bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of preoperative inflammatory indices and postoperative pneumonia on postoperative atrial fibrillation in patients with non-small cell lung cancer: a retrospective study
Authors: Ruan Yingding , Han Jianwei , Yang Aiming , Ding Qingguo , Zhang Ting
Published: July 2024

Background

This study aimed to evaluate the impact of preoperative inflammatory indices and postoperative pneumonia (POP) on postoperative atrial fibrillation (POAF) in non–small cell lung cancer (NSCLC) patients.

Methods

All consecutive patients who underwent pulmonary resection at our hospital (January 2016-October 2019) were enrolled. Preoperative inflammatory indices, demographic data, surgical details, and postoperative conditions were analyzed. Univariate and multivariate analyses of risk factors associated with POAF were also conducted.

Results

Among the 382 patients included in the study, 32 (8.38%) developed POAF. Compared to non-POAF patients, POAF patients had greater incidence of POP (P = 0.09). Approximately 31 patients (96.9%) developed atrial fibrillation within three days after surgery. The POAF group had a significantly greater mean age (68.94 years) than did the non-POAF group (63 years) (P = 0.002). Additionally, compared to non-POAF patients, POAF patients exhibited an increased number of resected mediastinal lymph nodes (P < 0.001) and mediastinal lymph node stations (P < 0.001).The POAF group also had a greater intraoperative blood volume (P = 0.006), longer surgical duration (P = 0.022), and greater drainage volume (P = 0.003). IA/B stage (P < 0.001) and IIIA/B stage(P < 0.001), and lobectomy resection (P = 0.008) and wedge resection (P = 0.023) were also associated with POAF. Compared to those in the non-POAF group, the POAF group had longer postoperative hospital stays (10.54 days vs. 9 days; P = 0.001) and longer drainage times (7 days vs. 5 days; P = 0.004). Multivariate analysis revealed age, POP, and stage IIIA/B as independent influencing factors of POAF in NSCLC patients.

Conclusion

Preoperative inflammatory indices were not significantly associated with POAF, but age, POP, and stage IIIA/B were identified as independent influencing factors. Advanced-stage NSCLC patients may have a greater susceptibility to POAF than early-stage patients, although further validation is needed. Additionally, POAF was linked to a longer postoperative hospital stay.
Based on network pharmacology and molecular docking to explore the potential mechanism of shikonin in periodontitis
Authors: Zhao Qingliang , Wang Kun , Hou Lin , Guo Lin , Liu Xiangyan
Published: July 2024

Objectives

To investigate the potential mechanisms of shikonin in preventing and treating periodontitis using network pharmacology and molecular docking methods.

Materials and methods

The targets of shikonin were obtained in TCMSP and SEA databases, and targets of periodontitis were gathered from the OMIM, GeneCards and Drugbank Databases. The intersecting targets were entered into the DAVID database to obtain the relevant biological functions and pathways by GO and KEGG enrichment analysis. The obtained targets were analysed the protein–protein interaction (PPI) in STRING platform. In Cytoscape 3.8.0, the network analysis function with the MCODE plug-in were used to obtain the key targets, of shikonin and periodontitis. Molecular docking and molecular dynamics simulation (MD) were used to assess the affinity between the shikonin and the key targets.

Results

Shikonin was screened for 22 targets and periodontitis was screened for 944 targets, the intersecting targets were considered as potential therapeutic targets. The targets played important roles in cellular response to hypoxia, response to xenobiotic stimulus and positive regulates of apoptotic process by GO enrichment analysis. 10 significant pathways were analyzed by KEGG, such as human cytomegalovirus infection and PI3K-Akt signaling pathway, etc. Cytoscape software screened the key genes including AKT1, CCL5, CXCR4, PPARG, PTEN, PTGS2 and TP53. Molecular docking and MD results showed that shikonin could bind stably to the targets.

Conclusions

The present study enriched the molecular mechanisms in periodontitis with shikonin, providing potential therapeutic targets for periodontitis.
Ethnic inequalities in coverage and use of women’s cancer screening in Peru
Authors: Intimayta-Escalante Claudio
Published: July 2024

Objective

This study aimed to assess ethnic inequalities in the coverage and utilization of cancer screening services among women in Peru.

Methods

Data from the 2017–2023 Demographic and Family Health Survey in Peru were analyzed to evaluate ethnic disparities in screening coverage for breast and cervical cancer, including clinical breast examination (CBE), Pap smear test (PST), and mammography. Measures such as the GINI coefficient and Slope Index of Inequality (SII) were used to quantify coverage and utilization disparities among ethnic groups.

Results

The study included 70,454 women aged 30–69. Among women aged 40–69, 48.31% underwent CBE, 84.06% received PST, and 41.69% underwent mammography. It was found inequalities in coverage for any cancer screening (GINI: 0.10), mammography (GINI: 0.21), CBE (GINI: 0.19), and PST (GINI: 0.06), in 25 Peruvian regions. These inequalities were more pronounced in regions with larger populations of Quechua, Aymara, and Afro-Peruvian women. In rural areas, Quechua or Aymara women (SII: -0.83, -0.95, and − 0.69, respectively) and Afro-Peruvian women (SII: -0.80, -0.92, and − 0.58, respectively) experienced heightened inequalities in the uptake of CBE, mammography, and PST, respectively. Like Quechua or Aymara women (SII: -0.50, SII: -0.52, and SII: -0.50, respectively) and Afro-Peruvian women (SII: -0.50, SII: -0.58, and SII: -0.44, respectively) with only a primary education.

Conclusion

Ethnic inequalities affect breast and cervical cancer screening coverage across regions in Peru. In Quechua, Aymara, and Afro-Peruvian women the uptake of mammography, CBE, and PST was less frequently than their white or mestizo counterparts. These inequalities are attributed to sociodemographic conditions such as lower education levels and residence in rural or non-capital areas.
Translation and psychometric analysis of urdu version of modified polycystic ovary syndrome health related quality of life questionnaire (MPCOSQ-U)
Authors: Zaman Rabbiya , Ehsan Sarah , Fatima Abeer , Obaid Sumaiyah , Shahzadi Javeria
Published: July 2024

Background

Polycystic ovary syndrome is a metabolic disorder prevalent among females of reproductive age. The symptoms of PCOS profoundly affect the quality of life of these females. Outcome measures specific to PCOS are crucial to the management of these patients. The MCPOSQ is a validated tool to measure the health-related quality of life specific to PCOS. The purpose of this study was to translate the modified polycystic ovary syndrome quality of life questionnaire (MPCOSQ) and to determine the reliability and validity of the modified polycystic ovary syndrome quality of life questionnaire Urdu version (MPCOSQ-U).

Methodology

This cross-sectional study was conducted in Islamabad/Rawalpindi. The MPCOSQ was translated to Urdu and validated by expert gynaecologists. The MPCOSQ-U and SF-36 were administered to one hundred eighty females with PCOS. The MPCOSQ-U was evaluated for internal consistency, test-retest reliability, factor analysis, face validity, content validity and construct validity.

Results

The average age (years) of the females was 25.27(1.83). The MPCOSQ-U showed excellent test-retest reliability and internal consistency (ICC2,1=0.95, Cronbach’s α = 0.97). The content validity index (CVI) was 0.92. There was a statistically significant but weak positive correlation between MPCOSQ-U and SF-36 (r = .186, p = .012).

Conclusion

The Urdu version of the modified version of the polycystic ovarian syndrome quality of life questionnaire is a validated and reliable tool to assess the quality of life of Pakistani females with PCOS. This is an important step to cover the language barrier, which influences the outcome assessment in PCOS.
Leveraging shortest dependency paths in low-resource biomedical relation extraction
Authors: Enayati Saman , Vucetic Slobodan
Published: July 2024

Background

Biomedical Relation Extraction (RE) is essential for uncovering complex relationships between biomedical entities within text. However, training RE classifiers is challenging in low-resource biomedical applications with few labeled examples.

Methods

We explore the potential of Shortest Dependency Paths (SDPs) to aid biomedical RE, especially in situations with limited labeled examples. In this study, we suggest various approaches to employ SDPs when creating word and sentence representations under supervised, semi-supervised, and in-context-learning settings.

Results

Through experiments on three benchmark biomedical text datasets, we find that incorporating SDP-based representations enhances the performance of RE classifiers. The improvement is especially notable when working with small amounts of labeled data.

Conclusion

SDPs offer valuable insights into the complex sentence structure found in many biomedical text passages. Our study introduces several straightforward techniques that, as demonstrated experimentally, effectively enhance the accuracy of RE classifiers.
Balancing act: exploring work-life balance among nursing home staff working long shifts
Authors: Ingstad Kari , Haugan Gørill
Published: July 2024

Background

Nursing home staff often face challenges in achieving a satisfactory work-life balance, particularly because of the nature of shift work. While long shifts offer extended periods off work, their impact on the delicate balance between work and leisure remains understudied in the context of nursing homes. This study investigated the experiences of nursing home staff in Norway working long shifts lasting 12–14 h and their perceptions of the balance between family life and work.

Methods

Eighteen nursing home staff members were interviewed following a semi-structured qualitative approach. The participants worked in three types of long shifts and provided insights into their experiences, addressing issues such as work hours, shift patterns, and work-family balance.

Results

The study revealed four main categories: (1) impact of long shifts on family life—the highs and lows; (2) maximizing time off with long shifts; (3) reducing job stress with long shifts; and (4) full-time work leads to predictable hours and stable income. The participants emphasised the distinct separation between work and leisure during long shifts, acknowledging limited social life during working periods but appreciating extended periods off. Family life posed challenges, especially with young children, but the participants found benefits in the longer periods of family time during days off. Longer rest periods and reduced commuting time were perceived as advantages of long shifts, contributing to better sleep, reduced stress and overall well-being. Long shifts also allowed for more predictable working hours and income, supporting a stable work-life balance.

Conclusion

Balancing work and family life involves more than just the number of hours spent at work; it also encompasses the quality of those hours both at work and at home. Our findings underscore the complex interplay between work and family life for nursing home staff working long shifts. While challenges exist, benefits such as extended time off, improved sleep, reduced stress, and predictable working hours contribute positively to their work-life balance. Long shifts in nursing homes offer a unique perspective on achieving work-life balance, revealing both the challenges and advantages inherent in such schedules. Understanding the experiences of nursing home staff in this context can inform future innovations in shift scheduling, promoting a more balanced and sustainable work environment for healthcare professionals. For some healthcare staff, extended shifts can lead to a better work-life balance.
Raters and examinees training for objective structured clinical examination: comparing the effectiveness of three instructional methodologies
Authors: Guerrero Jefferson Garcia , Alqarni Ayidah Sanad , Estadilla Lorraine Turiano , Benjamin Lizy Sonia , Rani Vanitha Innocent
Published: July 2024

Background

Utilizing the objective structured clinical examination (OSCE) ensures objectivity when it comes to the assessment of nursing students’ skills and competency. However, one challenge in OSCE integration is rater and examinee training and orientation.

Aim

This study employed a quasi-experimental design to evaluate the effectiveness of different instructional methodologies in training and preparing raters and examinees for the OSCE.

Methods

Participants were divided into three group of training methodologies: online, simulation, and traditional lecture (six raters and 18 examinees were assigned to each group). A total of 18 raters and 54 examinees partook.

Results

The study found that raters trained through simulation exhibited a slight agreement with their rates, compared to those who were trained online and in traditional lectures. Moreover, examinees who were trained through the simulation methodology performed better compared to those trained via the other methodologies.

Conclusions

The study findings indicate that using simulation by training raters and examinees in the OSCE is the most effective approach.
Machine learning for accurate detection of small airway dysfunction-related respiratory changes: an observational study
Authors: Xu Wen-Jing , Shang Wen-Yi , Feng Jia-Ming , Song Xin-Yue , Li Liang-Yuan , Xie Xin-Peng , Wang Yan-Mei , Liang Bin-Miao
Published: July 2024

Background

The use of machine learning(ML) methods would improve the diagnosis of small airway dysfunction(SAD) in subjects with chronic respiratory symptoms and preserved pulmonary function(PPF). This paper evaluated the performance of several ML algorithms associated with the impulse oscillometry(IOS) analysis to aid in the diagnostic of respiratory changes in SAD. We also find out the best configuration for this task.

Methods

IOS and spirometry were measured in 280 subjects, including a healthy control group (n = 78), a group with normal spirometry (n = 158) and a group with abnormal spirometry (n = 44). Various supervised machine learning (ML) algorithms and feature selection strategies were examined, such as Support Vector Machines (SVM), Random Forests (RF), Adaptive Boosting (ADABOOST), Navie Bayesian (BAYES), and K-Nearest Neighbors (KNN).

Results

The first experiment of this study demonstrated that the best oscillometric parameter (BOP) was R5, with an AUC value of 0.642, when comparing a healthy control group(CG) with patients in the group without lung volume-defined SAD(PPFN). The AUC value of BOP in the control group was 0.769 compared with patients with spirometry defined SAD(PPFA) in the PPF population. In the second experiment, the ML technique was used. In CGvsPPFN, RF and ADABOOST had the best diagnostic results (AUC = 0.914, 0.915), with significantly higher accuracy compared to BOP (p < 0.01). In CGvsPPFA, RF and ADABOOST had the best diagnostic results (AUC = 0.951, 0.971) and significantly higher diagnostic accuracy (p < 0.01). In the third, fourth and fifth experiments, different feature selection techniques allowed us to find the best IOS parameters (R5, (R5-R20)/R5 and Fres). The results demonstrate that the performance of ADABOOST remained essentially unaltered following the application of the feature selector, whereas the diagnostic accuracy of the remaining four classifiers (RF, SVM, BAYES, and KNN) is marginally enhanced.

Conclusions

IOS combined with ML algorithms provide a new method for diagnosing SAD in subjects with chronic respiratory symptoms and PPF. The present study’s findings provide evidence that this combination may help in the early diagnosis of respiratory changes in these patients.
Role of long noncoding RNAs in diabetes-associated peripheral arterial disease
Authors: Tapia Alonso , Liu Xuejing , Malhi Naseeb Kaur , Yuan Dongqiang , Chen Muxi , Southerland Kevin W. , Luo Yingjun , Chen Zhen Bouman
Published: July 2024

Diabetes mellitus (DM) is a metabolic disease that heightens the risks of many vascular complications, including peripheral arterial disease (PAD). Various types of cells, including but not limited to endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and macrophages (MΦs), play crucial roles in the pathogenesis of DM-PAD. Long non-coding RNAs (lncRNAs) are epigenetic regulators that play important roles in cellular function, and their dysregulation in DM can contribute to PAD. This review focuses on the developing field of lncRNAs and their emerging roles in linking DM and PAD. We review the studies investigating the role of lncRNAs in crucial cellular processes contributing to DM-PAD, including those in ECs, VSMCs, and MΦ. By examining the intricate molecular landscape governed by lncRNAs in these relevant cell types, we hope to shed light on the roles of lncRNAs in EC dysfunction, inflammatory responses, and vascular remodeling contributing to DM-PAD. Additionally, we provide an overview of the research approach and methodologies, from identifying disease-relevant lncRNAs to characterizing their molecular and cellular functions in the context of DM-PAD. We also discuss the potential of leveraging lncRNAs in the diagnosis and therapeutics for DM-PAD. Collectively, this review provides a summary of lncRNA-regulated cell functions contributing to DM-PAD and highlights the translational potential of leveraging lncRNA biology to tackle this increasingly prevalent and complex disease.

Graphical Abstract
Breastfeeding among women employed in Mexico’s informal sector: strategies to overcome key barriers
Authors: Goodman Julia M. , Lara-Mejía Vania , Hernández-Cordero Sonia , Vilar-Compte Mireya
Published: July 2024

Background

Rates of exclusive breastfeeding fall below recommended levels, particularly among women in paid employment. In Mexico, more than half of women are in informal employment, meaning they lack many of the protections that may support breastfeeding.

Methods

In-depth interviews with 15 key informants representing government agencies (n = 6 organizations), NGOs (n = 4), international organizations (n = 2), and academia (n = 2) in Mexico. Interviews were conducted between March and June 2023. To understand and describe barriers to breastfeeding among informally employed women in Mexico according to key informants and the current and potential policies to address these barriers, we conducted a qualitative thematic analysis.

Results

Current policies to promote, protect, and support breastfeeding predominantly apply to all employed women, but respondents expressed concern that they did not provide adequate protection for women in informal employment. Additional themes concerned the need for relevant programs to be institutionalized and coordinated, discussions of breastfeeding as a right, and the legal equivalence (whether true in practice or not) of formal and informal workers.

Conclusions

Women employed in Mexico’s informal sector face a dearth of maternity protections. According to key informants, few policies exist to promote, protect, and support breastfeeding among employed women, in general, but the economic vulnerability and challenging working conditions of women in informal employment exacerbates their situation. The lack of access to formal labor protections, such as paid maternity leave, creates a significant barrier to breastfeeding for women in the informal sector. Recommendations include short-term policies to fill gaps in social protection for informally employed women, as well as longer-term solutions such as the development of universal social protection programs and supporting formalization.
Impact of exercise dosages based on American College of Sports Medicine recommendations on lipid metabolism in patients after PCI: a systematic review and meta-analysis of randomized controlled trials
Authors: Wen Qing , Mao Xiao-Rong , Wen Juan , Yang Xiao-Juan , Chen Juan , Han Hu-Kui , Tang Xiao-Li , Ma Qun-Hua
Published: July 2024

Background

The impact of exercise dosages based on American College of Sports Medicine(ACSM) recommendations on lipid metabolism in patients after PCI remains unclear. This study conducted a meta-analysis of reported exercise dosages from the literature to address this knowledge gap.

Methods

A comprehensive search of databases was conducted to identify eligible randomized controlled studies of exercise interventions in patients after PCI, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Based on the recommended exercise dosages from ACSM for patients with coronary heart disease, exercise doses in the literature that met the inclusion criteria were categorized into groups that were highly compliant with ACSM recommendations and those with low or uncertain ACSM recommendations. The topic was the effect of exercise dose on lipid metabolism in post-PCI patients. This was assessed using standardized mean difference (SMD) and 95% confidence intervals (95% CI) for changes in triglycerides, total cholesterol, LDL, and HDL.

Results

This systematic review included 10 randomized controlled studies. The subgroup analysis revealed statistically significant differences in the high compliance with ACSM recommendations group for triglycerides [SMD=-0.33 (95% CI -0.62, -0.05)], total cholesterol [SMD=-0.55 (95% CI -0.97, -0.13)], low-density lipoprotein [SMD=-0.31 (95% CI -0.49, -0.13)], high-density lipoprotein [SMD = 0.23 (95% CI 0.01, 0.46)], and body mass index [SMD=-0.52 (95% CI -0.87, -0.17)]. Compared to the low or uncertain compliance with ACSM recommendations group, the high compliance group exhibited significant differences in improving TC levels (-0.55(H) vs. -0.46(L)), HDL levels (0.23(H) vs. 0.22(L)), and BMI (-0.52(H) vs. -0.34(L)).

Conclusions

This study supports that high compliance with ACSM-recommended exercise dosages has significant impacts on improving TC levels, HDL levels, and BMI. However, no advantage was observed for TG or LDL levels.
Nebulized milk exosomes loaded with siTGF-β1 ameliorate pulmonary fibrosis by inhibiting EMT pathway and enhancing collagen permeability
Authors: Qiu Chong , Zhao Zhenyu , Xu Chenglin , Yuan Ranran , Ha Yuxuan , Tu Qingchao , Zhang Houqian , Mu Zhen , Xin Quanlin , Tian Yu , Wang Aiping , Wang Hongbo , Shi Yanan
Published: July 2024

Pulmonary Fibrosis (PF) is a fatal disease in the interstitial lung associated with high mortality, morbidity, and poor prognosis. Transforming growth factor-β1 (TGF-β1) is a fibroblast-activating protein that promotes fibrous diseases. Herein, an inhalable system was first developed using milk exosomes (M-Exos) encapsulating siRNA against TGF-β1 (MsiTGF-β1), and their therapeutic potential for bleomycin (BLM)-induced PF was investigated. M-siTGF-β1 was introduced into the lungs of mice with PF through nebulization. The collagen penetration effect and lysosomal escape ability were verified in vitro. Inhaled MsiTGF-β1 notably alleviated inflammatory infiltration, attenuated extracellular matrix (ECM) deposition, and increased the survival rate of PF mice by 4.7-fold. M-siTGF-β1 protected lung tissue from BLM toxicity by efficiently delivering specific siRNA to the lungs, leading to TGF-β1 mRNA silencing and epithelial mesenchymal transition pathway inhibition. Therefore, M-siTGF-β1 offers a promising avenue for therapeutic intervention in fibrosis-related disorders.
Clinical and genetic characteristics of Chinese pediatric and adult patients with hereditary spherocytosis
Authors: Wu Chongjun , Yan Yixin , Xiong Ting , Jiang Wen , Xu Jing , Rao Yanfei , Ao Jianyun , Xu Chun , Li Xuehong , Qi Longwang , Zheng Wenhong , Li Wenjin , Xu Zhongjin , Yang Yu , Li Zhenjiang
Published: July 2024

Objective

This study aimed to investigate the clinical features, pathogenic gene variants, and potential genotype–phenotype correlations in Chinese patients with hereditary spherocytosis (HS).

Methods

Retrospective analysis of clinical data and molecular genetic characteristics was conducted on patients diagnosed with HS at Jiangxi Provincial Children's Hospital, the Second Affiliated Hospital of Nanchang University, Pingxiang People's Hospital and The Third People's Hospital of Jingdezhen between November 2017 and June 2023. Statistical analyses were performed to compare and analyze the red blood cell (RBC), hemoglobin (HB), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) data between and within groups based on different mutations and age groups (< 14 and ≥ 14 years).

Results

A total of 34 HS patients were included in this study, comprising 22 children (64.70%) and 12 adults (35.30%). The probands who underwent genetic testing were derived from 34 unrelated families. Thirty-two variants were tested and 9 of them are novel. Eighteen cases had ANK1 variants, 15 had SPTB variants, and 1 had SLC4A1 variant. 25 patients performed core family members underwent genetic testing, 17 (68.0%, 17/25) were de novo, 5 (20.0%, 5/25) were maternally inherited, and 3 (12.0%, 3/25) were paternally inherited. ANK1-HS patients exhibited more severe anemia compared to cases with SPTB-HS, showing lower levels of RBC and HB (P < 0.05). Anemia was more severe in patients diagnosed in childhood than in those diagnosed in adulthood. Within the ANK1-HS group, MCH levels in adult patients was significantly higher than those in children (P < 0.05), while there were no significant differences in RBC, HB, MCV, and MCHC levels between two groups. Adult patients with SPTB-HS had significantly higher levels of RBC, HB, and MCH than pediatric patients (P < 0.05), while MCV and MCHC levels showed no significant statistical differences.

Conclusion

This study conducted a comparative analysis of phenotypic characteristics and molecular genetics in adult and pediatric patients diagnosed with HS, confirming that pediatric ANK1-HS patients exhibit a more severe anemic phenotype compared to SPTB-HS patients, while the severity of HS in adults does not significantly differ between different causative genes.
Frontier and hot topics in the application of hydrogel in the biomedical field: a bibliometric analysis based on CiteSpace
Authors: Sun Weiming , Wu Wendi , Dong Xiangli , Yu Guohua
Published: July 2024

Hydrogels are formed of crosslinked polymer chains arranged in three-dimensional (3D) networks. These chains have good water-containing capacity and are soft and malleable. Hydrogels have good biocompatibility due to their significant water content, flexible structure, and numerous holes. These characteristics make them analogous to biological tissues. Despite the publication of 8700 literature related to hydrogel biomedical applications in the past 52 years (1973 ~ 2024), studies on the use of hydrogels in biomedicine are few. To gain a comprehensive understanding of their current development status, research trends, and prospects in the biomedical application field, it is imperative to conduct a thorough retrospective analysis. In this study, we employ bibliometric analysis and CiteSpace software to quantitatively and visually analyze articles published in this field. Firstly, we provide a quantitative analysis of authorship and institutional publications over the past 52 years to elucidate the fundamental development status regarding hydrogel biomedical applications. Secondly, we did visual studies on terms that are high-frequency, explosive, keyword clustering, and so on, to understand the directionality and evolution of the main research hotspots during each period. Notably, our findings emphasize that fabricating hydrogels into wound healing-promoting dressings emerges as a prominent hotspot within the application field. We anticipate that this paper will inspire researchers with novel ideas for advancing hydrogel applications in biomedicine.
AAV-NRIP gene therapy ameliorates motor neuron degeneration and muscle atrophy in ALS model mice
Authors: Chen Hsin-Hsiung , Yeo Hsin-Tung , Huang Yun-Hsin , Tsai Li-Kai , Lai Hsing-Jung , Tsao Yeou-Ping , Chen Show-Li
Published: July 2024

Background

Amyotrophic lateral sclerosis (ALS) is characterized by progressive motor neuron (MN) degeneration, leading to neuromuscular junction (NMJ) dismantling and severe muscle atrophy. The nuclear receptor interaction protein (NRIP) functions as a multifunctional protein. It directly interacts with calmodulin or α-actinin 2, serving as a calcium sensor for muscle contraction and maintaining sarcomere integrity. Additionally, NRIP binds with the acetylcholine receptor (AChR) for NMJ stabilization. Loss of NRIP in muscles results in progressive motor neuron degeneration with abnormal NMJ architecture, resembling ALS phenotypes. Therefore, we hypothesize that NRIP could be a therapeutic factor for ALS.

Methods

We used SOD1 G93A mice, expressing human SOD1 with the ALS-linked G93A mutation, as an ALS model. An adeno-associated virus vector encoding the human NRIP gene (AAV-NRIP) was generated and injected into the muscles of SOD1 G93A mice at 60 days of age, before disease onset. Pathological and behavioral changes were measured to evaluate the therapeutic effects of AAV-NRIP on the disease progression of SOD1 G93A mice.

Results

SOD1 G93A mice exhibited lower NRIP expression than wild-type mice in both the spinal cord and skeletal muscle tissues. Forced NRIP expression through AAV-NRIP intramuscular injection was observed in skeletal muscles and retrogradely transduced into the spinal cord. AAV-NRIP gene therapy enhanced movement distance and rearing frequencies in SOD1 G93A mice. Moreover, AAV-NRIP increased myofiber size and slow myosin expression, ameliorated NMJ degeneration and axon terminal denervation at NMJ, and increased the number of α-motor neurons (α-MNs) and compound muscle action potential (CMAP) in SOD1 G93A mice.

Conclusions

AAV-NRIP gene therapy ameliorates muscle atrophy, motor neuron degeneration, and axon terminal denervation at NMJ, leading to increased NMJ transmission and improved motor functions in SOD1 G93A mice. Collectively, AAV-NRIP could be a potential therapeutic drug for ALS.
Risk factors for severe and fatal childhood unintentional injury: a systematic review protocol
Authors: Beaulieu Emilie , Herrera Norma Maria Perez , Boutin Amélie
Published: July 2024

Background

Unintentional injuries are a leading cause of death among children aged 1–19 years worldwide. Systematic reviews assessing various risk factors for different childhood injuries have been published previously. However, most of the related literature does not distinguish minor from severe or fatal injuries. This study aims to describe and summarize the current knowledge on the determinants of severe and fatal childhood unintentional injuries and to discuss the differences between risk factors for all injuries (including minor injuries) and severe and fatal injuries. The study also aims to quantify the reduction in childhood injuries associated with a reduction in exposure to some of the identified risk factors in the Canadian population.

Methods

A systematic review and meta-analysis will be conducted by searching MEDLINE, Embase, CINAHL, and Web of Science. Observational and experimental cohort studies assessing children and adolescents aged ≤ 19 years old and determinants of severe and fatal unintentional injury, such as personal behaviors, family and environmental characteristics, and socioeconomic and geographic context, will be eligible. The main outcome will be a composite of any severe or fatal unintentional injuries (including burns, drowning, transport-related injuries, and falls). Any severity measurement scale will be accepted as long as severe cases require at least one hospital admission. Two authors will independently screen for inclusion, extract data, and assess the quality of the data using the Cochrane ROBINS-E tool. Meta-analysis will be performed using random effects models. Subgroup analyses will examine age subgroups and high- vs low-income countries. Sensitivity analysis will be conducted after restricting analyses to studies with a low risk of bias. Attributable fractions will be computed to assess the burden of identified risk factors in the Canadian population.

Discussion

Given the numerous determinants of childhood injuries and the challenges that may be involved in identifying which individuals should be prioritized for injury prevention efforts, this evidence may help to inform the identification of high-risk children and prevention interventions, considering the disproportionate consequences of severe and fatal injuries. This evidence may also help pediatric healthcare providers prioritize counseling messaging.

Systematic review registration

PROSPERO CRD42023493322.
Exploring heart rate variability in polycystic ovary syndrome: implications for cardiovascular health: a systematic review and meta-analysis
Authors: Mirzohreh Seyedeh Tarlan , Panahi Padideh , Heidari Fariba
Published: July 2024

Objectives

Polycystic ovary syndrome (PCOS) is a prevalent and complex endocrine disorder that affects women of reproductive age. It has significant implications for female endocrine function, reproductive health, and metabolic disturbances, including insulin resistance, impaired glucose tolerance, and dyslipidemia. Studies have shown that decreased heart rate variability (HRV), a marker of autonomic dysfunction, is associated with adverse cardiovascular events. Recent research has focused on investigating autonomic function in PCOS, and some studies have suggested altered autonomic drive in these patients. The aim of this systematic review and meta-analysis was to evaluate cardiac autonomic function by analyzing HRV in women with PCOS.

Methods

This systematic review was prepared using PRISMA reporting guidelines. The databases searched were PubMed, Scopus, Web of Science, and Cochrane. Risk of Bias was assessed using ROBINS-I for non-RCTs. The GRADE approach was employed to evaluate the level of certainty in the evidence for each outcome. In order to identify the underlying cause of high heterogeneity, a subgroup analysis was conducted. Sensitivity analysis was checked. A random effect model was used and calculated a pooled standardized mean difference (SMD) with a 95% confidence interval (CI).

Results

Seventeen articles were included in the final analysis, varied in quality, ranging from a "low" to a "high risk of bias". Combined analyses indicated a notable decrease in HRV among individuals with PCOS compared to the control group. Significant changes were observed in SDNN (SMD: -0.763, 95%CI [-1.289 to -0.237],p=0.004), PNN50 (SMD: -1.245, 95%CI [-2.07, -0.419],p=0.003), LF/HF ratio (SMD: 0.670, 95%CI [0.248, 1.091],p=0.002), HFnu (SMD: -0.873, 95%CI [-1.257, -0.489],p=0.000), LFnu (SMD: 0.840, 95%CI [0.428, 1.251],p=0.000) and TP (SMD: -1.997, 95%CI [-3.306, -0.687],p=0.003). The heterogeneity was partially explained by types of study design. Subgroup analysis revealed significant alterations of HRV in normal-weighted and overweight PCOS cases. Conversely, no significant changes in HRV were observed in obese PCOS cases.

Conclusion

The findings of this meta-analysis provide evidence suggesting diminished HRV in individuals with PCOS compared to non-PCOS control group.
A three-arm randomized phase II study of dostarlimab alone or with bevacizumab versus nonplatinum chemotherapy in recurrent gynecological clear cell carcinoma: DOVE (APGOT-OV7/ENGOT-ov80 study).
Authors: Lee Jung-Yun , Tan David Shao Peng , Ray-Coquard Isabelle Laure , Lee Jung Bok , Kim Byoung-Gie , Van Nieuwenhuysen Els , Huang Ruby Yun-Ju , Tse Ka Yu , Gonzalez Martin Antonio , Scott Clare L. , Hasegawa Kosei , Wilkinson Katie , Yang Eunyeong , Kristeleit Rebecca
Published: July 2024

TPS5627

Background: Recurrent gynecological clear cell carcinoma (rGCCC) is known for low objective response rates to chemotherapy. Prior preclinical and clinical data suggests potential synergy of immune checkpoint inhibitor adding bev in rGCCC. Dostarlimab, a humanized monoclonal antibody targeting PD-1, combined with the anti-angiogenic bevacizumab, presents a novel therapeutic approach. The aim of the present study is to investigate the efficacy of dostarlimab +/- bevacizumab in rGCCC. Methods: DOVE is a global, multicenter, international, open-label, randomized phase 2 study of dostarlimab +/- bevacizumab with standard chemotherapy in patients with rGCCC. It enrolls 198 patients with rGCCC, assigning them to one of three groups in a 1:1:1 ratio: Group A (dostarlimab monotherapy), Group B (dostarlimab + bevacizumab), Group C: investigator’s choice chemotherapy. Patients with PD on Group A or Group C were allowed to crossover to Group B. Stratification factors are prior bevacizumab use, prior lines of therapy (1 vs. >1), and primary site (ovarian vs. non-ovarian). Key inclusion criteria are histologically proven confirmed recurrent or persistent clear cell carcinoma of the ovary, endometrium, cervix, vagina and vulva, up to 5 prior lines of therapies, disease progression within 12 months after platinum-based chemotherapy, and measurable disease. Key exclusion criteria are prior treatment with an anti PD-1, anti PD-L1, or anti PD-L2 agent. The primary endpoint is progression-free survival by investigator. The secondary endpoints include ORR, DCB, DCR, PFS2, OS, and toxicity. Exploratory objectives include immune biomarker. The study, commencing in Jan 2024, is registered with Clinicaltrials.gov (NCT06023862). Clinical trial information: NCT06023862 .
Tyrosine Kinase Inhibitors With and Without Up-Front Stereotactic Radiosurgery for Brain Metastases From
EGFR
and
ALK
Oncogene–Driven Non–Small Cell Lung Cancer (TURBO-NSCLC)
Authors: Pike Luke R.G. , Miao Emily , Boe Lillian A. , Patil Tejas , Imber Brandon S. , Myall Nathaniel J. , Pollom Erqi L. , Hui Caressa , Qu Vera , Langston Jacob , Chiang Veronica , Grant Michael , Goldberg Sarah B. , Palmer Joshua D. , Prasad Rahul N. , Wang Tony J.C. , Lee Albert , Shu Catherine A. , Chen Lanyi Nora , Thomas Nicholas J. , Braunstein Steve E. , Kavanagh Brian D. , Camidge D. Ross , Rusthoven Chad G.
Published: July 2024

PURPOSE

Newer-generation tyrosine kinase inhibitors (TKIs) for non–small cell lung cancer (NSCLC) with epidermal growth factor receptor (
EGFR
) mutations and anaplastic lymphoma kinase (
ALK
) rearrangements have demonstrated high CNS activity. The optimal use of up-front stereotactic radiosurgery (SRS) for brain metastases (BM) in patients eligible for CNS-penetrant TKIs is controversial, and data to guide patient management are limited.

MATERIALS AND METHODS

Data on TKI-naïve patients with EGFR- and ALK-driven NSCLC with BM treated with CNS-penetrant TKIs with and without up-front SRS were retrospectively collected from seven academic centers in the United States. Time-to-CNS progression and overall survival (OS) were analyzed, with multivariable adjustment in Fine & Gray and Cox proportional hazards models for clinically relevant factors.

RESULTS

From 2013 to 2022, 317 patients were identified (200 TKI-only and 117 TKI + SRS). Two hundred fifty (79%) and 61 (19%) patients received osimertinib and alectinib, respectively. Patients receiving TKI + SRS were more likely to have BM ≥1 cm (
P
< .001) and neurologic symptoms (
P
< .001) at presentation. Median OS was similar between the TKI and TKI + SRS groups (median 41
v
40 months, respectively;
P
= .5). On multivariable analysis, TKI + SRS was associated with a significant improvement in time-to-CNS progression (hazard ratio [HR], 0.63 [95% CI, 0.42 to 0.96];
P
= .033). Local CNS control was significantly improved with TKI + SRS (HR, 0.30 [95% CI, 0.16 to 0.55];
P
< .001), whereas no significant differences were observed in distant CNS control. Subgroup analyses demonstrated a greater benefit from TKI + SRS in patients with BM ≥1 cm in diameter for time-to-CNS progression and CNS progression-free survival.

CONCLUSION

The addition of up-front SRS to CNS-penetrant TKI improved time-to-CNS progression and local CNS control, but not OS, in patients with BM from EGFR
-
and ALK-driven NSCLC. Patients with larger BM (≥1 cm) may benefit the most from up-front SRS.
Life-Threatening Tracheal Tube Obstruction by Vernix Caseosa in a Newborn: A Case Report
Authors: Iwai Takero , Kawatsu Yuta , Kojima Taiki
Published: July 2024

Accurate diagnosis and optimal management of sudden intraoperative ventilatory failure is crucial in children. Herein, we report the case of a newborn who underwent pacemaker implantation immediately after birth via cesarean delivery. The vernix caseosa caused a partial tracheal obstruction and was dislodged during tracheal tube suctioning, leading to complete obstruction of the tracheal tube. Diagnosis of tracheal tube obstruction was challenging because the obstruction occurred immediately after airway suctioning, which is performed to rule out tracheal tube obstruction. Anesthesiologists must consider airway obstruction from high-viscosity vernix caseosa as a possibility immediately after airway suctioning in newborns.
New Evidence From Census 2020 on the Residential Segregation of Same-Sex Households: A Research Note
Authors: Spring Amy , Ghaziani Amin
Published: July 2024

The 2020 decennial census provides new insights into the demography of same-sex households and can shed light on ongoing debates in urban and gayborhood studies. Although the U.S. Census gives a vast undercount of the LGBTQ population, it is still the largest source of nationally representative data on same-sex households and is accessible over three time points (2000, 2010, 2020). In this research note, we use 2020 census data to examine the residential patterns of same-sex households down to the neighborhood level. By employing the index of dissimilarity, we present results for the 100 largest U.S. cities and 100 largest metropolitan areas that demonstrate moderate yet persistent segregation. In a continuation of prior trends, male same-sex households remain more segregated from different-sex households than do female same-sex households. We find moderate levels of within-group segregation by gender and marital status—representing new demographic trends. Finally, metropolitan areas have a higher dissimilarity index than cities, revealing greater levels of segregation when factoring in suburban areas. We discuss these trends in light of debates regarding the spatial organization of sexuality in residential contexts and outline future avenues for research utilizing recently released 2020 census data.
Εννοιολογική αλλαγή
Authors: Χριστοδούλου Παναγιώτα
Published: July 2024

Ο μαθητικός πληθυσμός συχνά δυσκολεύεται να κατανοήσει τις επιστημονικές έννοιες. Η Εννοιολογική Αλλαγή (ΕΑ) αναφέρεται στη διαδικασία με την οποία οι μαθητές μεταβάλλουν τις αφελείς θεωρίες τους, ώστε να συμφωνούν με την επιστημονική άποψη. Μέχρι τώρα, οι επιστήμονες έχουν εντοπίσει συγκεκριμένες προϋποθέσεις και εργαλεία που μπορούν να χρησιμοποιηθούν από τους εκπαιδευτικούς για να προωθήσουν την ΕΑ. Σκοπός της διατριβής είναι να εξετάσει, αν τα Ρομπότ Κοινωνικής Αρωγής (ΡΚΑ) μπορούν να επιφέρουν ανάλογα αποτελέσματα με τους εκπαιδευτικούς για την απόκτηση γνώσεων υπό το πρίσμα της ΕΑ, ή αν απαιτείται επανεξέταση της εκπαίδευσης για την ΕΑ. Η διατριβή αποτελείται από τρεις διαδοχικές μελέτες. Η πρώτη μελέτη χρησιμοποιεί ομάδες εστίασης (Ν=24) για να διερευνήσει τις αντιλήψεις των εκπαιδευτικών σχετικά με την προσωπικότητα ενός ΡΚΑ και να καθοδηγήσει το σχεδιασμό της. Η δεύτερη μελέτη στοχεύει να επιβεβαιώσει τη δομή της προσωπικότητας ενός ΡΚΑ μέσω ποσοτικής έρευνας (Ν=547). Η τρίτη μελέτη διερευνά τον ρόλο του ΡΚΑ στην απόκτηση γνώσεων από μαθητές και μαθήτριες (Ν=101) παιδικής (10-12 ετών) και εφηβικής (13-15 ετών) ηλικίας, την επίδραση δημογραφικών παραγόντων και το ρόλο της επιστημικής εμπιστοσύνης στο ΡΚΑ. Τα αποτελέσματα της πρώτης μελέτης δείχνουν, ότι οι εκπαιδευτικοί βλέπουν το ΡΚΑ είτε ως «δράστη διδασκαλίας» είτε ως «βοηθό», αποδίδοντας στον πρώτο ρόλο εξειδικευμένα χαρακτηριστικά ανάλογα με εκείνα που δείχνουν οι εκπαιδευτικοί κατά τη διδασκαλία. Η δεύτερη μελέτη επιβεβαιώνει δύο διαστάσεις της ρομποτικής προσωπικότητας: την «Αυθεντία» και τον «Διευκολυντή», που συνδέονται με έναν δεύτερης τάξης παράγοντα, τον οποίο δεδομένης της ερμηνευτικής αξίας του ονομάσαμε «παιδαγωγική προσωπικότητα» ενός ΡΚΑ για την εκπαίδευση. Η τρίτη μελέτη έδειξε, ότι τα ΡΚΑ μπορούν να υποστηρίξουν την απόκτηση γνώσεων σε μαθητές παιδικής και εφηβικής ηλικίας, χωρίς όμως η προσωπικότητα του ρομπότ να διαφοροποιεί τα αποτελέσματα. Το φύλο των μαθητών δεν επηρεάζει την επίδραση της ρομποτικής προσωπικότητας στην απόκτηση γνώσεων, ενώ αναφορικά με την ηλικία, στις εκ των υστέρων μετρήσεις οι διαφορές μεταξύ των παιδιών και των εφήβων σχεδόν εξαλείφθηκαν. Οι γενικές επιδόσεις των μαθητών και μαθητριών επηρεάζουν την επίδραση της ρομποτικής προσωπικότητας στην απόκτηση γνώσεων, ενώ η επιστημική εμπιστοσύνη στο ΡΚΑ δεν προβλέπει την απόκτηση γνώσεων. Συμπερασματικά, τα ευρήματα της διατριβής αναδεικνύουν την ανάγκη μετασχηματισμού της εκπαίδευσης για την ΕΑ, όταν αυτή προωθείται από τα ΡΚΑ.
The Lord’s Prayer In Finnish by Georg Bruno from 16th century
Authors: Kazakėnaitė Ernesta , Kallio Petri
Published: July 2024

This article briefly presents a new handwritten version of the Lord’s Prayer in Finnish that is currently stored in the National Library of Sweden. It is found in a manuscript attributed to Georg Bruno and dated to the late 16th century. Here we discuss its status and identify its sources. We also question some of the ideas of an earlier researcher of this manuscript.

Kokkuvõte. Ernesta Kazakėnaitė, Petri Kallio: Georg Bruno soomekeelne meieisapalve 16. sajandist. Aastal 1955 leidis Lätis sündinud Rootsi teoloog Haralds Biezais Rootsi Rahvusraamatukogu arhiivist 16. sajandi käsikirja, mis sisaldas ühe esimestest lätikeelsetest meieisapalvetest. Tõenäoliselt Georg Bruno poolt kirjutatud käsikirjas on veel 19 muukeelset meieisapalvet, mis on seni uurimata. Artikkel esitab filoloogilise ülevaate käsikirja soomekeelsest meieisapalvest, mis osutub koopiaks Sebastian Münsteri raamatu Cosmographei 1561. aasta trükist.
Three-Dimensional Mentoring Model for the Personal and Professional Development of Young Teachers in Educational Organizations
Authors: Selinenkova A. , Zenkina S.
Published: July 2024

This article discusses a new model of mentoring in a general education organization, which is aimed at adaptation, development of not only professional, but also personal development of a young teacher. There are three vectors of the mentoring model, and functions and features are described for each. The authors show the logic of changing one vector to another and the signs of their transition. The development of a young teacher is considered from two angles: «vertical» and «horizontal».