bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perioperative tislelizumab plus chemotherapy for locally advanced resectable thoracic esophageal squamous cell carcinoma trial: a prospective single-arm, phase II study (PILOT trial)
Authors: Ding Chengzhi , Guo Yijun , zhou Yaning , He Yi , Chen Chunji , Zhang Ming , Guo Xufeng 
Published: December 2023

Abstract
Background
The promising therapeutic outcomes of neoadjuvant immunotherapy combined with chemotherapy in the treatment of locally advanced esophageal squamous cell carcinoma (ESCC) have been confirmed by several phase II clinical trials and have been widely demonstrated in clinical work. Theoretically, postoperative adjuvant immunotherapy may further improve the therapeutic effect, but there is still lack of evidence. The aim of this study was to analyse the safety and efficacy of perioperative immunotherapy (tislelizumab) in locally advanced resectable thoracic ESCC (PILOT trial).

Methods
Seventy-three eligible patients with pathologically confirmed thoracic ESCC of clinical T1b-3N1-3M0 or T3N0M0 stage were allocated to receive neoadjuvant immunotherapy (tislelizumab 200 mg d1, q3w × 2 cycles) plus chemotherapy (nad-paclitaxel 260 mg/m2 d1 + carboplatin AUC = 5 d1, q3w × 2 cycles) treatment. Patients with pathologic complete response (pCR) after esophagectomy received adjuvant tislelizumab (200 mg every 3 weeks for up to one year), and patients with non-pCR were assigned adjuvant tislelizumab plus chemotherapy for two cycles and then maintenance tislelizumab (200 mg every 3 weeks for up to 15 cycles). The primary endpoint of this study is 2-year disease-free survival (DFS) in non-pCR patients. The secondary endpoints include pCR rate, major pathological response rate, 2-year DFS in pCR patients, R0 resection rate, adverse events, and overall survival.

Discussion
This protocol was reviewed and approved by the Ethics Committee of Shanghai Chest Hospital (IS23059). This is the first prospective clinical trial to investigate the safety and efficacy of perioperative immunotherapy for locally advanced resectable thoracic ESCC. We hypothesize that perioperative immunotherapy could be a promising therapeutic strategy that can provide better 2-year DFS in non-pCR patients.

Trial registration
ClinicalTrial.gov: NCT0605633.
Predictors of mortality among under-five children in rural Ethiopia: a cross sectional study
Authors: Gebrerufael Gebru Gebremeskel , Hagos Bsrat Tesfay 
Published: December 2023

Abstract
Background
Under-five child mortality (UFCM) is one of the major significant and sensitive indicators of the health status of the public. Although the world has seen a remarkable and substantial decrease in UFCM since 1990, its progression rate still remains alarmingly high in Sub-Saharan African (SSA) countries, particularly in Ethiopia. Therefore, this study aimed to assess associations between mortality and under-five children in rural Ethiopia.

Methods
This study used a secondary data analysis of the 2019 Ethiopia Mini Demographic and Health Survey (EMDHS) report. A total of 4,425 under-five children were included in the final analysis. The Kaplan-Meier (K-M) and Cox proportional hazard (PH) model analyses were utilized to estimate survival time and investigate the major predictors of mortality in under-five children, respectively. An adjusted hazard ratio (AHR) along with a 95% confidence interval (CI) was employed to measure the association size and direction of the association (STATA 12).

Results
The study showed that 6.2% (95% CI: 5.43, 6.86) of children died beforehand celebrating their fifth birthday in rural Ethiopia. The multivariable Cox PH regression model analysis revealed associations of large spacing preceding birth interval (16–26 months) (AHR = 0.61; 95% CI: (0.402–0.920)), 27–38 months (AHR = 0.72; 95% CI: (0.496–1.03)), and ≥ 39 months, multiple births (AHR = 3.9; 95% CI: (2.77–5.62)), being breastfeeding (AHR = 0.13; 95% CI: (0.099–0.162)), and unvaccinated child (AHR = 11.6; 95% CI: (1.62–83.1)) were significant associations of under-five children mortality.

Conclusions
In this study, the UFCM rate was present, with 6.2% in the rural areas of Ethiopia. The birth type, preceding birth interval, vaccination of the child, and breastfeeding are identified as significant associations with under-five child mortality in rural Ethiopia. Therefore, public health interventions should be given attention to multiple births, unvaccinated, and non-breastfeeding children, as well as mothers’ better encouragement to have a large spacing preceding the birth interval. Moreover, investigators should conduct continuous research on UFCM, which is imperative to provide current information and inform interventions in a timely manner.
Additive interactions between obesity and insulin resistance on hypertension in a Chinese rural population
Authors: Li Xiaoxia , Chang Xiaoyu , Dang Yuanyuan , Xue Yixuan , Wang Qingan , Liu Wanlu , Yin Ting , Zhao Yi , Zhang Yuhong 
Published: December 2023

Abstract
Background
Adiposity and insulin resistance (IR) are closely associated with hypertension; however, the role of interactions between obesity phenotypes and IR in hypertension is unclear. This study aimed to evaluate the interactions of body mass index (BMI), waist circumference (WC), and body fat percentage (BF%) with IR on hypertension risk.

Methods
We analyzed data from 4888 participants (mean age 57 years, 41.2% men) in the China Northwest Natural Population Cohort, Ningxia Project. BMI, WC, and BF% were determined using bioelectrical impedance analysis devices. IR was estimated using a homeostasis model assessment index (HOMA-IR). Multivariable-adjusted logistic regression was used to evaluate the association between HOMA-IR and hypertension risk. We calculated the relative excess risk and attributable proportion with their 95% confidence intervals (CIs) to assess whether adiposity phenotypes modified the effect of HOMA-IR on hypertension risk.

Results
The crude prevalence of hypertension was 52.2%. The multivariable-adjusted odds ratio of HOMA-IR was 1.80 (95% CI: 1.23–2.65) for the risk of hypertension in the highest versus the lowest quartiles, but this association became marginal in models further adjusting for BMI, WC, and BF% (P for trend = 0.056). Relative excess risk and attributable proportion for interaction between high HOMA-IR and high BF% were 0.32 (0.04–0.59) and 0.33 (0.06–0.60), respectively. Additionally, high truncal and leg BF% and high HOMA-IR accounted for the hypertension risk in women, but not in men. We did not observe any significant interactions between BMI or WC and HOMA-IR on hypertension.

Conclusion
BF% modified the association between IR and increased risk of hypertension in women with high truncal and leg BF%, but not in men.
MRI-based navigated cryosurgery of extra-abdominal desmoid tumors using skin fiducial markers: a case series of 15 cases
Authors: Segal Ortal , Benady Amit , Pickholz Eliana , Ovadia Joshua E. , Druckmann Ido , Dadia Solomon , Rath Ehud , Albagli Assaf , Efrima Ben 
Published: December 2023

Abstract
Background
Precision surgery is becoming increasingly important in the field of Orthopaedic Oncology. Image-guided percutaneous cryosurgery (CRA) has emerged as a valid treatment modality for extra-abdominal desmoid tumors (EDTs). To date, most CRA procedures use CT-based guidance which fails to properly characterize tumor segments. Computer-guided MRI navigation can address this issue however, the lack of a fixed landmark for registration remains a challenge. Successful CRA correlates directly with precision approaches facilitated by intraoperative imaging guidance. This is the first study that attempts to assess the feasibility and efficacy of a novel approach of using skin fiducial markers to overcome the challenge of a MRI-based navigation CRA for symptomatic or progressive EDTs.

Methods
In this retrospective study conducted between 2018 and 2020, 11 patients at a single center with symptomatic or progressive EDTs were treated with CRA using intraoperative MRI navigation. Fifteen cryosurgery procedures were performed, each adhering to a personalized pre-operative plan. Total tumor size, viable and non-viable portions pre- and post-operation, and SF-36 questionnaire evaluating subjective health were recorded.

Results
All CRAs demonstrated 100% adherence to the predetermined plan. Overall, tumor size decreased Median= -56.9% [-25.6, -72.4]) with a reduction in viable tissue, (Median= -80.4% [-53.3, -95.2]). Four patients required additional CRAs. Only one patient’s tumor did not reduce in size. One patient suffered from local muscle necrosis. Pre-operation, the average physical and mental scores 41.6 [29.4, 43] and 26.3 [17.6, 40.9] respectively. Post-operation, the average physical and mental scores were 53.4[38, 59.7] and 38 [31.2, 52.7] respectively.

Conclusion
These findings provide an early indication of the feasibility and efficacy of performing percutaneous cryosurgery using skin fiducial marker registration for MRI-computed navigation to treat EDTs safely. Larger cohorts and multicenter evaluations are needed to determine the efficacy of this technique.
Shape-memory sawtooth-arm embracing clamp used in complex femoral revision hip arthroplasty for stem stability: average 9-year follow-up study
Authors: Hu Yi , Xu Zhengquan , Qiao Hua , Kong Keyu , Li Huiwu , Zhang Jingwei 
Published: December 2023

Abstract
Background
Nickel-Titanium shape-memory sawtooth-arm embracing clamps (SSECs) have been used in revision total hip arthroplasties (rTHAs) to protect stem stability. This study was to introduce this technique and report its mid to long-term clinical and radiographic outcomes.

Methods
We retrospectively reviewed all patients implanted with SSECs in our department from January 2008 to December 2015. 41 patients (41 hips) were finally included. Radiographs and Harris hip scores (HHS) were collected. Radiographs were blindly analyzed for evidence of loosening, subsidence and stress shielding. HHS were compared to previous records by student’s t tests. The average follow-up period was 9.3 years.

Results
All stems were stably fixed with no signs of loosening. The mean stem subsidence was 0.9 mm (range, 0 to 3 mm). Only one patient (2.4%) demonstrated the fourth degree of stress shielding, with the others none or minor bone resorption. The mean HHS at the final follow-up was 84.2 (range, 81 to 91), which was improved from 17.4 (range, 0 to 37) before surgery. No implant failures or re-revisions occurred. Dislocation occurred in 1 case during the follow-up period.

Conclusions
The SSEC protected stem fixation and achieved favorable clinical and radiographic outcomes in this 9-year follow-up study. It offered an additional extramedullary fixation option for surgeons to choose from in treating complex femoral revision arthroplasties.
Artichoke (Cynara scolymus L.) water extract alleviates palmitate-induced insulin resistance in HepG2 hepatocytes via the activation of IRS1/PI3K/AKT/FoxO1 and GSK-3β signaling pathway
Authors: Deng Aihua , Wang Yun , Huang Kerui , Xie Peng , Mo Ping , Liu Fengying , Chen Jun , Chen Kaiyi , Wang Yun , Xiao Bing 
Published: December 2023

Abstract
Background
Artichoke (Cynara scolymus L.) is a typical element of a traditional Mediterranean diet and has potential health advantages for insulin resistance (IR) and type 2 diabetes mellitus (T2DM). This study aims to evaluate the effect and underlying mechanism of artichoke water extract (AWE) on palmitate (PA)-induced IR in human hepatocellular carcinoma (HepG2) cells.

Methods
The effect of AWE on cell viability was determined using CCK8 assay. Cellular glucose uptake, glucose consumption, glucose production, and glycogen content were assessed after AWE treatment. The gene expression and protein levels were examined by real-time polymerase chain reaction (qRT-PCR) and western blotting.

Results
The results showed that AWE dose-dependently increased cell viability in IR HepG2 cells (P < 0.01). AWE treatment significantly promoted glucose uptake and consumption, decreased glucose production, and increased the cellular glycogen content in IR HepG2 cells (P < 0.01). Mechanistically, AWE elevated the phosphorylation and total protein levels of major insulin signaling molecules in IR HepG2 cells, which resulted in a decrease in the expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) and the inhibition of glycogen synthase (GS) phosphorylation in IR HepG2 cells. Furthermore, the protective effect of AWE on IR HepG2 cells might be ascribed to the inhibition of the endoplasmic reticulum (ER) stress.

Conclusion
We conclude that AWE may improve glucose metabolism by regulating IRS1/PI3K/AKT/FoxO1 and GSK-3β signaling associated with the inhibition of ER stress in IR HepG2 cells induced by PA.
Ammidin ameliorates myocardial hypoxia/reoxygenation injury by inhibiting the ACSL4/AMPK/mTOR-mediated ferroptosis pathway
Authors: Han Yue , Yuan Hui , Li Fengxiang , Yuan Yueying , Zheng Xuezhi , Zhang Xudong , Sun Jian 
Published: December 2023

Abstract
Objective
The aim of the present study was to investigate the therapeutic effect of ammidin on hypoxia/reoxygenation (H/R) injury in primary neonatal rat cardiomyocytes by observing the role of ferroptosis in the process of H/R injury, and to verify its target and regulatory signaling pathways.

Methods
The network pharmacology analysis was used to predict the biological processes, core targets and related signaling pathways of Angelica dahurica in the treatment of ferroptosis. Cell viability was assessed using live cell imaging and cell counting kit-8. Lactate dehydrogenase (LDH), reactive oxygen species (ROS) production, and malondialdehyde (MDA), superoxide dismutase (SOD) and mitochondrial membrane potential (MMP) content were determined to assess the level of ferroptosis. Western blotting was performed to measure protein expression.

Results
Network pharmacology predicted that Acyl-CoA synthetase long chain family member 4 (ACSL4) was highly associated with myocardial H/R injury in the intersection of Angelica dahurica and ferroptosis. The top three active components of Angelica dahurica were found to be mandenol, alloisoimperatorin and ammidin, among which ammidin was found to have the strongest binding to the target proteins of the ACSL4/AMPK/mTOR pathway. H/R reduced the viability of cardiomyocytes, while the inhibition of ferroptosis by ferrostatin-1 alleviated the H/R-induced inhibition of cardiomyocyte viability. This was evidenced by the increased cell viability, SOD release, MMP level and glutathione peroxidase 4 (GPX4) protein expression, as well as the decreased LDH and MDA release and ROS production and ACSL4 protein expression (P < 0.05). To verify the existence of ferroptosis in myocardial hypoxia/reoxygenation injury. In addition, ammidin increased cell viability and GPX4 protein expression (P < 0.05), decreased ROS generation, and MDA and MTT expression (P < 0.05), then inhibited ferroptosis, and finally alleviated myocardial H/R injury by regulating the ACSL4/AMPK signaling pathway.

Conclusions
Network pharmacology was used to predict the correlation between ammidin and ferroptosis following myocardial H/R injury. It was demonstrated that ammidin may regulate ferroptosis by inhibiting the ACSL4/AMPK/mTOR signaling pathway and reduce H/R injury in cardiomyocytes.
Development of a low-cost congenital abdominal wall defect simulator (wall-go) for undergraduate medical education: a validation study
Authors: Medeiros Gabriel Araújo , Gualberto Igor José Nogueira , da Silva Carlos Henrique Nascimento Domingue , Diniz Ana Maria Bicudo , de Santana Jan Beatriz Felinto , Volpe Fábio Perecin , Gadde Rahul , Mazzo Alessandra , de Oliveira Rodrigo Cardoso , Sbragia Lourenço 
Published: December 2023

Abstract
Background
Congenital Anomalies were responsible for 303,000 deaths in the neonatal period, according to the WHO, they are among the world’s top 20 causes of morbidity and mortality. Expensive simulators demonstrate several diseases, but few are related to congenital anomalies. This study aims to develop, validate, and evaluate low-cost simulator models (WALL-GO) of the most common abdominal wall defects, gastroschisis, and omphalocele, to enable diagnosis through an accessible tool with study value and amenable to replication.

Methods
Market research was conducted to find materials to build low-cost models. The researchers built the model and underwent validation assessment of the selected experts who scored five or more in the adapted Fehring criteria. The experts were assessed through a 5-point Likert scale to 7 statements (S1-7). Statements were assigned values according to relevance in face and transfer validities. Concomitantly, the model was also evaluated by students from 1st to 5th year with the same instruments. Content Validity Indexes (CVIs) were considered validated between groups with concordance greater than 90%. Text feedback was also collected. Each statement was subjected to Fisher’s Exact Test.

Results
Gastroschisis and omphalocele model costs were US $15 and US $27, respectively. In total, there were 105 simulator evaluators. 15 experts were selected. Of the 90 students, there were 16 (1st year), 22 (2nd), 16 (3rd), 22 (4th), and 14 (5th). Students and experts obtained CVI = 96.4% and 94.6%, respectively. The CVIs of each statement were not significantly different between groups (p < 0,05).

Conclusions
The WALL-GO models are suitable for use and replicable at a manufacturable low cost. Mannequins with abdominal wall defects are helpful in learning to diagnose and can be applied in teaching and training health professionals in developing and low-income countries.
The effect of health literacy intervention on adherence to medication of uncontrolled hypertensive patients using the M-health
Authors: Karami Maryam , Ashtarian Hossein , Rajati Mojgan , Hamzeh Behrooz , Rajati Fatemeh 
Published: December 2023

Abstract
Background
Given that patients’ medication adherence is regarded as the major part of disease control and improving health literacy can be effective in promoting adherence to healthy behaviors, the present study aimed to investigate the effect of health literacy intervention based on the medication adherence among uncontrolled hypertensive patients using mobile health (M-health).

Methods
An interventional study with a quasi-experimental design, was conducted on 118 uncontrolled hypertensive patients. Participants were randomly divided into the intervention (n = 59) and control (n = 59) groups using blocked randomization. In the intervention group, a mobile health (M-health) program was designed using programmed instruction to improve patients’ health literacy over a period of 3 months. Data was collected by administering health literacy and medication adherence questionnaires to participants before and after the intervention. The analysis involved using the independent sample t-test to compare the variables before and after the study.

Results
Before the intervention, the total score of health literacy was 33.34 and 33.14 in the intervention and control groups, respectively. After the intervention, it increased to 40.36 and 34.20 in the intervention and control groups, respectively, which was statistically significant in the intervention group (p = 0.01). Moreover, the medication adherence score of the intervention group significantly increased after the intervention. Both systolic and diastolic blood pressure decreased in the intervention group. However, it should be noted that the decrease in systolic blood pressure by 148.98 was statistically significant, while the decrease observed in diastolic blood pressure in the intervention group was not statistically significant (p = 0.08).

Conclusion
The application of programmed instruction through M-Health has shown a positive effect on the health literacy of uncontrolled hypertensive patients. In addition to detecting and treating patients, it is important to prioritize the improvement of health literacy in terms of medication adherence and the adoption of healthy behaviors.
“It’s about time they taught us”: a qualitative study evaluating the barriers to finding and screening child contacts under five at risk for TB in Gauteng Province, South Africa from the provider and caregiver perspectives
Authors: Munedzimwe Fadzai , Chetty-Makkan C. M. , Mukora R. , Charalambous S. , Turner K. , Chihota V. 
Published: December 2023

Abstract
Background
Inadequate numbers of children under five years of age who are exposed to tuberculosis (TB) in the home (child contact) are initiated on TB preventive treatment (TPT) in South Africa. We assessed barriers of initiating isoniazid preventive therapy (IPT) in this age group.

Methods
We conducted a qualitative study at two primary health clinics in the Ekurhuleni district in Gauteng Province. Between April and July 2019, we enrolled facility managers, TB staff and parents or legal guardians of child contacts (caregivers) attending for care, at the two facilities. Semi-structured questionnaires, facility observations and in-depth interviews using a semi-structured interview guide were used to collect data. Findings from the semi-structured questionnaires with facility staff and facility observations were summarized. Thematic analysis with a deductive approach was used to analyse the data from the in-depth interviews with caregivers.

Results
Two facility managers took part in the study and were assisted to complete the semi-structured questionnaires by TB staff. Fifteen caregivers aged between 18 and 43 years were interviewed of which 13 (87%) were female. Facility managers and TB staff (facility staff) felt that even though caregivers knew of family members who were on TB treatment, they delayed bringing their children for TB screening and TPT. Facility staff perceived caregivers as not understanding the purpose and benefits of TB prevention strategies such as TPT. Caregivers expressed the desire for their children to be screened for TB. However, caregivers lacked knowledge on TB transmission and the value of TB prevention in children at high risk of infection.

Conclusion
While facility staff perceived caregivers to lack responsibility, caregivers expressed limited knowledge on the value of screening their children for TB as reasons for not accessing TB preventive services. Health education on TB transmission, screening, and TB prevention strategies at a community level, clinics, creches, schools and via media are important to achieve the global end TB goal of early detection and prevention of TB.