bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating atezolizumab in patients with urinary tract squamous cell carcinoma (AURORA): study protocol for a single arm, open-label, multicentre, phase II clinical trial
Authors: Crabb Simon , Wickens Robin , Jane-Bibby Sarah , Dunkley Denise , Lawrence Megan , Knight Allen , Jones Robert , Birtle Alison , Huddart Robert , Linch Mark , Martin Jonathan , Coleman Adam , Boukas Konstantinos , Markham Hannah , Griffiths Gareth 
Published: September 2023

Abstract
Background
Bladder and urinary tract cancers account for approximately 21,000 new diagnoses and 5,000 deaths annually in the UK. Approximately 90% are transitional cell carcinomas where advanced disease is treated with platinum based chemotherapy and PD-1/PD-L1 directed immunotherapy. Urinary tract squamous cell carcinoma (UTSCC) accounts for about 5% of urinary tract cancers overall making this a rare disease. We have yet to establish definitive systemic treatment options for advanced UTSCC.
Preliminary translational data, from UTSCC patient tumour samples, indicate high PD-L1 expression and tumour infiltrating lymphocytes in a proportion of cases. Both of these features are associated with differential gene expression consistent with a tumour/immune microenvironment predicted to be susceptible to immune checkpoint directed immunotherapy which we will evaluate in the AURORA trial.

Methods
AURORA is a single arm, open-label, multicentre,UK phase II clinical trial. 33 patients will be recruited from UK secondary care sites. Patients with UTSCC, suitable for treatment with palliative intent, will receive atezolizumab PD-L1 directed immunotherapy (IV infusion, 1680 mg, every 28 days) for one year if tolerated. Response assessment, by cross sectional imaging will occur every 12 weeks. AURORA uses a Simon’s 2-stage optimal design with best overall objective response rate (ORR, by RECIST v1.1) at a minimum of 12 weeks from commencing treatment as the primary endpoint. Secondary endpoints will include overall survival, progression-free survival, duration of response, magnitude of response using waterfall plots of target lesion measurements, quality of life using the EORTC QLQ-C30 tool, safety and tolerability (CTCAE v5) and evaluation of potential biomarkers of treatment response including PD-L1 expression. Archival tumour samples and blood samples will be collected for translational analyses.

Discussion
If this trial shows atezolizumab to be safe and effective it may lead to a future late phase randomised controlled trial in UTSCC. Ultimately, we hope to provide a new option for treatment for such patients.

Trial registrations
EudraCT Number: 2021-001995-32 (issued 8th September 2021); ISRCTN83474167 (registered 11 May 2022); NCT05038657 (issued 9th September 2021).
Measurement of work-related psychological injury with depressive symptoms
Authors: Tanaka Mari , Hirano Yoshiyuki , Takanashi Rieko , Numata Noriko , Sutoh Chihiro , Yoshikawa Tomohiro , Shimizu Eiji 
Published: September 2023

Abstract
Objective
This study aimed to measure the level of psychological injury caused by work-related stress as well as the severity of depression among workers.

Method
First, we conducted an online survey and recruited 500 workers diagnosed with depression or adjustment disorder to investigate what type of stress they experienced within six months before onset. Second, we conducted another online survey and recruited 767 participants who experienced some form of work-related stress. All the participants were classified into four groups by whether or not they were diagnosed with depression and whether or not they quit their jobs due to work-related stress. We used the Impact of Event Scale-Revised (IES-R) to measure psychological injury caused by work-related stressful events and the Patient Health Questionnaire (PHQ)-9 to assess the severity of depression.

Results
In study 1, 62.4% of workers diagnosed with depression or adjustment disorder experienced work-related stress within six months before onset. In study 2, the IES-R mean scores were 40.7 (SD = 23.1) for Group A (workers with depression and quit their jobs) and 36.67 (SD = 23.4) for Group B (workers with depression but stayed at their jobs), with both exceeding the cut-off point (24/25) of PTSD (Post-Traumatic Stress Disorder), while the mean score of Group C (workers who did not have depression but quit their jobs because of work-related stress) was 20.74 (SD = 21.2), and it was 13.89 (SD = 17.4) for Group D (workers who had work-related stress but stayed at their jobs), with both of them below the cut-off point of PTSD. The total scores of IES-R of Group A and Group B were significantly higher than those of Group C and Group D(p < 0.001). There was a significant positive correlation between the scores of IES-R and PHQ-9 for all four groups (r = 0.708).

Conclusions
This study suggests that it is necessary to measure not only depressive symptoms but also the level of psychological injury resulting from stressful events in the workplace to assess workers with depression.
Pharmacotherapy literacy level and predictors of low literacy among diabetes mellitus type 2 patients in Serbia
Authors: Levic Marija , Bogavac-Stanojevic Natasa , Ubavic Stana , Krajnovic Dusanka 
Published: September 2023

Abstract
Background
Pharmacotherapy literacy (PTHL) is a specific ability to safely access, appraise and understand the available information concerning medication and to calculate and act accordingly. The concept of PTHL is mostly unknown for the majority of diabetes mellitus type 2 (DMT2) patients in Serbia. With diabetes being one of the major public health problems in Serbia with a prevalence of 9.1%, this two-study research aims at constructing performance-based instrument and estimating the prevalence of PTHL levels and identification of predictors of low PTHL scores in patients with DMT2.

Methods
Multistage study was performed to adapt the existing performance–based instrument (PTHL-SR) into specific questionnaire for DMT2 population (PTHL-DM instrument). PTHL levels were assessed through cross-sectional study categorising patients into groups of low, medium, and high PTHL levels. We considered 19 predictors for low PTHL scores, from sociodemographic characteristics, health behaviours and health characteristics, access to health-related information and empowerment-related indicators. Univariate and multivariate logistic regression analyses were used to determine independent predictors of low PTHL.

Results
The final 15-item PTHL-DM instrument proved to have satisfactory reliability (KR20 = 0.475) and internal reliability [ICC for the whole instrument was 0.97 with 95% confidence intervals (0.95–0.99)]. Positive correlation (rho = 0.69) between PTHL-DM score (15 questions) and the total PTHL-SR score (14 questions) was also observed.
It was demonstrated that the majority of 350 patients had low PTHL (62%), and only 5% high PTHL level. Mean score on PTHL-DM was 7.8 ± 2.3. Probability of low PTHL increased among smokers, patients with low interest in health and those who estimated their health as bad. Patients who used pharmacists as sourse of information were less likely to be pharmacotherapy illiterate. Combined therapy with insulin and Oral Hypoglycemic Agents was associated with higher PTHL.

Conclusions
Our data indicate that specific PTHL-DM tool is objective, valid, and reliable. It was found that low level of PTHL prevailed among DMT2 patients. Medication literacy is influenced by age, residence, education, and family status. Patients with better health literacy also reported better health behaviours. Different patient empowerment programs and approaches aimed at raising PTHL would be essential to improve self-management and control of this widespread chronic disease in Serbia.
Developmental implications of prenatal opioid exposure among school-aged children: a mixed methods and community-initiated analysis
Authors: Wilkinson Andra , Rackers H. S. , Harmon T. M. 
Published: September 2023

Abstract
Background
Growing research points to potential long-term developmental implications of prenatal opioid exposure for children. Yet, polysubstance use and adverse childhood experiences are raised as potential confounders. Further, there is a lack of data on school-age children and the children’s strengths.

Methods
Parents and caregivers of children with prenatal opioid exposure worked with the study team to design, collect, and descriptively analyze mixed method data. Data were collected through survey (n = 148) and two focus groups (n = 15) from a convenience sample in mostly West Virginia and Massachusetts.

Results
Nearly half of the children in the sample were diagnosed with multiple developmental delays, behavioral health conditions, and specific learning disorders. Roughly 85% of children have behavioral challenges. Associations between prenatal opioid exposure and negative developmental outcomes did not vary by type of opioid nor by polysubstance use, while controlling for adverse childhood experiences. Importantly, over 80% of families also reported their child’s strengths, including empathy, social magnetism, and their resilience.

Conclusions
The challenges for children born with prenatal opioid exposure may extend into school-age. The results are consistent with prior research on younger children, suggesting a need for best practices for caring for these children beyond the neonatal stage.
Measuring COVID-19 related stress and its associated factors among the parents of school-aged children during the first lockdown in France
Authors: Bourion-Bédès Stéphanie , Rousseau Hélène , Batt Martine , Beltrand Carole , Machane Rabah , Tarquinio Pascale , Tarquinio Cyril , Baumann Cédric 
Published: September 2023

Abstract
Background
The COVID-19 pandemic placed important challenges on parents, as they had to meet various demands during lockdown, including childcare, work and homeschooling. Therefore, the current study aimed to investigate perceived stress levels among the parents of school-aged children and explore their association with sociodemographic, environmental and psychological factors during lockdown.

Methods
A cross-sectional study was conducted among the parents of school-aged children ages 8 to 18, who lived in the Grand Est region of France during the first wave of the pandemic. An online survey collected sociodemographic data, living and working conditions, and exposure to COVID-19 as well as parent’s levels of perceived stress (PSS-10), self-perceived health status (SF-12), social support (MSPSS) and resilience (BRS). Multivariable logistic regression models were conducted to evaluate the association between moderate to severe perceived stress and various factors.

Results
In total, 734 parents were included. The results indicated that 47% were experiencing moderate stress and 7.2% were experiencing severe stress. Factors most strongly associated with risk of moderate to severe levels of stress were lower levels of parental resilience (OR = 3.8, 95% CI: 2.2–6.6) and poor self-perceived mental health status (OR = 7.3, 95% CI: 5.0–10.8). The following risk factors were also identified: female sex; being in the age range of 35–44; difficulties isolating and contracting COVID-19, which involved hospitalization and separation or isolation from family. The support of friends (OR = 0.8, 95% CI: 0.7–1.0) and family (OR = 0.5, 95% CI: 0.3–0.8) were protective factors.

Conclusions
These findings suggest that supportive and preventive programs should focus on the improvement of resilience and mental health management to promote parents’ wellbeing. Research has to focus both on individuals’ inner potential for increasing resilience and the environmental resources to be activated. Building and boosting resilience among parents could serve as a protective factor against negative outcomes for them and their families.
A dietary pattern of frequent plant-based foods intake reduced the associated risks for atopic dermatitis exacerbation: Insights from the Singapore/Malaysia cross-sectional genetics epidemiology cohort
Authors: Lim Jun Jie , Reginald Kavita , Say Yee-How , Liu Mei Hui , Chew Fook Tim 
Published: September 2023

Abstract
Background
The prevalence of atopic dermatitis (AD) has been increasing in recent years, especially in Asia. There is growing evidence to suggest the importance of dietary patterns in the development and management of AD. Here, we seek to understand how certain dietary patterns in a Singapore/Malaysia population are associated with various risks of AD development and exacerbation.

Methods
A standardized questionnaire following the International Study of Asthma and Allergies in Childhood (ISAAC) guidelines was investigator-administered to a clinically and epidemiology well-defined allergic cohort of 13,561 young Chinese adults aged 19–22. Information on their sociodemographic, lifestyle, dietary habits, and personal and family medical atopic histories were obtained. Allergic sensitization was assessed by a skin prick test to mite allergens. Spearman’s rank-order correlation was used to assess the correlation between the intake frequencies of 16 food types. Dietary patterns were identified using principal component analysis. Four corresponding dietary scores were derived to examine the association of identified dietary patterns with allergic sensitization and AD exacerbations through a multivariable logistic regression that controlled for age, gender, parental eczema, BMI, and lifestyle factors.

Results
The correlation is the strongest between the intake of butter and margarine (R = 0.65). We identified four dietary patterns, “high-calorie foods”, “plant-based foods”, “meat and rice”, and “probiotics, milk and eggs”, and these accounted for 47.4% of the variance in the dietary habits among the subjects. Among these patterns, moderate-to-high intake of “plant-based foods” conferred a negative association for chronic (Adjusted odds ratio (AOR): 0.706; 95% confidence interval (CI): 0.589–0.847; p < 0.001) and moderate-to-severe AD (AOR: 0.756; 95% CI: 0.638–0.897; p < 0.01). “Meat and rice” and “probiotics, milk and eggs” were not significantly associated with AD exacerbation. While frequent adherence to “high-calorie foods” increased the associated risks for ever AD and moderate-to-severe AD, having a higher adherence to “plant-based foods” diminished the overall associated risks.

Conclusions
Frequent adherence to “plant-based foods” was associated with reduced risks for AD exacerbation in young Chinese adults from Singapore/Malaysia. This provides the initial evidence to support the association between dietary factors and AD. Further research is needed to better understand the pathomechanisms underlying diet and AD exacerbations.
Association of living arrangements with all-cause mortality among older adults: a propensity score–matched cohort study
Authors: Pu Lining , Zhang Jingni , He Xiaoxue , Pan Degong , Wang Huihui , Zhang Xue , Sun Xian , Liu Xiaojuan , He Shulan , Li Jiangping 
Published: September 2023

Abstract
Background
Many studies exist on the living arrangements and health status of older adults, but the findings have been inconsistent. Therefore, we examined the relationship between living arrangements and all-cause mortality in older adults.

Methods
This perspective study was based on the Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 2011 to 2018. We used a sample aged 65 years and over included in the study in 2011. Propensity score matching was performed to minimize bias and Cox proportional hazards regression models were conducted.

Results
A total of 7,963 participants were included. Of these, 1,383 were living alone, 6,424 were living with families, and 156 were living in nursing homes. In the propensity score-matched cohort, older adults living alone had a significantly lower risk of all-cause mortality than those living with families (hazard ratio 0.85; 95% confidence intervals 0.76 to 0.95). Living alone was prominently associated with a decline in mortality compared with living in nursing homes (hazard ratio 0.61; 95% confidence intervals 0.44 to 0.84). There was no significant difference in mortality between living in nursing homes and living with families (hazard ratio 1.19; 95% confidence intervals 0.89 to 1.60). Subgroup analyses indicated that there was no significant interaction with age, sex, education, or residence.

Conclusions
The risk of all-cause mortality was significantly lower in older adults living alone than in those living with families or living in nursing homes. This article’s findings suggest the need to adopt multiple approaches to meet the needs of senior care services.
Laparoscopic resection for gastric schwannoma larger than 30 mm with long-term outcomes
Authors: Jiang Xuetong , Zhao Mingzuo , Wu Jianqiang , Ding Yang , Wang Jian 
Published: September 2023

Abstract
Background and aims
Laparoscopic resection has been reported as effective and safe for gastric schwannoma (GS) in the form of case reports. However, study on laparoscopic surgery in patients with GS larger than 30 mm has been rarely reported. To this end, the present study aimed to evaluate the safety and efficacy of laparoscopic resection for the treatment of GS larger than 30 mm and its long-term outcomes.

Methods
This is a retrospective case series study of patients with GS larger than 30 mm who underwent laparoscopic resection at our hospital between January 2014 and December 2020. Clinical pathology, surgical and follow-up data were collected and analyzed.

Results
A total of 10 patients with a mean age of 51.6 years were included. Seven tumors were located in gastric body, 2 in antrum and 1 in fundus. Laparoscopic gastric wedge resection was performed in 7 patients, while laparoscopic gastric local resection was performed in 3 patients. All patients achieved complete resection. The mean operation time was 112.6 ± 34.3 min, and the mean postoperative hospital stay was 13.8 ± 5.1 days. Postoperative gastroplegia occurred in 2 patients and was treated with conservative therapy. No recurrence, metastasis or residue was found during the follow-up of mean 45.1 months.

Conclusions
Laparoscopic resection is a safe and effective method for treating GS larger than 30 mm with favorable long-term follow-up outcomes. Laparoscopic resection may be considered as the first-line treatment for GS larger than 30 mm.
Circ_072697 knockdown promotes advanced glycation end products-induced cell proliferation and migration in HaCaT cells via miR-3150a-3p/KDM2A axis
Authors: Tian Ming , Tang Jiajun , Huang Rong , Dong Jiaoyun , Jia Huiying 
Published: September 2023

Abstract
Objective
Diabetes foot ulcer (DFU) is a serious complication of diabetes, which can lead to significant mortality and amputation rate. Our previous study found circ_072697 was highly expressed in DFU tissues, but the regulatory mechanism of circ_072697 in DFU remains unclear.

Methods
The relative expressions of circ_072697, miR-3150a-3p, and KDM2A in DFU patients or advanced glycation end products (AGEs)-treated HaCaT cells (used as DFU cell model) were determined by using qRT-PCR. Cell proliferation and migration abilities were determined by using CCK-8 and Transwell assays. The interaction between miR-3150a-3p with circ_072697 or KDM2A were verified by RNA immunoprecipitation (RIP) and dual-luciferase reporter assays. Furthermore, the protein expression of genes involved in MAPK signaling pathway was detected by western blot.

Results
The expression of circ_072697 was significantly upregulated in DFU tissues, while the expression of miR-3150a-3p was downregulated. Circ_072697 knockdown promoted the proliferation and migration of AGEs-treated HaCaT cells. miR-3150a-3p was confirmed as a target of circ_072697 and its inhibitor reversed the promotion effects of circ_072697 knockdown on biological behavior of cells. In addition, KDM2A was considered as a target of miR-3150a-3p and it was highly expressed in DFU samples. Importantly, circ_072697 could regulate KDM2A expression through sponging miR-3150a-3p, and this axis had effect on the MAPK signaling pathway.

Conclusions
Overall, circ_072697 regulated the biological behaviors of keratinocytes in DFU via miR-3150a-3p/KDM2A axis and MAPK signaling pathway, revealing a new insight into the pathogenesis and potential therapeutic targets of DFU.
Population attributable fractions of fatty liver disease for type 2 diabetes Mellitus
Authors: Xu Jingyuan , Wu Longyun , Deng Jiang , Yang Longbao , Wang Yatao , Tian Hongyang , Ji Yajun , Xia Qiaoyun , Han Zhiyi , Cheng Yan , Lu Xiaolan 
Published: September 2023

Abstract
Purpose
To determine the population attributable fraction (PAF) of fatty liver disease (FLD) for type 2 diabetes mellitus (T2DM) and compare it to the PAFs of other metabolic abnormalities.

Methods
We conducted a 10-year retrospective cohort study of 33,346 individuals in Karamay Central Hospital of Xinjiang. Individuals were followed up for T2DM occurrence based on FBS. The PAFs of FLD were calculated generally and respectively in different sex and age groups. A comparison of the PAF of FLD and that of other metabolic abnormalities, as well as the PAFs of FLD in different groups classified based on age and sex, was performed using Cox regression.

Results
During an average follow-up period of 3.71 years, 1486 T2DM were diagnosed. The incidence density of T2DM was 1.2/100 person-years, and cumulative incidence rate was 4456.31/100,000 person-years. Partial PAF (PAFp) of FLD in the entire population was 23.11%. In the male population, PAFp was higher at 30–40 years old. In the female population, it was higher when age ≥ 60 years old. In multivariable Cox regression model, FLD, male sex, age ≥ 45 years old, overweight, hypertriglyceridaemia, and systolic hypertension were independent risk factors for T2DM, with corresponding PAFp of 25.00%, 24.99%, 36.47%, 24.96%, 5.71%, and 6.76%, respectively. Age ≥ 45 years old showed the highest PAFp and adjusted hazard ratio, followed by FLD.

Conclusions
FLD contributes more to T2DM incidence than other metabolic disorders. Particular attention should be given to male populations of 30–40 and female populations above 60 for FLD prevention and treatment.
Incidence, clinical characteristics, and survival outcomes of ovarian strumal diseases: a retrospective cohort study
Authors: Li Sijian , Hong Ruping , Yin Min , Zhang Tianyu , Zhang Xinyue , Yang Jiaxin 
Published: September 2023

Abstract
Background
Struma ovarii (SO) is a rare tumor and may transform into ovarian strumal carcinoid (OSC) and/or malignant struma ovarii (MSO), but the incidence, clinical characteristics, and survival outcomes have not been well defined.

Methods
We conducted a retrospective study of patients with ovarian strumal diseases treated in the our hospital between 1980 and 2022. Subgroup analyses of SO, OSC, and MSO were subsequently performed.

Results
A total of 275 cases (2.14%) were identified in a cohort of 12,864 patients with ovarian teratomas, where SO, OSC, and MSO accounted for 83.3%, 12.0%, and 4.7% of cases, respectively. There were no significant differences in age, tumor sizes, elevated tumor markers, and ascites among the three subgroups. At initial treatment, all patients with SO or OSC had FIGO stage I disease except one SO patient presenting metastatic disease, ten patients had MSO confined to the ovary, whereas other three patients had metastatic diseases. Two patients with SO respectively relapsed at peritoneum and anterior mesorectum, while none of the OSC patients presented tumor recurrence or death despite different surgical procedures employed. The 5-year recurrence-free survival rate was 88.9%, and only one death occurred at 9.5 years after diagnosis in patients with MSO. Radioiodine therapy showed satisfactory therapeutic efficacy, but these patients showed poor responses to the chemotherapy.

Conclusion
2.14% of ovarian teratoma could be classified as SO, of which 12.0% and 4.7% of SO may transform into OSC and MSO, repsectively. The survival outcomes were excellent even after SO transformed into OSC or MSO.

Synopsis
SO occupied 2.14% of ovarian teratoma, where 12.0% and 4.7% of SO may transform into OSC and MSO, respectively, and had excellent survival outcomes.