bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neighborhood environment associations with cognitive function and structural brain measures in older African Americans
Authors: Chaar Dima L. , Tu Le , Moore Kari , Du Jiacong , Opsasnick Lauren A , Ratliff Scott M , Mosley Thomas H , Kardia Sharon L. R. , Zhao Wei , Zhou Xiang , Diez Roux Ana V , Faruque Fazlay S , Butler Kenneth R , Smith Jennifer A 
Published: January 2025

Abstract

Background
Since older adults spend significant time in their neighborhood environment, environmental factors such as neighborhood socioeconomic disadvantage, high racial segregation, low healthy food availability, low access to recreation, and minimal social engagement may have adverse effects on cognitive function and increase susceptibility to dementia. DNA methylation, which is associated with neighborhood characteristics as well as cognitive function and white matter hyperintensity (WMH), may act as a mediator between neighborhood characteristics and neurocognitive outcomes.

Methods
In this study, we examined whether DNA methylation in peripheral blood leukocytes mediates the relationship between neighborhood characteristics and cognitive function (N = 542) or WMH (N = 466) in older African American (AA) participants without preliminary evidence of dementia from the Genetic Epidemiology Network of Arteriopathy (GENOA).

Results
For a 1-mile buffer around a participant’s residence, each additional fast food destination or unfavorable food store with alcohol per square mile was nominally associated with a 0.05 (95%CI: 0.01, 0.09) and a 0.04 (0.00, 0.08) second improvement in visual conceptual tracking score, respectively. Also, each additional alcohol drinking place per square mile was nominally associated with a 0.62 (0.05, 1.19) word increase in delayed recall score, indicating better memory function (all p < 0.05). Neighborhood characteristics were not associated with WMH. We did not find evidence that DNA methylation mediates the observed associations between neighborhood characteristics and cognitive function.

Conclusions
The presence of fast food destinations and unfavorable food stores with alcohol was associated cognitive measures, possibly due to greater social interaction provided in these venues. However, replication of these findings is necessary. Further examination of the potential pathways between the neighborhood environment and cognitive function/WMH may allow the development of potential behavioral, infrastructural, and pharmaceutical interventions to facilitate aging in place and healthy brain aging in older adults, especially in marginal populations that are most at risk.
Drug-target binding affinity prediction based on power graph and word2vec
Authors: Hu Jing , Hu Shuo , Xia Minghao , Zheng Kangxing , Zhang Xiaolong 
Published: January 2025

Abstract

Background
Drug and protein targets affect the physiological functions and metabolic effects of the body through bonding reactions, and accurate prediction of drug-protein target interactions is crucial for drug development. In order to shorten the drug development cycle and reduce costs, machine learning methods are gradually playing an important role in the field of drug-target interactions.

Results
Compared with other methods, regression-based drug target affinity is more representative of the binding ability. Accurate prediction of drug target affinity can effectively reduce the time and cost of drug retargeting and new drug development. In this paper, a drug target affinity prediction model (WPGraphDTA) based on power graph and word2vec is proposed.

Conclusions
In this model, the drug molecular features in the power graph module are extracted by a graph neural network, and then the protein features are obtained by the Word2vec method. After feature fusion, they are input into the three full connection layers to obtain the drug target affinity prediction value. We conducted experiments on the Davis and Kiba datasets, and the experimental results showed that WPGraphDTA exhibited good prediction performance.
Echocardiographic phenotypes of diabetic myocardial disorder: evolution over 15 months follow-up in the ARISE-HF trial
Authors: Marwick Thomas H. , Lam Carolyn , Liu Yuxi , Del Prato Stefano , Rosenstock Julio , Butler Javed , Ezekowitz Justin , Ibrahim Nasrien E. , Tang W. H. Wilson , Zannad Faiez , Perfetti Riccardo , Januzzi James L. 
Published: January 2025

Abstract

Background
Diabetic myocardial disorder (DbMD, evidenced by abnormal echocardiography or cardiac biomarkers) is a form of stage B heart failure (SBHF) at high risk for progression to overt HF. SBHF is defined by abnormal LV morphology and function and/or abnormal cardiac biomarker concentrations.

Objective
To compare the evolution of four DbMD groups based on biomarkers alone, systolic and diastolic dysfunction alone, or their combination.

Methods
The Aldose Reductase Inhibition for Stabilization of Exercise Capacity in Heart Failure (ARISE-HF) trial was a Phase 3 randomised trial of an aldose reductase inhibitor in patients with well-controlled type 2 diabetes mellitus (T2DM). The 1858 potential participants (age 67 ± 7 years; 50% women) were screened for SBHF based on abnormal echocardiography or biomarkers (N-terminal pro-B-type natriuretic peptide ≥ 40 ng/L or high sensitivity cardiac troponin T ≥ 10 ng/L [women] and ≥ 16 ng/L [men]). Exercise capacity (peak VO2) was reduced in 669 with DbMD (age 68 ± 7, 50% women), and peak VO2 was reassessed at 15 months.

Results
The 1463 (79%) participants with DbMD were allocated to four clusters; 907 (49%) showed isolated elevation of cardiac biomarkers, 301 (16%) with systolic dysfunction/hypertrophy, 162 (9%) with diastolic dysfunction and 93 (5%) comprised an overlap cluster (combined diastolic, systolic or LV geometric abnormalities). Reduced VO2 (< 75% predicted) was present in 669 (46%); 72% of those with both systolic and diastolic dysfunction, 56% of those with systolic dysfunction and LVH, 53% of those with diastolic dysfunction and 38% with biomarkers alone (p < 0.0001). In 669 patients followed over 15 months, there was a similar small decrement in VO2 in all groups.

Conclusions
Among individuals with T2DM and SBHF, reduced functional capacity is most prevalent in those with multiple physiological disturbances. However, there was no difference between phenogroups in the evolution of exercise intolerance.

Trial Registration: ARISE-HF, NCT04083339.
Improving 10-year cardiovascular risk prediction in patients with type 2 diabetes with metabolomics
Authors: Xie Ruijie , Seum Teresa , Sha Sha , Trares Kira , Holleczek Bernd , Brenner Hermann , Schöttker Ben 
Published: January 2025

Abstract

Background
Existing cardiovascular risk prediction models still have room for improvement in patients with type 2 diabetes who represent a high-risk population. This study evaluated whether adding metabolomic biomarkers could enhance the 10-year prediction of major adverse cardiovascular events (MACE) in these patients.

Methods
Data from 10,257 to 1,039 patients with type 2 diabetes from the UK Biobank (UKB) and the German ESTHER cohort, respectively, were used for model derivation, internal and external validation. A total of 249 metabolites were measured with nuclear magnetic resonance (NMR) spectroscopy. Sex-specific LASSO regression with bootstrapping identified significant metabolites. The enhanced model’s predictive performance was evaluated using Harrell’s C-index.

Results
Seven metabolomic biomarkers were selected by LASSO regression for enhanced MACE risk prediction (three for both sexes, three male- and one female-specific metabolite(s)). Especially albumin and the omega-3-fatty-acids-to-total-fatty-acids-percentage among males and lactate among females improved the C-index. In internal validation with 30% of the UKB, adding the selected metabolites to the SCORE2-Diabetes model increased the C-index statistically significantly (P = 0.037) from 0.660 to 0.678 in the total sample. In external validation with ESTHER, the C-index increase was higher (+ 0.043) and remained statistically significant (P = 0.011).

Conclusions
Incorporating seven metabolomic biomarkers in the SCORE2-Diabetes model enhanced its ability to predict MACE in patients with type 2 diabetes. Given the latest cost reduction and standardization efforts, NMR metabolomics has the potential for translation into the clinical routine.

Graphical abstract
The roles of KRAS in cancer metabolism, tumor microenvironment and clinical therapy
Authors: Ma Qinglong , Zhang Wenyang , Wu Kongming , Shi Lei 
Published: January 2025

Abstract
KRAS is one of the most mutated genes, driving alternations in metabolic pathways that include enhanced nutrient uptaking, increased glycolysis, elevated glutaminolysis, and heightened synthesis of fatty acids and nucleotides. However, the beyond mechanisms of KRAS-modulated cancer metabolisms remain incompletely understood. In this review, we aim to summarize current knowledge on KRAS-related metabolic alterations in cancer cells and explore the prevalence and significance of KRAS mutation in shaping the tumor microenvironment and influencing epigenetic modification via various molecular activities. Given that cancer cells rely on these metabolic changes to sustain cell growth and survival, targeting these processes may represent a promising therapeutic strategy for KRAS-driven cancers.
The role of luteinizing hormone activity in spermatogenesis: from physiology to clinical practice
Authors: Esteves Sandro C. , Humaidan Peter 
Published: January 2025

Abstract
The production of spermatozoa, a process known as spermatogenesis, is primarily controlled by follicle-stimulating hormone (FSH) and luteinizing hormone (LH)-driven testosterone. LH acts on the Leydig cells, stimulating steroid production, predominantly testosterone, and activating critical inter-related spermatogenesis regulatory pathways. Despite evidence that exogenous gonadotropins containing LH activity can effectively restore spermatogenesis in males with hypogonadotropic hypogonadism, the use of these drugs to treat other forms of male infertility is the subject of an ongoing debate. In this review, we delve into the molecular properties and functions of LH activity in spermatogenesis regulation and explore available preparations for therapeutic use. We also examine the evidence regarding the effectiveness of LH-containing drugs in treating specific male infertility conditions and identify the main areas for future research. Our review highlights the critical role of LH in spermatogenesis and emphasizes the potential of LH-containing drugs in treating male infertility. However, further research is required to completely elucidate the mechanisms underlying the effects of LH activity on sperm production and to establish the most effective dosages and treatment durations.
Characterization of a chitinase from Trichinella spiralis and its immunomodulatory effects on allergic airway inflammation in mice
Authors: Xu Jia , Yao Ye , Zhuang Qisheng , Li Zixuan , Zhang Min , Wang Shouan , Hu Hongxin , Ye Jianbin 
Published: January 2025

Abstract

Background
A fundamental tenet of the hygiene theory is the inverse association between helminth infections and the emergence of immune-mediated diseases. Research has been done to clarify the processes by which helminth-derived molecules can inhibit immunological disorders. This study aimed to evaluate the ability of Trichinella spiralis chitinase (Ts-chit) to ameliorate the symptoms of allergic airway inflammation.

Methods
Recombinant Trichinella spiralis chitinase (rTs-chit) was expressed in Escherichia coli BL21, and its structural homology to murine acidic mammalian chitinase (AMCase) was comprehensively analyzed. The expression of Ts-chit was examined across all T. spiralis life stages. To explore its immunomodulatory potential, a murine model of allergen-induced airway inflammation was established. The effects of rTs-chit were evaluated by assessing airway hyperresponsiveness and cytokine profiles in bronchoalveolar lavage fluid and performing detailed histopathological and immunohistochemical analyses.

Results
Recombinant Ts-chit (rTs-chit) was successfully expressed in E. coli BL21, showing strong structural similarity to murine acidic mammalian chitinase (AMCase). Expression profiling revealed that Ts-chit is present throughout all stages of the T. spiralis life cycle. In an allergic airway inflammation model, rTs-chit reduced weight loss and lung inflammation, lowering inflammatory cell infiltration and Th2 cytokines (IL-4, IL-5, IL-13) while increasing the immunosuppressive cytokine IL-10. Additionally, rTs-chit treatment decreased the expression of GATA3, arginase-1, MCP-1, CCL-11, and AMCase, along with reducing OVA-specific IgE, IgG, and IgG1 levels, suggesting its potential as an immunomodulatory agent.

Conclusions
This study highlights rTs-chit’s potential as a therapeutic agent for allergic airway diseases, leveraging its structural similarity to host chitinases to regulate Th2 responses and inflammatory pathways. The findings provide new insights into helminth-derived proteins as promising candidates for immune-based therapies.

Graphical Abstract
Pathogen delivery route impacts disease severity in experimental Mycoplasma ovipneumoniae infection of domestic lambs
Authors: Jacobson Bryan Tegner , DeWit-Dibbert Jessica , Zanca LaShae , Sonar Sobha , Hardy Carol , Throolin Michael , Brewster Patricia C. , Andujo Kaitlyn , Jones Kerri , Sago Jonathon , Smith Stephen , Bowen Lizabeth , Bimczok Diane 
Published: January 2025

Abstract

M. ovipneumoniae is a respiratory pathogen that can cause mild to moderate pneumonia and reduced productivity in domestic lambs. However, studies on both natural and experimental M. ovipneumoniae infection have reported highly variable clinical signs and pathology. Here, we assessed the impact of administering M. ovipneumoniae to the upper respiratory tract (URT) or to the lower respiratory tract (LRT) of two-month-old specific pathogen-free lambs. Lambs were inoculated with PBS (control) or with ceftiofur-treated nasal wash fluid obtained from sheep with natural M. ovipneumoniae infection, monitored for eight weeks, and subsequently euthanized. All lambs in the URT and LRT groups developed a stable infection with M. ovipneumoniae. M. ovipneumoniae infection led to lower weight gains and mild respiratory disease, with significantly greater effects following LRT inoculation compared to URT inoculation. At necropsy, lambs inoculated via the LRT showed consolidation of the cranial lung lobes. In addition, histological signs of alveolar, bronchiolar, and interstitial inflammation were significantly more severe in the LRT compared to the URT group. M. ovipneumoniae loads in the trachea and bronchi also were significantly higher after LRT than URT inoculation. Interestingly, 9/10 inoculated lambs also tested positive for M. haemolytica in nasal swab but not in bronchial swab samples. In summary, our study suggests that bypassing protective mechanisms of the URT by delivering respiratory pathogens to the LRT leads to more severe respiratory disease and lung damage than delivery to the URT.
Optimization and characterization studies of poultry waste valorization for peptone production using a newly Egyptian Bacillus subtilis strain
Authors: Saeed Hajar , Ragaey Anthony , Samy Ziad , Ashraf Viola , ElMostafa Aly , Ahmad Norhan , Bebawy Enjy , Sorour Nour ElHoda M. , El-Sayed Salwa M. , Bakry Ashraf , Ebeed Naglaa , Elhariry Hesham , El-Noby Thanaa , Abu-Hussien Samah H. 
Published: January 2025

Abstract
Valorization of poultry waste is a significant challenge addressed in this study, which aimed to produce cost-effective and sustainable peptones from poultry waste. The isolation process yielded the highly potent proteolytic B.subtilis isolate P6, identified through 16S rRNA gene sequencing to share 94% similarity with the B.subtilis strain KEMET024 (GenBank accession number PP694485.1) and deposited in MIRCEN culture collection, Cairo, Egypt as EMCC 998871. It reached optimal production levels during 24 h of incubation, with biomass at 2.5 g/L, protease activity at 455 U/mL, and total amino acid (TAA) concentration at 208 mg/mL. For screening the most significant factors for peptone production, the Plackett–Burman design identified meat and bone meal concentration as the main significant factor influencing total amino acid reaching 420 mg/mL. BOX-Behnken design optimized peptone production increasing its production level by twofold to reach 2850 U/mL of protease activity and 580 mg/mL of total amino acids. The produced peptone demonstrated a superior amino acid profile compared to commercial peptones, with a remarkably higher total amino acid content of 621.556 mg/g and elevated levels of essential amino acids like aspartic acid (37.745%), glutamic acid (90.876%), glycine (117.272%), and alanine (50.373%). Characterization revealed optimal pH and temperature conditions of around pH 8 and 50–60°C, respectively, for the proteolytic activity. The Michaelis–Menten and Lineweaver–Burk plots determined a Km of 0.5 mg/mL and Vmax of 174.08 U/mL suggesting cooperative substrate binding and providing insights into the enzyme’s maximum rate and affinity. The produced peptone exhibited minimal cytotoxicity at lower concentrations (≤ 1 mg/mL), with cell viability exceeding 94% against normal human skin fibroblast (HSF) cells. However, higher concentrations (≥ 3 mg/mL) displayed increased cytotoxic effects. Moreover, the results strongly indicate that the produced peptone, particularly at 0.5% concentration, is an effective nitrogen source for B. subtilis cultivation, demonstrating its potential for biotechnological applications. This study successfully valorized poultry waste by developing a sustainable and cost-effective alternative to commercial peptones, contributing to waste valorization and sustainable biotechnological processes.

Graphical abstract
Trends in Israel's Medical Administration subspecialty, 1987–2022
Authors: Angel Yoel , Goldshtein Hadar , Barel Nevo , Fire Gil , Halberthal Michael , Niv-Yagoda Adi 
Published: January 2025

Abstract

Background
Israel is unique in offering a formal subspecialty in Medical Administration and mandating it for physicians applying for senior roles. Data on the prevalence and characteristics of these specialists are limited.

Methods
The national registry of licensed physicians was used to identify all living physicians who completed the Medical Administration subspecialty by December 31, 2022. Data on year of medical licensing, city of residence, and list of additional recognized specialties along with their respective date of completion were extracted. Websites of key public health organizations were sampled to identify qualifications of persons in senior leadership positions.

Results
Since 1987, 277 physicians have completed the Medical Administration subspecialty, with a significant increase in annual certifications from 4.5 in 2015 (interquartile range [IQR] 4–6) to 13 (IQR 10.5–15) in 2022 (p < 0.001). Specialists completed the subspecialty a median of 18 years (IQR 13–21) post-licensing, with 269 physicians (97.1%) holding additional specialties, primarily in Internal Medicine, Pediatrics, Family Medicine, or Public Health. Compared to the general physician population, some base specialties like Public Health are over-represented while others, like Anesthesiology, are under-represented. Only 40 (14.4%) specialists reside outside major metropolitan areas. Nineteen (61.3%) general hospital CEOs, 2 (20%) psychiatric hospital CEOs, 13 (35.1%) Ministry of Health and 4 (7.8%) Sick Fund executives are specialists in Medical Administration (p < 0.005).

Conclusions
The steady growth in the number of specialists in Medical Administration demonstrates the sustainability and scalability of this model, which may serve as a template for other healthcare systems. However, the limited representation of these specialists in senior roles of some organizations, and their concentration within certain specialties and regions, indicates areas for policy attention to enhance leadership diversity and reduce healthcare disparities.
Evidence Communication Rules for Policy (ECR-P) critical appraisal tool
Authors: Danopoulos Evangelos , Aston John A. D. , Shah Aarushi , Schneider Claudia R. 
Published: January 2025

Abstract

Background
Scientific papers increasingly put forward scientific-based policy recommendations (SPRs) as a means of closing the circle of science, policy and practice. Assessing the quality of such SPRs is crucial, especially within the context of a systematic review. Here, we present ECR-P (Evidence Communication Rules for Policy)—a critical appraisal tool that we have developed, which can be used in assessing not only the quality of SPRs but also the quality of their evidence base and how effectively these have both been communicated.

Methods
The rationale behind ECR-P centres on three dimensions of quality; two are the well-established concepts of internal and external validity. Here, we introduce a third—evidence communication—encompassing both evidence veracity and quality of communication. Elements of the three dimensions of quality are considered within the context of the five rules of evidence communication. These are as follows: inform, not persuade; offer balance, not false balance; disclose uncertainties; state evidence quality and pre-empt misunderstandings.

Results
Development of ECR-P has been carried out by an interdisciplinary team and was piloted with a systematic review reported more fully elsewhere. ECR-P comprises a set of preliminary considerations which capture key aspects for the assessment, leading on to the main tool whose structure is domain-based, each domain mapping to one of the five rules of evidence communication. The domains include 25 signalling questions designed to obtain essential information for the critical appraisal. The questions focus on either the study’s evidence or the policy recommendations. Domain-based judgement is derived from responses to the signalling questions and an accompanying algorithm, followed by an overall quality judgement.

Conclusions
ECR-P has been designed to provide a standardised and transparent approach to assess the quality and communication of SPRs and their evidence base. The tool, which could be applied across all scientific fields, has been developed to fit primarily with the systematic reviewing process but could also serve as a stand-alone tool. Besides review assessors, it can also be used by policymakers, researchers, peer reviewers, editors and any other stakeholders interested in evidence-based policymaking and high-quality evidence communication. We encourage further independent testing of the tool in real-world evidence-based research.