bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tolerability and efficacy of Mycobacterium avium complex pulmonary disease treatment in elderly patients
Authors: Shinfuku Kyota , Hara Hiromichi , Okuda Keitaro , Miyagawa Hanae , Takasaka Naoki , Ishikawa Takeo , Araya Jun 
Published: February 2025

Abstract

Background

Mycobacterium avium complex pulmonary disease (MAC-PD) is considered to be increasing worldwide. In Japan, the number of elderly MAC-PD patients requiring treatment is also expected to increase due to the aging society. However, reduced organ function in elderly patients makes it often difficult to continue or complete multidrug treatment due to adverse drug reactions (ADRs). Therefore, this study aimed to identify clinical factors associated with treatment tolerability, efficacy, and ADRs in elderly MAC-PD patients.

Methods
We retrospectively reviewed the medical records of 102 patients with MAC-PD aged ≥ 75 years between January 2014 and March 2023. Forty-six patients were treated with multidrug regimens (treatment group), and 56 were observed without treatment (observation group). The treatment group was divided into the treatment continuation group (n = 28) who were treated without interruption for ≥ 12 months, and the treatment interruption group (n = 18). A comparative study was conducted in each group to examine tolerability, efficacy, and ADRs.

Results
A two-drug regimen of ethambutol (EB) and macrolides without rifampicin (RFP) was associated with treatment continuation (p = 0.026). The treatment continuation group was superior to the observation group regarding symptoms change, sputum conversion rate, and chest computed tomography scores. The most common ADRs were gastrointestinal disorders, which may be related to RFP. Treatment efficacy of the two-drug regimen was non-inferior, and no cases of macrolide resistance were observed.

Conclusions
The two-drug regimen of EB and macrolide without RFP may be a tolerable and effective treatment for elderly MAC-PD patients.
Comprehensive investigation of ergonomic challenges and predictors of work-related musculoskeletal disorders among intensive care unit nurses of Western India through convergent mixed methods study
Authors: Detroja Sonali , Mahajan Rajkumar , Sheth Ankit 
Published: February 2025

Abstract

Background
Work-related musculoskeletal disorders (WRMSDs) are significant concern in intensive care units (ICUs) due to distinct work environment. This study aims to comprehensively investigate determinants of WRMSDs and ergonomic challenges, specific to ICU nurses, providing valuable insights for targeted interventions.

Methods
In this six-month convergent mixed methods study, 200 consenting nurses with over one year of experience from seven ICUs across three public tertiary hospitals of Ahmedabad participated. Structured questionnaires were used to collect data on socio-demographics, occupation, physical and workplace factors, risk perception, and musculoskeletal pain (through modified Nordic Musculoskeletal Questionnaire) and ergonomic issues using REBA (Rapid Entire Body Assessment) scale. Qualitative insights were obtained through in-depth interviews until saturation of responses. Statistical analysis involved chi-square, t-test and logistic regression, with a significance level set at p < 0.05. Thematic analysis was used to interpret the findings of qualitative study.

Results
The study included predominantly female ICU nurses (78%) with a mean age of 34 years. A high prevalence of WRMSDs (84%) was observed, with the lower back and neck being the most affected regions. Nurses with WRMSDs reported significantly higher mean scores for physical factors (15.1 vs. 11.1, p = 0.00), physical workload (12.8 vs. 10.7, p = 0.001), work environment (13.1 vs. 10.1, p = 0.00), and risk perception (11.8 vs. 8.9, p = 0.00) compared to those without WRMSDs. Logistic regression identified key risk factors for WRMSDs, including longer ICU tenure [OR = 1.4 (1.13–1.66)], high shift frequency [OR = 2.7 (1.27–5.95)], higher physical factor score [OR = 1.2 (1.05–1.42)], higher physical workload score [OR = 1.2 (1.09–1.49)], higher risk perception [OR = 1.3 (1.10–1.78)], and lack of exercise [OR = 0.5 (0.27–0.93)]. The qualitative findings highlighted key ergonomic challenges, including inadequate equipment, heavy patient loads, poor posture during tasks, and insufficient breaks, contributing to WRMSDs among ICU nurses.

Conclusion
The findings underscore urgent need for targeted interventions to address risk factors associated with WRMSDs, including ergonomic training, workplace modifications, and education programs to enhance risk awareness and preventive behaviours. Future research should focus on developing and evaluating comprehensive interventions that integrate both physical and work environment factors to effectively mitigate WRMSDs among ICU nurses.
Design and assessment of lipase-CuO nanoparticle conjugates for enhanced antimicrobial efficacy against clinical pathogens
Authors: Handak Eman M. , Amin Dina H. , Elhateir Mai M. 
Published: February 2025

Abstract
In the battle against clinical infections particularly the resistant pathogens, the creation of new antimicrobial drugs is essential. This study focuses on synthesis and characterization of Lipase-CuO nanoparticle conjugates in order to investigate their antibacterial efficiency. Lipase enzyme and CuO nanoparticles were synthesized biologically by specific selected fungal strains. Statistical optimization of lipase enzyme was done using a Plackett-Burman design giving two enhancement models for lipase production with increasing in productivity up to 143.43% (2800 U/ml). Copper oxide (CuO) nanoparticles were characterized using visual indication of greenish color formation, UV-vis spectrum analysis which revealed a strong peak at 300 nm. Also, CuO nanoparticles appeared as distinct, well-dispersed spherical particles with average size of 71.035 nm using TEM, while conjugate appears as large protein molecules linked to the nanoparticles. Also, using techniques like energy dispersive X-ray (EDAX) the resultant conjugates formation was confirmed as the elemental analysis approved its formation. The antimicrobial activity of Lipase-CuO nanoparticles conjugates was tested against a range of clinical pathogens. The results demonstrated a significant increase in antimicrobial potency compared to both CuO nanoparticles and lipase alone particularly against E. coli strain NRC B-3703 with remarkable increase of 373.6% and 75% followed by S. aureus with increase of 50 and 42.8%compared to that of individual CuO nanoparticles and lipase enzyme, respectively. These findings suggest that Lipase-CuO nanoparticle conjugates hold great promise as a novel antimicrobial strategy, offering a potential solution to combat bacterial infections, especially those caused by multidrug-resistant strains. The study highlights the importance of nanotechnology in enhancing the efficacy of traditional antimicrobial agents and opens new avenues for targeted antimicrobial therapies.
Defining competence profiles in obstetrics and gynecology using the modified requirement tracking questionnaire
Authors: Tarasi Baptiste , Oubaid Viktor , Baud David 
Published: February 2025

Abstract

Background
Data about the competencies needed for physicians in obstetrics and gynecology (O&G) is currently insufficient. The aim of this study is to define the competence profile needed in this sector for daily professional activity, in order to account for these criteria in future recruitment.

Methods
The modified requirement-tracking questionnaire (R-track) was sent to 307 physicians working in the field of O&G with different training levels and practice locations. The R-track is designed to assess professional competence profiles and contains 66 items covering the following eight competence areas: “Mental abilities”, “Social sensibility”, “Psychomotor and multitasking abilities”, “Solutions orientation”, “Social interactive competences”, “Personality traits”, “Verbal competences” and “Resistance capacity”. The mean scores of single items and competence areas were calculated. Results were compared between gender, training level, and place of practice.

Results
The participation rate was 65.5%, with 201 physicians returning the questionnaire. In this sample, 50.2% of them were in training and 49.8% were practicing O&G specialists. The proportion of physicians working in a hospital setting was 64.7% while 30.3% worked in private practice. The competence areas “Social sensibility” and “Psychomotor & multitasking abilities” appear to be the most important for daily professional activity. At the item level, “Stress resistance”, followed by “Workload management” and “Tactfulness” were considered as the most valuable characteristics. Differences between gender, level of training, and place of practice were not significant.

Conclusion
The identified competence profile could serve as a basis for developing a new method of O&G residency selection. In addition, such a profile could help medical students to decide on a professional specialization at a very early stage by comparing their personal competence profile with the one in the field or with their mentors.
The association between TyG index and cardiovascular mortality is modified by antidiabetic or lipid-lowering agent: a prospective cohort study
Authors: Fang Changchang , Peng Nanqin , Cheng Jiang , Zhang Xiyu , Gu Wenli , Zhu Zicheng , Yin Xiaoping , Yan Zhiwei , Zhang Jing , Yu Peng , Liu Xiao 
Published: February 2025

Abstract

Background
The triglyceride-glucose (TyG) index is recognized as an alternative measure of insulin resistance (IR) and has been linked to the risks of cardiovascular disease (CVD) and mortality. This study aimed to evaluate whether the association between the TyG index and CVD mortality is influenced by the use of antidiabetic and hypolipidemic agents, given their potential modifying effects on the TyG index.

Methods
Participants from the National Health and Nutrition Examination Survey (1999–2018) were included in the study. Mortality outcomes were tracked through linkage with National Death Index records until December 31, 2019. Data on the use of antidiabetic and hypolipidemic medications (including prescribed insulin, diabetic pills, and cholesterol-lowering agents) were self-reported by participants.

Results
A total of 5,046 adults (representing 42,753,806 individuals, weighted mean age 61.08 years [SE: 0.24]; 49.35% female) were analyzed. The TyG index was significantly associated with all-cause and CVD mortality, and these associations were modified by the use of antidiabetic and hypolipidemic agents (p < 0.01). Significant interactions were observed between the TyG index and the use of these agents for mortality outcomes after full adjustments (p-value for interaction < 0.05). Exposure-effect analysis revealed a U-shaped relationship between TyG index levels and the risks of all-cause and CVD mortality in participants using these agents, while a linear positive relationship was observed in participants not using these agents.

Conclusions
The use of antidiabetic and hypolipidemic agents modify the association between the TyG index and all-cause and CVD mortality. These findings suggest that future studies on the TyG index and its relationship with CVD and mortality should account for the modifying effects of these agents.

Graphical abstract
Barriers to health equity in the United States of America: can they be overcome?
Authors: Chen Allen M. 
Published: February 2025

Abstract
Health equity—defined by the Centers for Disease Control and Prevention as " the state in which everyone has a fair and just opportunity to attain their highest level of health—” represents one of the most critical issues facing modern societies. While seemingly an increasing focus of policymakers in recent years, this concept is hardly a novel one. In 1948, the inaugural Constitution of the newly founded World Health Organization clearly stated that “the enjoyment of the highest attainable standard of health is one of the fundamental rights of every human being without distinction of race, religion, political belief, economic or social condition.” Yet nearly a century later, it is arguable how much progress society has made in achieving health equity, particularly in the United States of America where numerous factors at both the level of the individual and population contribute to significant complexity with respect to healthcare access and delivery. The purpose of this review is to thus outline the barriers to health equity so that thoughtful discourse can be promoted to create a more even playing field for the lives of the disadvantaged and underserved in the future.
Clinically meaningful improvements after gene therapy for aromatic L-amino acid decarboxylase deficiency (AADCd) in the Peabody Developmental Motor Scale, Second Edition (PDMS-2) and correlation with Bayley-III scores and motor milestones
Authors: Hwu Wuh-Liang , Lee Hui-Min , Peipert John Devin , Zhang Rongrong , Werner Christian , Sierra J. Rafael , O’Connell Thomas , Woolley Jonathan J. , Crowell Marjorie , Wang Antonia , Tomazos Ioannis 
Published: February 2025

Abstract

Background
Aromatic L-amino acid decarboxylase deficiency (AADCd) is a rare genetic disorder characterized by movement disorders, motor and autonomic dysfunction, and developmental delays. The gene therapy eladocagene exuparvovec has become available in some regions; pooled clinical trial results demonstrate continuous long-term improvement in motor development and cognitive function. We sought to characterize clinically meaningful change in motor function, as measured by Total Peabody Developmental Motor Scales-Second Edition (PDMS-2) score, and assess correlations with cognition and language domains of the Bayley-III and motor milestone (MM) achievement.

Methods
Data from N = 30 patients from three single-arm clinical studies of eladocagene exuparvovec were analyzed. Anchor-based estimation of the meaningful score difference (MSD) of Total PDMS-2 score was conducted using mean-difference and receiver operating characteristic curve (ROC) approaches. MM achievement served as the anchor defining meaningful change.

Results
An MSD of 40 points for Total PDMS-2 score was selected for analysis as it yielded specificity > 0.95 using the ROC approach, and generally aligned with the mean-difference approach. Cumulative incidence analysis reflected that 50% of patients treated with eladocagene exuparvovec may achieve the MSD of 40-point change in Total PDMS-2 score at 6 months, and 86% at 18 months. Correlations between measures were of large magnitude and improved over time (Month 6: r = 0.599 [p = 0.0032]; Month 18: r = 0.796 [p = 0.0002]; Month 60: r = 0.861 [p = 0.0007]).

Conclusions
The MSD of 40 points for Total PDMS-2 score enables the interpretation of changes observed in patients with AADCd, and suggests that treatment with eladocagene exuparvovec leads to significant improvements in motor and cognitive function.
Disparate and shared transcriptomic signatures associated with cortical atrophy in genetic behavioral variant frontotemporal degeneration
Authors: Shen Ting , Vogel Jacob W. , Van Deerlin Vivianna M. , Suh EunRan , Dratch Laynie , Phillips Jeffrey S. , Massimo Lauren , Lee Edward B. , Irwin David J. , McMillan Corey T. 
Published: February 2025

Abstract

Background
Cortical atrophy is a common manifestation in behavioral variant frontotemporal degeneration (bvFTD), exhibiting spatial heterogeneity across various genetic subgroups, which may be driven by distinct biological mechanisms.

Methods
We employed an integrative imaging transcriptomics approach to identify both disparate and shared transcriptomic signatures associated with cortical thickness in bvFTD with C9orf72 repeat expansions or pathogenic variants in GRN or MAPT. Functional enrichment analyses were conducted on each gene list significantly associated with cortical thickness. Additionally, we mapped neurotransmitter receptor/transporter density maps to the cortical thickness maps, to uncover different correlation patterns for each genetic form. Furthermore, we examined whether the identified genes were enriched for pathology-related genes by using previously identified genes linked to TDP-43 positive neurons and genes associated with tau pathology.

Results
For each genetic form of bvFTD, we identified cortical thickness signatures and gene sets associated with them. The cortical thickness associated genes for GRN-bvFTD were significantly involved in neurotransmitter system and circadian entrainment. The different patterns of spatial correlations between synaptic density and cortical thinning, further confirmed the critical role of neurotransmission and synaptic signaling in shaping brain structure, especially in the GRN-bvFTD group. Furthermore, we observed significant overlap between genes linked to TDP-43 pathology and the gene sets associated with cortical thickness in C9orf72-bvFTD and GRN-bvFTD but not the MAPT-bvFTD group providing specificity for our associations. C9orf72-bvFTD and GRN-bvFTD also shared genes displaying consistent directionality, with those exhibiting either positive or negative correlations with cortical thickness in C9orf72-bvFTD showing the same direction (positive or negative) in GRN-bvFTD. MAPT-bvFTD displayed more pronounced differences in transcriptomic signatures compared to the other two genetic forms. The genes that exhibited significantly positive or negative correlations with cortical thickness in MAPT-bvFTD showed opposing directionality in C9orf72-bvFTD and GRN-bvFTD.

Conclusions
Overall, this integrative transcriptomic approach identified several new shared and disparate genes associated with regional vulnerability with increased biological interpretation including overlap with synaptic density maps and pathologically-specific gene expression. These findings illuminated the intricate molecular underpinnings contributing to the heterogeneous nature of disease distribution in bvFTD with distinct genetic backgrounds.
Pharmacological activity of OST-01, a natural product from baccharis coridifolia, on breast cancer cells
Authors: Kang HyunJun , Hoang Dinh Hoa , Valerio Melissa , Pathak Khyatiben , Graff William , LeVee Alexis , Wu Jun , LaBarge Mark A. , Frankhouser David , Rockne Russell C. , Pirrotte Patrick , Zhang Bin , Mortimer Joanne , Nguyen Le Xuan Truong , Marcucci Guido 
Published: February 2025

Abstract
Natural products have long been a viable source of therapeutic agents, providing unique structures and mechanisms that may be beneficial for cancer treatment. Herein we first report on the anticancer activity OST-01, a natural product from Baccharis Coridifolia, on breast cancer cells, including triple-negative breast cancer (TNBC). OST-01 significantly inhibited cell proliferation and oncogenic activities of TNBC cells in vitro. OST-01 also markedly inhibited TNBC tumor growth in vivo, with > 50% reduction in tumor size compared to vehicle control treatment in different in vivo models, i.e., cell line-derived (CDX), patient-derived (PDX), and mammary fat pad xenografts. Mechanistically, OST-01 induces ferroptosis by downregulating LRP8-regulated selenoproteins, i.e., GPX4. A shift from a basal-mesenchymal to a luminal-epithelial state of breast cancer stem cells (BCSCs) as supported by the downregulation of stemness (e.g., CD44) and mesenchymal (e.g., FN1 and vimentin) markers, along with the upregulation of differentiation markers (e.g., CD24) and luminal-epithelial markers (e.g., CK19), was also observed.
Metabolic consequences and nailfold capillary changes in children with familial Mediterranean fever
Authors: Abo Hola Ahmed S. , El Zayat Rania S. , Shehata Wafaa Ahmed , Elashmawy Mai I. , Khalaf Noha E. , El Zefzaf Heba M. S. 
Published: February 2025

Abstract

Background
There’s an increasing role of nailfold capillaroscopy in the evaluation of peripheral vascular disease in chronic inflammatory disorders. Familial Mediterranean fever (FMF) is one such disorder, which raises concerns about increased cardiovascular risk, with scarce data available in children. Therefore, we aimed to evaluate insulin resistance, lipid profile, atherogenic indices, and nailfold capillary (NC) changes in children with FMF.

Methods
Fifty-four children diagnosed with FMF were evaluated by measuring complete blood count, ESR, CRP, serum amyloid A (SAA), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), lipid profile, and atherogenic indices, along with a nailfold capillaroscopic examination, both during acute attacks and attack-free periods.

Results
During attack-free periods, patients exhibited higher total leucocytic counts, ESR, CRP, SAA, HOMA-IR, total cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDL-C), Castelli’s risk index I (CRI I), and atherogenic coefficient (AC), and a lower hemoglobin level than controls. Additionally, the NC examination identified avascular areas in 14.8% of patients, tortuosities in 18.5%, enlargements in 14.8%, and microhemorrhages in 7.4%. These parameters showed significant increases during acute attacks. HOMA-IR showed positive correlations with TC, non-HDL-C, CRI I, and AC; however, NC changes were strongly connected with disease duration and SAA.

Conclusions
Insulin resistance, alterations in serum lipids and atherogenic indices, and NC changes significantly endure in children with FMF during attack-free periods compared to controls, with more prominence during acute attacks. These parameters are linked to subclinical vascular injury and elevated cardiovascular risk, so their monitoring is crucial in these patients for early detection and intervention.
How long does it take to start minimal enteral feeding in preterm Neonates admitted to NICUs in Southern Oromia, Ethiopia?
Authors: Fikrie Anteneh , Yambo Terefu , Edin Alo , Gelchu Miesa , Hailu Dejene , Spigt Mark 
Published: February 2025

Abstract

Background
The timely initiation of trophic feeding (TF) is crucial for premature newborns, but challenging due to immaturity, respiratory instability, abdominal distension, resource scarcity, and healthcare worker expertise. Moreover, there is a dearth of information on predictors of full trophic feeding time. Therefore, this retrospective cohort study aimed to investigate the time it takes and its predictors to initiate minimal enteral feeding in preterm neonates in Southern Oromia, Ethiopia.

Method
A facility-based retrospective follow up study was conducted among 434 randomly selected preterm neonates admitted to NICU of Bule Hora University Teaching Hospital and Yabello General Hospital from January 1, 2021 to December 30, 2022. Data were extracted by a pretested structured checklist, entered into Epidata 3.1 and then transferred to Stata version 17 for analysis. Kaplan Meier survival curve and log rank test were used to estimate survival time and a statistical comparison respectively. Bivariable and multivariable cox proportional hazard model was fitted to identify predictors of time to initiate TF and their outputs are presented using Adjusted Hazard Ratio (AHR) with 95% Confidence Intervals (CIs).

Result
The overall incidence density of TF initiation was reported as 43.6 per 100 neonate-days. Moreover, the median (IQR) time to initiate TF was found to be 2 (1–4) days. Neonates delivered vaginally had a higher likelihood of early TF initiation (AHR: 1.64, CI: 1.26, 2.13), while those born between 32 and 34 weeks (AHR: 0.61, CI: 0.46, 0.81), VLBW neonates (AHR: 0.45, CI: 0.34, 0.60), neonates without KMC (AHR: 0.59, CI: 0.46, 0.79), and those in level II hospitals were less likely to start TF promptly (AHR: 0.78, CI: 0.62, 0.99). Furthermore, neonates with sepsis (AHR: 1.76, CI: 1.36, 2.28) and hypothermia (AHR: 1.51, CI: 1.19, 1.93) had delayed TF initiation.

Conclusion
We observed a significant low rate of early TF initiation and higher death rate of preterm newborn in our study as compared to the global. Preterm neonates with lower GA, no KMC, and a VLBW are more likely to have a delayed initiation. Our results highlight that staff training on identifying neonates suitable for TF, and ensuring adequate resources for KMC in all NICU levels should be considered.