differentially translated genes (DTGs) rescued by LTG in the brains of these mice. To gain further insights into the potential functions and pathways of these LTG-rescued DTGs, gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed. RNA expression, protein levels, and translational efficiency were assessed to explore how LTG regulated gene expression processes in AD-related DTGs. Additionally, Aβ42 peptide-stimulated primary neurons were used to uncover the potential mechanisms and signaling pathway by which LTG mitigated oxidative stress under AD context.

Results

For the first time, we reveal that LTG inactivates mitochondrial complexes in the brains of APP/PS1 mice by suppressing the translational efficiency of mitochondrial complexes-related genes. More importantly, we demonstrate that LTG mitigates mitochondrial-mediated oxidative stress in neurons within the context of AD by activation of SIRT6/PGC-1α pathway.

Conclusions

These findings provide further insights into the mechanisms underlying the protective effects of LTG against AD.
Effectiveness of digital behaviour change interventions for promoting physical activity in adolescents with overweight and obesity: A systematic review and meta-analysis
Authors: Jahn Kassim Puteri Shanaz , Muhammad Noor Azimah , Abdul Rahman Nur Faraheen , Sidik Sherina Mohd , Essau Cecilia A. , Shah Shamsul Azhar
Published: January 2025

Background

Obesity in adolescence is associated with many adverse health and well-being outcomes. Physical activity plays an important role in the prevention of obesity; however, many adolescents with overweight and obesity are physically inactive. Digital behaviour change interventions (DBCI) are increasingly used to increase physical activity; however, there is insufficient evidence on their use in promoting physical activity among adolescents with overweight and obesity, including its active components. This review aims to evaluate the effectiveness of DBCIs in promoting physical activity among adolescents with overweight and obesity and to identify the behaviour change techniques (BCTs) used in these interventions.

Methods

Seven electronic databases were searched for randomized controlled trials and quasi-experimental studies evaluating DBCIs for physical activity promotion in adolescents with overweight and obesity aged 10–19 years. The risk of bias in the included studies was assessed using Cochrane's Risk of Bias tool 2 and ROBINS-I tool. Meta-analyses were performed using random effects models. The BCTs used within the DBCIs were coded using the Behaviour Change Technique taxonomy (v1).

Results

Eighteen studies involving 1769 participants were included. DBCIs showed a large, significant positive effect on total physical activity (SMD = 1.61, 95% CI: [0.56, 2.66], p = 0.003), but non-significant effects on moderate-to-vigorous physical activity (MVPA) (SMD = 0.16, 95% CI: [−0.39, 0.71], p = 0.56) and step count (SMD = −0.10, 95% CI: [−0.52, 0.32], p = 0.65). High heterogeneity was observed in total physical activity and MVPA analyses. The most frequently used BCTs were information about health consequences, goal setting, self-monitoring, feedback on behaviour and social support.

Conclusion

DBCIs can effectively promote overall physical activity among adolescents with overweight and obesity, although their impact on MVPA and step count remains unclear. Future research should focus on optimizing BCT combinations and improving long-term engagement while addressing intervention effect variability.

Systematic review registration

PROSPERO CRD42021270008
Analysing media portrayals of people with substance use disorder and addiction: A scoping review
Authors: Bosworth Kristin Taylor , Massey Zachary B , Boyle MaCee , Henry Nicole , McGough Katherine G , Ashford Alyssa , Rains Ella B , Battle Jessica D , Kelly Paris , Malaker Pias , Tilhou Alyssa Shell
Published: January 2025

Stigma about substance use disorders (SUDs) is a barrier to treatment and care. Media portrayals of SUDs influence public perceptions of people with SUDs and form the foundation for societal opinions and perspectives. For this reason, it is crucial to evaluate how the media portrays SUDs. This paper examines how the mass media portrays individuals with SUDs and how these portrayals reinforce negative stereotypes. It also evaluates the influence of media portrayals and the intersection of skin colour with these depictions. Additionally, this paper advocates for communication strategies that aim to destigmatize SUDs to enhance public education and encourage treatment-seeking behaviour. We used a scoping review approach, searching PubMed for medical subject heading (MeSH) terms ‘(addiction) and (portrayal)’ ( n = 58) and ‘(addiction) and (portrayal) and (media)’ ( n = 37). The search yielded 58 unique peer-reviewed articles (duplicates removed; n = 37). Of these, 42 did not meet our topic criteria, leaving 16 articles for analysis. Inductive thematic coding was performed on the 16 articles and uncovered eight portrayal themes: (1) positive endorsement ( n = 8, 50.0%), (2) violent or dangerous ( n = 7, 43.8%), (3) criminal ( n = 6, 37.5%), (4) risky behaviours ( n = 6, 37.5%), (5) policy-making ( n = 5, 31.3%), (6) unreliable, unstable or uncontrollable ( n = 3, 18.8%), (7) interventions or treatments ( n = 3, 18.8%), and (8) celebrity ( n = 3, 18.8%). These themes were observed in four types of media: entertainment media ( n = 9), social media ( n = 1), news media ( n = 7) and marketing media ( n = 5). The findings show that media portrayals of individuals with SUDs continue to reinforce negative stereotypes. Effective campaigns to counter this portrayal with anti-stigmatizing communication of addiction-related topics require collaboration between patients as partners, experts in addiction science and science communicators.
Understanding Patient Registries for Diabetes: A Scoping Review of Published Literature
Authors: Moayad Lana , Alliston Paige , Khalid Saira , Fitzpatrick-Lewis Donna , Gerstein Hertzel C. , Sherifali Diana
Published: January 2025

Background: Diabetes registries have grown in prevalence and incorporated patient engagement opportunities to support diabetes management. We aimed to understand the goals, purpose, and context for diabetes registries defined as patient-focused and how people with diabetes are engaging with these registries. Methods: We searched Pubmed, MEDLINE, Embase, and Emcare using the following criteria: (1) the population is people with diabetes mellitus, including type 1, type 2, and/or gestational diabetes; and (2) the study describes a patient focused registry. Results: The search identified 346 citations, 9 of which were included. The goals of the registries included: developing referral systems, evaluating community-based interventions, collecting self-reported data, improving access to care, and fostering diabetes communities. The delivery settings were community-based, outpatient, or primary care. The methods of delivery and level of patient engagement varied between registries. Conclusions: This scoping review identified 9 diabetes registries, with varying goals, purposes and levels of patient engagement. It highlights a need for registries centered on people with diabetes to promote engagement and facilitate long-term diabetes self-management.
Cognitive diagnosis of high school students’ set knowledge based on the DINA model
Authors: Mi Qi , Wu Xinyue , Yin Zhaoyang , Xu Zhangtao
Published: January 2025

In recent years, scholars have increasingly focused on the cognitive diagnostic model, which is widely used in educational and psychological assessments. This study carries out a cognitive diagnosis of high school students’ understanding of set knowledge via the deterministic inputs, noisy “and” gate model (the DINA model). The results indicate that the cognitive attributes and attribute hierarchies established by this study are reasonable. It is observed that 44.21% of students exhibit proficiency in all attributes, which is inseparable from the fact that set knowledge is fundamental knowledge, and 89.25% of the students’ mastery patterns belong to the ideal mastery patterns, which indicates that the distribution of high school students’ cognitive model on set knowledge is relatively concentrated. The research results also further illustrate that cognitive diagnosis can compensate for the shortcomings of traditional tests and provide a more comprehensive assessment approach. Through the results of cognitive diagnosis, teachers and students can better understand the situation of set learning and conduct more effective teaching and learning.
Computational analysis of congenital heart disease associated SNPs: unveiling their impact on the gene regulatory system
Authors: Vashisht Shikha , Parisi Costantino , Winata Cecilia L.
Published: January 2025

Congenital heart disease (CHD) is a prevalent condition characterized by defective heart development, causing premature death and stillbirths among infants. Genome-wide association studies (GWASs) have provided insights into the role of genetic variants in CHD pathogenesis through the identification of a comprehensive set of single-nucleotide polymorphisms (SNPs). Notably, 90–95% of these variants reside in the noncoding genome, complicating the understanding of their underlying mechanisms. Here, we developed a systematic computational pipeline for the identification and analysis of CHD-associated SNPs spanning both coding and noncoding regions of the genome. Initially, we curated a thorough dataset of SNPs from GWAS-catalog and ClinVar database and filtered them based on CHD-related traits. Subsequently, these CHD-SNPs were annotated and categorized into noncoding and coding regions based on their location. To study the functional implications of noncoding CHD-SNPs, we cross-validated them with enhancer-specific histone modification marks from developing human heart across 9 Carnegie stages and identified potential cardiac enhancers. This approach led to the identification of 2,056 CHD-associated putative enhancers (CHD-enhancers), 38.9% of them overlapping with known enhancers catalogued in human enhancer disease database. We identified heart-related transcription factor binding sites within these CHD-enhancers, offering insights into the impact of SNPs on TF binding. Conservation analysis further revealed that many of these CHD-enhancers were highly conserved across vertebrates, suggesting their evolutionary significance. Utilizing heart-specific expression quantitative trait loci data, we further identified a subset of 63 CHD-SNPs with regulatory potential distributed across various cardiac tissues. Concurrently, coding CHD-SNPs were represented as a protein interaction network and its subsequent binding energy analysis focused on a pair of proteins within this network, pinpointed a deleterious coding CHD-SNP, rs770030288, located in C2 domain of MYBPC3 protein. Overall, our findings demonstrate that SNPs have the potential to disrupt gene regulatory systems, either by affecting enhancer sequences or modulating protein-protein interactions, which can lead to abnormal developmental processes contributing to CHD pathogenesis.
Correlation and diagnostic significance of CD4 T cell subsets and NLRP3 inflammasome in ulcerative colitis: the role of the NLRP3/T-bet/GATA3 axis
Authors: Hu Yingnan , Tang Jingyi , Yu Dian , Su Shuo , Fang Jintao , Xia Linying , Xu Wenjun , Zhu Weihan , Song Ninping , Wang Fengyong , Diao Dechang , Zhang Wei
Published: January 2025

Background and aim

Ulcerative colitis (UC) is characterized by complex immunological interactions involving CD4 T cell subsets and the NLRP3 inflammasome, which influence inflammatory responses. This investigation focused on delineating the activation profiles of these components and their correlation with disease severity and activity, assessing their diagnostic implications in UC.

Methods

We conducted immunohistochemistry and ELISA assays to measure markers expression of CD4 T cell subsets and the NLRP3 inflammasome in UC patients versus controls. Findings were validated using correlation analysis, molecular docking and ROC curves.

Results

UC patients displayed increased Th1 (T-bet, TNF-α), Th2 (GATA3, IL-6), and Th17 (RORγt, IL-17, IL-22, IL-23) markers versus controls. Additionally, Th1 and Th2 cytokines (IL-2 and IL-4) were significantly elevated in severe UC, while Treg markers (FOXP3, IL-10, TGF-β1) were elevated only in mild-to-moderate UC. Enhanced NLRP3 inflammasome activation, indicated by elevated NLRP3, Caspase-1, and IL-1β levels. These molecular patterns, confirmed through correlation analysis and molecular docking, underscored strong correlations among NLRP3, T-bet, and GATA3, supporting the proposed NLRP3/T-bet/GATA3 axis. This axis, along with other biomarkers, showed strong associations with UC severity, Mayo score, UCEIS, demonstrated relatively high diagnostic value.

Conclusion

The NLRP3/T-bet/GATA3 axis provides a referable strategy for multi-targeted combined treatment of UC and may serve as potential biomarkers for enhancing diagnostic accuracy and guiding therapy.
Lifetime progression of IgA nephropathy: a retrospective cohort study with extended long-term follow-up
Authors: Rivedal Mariell , Nordbø Ole Petter , Haaskjold Yngvar Lunde , Bjørneklett Rune , Knoop Thomas , Eikrem Øystein
Published: January 2025

Background

IgA nephropathy (IgAN) exhibits an unpredictable trajectory, creating difficulties in prognostication, monitoring, treatment, and research planning. This study provides a comprehensive depiction of the progression of kidney function throughout the disease course, from diagnosis to a span of 36 years post-diagnosis.

Methods

We utilized a cohort of 400 Norwegian IgAN patients, from diagnosis to the occurrence of death, initiation of kidney replacement therapy (KRT), or the latest follow-up. Recorded proteinuria (n = 2676) and creatinine (n = 8738) measurements were retrieved. Patients were divided into subgroups based on their specific estimated glomerular filtration rate (eGFR) slopes.

Results

Median follow-up was 16 years. During this period, 34% of patients either died or initiated KRT. Among patients who reached endpoint, the median duration from diagnosis to the initiation of KRT or death was 8 years. Notably, 34% of the cohort exhibited a stable disease course, characterized by an eGFR decline of less than 20% between two consecutive measurements. Differences in subsequent disease trajectories among two subgroups with similar eGFR levels at diagnosis could not be accounted for by variations in treatment strategies. Among patients with proteinuria < 1 g/24 h in less than half of the measurements, KRT was five times more prevalent compared to those with more than half of the measurements recording proteinuria < 1 g/24 h (p-value = 0.001).

Conclusions

While a significant proportion of IgAN patients reach kidney failure within their lifetimes, outcomes vary widely. Clinical data at diagnosis offer limited insights into long-term risks. Enhanced risk stratification necessitates data collection at multiple time points.
Robust circulating microRNA signature for the diagnosis and early detection of pancreatobiliary cancer
Authors: Mitsunaga Shuichi , Ikeda Masafumi , Ueno Makoto , Kobayshi Satoshi , Tsuda Masahiro , Miki Ikuya , Kuwahara Takamichi , Hara Kazuo , Takayama Yukiko , Matsunaga Yutaro , Hanada Keiji , Shimizu Akinori , Yoshida Hitoshi , Nomoto Tomohiro , Takahashi Kenji , Iwamoto Hidetaka , Iwama Hideaki , Hatano Etsuro , Nakata Kohei , Nakamura Masafumi , Sudo Hiroko , Takizawa Satoko , Ochiai Atsushi
Published: January 2025

Background

A new circulating biomarker superior to carbohydrate antigen 19–9 (CA19-9) is needed for diagnosing pancreatobiliary cancer (PBca). The aim of this study was to identify serum microRNA (miRNA) signatures comprising reproducible and disease-related miRNAs.

Methods

This multicenter study involved patients with treatment-naïve PBca and healthy participants. The optimized serum processing conditions were evaluated using t-distributed stochastic neighbor embedding (t-SNE) visualization. Serum miRNA candidates for disease association were selected using weighted gene coexpression network analysis (WGCNA). A miRNA signature combining multiple serum miRNAs was tested in exploratory, validation, and independent validation sets. The synthesis and secretion of diagnostic miRNAs were evaluated using human pancreatic cancer cells.

Results

In total, 284 (150 healthy and 134 PBca) of 827 serum samples were processed within 2 h of blood collection before freezing, distributed in the same area as that in the t-SNE map, and assigned to an exploratory set. The 193 optimized samples were assigned to either the validation (50 healthy, 47 PBca) or independent validation (50 healthy, 46 PBca) set. Index-1, a combination of five serum miRNAs (hsa-miR-1343-5p, hsa-miR-4632-5p, hsa-miR-4665-5p, hsa-miR-665, and hsa-miR-6803-5p) with disease association in WGCNA, showed a sensitivity and specificity of > 80% and an AUC outperforming that of CA19-9 in the exploratory, validation, and independent validation sets. The AUC of Index-1 was superior to that of CA19-9 (0.856 vs. 0.649, p = 0.038) for detecting T1 tumors. miR-665, a component of Index-1, was expressed in human pancreatic cancer cells, and its transfection inhibited cell growth.

Conclusions

The serum miRNA signature Index-1 is useful for detecting PBca and could facilitate the early diagnosis of PBca. These findings can help improve clinical PBca detection by providing an optimized biomarker that overcomes the limitations of the current standard.
First autochthonous case of Opisthorchis felineus in Austria
Authors: Kulmer Lisa-Maria , Unterköfler Maria Sophia , Vali Yasamin , Schwendenwein Ilse , Luckschander-Zeller Nicole
Published: January 2025

Background

Opisthorchis felineus is a feline pathogen with zoonotic potential that can be a causative agent of human opisthorchiasis and cholangiocarcinoma. In Europe, O. felineus is particularly endemic in Eastern European countries, while this parasite has also been sporadically detected in Germany, Italy and northern Poland. Parts of Asia, such as Russia, Ukraine and Kazakhstan, are also affected.

Methods

A 7-year-old female neutered European Shorthair cat, without any traveling history, presented in May 2023 with weight loss, anorexia and vomiting.

Results

The cat showed increased liver enzyme activities, hyperbilirubinemia and hyperammonemia consistent with the suspected diagnosis of cholangitis with consecutive hepatoencephalopathy. Eggs of O. felineus were detected by routine cytological examination of bile smears and PCR confirmed O. felineus.

Conclusions

This is the first report of autochthonous O. felineus infection in Austria.

Graphical Abstract
Impact of sodium alginate hydrogel containing bacteriophage peptides that specifically bind to the EtCab protein on the inhibition of Eimeria tenella infection
Authors: Chen Hang , Zhi Wenjing , Bai Bingrong , Anjum Faisal R. , Jia Zhipeng , Kong Rui , Liu Qiuju , Wang Biao , Ma Chunli , Ma Dexing
Published: January 2025

Avian coccidiosis, caused by the protozoan Eimeria, leads to significant economic losses for the poultry industry. In this study, bacteriophages that specifically bind to the calcium-binding protein (EtCab) of Eimeria tenella were selected using a biopanning process with a pIII phage display library. The recombinant EtCab protein served as the ligand in this selection process. The binding ability of target phages to the EtCab protein or E. tenella sporozoites was evaluated. The role of peptides corresponding to target phages in inhibiting the invasion of E. tenella sporozoites into cells was analysed using flow cytometry. Subsequently, the phages were encapsulated in sodium alginate to protect them from degradation in gastric fluid, which has a low pH value. Chickens were orally administered both microencapsulated and non-microencapsulated phages, and the protective effects against E. tenella infection were assessed. The binding mechanism of these peptides to the EtCab protein was investigated through in silico analysis. The results indicated that three specific phages (Y, G, and V) could bind effectively to recombinant EtCab protein as well as to sporozoite proteins. All three peptides, particularly Y and G, demonstrated significant inhibition of sporozoite invasion into cells in vitro. Additionally, oral administration of the encapsulated phages Y and G provided a higher level of protection against Eimeria infection compared to encapsulated phage V and the unencapsulated phages. Molecular docking studies revealed that three peptides, particularly Y and G, efficiently bind to the EtCab protein through hydrogen bonds. This study provides a reference for developing small molecular drugs targeting coccidiosis.
Effects of gestational diabetes mellitus and diabetes mellitus on lipid profile, antioxidants, hormones and electrolytes status in a population of Nigerian women
Authors: Akinjiyan Moses Orimoloye , Atiba Adeniran Samuel , Asaolu Modupe Fisayo
Published: January 2025

Aim

Gestational diabetes mellitus (GDM) cases are rising globally. This research examined the effects of GDM and diabetes mellitus whose hallmark is hyperglycemia on hormones, lipid profiles, electrolytes and antioxidants in freshly diagnosed women attending teaching hospitals in Ekiti State, Nigeria.

Methods

The cross-sectional design followed convenience sampling in four groups (n = 50): gestational diabetes women (GDM), normal pregnant women (NP), diabetes nonpregnant women (DM) and nondiabetes nonpregnant women (ND-NP). Blood samples were collected from fasting subjects through antecubital fossa. BMI, FPG, TC, TG, LDL-C, HDL-C, sodium, potassium and bicarbonate ions, MDA and antioxidants were investigated using standard procedures and spectrophotometer. Results were analysed using one-way ANOVA and p < 0.05 was used as significant difference.

Results

There was significant (p < 0.05) increase in FPG of GDM and DM (> 5.56 mmol/l) subjects compared to NP and ND-NP subjects. TC, TG, HDL-C and LDL-C were elevated in GDM and DM groups compared to NP and ND-NP groups. Sodium ion concentration was significantly (p˂0.05) elevated in ND-NP group relative to GDM and DM groups. There was significant (p < 0.05) increase in MDA levels in DM and NP groups compared to ND-NP. Superoxide dismutase activity was significantly (p < 0.05) greater in ND-NP than in DM and NP. Progesterone level was greater in GDM group than in other groups. The FSH concentration was lower in the GDM and NP groups than in the DM and ND-NP groups, and prolactin concentration was greater in the GDM group than in the NP.

Conclusion

This study suggested that GDM and DM could result in hormonal and electrolyte imbalances, elevated lipid profiles, and reduced antioxidant levels.
Development and application of sugarcane yellow leaf virus vectors in sugarcane
Authors: Yin Yuteng , Zhao Pingzhi , Sun Yanwei , Han Tian , Wang Mengrong , Yan Meixin , Wu Jianming , Zhou Hui , Ye Jian
Published: January 2025

The aphid-transmitted polerovirus, sugarcane yellow leaf virus (SCYLV), is one of the most widespread sugarcane viruses and causes huge economic losses to the global sugarcane production. Molecular studies and disease resistance breeding against SCYLV are impeded both by the lack of infectious clones and comprehensive knowledge of this virus. In this study, we present the development of the first infectious cDNA clone of SCYLV, which could efficiently infect Nicotiana benthamiana, Arabidopsis thaliana and sugarcane plants. SCYLV-based recombinant heterologous EGFP protein vector was also developed. Using this system, we identified the green peach aphid, Myzus persicae, as a new compatible transmission vector and recognized LC05-136 and GT10-2118 as more resistant cultivars of SCYLV than Badila. This system provides an indispensable resource for both SCYLV biological research and sugarcane breeding efforts.
Clinical Manifestations and Treatment Challenges in Infants and Children With Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency
Authors: Nokoff Natalie J , Buchanan Cindy , Barker Jennifer M
Published: January 2025

The most common form of congenital adrenal hyperplasia (CAH) is secondary to 21-hydroxylase deficiency (21OHD). This review will summarize the clinical manifestations, recommended treatments, monitoring, clinical challenges and management strategy, and treatment challenges in special situations for infants and children with classic CAH due to 21OHD. Specifically, we review newborn screening and the initial diagnosis, glucocorticoid and mineralocorticoid treatment, and recommended monitoring, including anthropometric and laboratory measures. Children with CAH may have premature adrenarche, precocious puberty, and early growth plate closure and have an increased risk of hypertension and overweight/obesity. Many 46,XX individuals will also have genital differences, which may include clitoromegaly and/or a urogenital sinus. We review psychosocial and surgical considerations, including suggestions on how to talk with children, family, and caregivers about bodily difference. These suggestions may be used by families and/or providers caring for individuals with CAH.
Measurements of Iodination in Thyroglobulin: A Step Toward the Next Generation of Thyroid Cancer Monitoring
Authors: Maus Anthony , Thompson Chris , Grebe Stefan K G
Published: January 2025

Thyroglobulin (Tg) is a 330-kDa homodimeric protein that that is the prohormone of thyroid hormones triiodothyronine (T3) and thyroxine (T4). The most critical steps of thyroid hormone synthesis by Tg are iodination and fusion of specific tyrosine residues that are in close proximity to each other in the folded Tg protein. The degree of Tg iodination has been studied widely to determine if it is correlated with thyroid autoimmune disease with mixed results, but these efforts have been limited by the lack of an effective quantitative technique. Simultaneously, the treatment of thyroid cancer has undergone a shift toward partial thyroidectomies, thus undermining the value of Tg measurements. A possible alternative to established monitoring techniques is measurement of Tg iodination states as it has been shown that tumor-derived Tg has significantly lower iodine content. Such measurements require a thorough understanding of normal iodination status. In this study, state-of-the-art liquid chromatography–tandem mass spectrometry (LC-MS/MS) instrumentation is used to perform bottom-up proteomics experiments and identify iodinated residues within commercially available Tg. Using this technique, sequence coverages greater than 90% were achieved, which resulted in identification of previously identified and novel hormone synthesis and donor sites. Based on the results of these discovery experiments, 5 iodination sites were selected for targeted quantitative LC-MS/MS measurements, which suggested that hormone synthesis occurs predominantly at Y24 and Y2766. The results presented herein lay the foundation for routine measurements of iodinated residues, which has the potential to overcome the limitations of current monitoring techniques and benefit patient care.
Simbiose industrial e redes de inovação
Authors: Lopes Gabriele da Cunha , Santos Juliana Moreira dos , Mazzo Gabriel Gusso , Pinto Edipo Vinicius Costa , Alves Fernanda Salvador
Published: January 2025

Objetivo: investigar o que tem sido pesquisado sobre a interação entre Redes de Inovação e a Simbiose Industrial.
Método: estudo bibliométrico associado ao fluxo de trabalho “Preferred Reporting Items for Systematic Reviews”. Dados coletados na Web of Science e Scopus. Análise de dados por meio do VoSViewer, revelando cinco clusters temáticos: “uso de recursos”, “cooperação estratégica”, “inovação nos modelos de negócio”, “potencial das redes” e “redes de inovação”.
Resultados e conclusão: os resultados enfatizam a relevância da sustentabilidade, a cooperação e a inovação na Simbiose Industrial. Necessidade de futuras pesquisas sobre redes de simbiose verde, comportamentos de stakeholders e cooperação em rede.
Implicações da pesquisa: o estudo oferece insights sobre a implementação de práticas de SI e REI, destacando seus benefícios econômicos e ambientais. Contribui para o conhecimento sobre a interseção entre SI e REI, sugerindo novas áreas de estudo e conscientização sobre a cooperação interindustrial e a inovação para a sustentabilidade.
Estimating the unit cost of voluntary medical male circumcision using surgical and device methods in integrated health settings in Kenya
Authors: Omondi Rodgers , Kioko Urbanus , Juma Ambrose , Serrem Kennedy , Korir Julius , Rotich Wesley , Bitange Deborah , Bhattacharjee Parinita , Moses Stephen
Published: January 2025

Background Successful voluntary medical male circumcision (VMMC) programmes need to integrate various programme elements into health service delivery to optimize resources. We estimated the unit cost for the delivery of VMMC services in integrated health settings designed to provide a package of services, including education, risk reduction counselling, condom promotion, HIV testing and information on the VMMC procedures, in Kenya. Methods An ingredient costing approach was used to estimate the unit cost in 5 health facilities, using surgical and device methods in Homabay and Kisumu counties, western Kenya. Data were collected retrospectively by reviewing financial and asset records in the health facilities located in rural and urban settings, for the period 2017–2018. Results The unit cost of delivering non-complicated VMMC procedures to infants aged 0-60 days was $14.05 (by device), to boys aged 10–14 years was USD $19.35 (range $13.99-$22.54) by surgery, and to adolescent and adults over 14 years was $19.34 (range $13.84-$22.85) by surgery and was $20.5 by device. The overall unit cost for delivering VMMC services with moderate and mild complications to infants was $17.88 and $18.78 respectively; to adolescents aged 10–14 years across all the sites were $23.33 and $22.18, respectively and to adolescents and adults above 14 years across all the sites were $25.31 and $22.31 respectively for surgical method and were $23.32 and $23.25 respectively for device method. The highest cost heads were related to direct cost heads related to direct staff cost, consumable drugs and supplies and non consumable supplies. Conclusions The average cost per VMMC using an integrated service model was much lower compared to results from previous costing studies which used a stand-alone delivery model. The provision of VMMC services within an integrated setting can be cost-saving.
The Federal Budget of Russia for 2025–2027
Authors: Smirnov I.
Published: January 2025

In the triennial of 2025-2027, as in the next six years, the main priorities of the Russian federal budget will remain the provision of financial resources to fulfill national tasks of social support for the population, strengthening the country’s defense and security, and technological development of domestic infrastructure.
Evolution of the Marketing Approach to Territorial Administration
Authors: Ilyasova E.
Published: January 2025

The article analyzes the historical formation of the marketing approach in territorial administration, both in Russia and abroad. On the basis of various approaches, the essence of territorial marketing is revealed, its features, goals and objectives are characterized, and attention is also focused on the relationship of types of marketing in territorial management. The actual problems of the theory and practice of the marketing approach in the management of territories are considered. The necessity of developing a conceptual system theory and practical developments in the field of territorial marketing is revealed. The article identifies a number of main problems, the solution of which will allow territorial marketing to be carried to a new level and increase its effectiveness.