bluuebunny/crossref_metadata_2025 huggingface dataset:
Positional relationships between a tracheal diverticulum and the tracheal tube under general anesthesia: a single-center observational and simulation study
Authors: Mitsuzawa Kunihiro , Kumagai Tsukasa , Uchida Haruo , Shimizu Toshiyuki
Published: November 2023

Background

Incomplete sealing of tracheal diverticula by a tracheal tube cuff during positive-pressure ventilation causes barotrauma but the concrete possibility of incomplete sealing has not been indicated.

We aimed to assess the possibility of incomplete sealing in a simulated situation of tracheal intubation for patients with tracheal diverticula with tube fixation where the tracheal tube’s vocal cord guide overlaps with the patient’s vocal cord.

Methods

We retrospectively assessed the characteristics of tracheal diverticula based on thoracic computed tomography data in our institution from January 2018 to July 2020. Then, we assessed the structural parameters of three single-lumen tracheal tubes (Parker Flex-Tip [Parker Medical, Bridgewater, CT, USA], Portex Soft Seal [ICU Medical, San Clemente, CA, USA], and Shiley TaperGuard [Medtronic, Dublin, Ireland]; 6.0–8.0 mm inner diameter size) and simulated the positional relationships between tracheal diverticula and the tracheal tube during tracheal intubation where the vocal cord guide overlaps with the patient’s vocal cord. We assessed each tube product’s possibility of incompletely sealing tracheal diverticula and the possibility of unintended bronchial intubation.

Results

In 5,854 patients, the prevalence of tracheal diverticula was 5.7%. The mean (SD) length from the vocal cord to the distal end of the tracheal diverticula was 52.2 (12.8) mm. Tracheal tubes with length from the distal end of the tracheal cuff to the vocal cord guide of ≥ 70 mm had a low risk of incompletely sealing tracheal diverticula (< 5%) and length from the distal end of the tube to the vocal cord guide of ≤ 95 mm had a low risk of unintended bronchial intubation (< 5%). No products in this study satisfied both outcomes.

Conclusions

Tube fixation, where the vocal cord guide overlaps with the patient’s vocal cord, is associated with risk of incompletely sealing of tracheal diverticula depending on the tube’s manufacturer and tube’s inner diameter size, although it was not a high risk. The use of small inner diameter sized tube relative to patient’s body size is high risk of incomplete sealing of tracheal diverticula.

Trial registration

This trial was prospectively registered at University Hospital Medical Information Network (UMIN). Clinical trial number and registry URL: UMIN000043317 (URL: https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000048055).
Accounting for clustering in automated variable selection using hospital data: a comparison of different LASSO approaches
Authors: Bollmann Stella , Groll Andreas , Havranek Michael M.
Published: November 2023

Background

Automated feature selection methods such as the Least Absolute Shrinkage and Selection Operator (LASSO) have recently gained importance in the prediction of quality-related outcomes as well as the risk-adjustment of quality indicators in healthcare. The methods that have been used so far, however, do not account for the fact that patient data are typically nested within hospitals.

Methods

Therefore, we aimed to demonstrate how to account for the multilevel structure of hospital data with LASSO and compare the results of this procedure with a LASSO variant that ignores the multilevel structure of the data. We used three different data sets (from acute myocardial infarcation, COPD, and stroke patients) with two dependent variables (one numeric and one binary), on which different LASSO variants with and without consideration of the nested data structure were applied. Using a 20-fold sub-sampling procedure, we tested the predictive performance of the different LASSO variants and examined differences in variable importance.

Results

For the metric dependent variableDuration Stay, we found that inserting hospitals led to better predictions, whereas for the binary variableMortality, all methods performed equally well. However, in some instances, the variable importances differed greatly between the methods.

Conclusion

We showed that it is possible to take the multilevel structure of data into account in automated predictor selection and that this leads, at least partly, to better predictive performance. From the perspective of variable importance, including the multilevel structure is crucial to select predictors in an unbiased way under consideration of the structural differences between hospitals.
Mersilene tape versus conventional sutures in transvaginal cervical cerclage: a systematic review and meta-analysis
Authors: feng Juntao , Wei Shisi , Pang Lihong
Published: November 2023

Objective

This study aimed to assess the effectiveness of Mersilene tape versus alternative suture types in prolonging singleton pregnancies as well as other pregnancy and neonatal outcomes, in cases of history-, ultrasound-, and exam-indicated cervical cerclage.

Methods

A systematic review was conducted to identify relevant studies comparing different suture types in cervical cerclage procedures. The primary outcome of interest was preterm birth (PTB) rate < 37, <35, < 28, and < 24 weeks. Statistical analyses were performed to determine the relationship between suture type and various outcomes.

Results

A total of five studies, including three randomized controlled trials (RCTs) and two retrospective studies, with a combined participation of 2325 individuals, were included. The pooled analysis indicated no significant association between suture type and PTB at less than 37 weeks of gestation (RR: 1.02, 95% CI: 0.65–1.60, p < 0.01, I2 = 74%). Women who received Mersilene tape had a higher risk of PTB at 34–37 weeks (RR: 2.62, 95% CI: 1.57–4.37, p = 0.69, I2 = 0%), but a lower risk of PTB at less than 34 weeks (RR: 0.43, 95% CI: 0.28–0.66, p = 0.66, I2 = 46%). No statistically significant differences were observed for PTB before 28 weeks (RR: 1, 95% CI: 0.65–1.53, p = 0.70, I2 = 0%), before 24 weeks (RR: 0.86, 95% CI: 0.60–1.23, p = 0.33, I2 = 0%), incidence of chorioamnionitis (RR: 0.97, 95% CI: 020-4.83, p < 0.01, I2 = 95%), neonatal intensive care unit (NICU) admission (RR: 0.79, 95% CI: 0.28–2.22, p = 0.08, I2 = 67%) and neonatal death (RR: 1.00, 95% CI: 0.42–2.35, p = 0.17, I2 = 48%).

Conclusion

Our findings suggest that Mersilene tape does not reduce the risk of PTB before 37, 28 or 24 weeks. We observed higher risk of preterm birth between 34 and 37 weeks with Mersilene tape but lower incidence before 34 weeks, a period with higher neonatal morbidity and mortality. Due to the limited number of studies, our results and their clinical significance should be interpreted with caution.
The survivin-ran inhibitor LLP-3 decreases oxidative phosphorylation, glycolysis and growth of neuroblastoma cells
Authors: Galiger Celimene , Zohora Fatema Tuj , Dorneburg Carmen , Tews Daniel , Debatin Klaus-Michael , Beltinger Christian
Published: November 2023

Background

Neuroblastoma (NB), the most common extracranial solid malignancy in children, carries a poor prognosis in high-risk disease, thus requiring novel therapeutic approaches. Survivin is overexpressed in NB, has pro-mitotic and anti-apoptotic functions, and impacts on oxidative phosphorylation (OXPHOS) and aerobic glycolysis. The subcellular localization and hence function of survivin is directed by the GTPase Ran.

Aim

To determine efficacy and modes of action of the survivin-Ran inhibitor LLP-3 as a potential novel therapy of NB.

Methods

Survivin and Ran mRNA expression in NB tumors was correlated to patient survival. Response to LLP-3 in NB cell lines was determined by assays for viability, proliferation, apoptosis, clonogenicity and anchorage-independent growth. Interaction of survivin and Ran was assessed by proximity-linked ligation assay and their subcellular distribution by confocal immunofluorescence microscopy. Expression of survivin, Ran and proteins important for OXPHOS and glycolysis was determined by Western blot, hexokinase activity by enzymatic assay, interaction of survivin with HIF-1α by co-IP, and OXPHOS and glycolysis by extracellular flux analyzer.

Results

High mRNA expression of survivin and Ran is correlated with poor patient survival. LLP-3 decreases viability, induces apoptosis, and inhibits clonogenic and anchorage-independent growth in NB cell lines, including those with MYCN amplification, and mutations of p53 and ALK. LLP-3 inhibits interaction of survivin with Ran, decreasing their concentration both in the cytoplasm and the nucleus. LLP-3 impairs flexibility of energy metabolism by inhibiting both OXPHOS and glycolysis. Metabolic inhibition is associated with mitochondrial dysfunction and attenuated hexokinase activity but is independent of HIF-1α.

Conclusion

LLP-3 attenuates interaction and concentration of survivin and Ran in NB cells. It controls NB cells with diverse genetic alterations, associated with inhibition of OXPHOS, aerobic glycolysis, mitochondrial function and HK activity. Thus, LLP-3 warrants further studies as a novel drug against NB.
Descemet membrane endothelial keratoplasty combined with presbyopia‐correcting and toric intraocular lenses – a narrative review
Authors: Rodríguez-Calvo-de-Mora Marina , Rocha-de-Lossada Carlos , Romano Vito , Rodríguez-Vallejo Manuel , Fernández Joaquín
Published: November 2023

Fuchs endothelial corneal dystrophy (FECD) is the leading indication for EK and may coexist with cataract and presbyopia. Notably, the outcomes of phacoemulsification in FECD patients are not as favorable as those in eyes without this condition. Historically, only monofocal intraocular lenses (IOLs) were recommended for these patients. However, recent reports have described the implantation of Premium-IOLs (such as Multifocal IOLs, Enhanced Depth of Focus IOLs, and Toric IOLs) in FECD eyes undergoing cataract surgery and Descemet membrane endothelial keratoplasty (DMEK). While the results are encouraging, they are not as optimal as those from unoperated eyes, especially when comparing simultaneous procedures to sequential ones. It’s advised to perform the DMEK first to improve the accuracy of IOL calculations. Still, even successfully operated eyes may experience secondary graft failure or graft rejection after DMEK. The success rate of a secondary DMEK is typically lower than that of the initial procedure. Furthermore, if the postoperative thickness after DMEK is less than anticipated, laser enhancements might not be an option. There’s a pressing need for more controlled and randomized clinical trials to ascertain the safety and effectiveness of Premium-IOLs for FECD eyes. This narrative review aims to collate evidence on the use of Premium IOL technologies in eyes receiving EK and to underscore key points for surgeons performing EK combined with cataract surgery.
Influence of bad oral habits upon the development of posterior crossbite in a preschool population
Authors: Galán-González Antonio F. , Domínguez-Reyes Antonia , Cabrera-Domínguez M. Eugenia
Published: November 2023

Background

A study is made of posterior crossbite in deciduous dentition and its possible association to extrinsic factors (bad oral habits).

Methods

A total of 1168 Spanish children between 3 and 6 years of age were included in the study. Exploration of the oral cavity was performed to assess the presence of crossbite (uni- or bilateral and/or functional), and a questionnaire was administered to the parents or caregivers to determine the presence of bad oral habits and their duration.

Results

In occlusion, 19.7% of the cases (n = 230) presented uni- or bilateral posterior crossbite. On adopting centric relation confronting the midlines, crossbite persisted in 165 children, indicating that 65 cases were due to premature contacts (functional crossbite). The identified favoring factors were pacifier use, thumb sucking, oral breathing and tongue thrusting or immature swallowing.

Discussion

Most studies in the literature report a relationship between posterior crossbite and bad oral habits. The proportion of posterior crossbites identified in our study (16.6%) is consistent with the data published by authors such as Kobayashi, Limeira or Paolantonio, among others, but differs from the results of Zhifei Zhou, Peres or Germa. In coincidence with most studies, we recorded a statistically significant association between posterior crossbite and bad oral habits.

Conclusions

Bad oral habits favor the appearance of posterior crossbite, and the duration of the habit, its intensity (in the case of thumb sucking) and type (in the case of pacifier use) act as influencing factors. Functional study characterized the types of posterior crossbites and identified those attributable to premature contacts. This aspect has not been addressed by previous studies, and we consider the findings to be very interesting for analyzing and identifying the features of true crossbites.
The self-care situation analysis of reproductive-aged women in Tehran: a survey study
Authors: Simbar Masoumeh , Kiani Zahra , Nasiri Zeinab , KhodaKarami Nahid , Nazarpour Soheila , Fakari Farzaneh Rashidi , Keyvanfar Sepideh , Majd Hamid Alavi
Published: November 2023

Background

Along with a global increase in the prevalence of infectious and non-communicable diseases, self-care with an emphasis on reproductive health Self-care has received special attention. Given the importance of women’s health, assessment of their self-care status using a valid and reliable tool seems to be necessary to determine the needs for future women’s reproductive health promotion interventions. The present study aimed to assess the women’s self-care at reproductive age in Tehran, to determine women’s health needs based on global guidelines for women’s health.

Methods

This was a descriptive cross-sectional study on 1051 women of reproductive age, living in Tehran. The Subjects were recruited using a multi-stage sampling method. The women completed a socio-demographic and valid and reliable questionnaire to assess their self-care status. The data were analyzed using SPSS 24 and by Pearson, Spearman, ANOVA, and regression tests.

Results

The mean score of self-care was 49.57 ± 23.50% in the reproductive-aged women. The lowest scores were related to psychosocial health (32.12 ± 29.93%) and reproductive-sexual health (49.74 ± 27.99%) respectively. There were significant positive correlations between the self-care and women’s education level (r = 0.180; p < 0.01), and husband’s education level (r = 0.272; p < 0.01), while there was a negative significant correlation between the self-care and the family size (r = - 0.135; p < 0.01).

Conclusion

The findings showed inadequate self-care among reproductive-aged women in Tehran. The most important challenge in their self-care behaviors was related to psychosocial and reproductive-sexual health. It seems to provide a package for promoting women’s self-care in four areas of physical, psychosocial, reproductive-sexual health, and screening tests, with an emphasis on the first two priorities, namely psychosocial and reproductive health necessary in Tehran.
Muslim women’s views and experiences of family planning in Saudi Arabia: a qualitative study
Authors: Alomair Noura , Alageel Samah , Davies Nathan , Bailey Julia V.
Published: November 2023

Background

Islamic beliefs are associated with decreased contraceptive use compared to other religions, and Muslim women’s contraceptive needs are often unmet. Research is needed to provide an in-depth understanding of the complex set of barriers to Muslim women’s contraceptive use. Therefore, we aimed to explore Muslim women’s awareness and experiences with family planning in Saudi Arabia and investigate barriers to contraceptive use and access to family planning.

Methods

A qualitative study using semi-structured interviews with women in a public hospital, in Riyadh, Saudi Arabia, between January and June 2019. Data was analysed using reflexive thematic analysis.

Results

Twenty-eight women participated in the study. Women’s contraceptive awareness was limited to two methods. Women expressed positive attitudes towards family planning and did not believe it is forbidden in Islam. Barriers to contraception use included lack of knowledge, misconceptions, fear of side effects, family and community and social norms. Many women expressed that they have the right to use contraception, even if their husbands disapprove. Our findings show that healthcare providers rarely offered contraceptive advice, even when requested. Healthcare providers often prescribe oral contraceptives without offering information on other methods available.

Conclusion

Our findings suggest that education plays a fundamental role in reproductive autonomy. Men’s role in family planning should be encouraged through sharing reproductive responsibility and supporting women’s contraceptive choices. Efforts should be directed towards improving women’s awareness of different methods of contraception.
Willingness toward post-mortem body donation to science at a Mexican university: an exploratory survey
Authors: Meester I. , Guajardo M. Polino , Ramos A. C. Treviño , Solís-Soto J. M. , Rojas-Martinez A.
Published: November 2023

Background

Voluntary post-mortem donation to science (PDS) is the most appropriate source for body dissection in medical education and training, and highly useful for biomedical research. In Mexico, unclaimed bodies are no longer a legal source, but PDS is legally possible, although scarcely facilitated, and mostly ignored by the general population. Therefore, we aimed to evaluate the attitude and willingness for PDS and to identify a sociodemographic profile of people with willingness toward PDS.

Methods

A validated on-line survey was distributed by the convenience method via the social networks of a Catholicism-inspired, private university in northern Mexico. Frequency analyses of all variables and coded free comments were complemented with association studies.

Results

Although the responder cohort (n = 143) was too small and biased to be representative of the university community (n = 13,500), willingness to post-mortem organ donation was 90.7% and to PDS 70.7%. In this cohort, PDS willingness had the strongest association with mature age (> 40 years old; P, 0.0008). Among young adults, willingness to PDS was the lowest among volunteers from technical and business schools and the highest among those from the social sciences (P, 0.009). Respondents from the social sciences were also the most consistent between attitude and behavior with respect to organ donation. A free comment option revealed respondents were interested in the unusual taboo topic.

Conclusions

A small, but sufficiently large proportion expressed willingness toward PDS. In our university cohort, which was biased in higher education and altruism, mature age and social interest were associated with PDS willingness.
Evaluating the impact of an information-based education and training platform on the incidence, severity, and coping resources status of workplace violence among nurses: a quasi-experimental study
Authors: Zhang Ying , Cai Jianzheng , Qin Ziyu , Wang Haifang , Hu Xiuying
Published: November 2023

Background

Workplace violence among nurses has emerged as a critical issue, posing a significant threat to their occupational safety. Education and training are the primary measures employed to prevent and respond to workplace violence. However, the current approaches have proven ineffective, possibly due to a lack of consideration for the specific needs of clinical nurses. Therefore, it is essential to explore the effectiveness of an informational education and training platform tailored to nurses' requirements. This study aimed to investigate the impact of such a platform on the incidence, severity, and coping resources of WPV in nurses.

Methods

This research was a quasi-experimental study. An information-based education and training platform focused on nurse workplace violence was developed through literature reviews, expert meetings, consultations with software development companies, and a trial run. A tertiary general hospital in Suzhou was selected, in which hospital district A was the intervention group and hospital district B was the control group. A total of 276 nurses were recruited, 140 in the intervention group and 136 in the control group. The nurses' incidence, severity, coping resources status, and evaluation of the application were measured before the intervention and at 1, 3, and 6 months after the intervention.

Results

The overall incidence of workplace violence, verbal aggression, and verbal threat among nurses showed statistically significant differences (P < 0.05) for the time effect, while the incidence of physical aggression demonstrated statistically significant differences (P < 0.05) for the between-group effect and the time effect. The severity of physical violence among nurses exhibited statistically significant differences (P < 0.05) for the between-group effect and time effect, and the severity of psychological violence showed statistically significant differences (P < 0.05) for the time effect. Nurses' total coping resources score and dimensions also showed statistically significant differences in terms of group, time, and interaction effects (P < 0.001). The evaluation questionnaire for the mobile application indicated usefulness scores of 2 (1, 2); ease of learning scores of 2 (1, 2); ease of use scores of 2 (1, 2); trust scores of 2 (1, 2.75); acceptance score of 1 (1, 2); and satisfaction scores of 2 (1, 2).

Conclusions

Implementing the nurse workplace violence information-based education and training platform proved beneficial in reducing the incidence and severity of workplace violence among nurses and enhancing their coping resources. This outcome suggested the platform's potential for further application and promotion in clinical settings.
Animal models of acute exacerbation of pulmonary fibrosis
Authors: Ye Xu , Zhang Mingrui , Gu Huimin , Liu Mengying , Zhao Yichao , Shi Yanchen , Wu Shufei , Jiang Cheng , Ye Xiaoling , Zhu Huihui , Li Qi , Huang Xinmei , Cao Mengshu
Published: November 2023

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive scarring interstitial lung disease with an unknown cause. Some patients may experience acute exacerbations (AE), which result in severe lung damage visible on imaging or through examination of tissue samples, often leading to high mortality rates. However, the etiology and pathogenesis of AE-IPF remain unclear. AE-IPF patients exhibit diffuse lung damage, apoptosis of type II alveolar epithelial cells, and an excessive inflammatory response. Establishing a reliable animal model of AE is critical for investigating the pathogenesis. Recent studies have reported a variety of animal models for AE-IPF, each with its own advantages and disadvantages. These models are usually established in mice with bleomycin-induced pulmonary fibrosis, using viruses, bacteria, small peptides, or specific drugs. In this review, we present an overview of different AE models, hoping to provide a useful resource for exploring the mechanisms and targeted therapies for AE-IPF.
Keratin 15 protects against cigarette smoke-induced epithelial mesenchymal transformation by MMP-9
Authors: Zhu Wensi , Han Linxiao , Wu Yuanyuan , Tong Lin , He Ludan , Wang Qin , Yan Yu , Pan Ting , Shen Jie , Song Yuanlin , Shen Yao , Zhu Qiaoliang , Zhou Jian
Published: November 2023

Background

Chronic obstructive pulmonary disease (COPD), a chronic inflammatory lung disease, is a leading cause of morbidity and mortality worldwide. Prolonged cigarette smoking (CS) that causes irreversible airway remodeling and significantly reduces lung function is a major risk factor for COPD. Keratin15+ (Krt15+) cells with the potential of self-renewal and differentiation properties have been implicated in the maintenance, proliferation, and differentiation of airway basal cells; however, the role of Krt15 in COPD is not clear.

Methods

Krt15 knockout (Krt15−/−) and wild-type (WT) mice of C57BL/6 background were exposed to CS for six months to establish COPD models. Krt15-CrePGR;Rosa26-LSL-tdTomato mice were used to trace the fate of the Krt15+ cells. Hematoxylin and eosin (H&E) and Masson stainings were performed to assess histopathology and fibrosis, respectively. Furthermore, lentivirus-delivered short hairpin RNA (shRNA) was used to knock down KRT15 in human bronchial epithelial (HBE) cells stimulated with cigarette smoke extract (CSE). The protein expression was assessed using western blot, immunohistochemistry, and enzyme-linked immunosorbent assay.

Results

Krt15−/− CS mice developed severe inflammatory cell infiltration, airway remodeling, and emphysema. Moreover, Krt15 knockout aggravated CS-induced secretion of matrix metalloproteinase-9 (MMP-9) and epithelial–mesenchymal transformation (EMT), which was reversed by SB-3CT, an MMP-9 inhibitor. Consistent with this finding, KRT15 knockdown promoted MMP-9 expression and EMT progression in vitro. Furthermore, Krt15+ cells gradually increased in the bronchial epithelial cells and were transformed into alveolar type II (AT2) cells.

Conclusion

Krt15 regulates the EMT process by promoting MMP-9 expression and protects the lung tissue from CS-induced injury, inflammatory infiltration, and apoptosis. Furthermore, Krt15+ cells transformed into AT2 cells to protect alveoli. These results suggest Krt15 as a potential therapeutic target for COPD.
ALKBH5-mediated CHAC1 depletion promotes malignant progression and decreases cisplatin-induced oxidative stress in gastric cancer
Authors: Chen Chunting , Zhai Ertao , Liu Yinan , Qian Yan , Zhao Risheng , Ma Yan , Liu Jianqiu , Huang Zhixin , Chen Jianhui , Cai Shirong
Published: November 2023

The m6a demethyltransferase ALKBH5 dynamically modulates gene expression and intracellular metabolic molecules by modifying RNA m6a in cancer cells. However, ALKBH5’s function in gastric cancer (GC) has remained controversial. This study demonstrates that ALKBH5 is highly expressed in GC. Silencing ALKBH5 hampers proliferation, and metastatic potential, and induces cell death in GC cells. Through a comprehensive analysis of the transcriptome and m6A sequencing, alterations in certain ALKBH5 target genes, including CHAC1, were identified. ALKBH5’s demethylation effect regulates CHAC1 RNA stability, leading to reduced CHAC1 expression. Moreover, CHAC1 modulates intracellular ROS levels, influencing the chemotherapy sensitivity of gastric cancer. In summary, our study unveils the pivotal role of the ALKBH5-CHAC1-ROS axis and highlights the significance of m6A methylation in gastric cancer.
Non-alcoholic fatty liver disease risk prediction model and health management strategies for older Chinese adults: a cross-sectional study
Authors: Pan Hong , Liu Baocheng , Luo Xin , Shen Xinxin , Sun Jijia , Zhang An
Published: November 2023

Background

Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver condition that affects a quarter of the global adult population. To date, only a few NAFLD risk prediction models have been developed for Chinese older adults aged ≥ 60 years. This study presented the development of a risk prediction model for NAFLD in Chinese individuals aged ≥ 60 years and proposed personalised health interventions based on key risk factors to reduce NAFLD incidence among the population.

Methods

A cross-sectional survey was carried out among 9,041 community residents in Shanghai. Three NAFLD risk prediction models (I, II, and III) were constructed using multivariate logistic regression analysis based on the least absolute shrinkage and selection operator regression analysis, and random forest model to select individual characteristics, respectively. To determine the optimal model, the three models’ discrimination, calibration, clinical application, and prediction capability were evaluated using the receiver operating characteristic (ROC) curve, calibration plot, decision curve analysis, and net reclassification index (NRI), respectively. To evaluate the optimal model’s effectiveness, the previously published NAFLD risk prediction models (Hepatic steatosis index [HSI] and ZJU index) were evaluated using the following five indicators: accuracy, precision, recall, F1-score, and balanced accuracy. A dynamic nomogram was constructed for the optimal model, and a Bayesian network model for predicting NAFLD risk in older adults was visually displayed using Netica software.

Results

The area under the ROC curve of Models I, II, and III in the training dataset was 0.810, 0.826, and 0.825, respectively, and that of the testing data was 0.777, 0.797, and 0.790, respectively. No significant difference was found in the accuracy or NRI between the models; therefore, Model III with the fewest variables was determined as the optimal model. Compared with the HSI and ZJU index, Model III had the highest accuracy (0.716), precision (0.808), recall (0.605), F1 score (0.692), and balanced accuracy (0.723). The risk threshold for Model III was 20%–80%. Model III included body mass index, alanine aminotransferase level, triglyceride level, and lymphocyte count.

Conclusions

A dynamic nomogram and Bayesian network model were developed to identify NAFLD risk in older Chinese adults, providing personalized health management strategies and reducing NAFLD incidence.
Association of insulin resistance with polycystic ovary syndrome phenotypes and patients’ characteristics: a cross-sectional study in Iran
Authors: Rahmatnezhad Leili , Moghaddam-Banaem Lida , Behroozi-Lak Tahereh , Shiva Afshin , Rasouli Javad
Published: November 2023

Background

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women. This disorder affects 6–15% of women of childbearing age worldwide. It is diagnosed with hyperandrogenism, polycystic ovaries, and chronic anovulation with insulin resistance. This study aimed to assess the prevalence of insulin resistance (IR) in 4 phenotypes of PCOS, and its relationship with demographic, clinical, and paraclinical individual characteristics in a sample of Iranian PCOS patients.

Methods

This particular cross-sectional investigation involved 160 female participants, aged between 18 and 45 years, who were receiving care at gynecology clinics in Urmia, northwestern Iran. All the participants had been diagnosed with PCOS and were categorized into one of four phenotypes. All the participants underwent clinical evaluations, paraclinical assessments, and ultrasound scans. IR was defined as HOMA-IR > 2.5. The statistical significance level was 0.05.

Results

Among the 160 participants, the prevalences of the 4 phenotypes were: A: 83 (51.9%), B: 37 (23.1%), C: 21 (13.1%), and D: 19 (11.9%). IR was detected in 119 participants (74.4%); its rate was significantly different between the 4 phenotypes (p-value: 0.008) as A: 62 (74.7%), B: 34 (91.9%), C: 12 (57.1%), D: 11 (57.9%). Linear and logistic regression analyses were performed to control confounding factors. In linear regression, PCOS phenotype, classic phenotype (A&B), economic status, and Hb levels were significantly related to HOMA-IR; in logistic regression Hb levels, exercise, economic status, and PCOS phenotypes were significantly associated with insulin resistance.

Conclusions

The most prevalent PCOS phenotype in this study was A. PCOS phenotypes were significantly related to insulin resistance and HOMA-IR, with the highest levels of insulin resistance and HOMA-IR observed in phenotype B. Determining the phenotype of PCOS may be helpful for better management of PCOS and its associated complications. However, further investigations are recommended in this regard.
Multi-omics study identifies that PICK1 deficiency causes male infertility by inhibiting vesicle trafficking in Sertoli cells
Authors: Jin Jing , Li Kaiqiang , Du Yaoqiang , Gao Fang , Wang Zhen , Li Weixing
Published: November 2023

Background

Infertility affects approximately 10–15% of reproductive-age men worldwide, and genetic causes play a role in one-third of cases. As a Bin-Amphiphysin-Rvs (BAR) domain protein, protein interacting with C-kinase 1 (PICK1) deficiency could lead to impairment of acrosome maturation. However, its effects on auxiliary germ cells such as Sertoli cells are unknown.

Purpose

The present work was aimed to use multi-omics analysis to research the effects ofPICK1deficiency on Sertoli cells and to identify effective biomarkers to distinguish fertile males from infertile males caused byPICK1deficiency.

Methods

Whole-exome sequencing (WES) was performed on 20 infertility patients with oligozoospermia to identify pathogenicPICK1mutations. Multi-omics analysis of aPICK1knockout (KO) mouse model was utilized to identify pathogenic mechanism. Animal and cell function experiments of Sertoli cell-specificPICK1KO mouse were performed to verify the functional impairment of Sertoli cells.

Results

Two loss-of-function deletion mutations c.358delA and c.364delA inPICK1resulting in transcription loss of BAR functional domain were identified in infertility patients with a specific decrease in serum inhibin B, indicating functional impairment of Sertoli cells. Multi-omics analysis ofPICK1KO mouse illustrated that targeted genes of differentially expressed microRNAs and mRNAs are significantly enriched in the negative regulatory role in the vesicle trafficking pathway, while metabolomics analysis showed that the metabolism of amino acids, lipids, cofactors, vitamins, and endocrine factors changed. The phenotype ofPICK1KO mouse showed a reduction in testis volume, a decreased number of mature spermatozoa and impaired secretory function of Sertoli cells. In vitro experiments confirmed that the expression of growth factors secreted by Sertoli cells inPICK1conditional KO mouse such as Bone morphogenetic protein 4 (BMP4) and Fibroblast growth factor 2 (FGF2) were decreased.

Conclusions

Our study attributed male infertility caused byPICK1deficiency to impaired vesicle-related secretory function of Sertoli cells and identified a variety of significant candidate biomarkers for male infertility induced byPICK1deficiency.
Health system productivity in sub-Saharan Africa: tuberculosis control in high burden countries
Authors: Atake Esso-Hanam
Published: November 2023

Background

Sixteen of the 30 countries with a high tuberculosis (TB) burden are in Sub-Saharan Africa (SSA). Over 25% of TB deaths occur in the Africa region. This study aims to estimate the productivity changes of TB programs in 16 SSA countries where TB is endemic.

Methods

We used Hicks-Moorsteen index to compute and decompose Total factor productivity (TFP), and the β-convergence and σ-convergence tests to check for convergence patterns among SSA countries.

Results

We found that technological change has been the main driver of the TFP growth, and that increasing technical efficiency may be the first objective in efforts to improve TFP of TB programs. Moreover, the convergence tests reveal significant homogeneity in terms of TFP change between SSA countries studied.

Conclusion

The findings suggest that improving technical efficiency of TB programs mainly calls for better resource allocation, capacity building in governance and management of programs, improved training of the health providers and stronger prevention policies. Policymakers must design models for integration of TB treatment under the universal health insurance schemes.
Protective role of IL-17-producing γδ T cells in a laser-induced choroidal neovascularization mouse model
Authors: Chang Yu-Hsien , Hsing Chung-Hsi , Chiu Chiao-Juno , Wu Yi-Rou , Hsu Sheng-Min , Hsu Yu-Hsiang
Published: November 2023

Background

Vision loss in patients with wet/exudative age-related macular degeneration (AMD) is associated with choroidal neovascularization (CNV), and AMD is the leading cause of irreversible vision impairment in older adults. Interleukin-17A (IL-17A) is a component of the microenvironment associated with some autoimmune diseases. Previous studies have indicated that wet AMD patients have elevated serum IL-17A levels. However, the effect of IL-17A on AMD progression needs to be better understood. We aimed to investigate the role of IL-17A in a laser-induced CNV mouse model.

Methods

We established a laser-induced CNV mouse model in wild-type (WT) and IL-17A-deficient mice and then evaluated the disease severity of these mice by using fluorescence angiography. We performed enzyme-linked immunosorbent assay (ELISA) and fluorescence-activated cell sorting (FACS) to analyze the levels of IL-17A and to investigate the immune cell populations in the eyes of WT and IL-17A-deficient mice. We used ARPE-19 cells to clarify the effect of IL-17A under oxidative stress.

Results

In the laser-induced CNV model, the CNV lesions were larger in IL-17A-deficient mice than in WT mice. The numbers of γδ T cells, CD3+CD4+RORγt+ T cells, Treg cells, and neutrophils were decreased and the number of macrophages was increased in the eyes of IL-17A-deficient mice compared with WT mice. In WT mice, IL-17A-producing γδ T-cell numbers increased in a time-dependent manner from day 7 to 28 after laser injury. IL-6 levels increased and IL-10, IL-24, IL-17F, and GM-CSF levels decreased in the eyes of IL-17A-deficient mice after laser injury. In vitro, IL-17A inhibited apoptosis and induced the expression of the antioxidant protein HO-1 in ARPE-19 cells under oxidative stress conditions. IL-17A facilitated the repair of oxidative stress-induced barrier dysfunction in ARPE-19 cells.

Conclusions

Our findings provide new insight into the protective effect of IL-17A in a laser-induced CNV model and reveal a novel regulatory role of IL-17A-producing γδ T cells in the ocular microenvironment in wet AMD.
Thoracic day surgery versus thoracic inpatient surgery for treatment of patients with lung cancer: a systematic review and meta-analysis
Authors: Shen Cheng , Che Guowei
Published: November 2023

Background

The successful implementation of the Enhanced recovery after surgery (ERAS) concept in thoracic surgery has made it possible to complete the surgery in the day surgery unit. However, it is still unclear whether day surgery for lung cancer patients can achieve the same or even better results.

Methods

A systematic literature search was completed in common databases for studies published before May 2022 and the data analyzed using the Review Manager 5.3 software.

Results

We ultimately included 7 retrospective articles that met our criteria for the study. The results of age, smoking status, comorbidity and pulmonary function tests in day surgery group were better than in inpatient surgery group. Minimally invasive surgical method with segmentectomy was more used in day surgery group than in normal surgery group. The 30-day mortality was also lower in Day surgery group and it displayed that early discharged patients had fewer overall complications than the inpatient surgery group.

Conclusions

We demonstrate that younger patients, patients receiving segmental resections by VATS, and those with better pulmonary function tests or without comorbidity can be discharged early with low rates of complications and 30-day mortality, especial with ERAS program.
Educational needs of patients, families, and healthcare professionals to support the patient journey in haemophilia gene therapy in the UK
Authors: Boyce Sara , Fletcher Simon , Jones April , Kohli Ruchika , Mangles Sarah , Ong Min , Pollard Debra , Sivasubramaniyam Sujan , Stephensen David , Stoner Nicola , Kazmi Rashid
Published: November 2023

With the first gene therapies for haemophilia approved by the European Commission, the US Food and Drug Administration, and the Medicines and Healthcare products Regulatory Agency, it is important to consider the remaining unmet needs and challenges that may arise throughout patients’ treatment journeys. We discuss existing unmet needs and important considerations prior to, during, and following haemophilia gene therapy treatment in the UK, and propose potential next steps. Key areas for attention are education, psychological support, and guidance on implementation. Strategies are urgently required to fulfil these needs. An immediate priority for information providers should be comprehensive education for people with haemophilia (PWH) and healthcare professionals (HCPs). Greater access to resources and training in psychological services will be required throughout the treatment pathway. More specific guidance is required to define the implementation model, criteria for accreditation, and responsibilities of care centres. Furthermore, PWH may revisit discussions with HCPs multiple times pre-infusion, thus the patient journey is unlikely to be linear. Consideration of these challenges, and of potential strategies to address them, will be integral to optimising the future success of this promising therapy.
Cancer-associated fibroblasts-derived CXCL12 enhances immune escape of bladder cancer through inhibiting P62-mediated autophagic degradation of PDL1
Authors: Zhang Zhao , Yu Yongbo , Zhang Zhilei , Li Dan , Liang Zhijuan , Wang Liping , Chen Yuanbin , Liang Ye , Niu Haitao
Published: November 2023

Background

Cancer-associated fibroblasts (CAFs), the predominant stromal cell of tumor microenvironment (TME), play an important role in tumor progression and immunoregulation by remodeling extracellular matrix (ECM) and secreting cytokines. However, little is known about the details of the underlying mechanism in bladder cancer.

Methods

Bioinformatics analysis was performed to analyze the prognostic value of CAFs and CXCL12 using GEO, TCGA and SRA databases. The effects of CXCL12 on bladder cancer progression were investigated through in vitro and in vivo assays. The biological mechanism of the effect of CXCL12 on PDL1 were investigated using western blotting, immunoprecipitation, RT-PCR, immunofluorescence, mass spectrometry, protein stability, and flow cytometry.

Results

The results demonstrated that CAFs-derived CXCL12 promoted cancer cell migration and invasion and upregulated PDL1. Mechanistically, upon binding to its specific receptor, CXCL12 activated the downstream JAK2/STAT3 pathway and rapidly up-regulated the expression of deubiquitinase CYLD. CYLD deubiquitinated P62 causing P62 accumulation, which in turn inhibited the autophagic degradation of PDL1. In vivo experiments demonstrated that blocking CXCL12 inhibited tumor growth, reduced tumor PDL1 expression and increased immune cell infiltration.

Conclusions

This study revealed a novel mechanism for the role of CXCL12 in P62-mediated PDL1 autophagic regulation. Combined application of CXCL12 receptor blocker and PD1/PDL1 blocker can more effectively inhibit PDL1 expression and enhance antitumor immune response. Targeting CAFs-derived CXCL12 may provide an effective strategy for immunotherapy in bladder cancer.
Attitudes and barriers to participation in window-of-opportunity trials reported by White and Asian/Asian British ethnicity patients who have undergone treatment for endometrial cancer
Authors: Mandane B. , Amirthanayagam A. , Patel N. , Darko N. , Moss E. L.
Published: November 2023

Purpose

Window-of-opportunity trials (WOT) are a study design that have been used to investigate drug activity in endometrial cancer (EC). Recruitment to cancer clinical trials by patients from ethnic minority groups is reported to be lower than for patients of White ethnicity.

Methods

A verbal questionnaire was conducted with White and Asian/Asian British ethnicity patients who had undergone treatment for EC. Strategic purposeful sampling was used to recruit patients from diverse social/educational backgrounds. Questions explored: background knowledge of clinical research, WOT study design, and views on medications that might be investigated. Thematic analysis was used to explore motivations for WOT participation and perceived barriers.

Results

In total, 21 patients were recruited to the study (15 White and 6 Asian/Asian British). Views on optimum time to receive trial information differed, preferences ranging from 'at the time of diagnosis' to 'a few days after diagnosis'. The choice of medication under investigation had a strong influence on potential willingness to participate, with greater interest reported in medications derived from vitamins or food supplements rather than hormone-based drugs. Potential barriers to participation included concern over potential side-effects and the emotional/physical burden of a cancer diagnosis prior to major surgery.

Discussion

This study provides important insights into patients’ views on WOT participation in EC and raises issues that need to be considered for future trial design and participant recruitment materials. The timing and format of study information and type of substance under investigation were factors influencing potential participation. Future studies should consider using multi-lingual visual information videos to address information needs, as this may encourage participation by ethnic minority patients.
Awareness with paralysis and symptoms of post-traumatic stress disorder among mechanically ventilated emergency department survivors (ED-AWARENESS-2 Trial): study protocol for a pragmatic, multicenter, stepped wedge cluster randomized trial
Authors: Fuller Brian M. , Driver Brian E. , Roberts Michael B. , Schorr Christa A. , Thompson Kathryn , Faine Brett , Yeary Julianne , Mohr Nicholas M. , Pappal Ryan D. , Stephens Robert J. , Yan Yan , Johnson Nicholas J. , Roberts Brian W.
Published: November 2023

Background

Awareness with paralysis (AWP) is memory recall during neuromuscular blockade (NMB) and can cause significant psychological harm. Decades of effort and rigorous trials have been conducted to prevent AWP in the operating room, where prevalence is 0.1–0.2%. By contrast, AWP in mechanically ventilated emergency department (ED) patients is common, with estimated prevalence of 3.3–7.4% among survivors given NMB. Longer-acting NMB use is a critical risk for AWP, and we have shown an association between ED rocuronium use and increased AWP prevalence. As NMB are given to more than 90% of ED patients during tracheal intubation, this trial provides a platform to test an intervention aimed at reducing AWP. The overall objective is to test the hypothesis that limiting ED rocuronium exposure will significantly reduce the proportion of patients experiencing AWP.

Methods

This is a pragmatic, stepped wedge cluster randomized trial conducted in five academic EDs, and will enroll 3090 patients. Per the design, all sites begin in a control phase, under observational conditions. At 6-month intervals, sites sequentially enter a 2-month transition phase, during which we will implement the multifaceted intervention, which will rely on use of nudges and defaults to change clinician decisions regarding ED NMB use. During the intervention phase, succinylcholine will be the default NMB over rocuronium. The primary outcome is AWP, assessed with the modified Brice questionnaire, adjudicated by three independent, blinded experts. The secondary outcome is the proportion of patients developing clinically significant symptoms of post-traumatic stress disorder at 30 and 180 days after hospital discharge. We will also assess for symptoms of depression and anxiety, and health-related quality of life. A generalized linear model, adjusted for time and cluster interactions, will be used to compare AWP in control versus intervention phases, analyzed by intention-to-treat.

Discussion

The ED-AWARENESS-2 Trial will be the first ED-based trial aimed at preventing AWP, a critical threat to patient safety. Results could shape clinical use of NMB in the ED and prevent more than 10,000 annual cases of AWP related to ED care.

Trial registration

ClinicalTrials.gov identifier NCT05534243. Registered 06, September 2022.