bluuebunny/crossref_metadata_2025_split huggingface dataset:
Humanized CD19 CAR-T cells in relapsed/refractory B-ALL patients who relapsed after or failed murine CD19 CAR-T therapy
Authors: An Lihong , Lin Yuehui , Deng Biping , Yin Zhichao , Zhao Defeng , Ling Zhuojun , Wu Tong , Zhao Yongqiang , Chang Alex H. , Tong Chunrong , Liu Shuangyou 
Published: April 2022

Abstract
Background
For CD19-positive relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL) after treatment with murine CD19 (mCD19) CAR-T, the reinfusion of mCD19 CAR-T cells may be ineffective due to anti-mouse single-chain variable fragment (scFv) antibody caused by mCD19 CAR. To overcome this immunogenicity, we applied humanized CD19 (hCD19) CAR-T cells to treat r/r B-ALL patients with prior mCD19 CAR-T therapy.

Methods
Nineteen pediatric and adult patients were included, 16 relapsed after and 3 were primarily resistant to mCD19 CAR-T. All patients presented with more than 5% blasts in bone marrow and/or extramedullary disease, and still showed CD19 antigen expression. Humanized CD19-CARs were lentiviral vectors carrying a second generation CAR with 4–1-BB co-stimulatory and CD3ζ signaling domains. Patient-derived cells were collected for producing CAR-T cells, the median dose of infused hCD19 CAR-T cells was 2.4 × 105/kg (range, 1.0–18.0 × 105/kg).

Results
hCD19 CAR-T resulted in a complete remission (CR) rate of 68% (13/19). Among 13 remission patients, 11 underwent allogeneic hematopoietic cell transplantation (allo-HCT) (3 were second HCT) and 10 remained in CR; the event-free survival rates at 12–18 months were 91% in 11 patients received following allo-HCT and 69% in all CR patients. Six cases had no response to hCD19 CAR-T, 3 died of disease progression; another 3 received salvage second transplantation, of them, 2 relapsed again (one died). Cytokine release syndrome (CRS) occurred in 95% (18/19) of patients, most CRS events were grade 1 and grade 2 (n = 17), there was only one grade 4 CRS. Two cases experienced grade 1 neurotoxicity.

Conclusions
Humanized CD19 CAR-T cell therapy could be a treatment option for CD19-positive B-ALL patients who relapsed after or resisted prior murine CD19 CAR-T, hCD19 CAR-T followed by allo-HCT provided a longer remission in CR patients. Nevertheless, the prognosis of non-responders to hCD19 CAR-T remained dismal.

Trial registration
Chinese Clinical Trial Registry/WHO International Clinical Trial Registry (ChiCTR1900024456, URL: www.chictr.org.cn); registered on July 12, 2019.
Prevalence and characteristics of somatic symptom disorder in the elderly in a community-based population: a large-scale cross-sectional study in China
Authors: Wu Yani , Tao Zhengyu , Qiao Yongxia , Chai Yezi , Liu Qiming , Lu Qifan , Zhou Hongmei , Li Shiguang , Mao Jialiang , Jiang Meng , Pu Jun 
Published: April 2022

Abstract
Introduction and objectives
The aging population is expected to reach 2 billion by 2050, but the impact of somatic symptom disorder (SSD) on the elderly has been insufficiently addressed. We aimed to clarify the prevalence of SSD in China and to identify physical and psychological differences between the elderly and non-elderly.

Methods
In this prospective multi-center study, 9020 participants aged (2206 non-elderly adults and 6814 elderly adults) from 105 communities of Shanghai were included (Assessment of Somatic Symptom in Chinese Community-Dwelling People, clinical trial number NCT04815863, registered on 06/12/2020). The Somatic Symptom Scale-China (SSS-CN) questionnaire was used to measure SSD. Depressive and anxiety disorders were assessed by the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), respectively.

Results
The prevalence of SSD in the elderly was higher than that in the non-elderly (63.2% vs. 45.3%). The elderly suffered more severe SSD (20.4% moderate and severe in elderly vs. 12.0% in non-elderly) and are 1.560 times more likely to have the disorder (95%CI: 1.399–1.739; p < .001) than the non-elderly. Comorbidity of depressive or anxiety disorders was 3.7 times higher than would be expected in the general population. Additionally, the results of adjusted multivariate analyses identified older age, female sex, and comorbid physical diseases as predictive risk factors of SSD in the elderly group.

Conclusions
With higher prevalence of common physical problems (including hypertension, diabetes mellitus and cardio/cerebrovascular disease), the elderly in Shanghai are more vulnerable to have SSD and are more likely to suffer from comorbid depressive and anxiety disorders. SSD screening should be given more attention in the elderly, especially among older females with several comorbid physical diseases.
What causes loneliness among household heads: a study based in primary setting in Mumbai, India
Authors: Yadav Vidya , Chauhan Shekhar , Patel Ratna 
Published: April 2022

Abstract
Background
With the pace of urbanization, symptoms of loneliness emerge as one of the most devastating mental illnesses among city dwellers in the modern age. The present study has tried to identify the potential factors and correlates which affect loneliness vulnerability.

Methods
The data for this study were collected from three different areas of Mumbai (i.e., Dadar, Bandra, and Chembur).This study was conducted through a cross-sectional household survey of household heads in the five different housing typologies/ localities between January and June 2016.A total of 450 household data were collected using the quota sampling method. Loneliness was the main dependent variable. The bivariate analysis was used to see the percentage of loneliness among respondents. Bivariate analysis for categorical data was carried out using the chi-square (χ2) test. Logistic regression analysis was performed to explore the correlates of loneliness among household heads. The probability of significance was set at 5%.

Results
It was found that around 7 percent of respondents often feel lonely, and 21 percent of respondents sometimes feel lonely in the last seven days preceding the survey date. Household heads with two or more chronic diseases had higher odds (OR = 4.87, CI = 1.52–15.57) of loneliness than household heads without any chronic disease. The odds of loneliness were almost 3 times higher (OR = 3.05; CI = 1.11–8.38) among females as compared to males. Household heads living alone (single) had higher odds (OR = 19.99; CI = 4.14–96.59) to suffer from loneliness than those living in a joint family.

Conclusion
Finding reveals that level of loneliness symptomatology in urban dwellers may be attributed significantly by individual (i.e., morbidity status and sex of respondent), social (i.e., personal relation) and residing locality characteristics. Community psychological intervention along with enhanced civic engagement can reduce level of loneliness in existing slum rehabilitees.
A cross-sectional study of alcohol consumption and alcoholic liver disease in Beijing: based on 74,998 community residents
Authors: Wang Huai , Gao Pei , Chen Weixin , Yuan Qianli , Lv Min , Bai Shuang , Wu Jiang 
Published: April 2022

Abstract
Background
The alcohol consumption pattern, alcoholic liver disease (ALD) prevalence and related risk factors among alcohol drinkers in Beijing haven’t been fully elucidated. Hence, a cross-sectional study was conducted to investigate potential link among these factors.

Methods
A two-stage stratified cluster sampling was carried out in Beijing. All participants were 25 years of age or older, possessed with medical insurance, and lived in Beijing for over 6 months. As part for this investigation, participants were asked to answer a questionnaire and undergo physical examination. The questionnaire included demographic information, alcohol intake, and medical history. The physical examination included physical and Fibrotouch tests. Moreover, 10 ml blood sample was collected from each subject to examine liver functions, perform routine blood, Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV).

Results
Overall, 74,988 residents participated in our study. The proportion of current drinkers among all participants was 46.10%. The differences in gender, region, age group, education, annual household income, and occupation among lifetime abstainers, former drinkers, non-weekly and weekly drinkers were significantly different (P<0.05). The ethanol intake between men and women, people living in urban and rural regions were significantly different (P<0.05). Strong spirits were commonly consumed by men, whereas, beers were commonly consumed by women. Drinking strong spirits generally lead to liver steatosis. In addition, ALD prevalence was 1.30% in participants over 25 years old. The differences in ALD prevalence between men and women, and among different age groups, were significant (P<0.05). Based on our analysis, ALD risk factors in Beijing included: gender (male), age (older than 35 years), high waist circumference, high blood pressure, high BMI, high blood sugar level, and being heavy drinkers.

Conclusion
Compared with other cities or regions in China, the level of alcohol consumption in Beijing is at an upper middle level. But the ALD prevalence is low likely because ethanol intake is relatively low. Our analysis revealed that heavy drinking is a major risk factor for ALD development. Hence, if alcohol consumption is unavoidable, we caution against heavy drinking.
The best postoperative adjuvant therapy for patients with early stage cervical adenosquamous carcinoma
Authors: Liu Yawen , Tu Haiyan , Zhang Lingling , Zhong Meiling , Wang Yanan , Li Ling , Xiang Xiaojun 
Published: April 2022

Abstract
Background
Cervical adenosquamous carcinoma (ASC) was previously thought to be a subtype of cervical adenocarcinoma, but recent studies have found that the clinical features of the two diseases are different. Moreover, the pathological characteristics, survival, prognosis, and optimal ASC therapy remain unknown. This study aims to retrospectively analyze the postoperative survival of patients with early-stage ASC and to evaluate their condition after treatment with postoperative concurrent chemoradiotherapy (CCRT) and prophylactic irradiation of the para-aortic lymphatic drainage area.

Methods
This study enrolled 131 patients with pathologically confirmed ASC screened from 3502 patients with confirmed stage I–II cervical cancer diagnosis who had completed surgical treatments in our hospital. Among the 131 enrolled patients, 75 patients received CCRT, 33 patients received chemotherapy (CT), and 23 patients did not receive adjuvant treatment (named surgery alone (S alone). Of the 75 patients CCRT, 43 patients received prophylactic irradiation of the para-aortic lymphatic drainage area. The efficacy of the postoperative treatments of patients among groups (CCRT, CT, and S alone) was compared.

Results
The median follow-up time, age, and overall survival (OS) were 76 months, 43 years, and 74 months, respectively. The 3- and 5-year survival rates were 82% and 71.4%, respectively. The median disease-free survival (DFS) was 64 months. Cox regression analysis showed that postoperative adjuvant treatment modalities and positive lymph node metastases were associated with OS and DFS. Patients who received CCRT treatment had higher OS and DFS than those with CT and S alone. Prophylactic irradiation of the para-aortic lymphatic drainage area did not improve the OS and DFS of patients with CCRT treatment. However, further subgroup analysis suggested that it might improve survival rates in patients who had positive pelvic lymph nodes as confirmed by postoperative pathology.

Conclusion
Postoperative CCRT improved the survival rates in patients with early-stage ASC. The value of prophylactic irradiation of the para-aortic lymphatic drainage area remains debatable, but it may benefit patients with pelvic lymph node involvement.
Post Laparoscopy Pain Reduction Project I (POLYPREP I): intraperitoneal normal saline instillation—a randomised controlled trial
Authors: Adlan Aizura Syafinaz Ahmad , Azhary Jerilee Mariam Khong , Tarmidzi Hairel Zulhamdi Mohd , Kamarudin Maherah , Lim Raymond Chung Siang , Ng Doris Sin Wen 
Published: April 2022

Abstract
Objectives
To evaluate the effect of intraperitoneal normal saline instillation (INSI) of 15 mL/kg body weight on postoperative pain after a gynaecological laparoscopic procedure.

Design
Randomised controlled trial.

Setting
University Hospital in Kuala Lumpur, Malaysia.

Participants
Patients aged 18–55 years, with American Society of Anaesthesiologists (ASA) classification I–II, scheduled for an elective gynaecological laparoscopic procedure for a benign cause.

Intervention
The patients were randomly allocated to two groups. In the intervention group, 15 mL/kg body weight of normal saline was instilled intraperitoneally, while the control group received the conventional combination of open laparoscopic trocar valves with gentle abdominal pressure to remove the retained carbon dioxide.

Main outcome measures
The outcomes measured were the mean pain scores for shoulder and upper abdominal pain at 24 h, 48 h, and 72 h postoperatively.

Results
A total of 68 women completed the study, including 34 women in each group. There was no difference in the shoulder pain score at 24 h, 48 h, and 72 h postoperatively. However, a significant improvement in the upper abdominal pain score after 48 h (95% confidence interval [CI] 0.34–1.52, p = 0.019) and 72 h (95% CI 0.19–0.26, p = 0.007) postoperatively were observed.

Conclusions
INSI of 15 mL/kg body weight does not lower postoperative shoulder pain compared to no fluid instillation. A modest pain score improvement was observed in the upper abdominal area at 48 h and 72 h after surgery. An INSI of up to 30 mL/kg body weight may be required to eliminate shoulder pain. Care must be taken before administering a higher amount of INSI, considering the potential risk of peritoneal adhesions.
Clinical registration ISRCTN Identifier: 87898051 (Date: 26 June 2019) https://doi.org/10.1186/ISRCTN87898051
Teaching design thinking as a tool to address complex public health challenges in public health students: a case study
Authors: Ingram Carolyn , Langhans Tessa , Perrotta Carla 
Published: April 2022

Abstract
Background
Developing a public health workforce that can understand problems from a population perspective is essential in the design of impactful user-centred responses to current population health challenges. Design Thinking, a user-driven process for problem-defining and solution-finding, not only has utility in the field of public health but stands as a potential mechanism for developing critical skills -such as empathy, creativity and innovation- amongst future professionals. Though the literature reflects the use of DT across many health sciences disciplines, less research has been published on how students apply learned concepts using real-world challenges of their choice and what difficulties they face during the process.

Methods
This case study evaluates achieved learning outcomes after the introduction of a design thinking block into post-graduate public health curriculum at the University College Dublin. Two independent assessors evaluated student learning outcomes and observed difficulties during the process by assessing group presentations to identify and understand any learning difficulties using an ad-hoc designed tool. The tool consisted of twelve items scored using a 5-point Likert scale. Student feedback, in the form of an online survey, was also analysed to determine their level of enjoyment, perceived learning outcomes and opinions on the course content.

Results
The assessors evaluated thirteen DT group presentations and reports from 50 students. The groups chose a range of topics from socialization of college students during Covid-19 to mental health challenges in a low-income country. Independent assessment of assignments revealed that the highest scores were reached by groups who explored a challenge relevant to their own lives (more than 80% of total possible points versus 60% class average). The groups that explored challenges more distant to themselves struggled with problem finding with a mean score of 2.05 (SD ± 1.2) out of 5 in that domain. The greatest difficulties were observed in problem finding and ideation. Though most students found the design thinking block enjoyable and relevant to their education, they recommended that the DT block be a stand-alone module. Students recognized that groups who chose a familiar topic experienced fewer difficulties throughout the process.

Conclusion
The study showed that DT learning outcomes were best achieved when students focused on challenges, they had either personally experienced or were familiar with. These findings provide insight for future iterations of DT workshops and support the teaching of user-centred approaches to future public health practitioners.
The influence of non-clinical pharmacists’ understanding of and attitudes towards pharmaceutical care on their willingness to serve as clinical pharmacists in China
Authors: Wan Chuchuan , Huang Yuankai , Chen Lei , Xi Xiaoyu 
Published: April 2022

AbstractBackgroundThe shortage of clinical pharmacists is severe in China, and transferring non-clinical pharmacists into clinical pharmacists serves as a feasible solution to this problem. In China, a one-year training programme is available for non-clinical pharmacists, and those who have finished the programme are certificated as clinical pharmacists. However, not all non-clinical pharmacists are willing to serve as clinical pharmacists, and their willingness to serve as clinical pharmacists may be related to their attitudes towards pharmaceutical care. This study aims to test whether non-clinical pharmacists’ attitudes towards pharmaceutical care is positively correlated with their willingness to serve as clinical pharmacists.MethodsA cross-sectional survey was conducted in secondary and tertiary hospitals in China to collect non-clinical pharmacists’ basic demographic information, attitudes towards pharmaceutical care and willingness to serve as clinical pharmacists. An ordered logistic regression analysis was performed to test the relationship between non-clinical pharmacists’ attitudes towards pharmaceutical care and their willingness to serve as clinical pharmacists.ResultsOne thousand five hundred eighty non-clinical pharmacists from 755 hospitals were invited to participate in the study. Finally, 1308 valid responses were obtained and the response rate reached 82.78%. The regression results (R2 = 0.052, chi-square = 174.024,p < 0.0001) suggested that attitudes towards pharmaceutical care had a positive impact on non-clinical pharmacists’ willingness to serve as clinical pharmacists (p < 0.01). Control variables, such as age (p < 0.05), marital status (p < 0.05), professional title (p < 0.1), educational level (p < 0.1), salary expectations (p < 0.01) and experience providing pharmaceutical care (p < 0.01), also influenced non-clinical pharmacists’ willingness to serve as clinical pharmacists.ConclusionsBased on the results, suggestions are made to increase non-clinical pharmacists’ willingness to serve as clinical pharmacists.
Improving public health sector service delivery in the Free State, South Africa: development of a provincial intervention model
Authors: Malakoane Benjamin , Heunis James Christoffel , Chikobvu Perpetual , Kigozi Nanteza Gladys , Kruger Willem Hendrik 
Published: April 2022

Abstract
Background
Public health sector service delivery challenges leading to poor population health outcomes have been observed in the Free State province of South Africa for the past decade. A multi-method situation appraisal of the different functional domains revealed serious health system deficiencies and operational defects, notably fragmentation of healthcare programmes and frontline services, as well as challenges related to governance, accountability and human resources for health. It was therefore necessary to develop a system-wide intervention to comprehensively address defects in the operation of the public health system and its major components.

Methods
This study describes the development of the ‘Health Systems Governance & Accountability’ (HSGA) intervention model by the Free State Department of Health (FSDoH) in collaboration with the community and other stakeholders following a participatory action approach. Documented information collected during routine management processes were reviewed for this paper. Starting in March 2013, the development of the HSGA intervention model and the concomitant application of Kaplan and Norton’s (1992) Balanced Scorecard performance measurement tool was informed by the World Health Organization’s (2007) conceptual framework for health system strengthening and reform comprised of six health system ‘building blocks.’ The multiple and overlapping processes and actions to develop the intervention are described according to the four steps in Kaplan et al.’s (2013) systems approach to health systems strengthening: (i) problem identification, (ii) description, (iii) alteration and (iv) implementation.

Results
The finalisation of the HSGA intervention model before end-2013 was a prelude to the development of the FSDoH’s Strategic Transformation Plan 2015–2030. The HSGA intervention model was used as a tool to implement and integrate the Plan’s programmes moving forward with a consistent focus on the six building blocks for health systems strengthening and the all-important linkages between them.

Conclusion
The model was developed to address fragmentation and improve public health service delivery by the provincial health department. In January 2016, the intervention model became an official departmental policy, meaning that it was approved for implementation, compliance, monitoring and reporting, and became the guiding framework for health systems strengthening and transform in the Free State.
Implementing the right care in the right place at the right time for non-alcoholic fatty liver disease (NAFLD-RRR study): a study protocol for a community care pathway for people with type 2 diabetes
Authors: Gracen Lucy , Hayward Kelly L. , Aikebuse Melanie , Russell Anthony , O’Beirne James , McPhail Steven , Irvine Katharine M. , Williams Suzanne , Valery Patricia C. , Powell Elizabeth E. 
Published: April 2022

Abstract
Background
Non-alcoholic fatty liver disease (NAFLD) is an emerging epidemic that affects approximately half of all people with type 2 diabetes. Those with type 2 diabetes are a high-risk NAFLD subgroup because of their increased risk of clinically significant liver-related outcomes from NAFLD which include hepatocellular carcinoma, cirrhosis-related complications and liver disease mortality. They may benefit from early detection of disease as this would allow at risk patients to access hepatocellular carcinoma surveillance, emerging drug trials for NAFLD and specialist hepatology care prior to emergence of liver-related complications.

Methods
This is a prospective cohort study aimed at incorporating and assessing a community care pathway for liver fibrosis screening into routine care for type 2 diabetes. Patients undergo a point of care assessment of hepatic steatosis and stiffness using FibroScan at the time of the routine diabetes appointment or when attending the clinic for blood tests in preparation for this appointment.

Discussion
We propose that implementation of a community-based NAFLD diagnosis, risk-stratification, and referral pathway for people with type 2 diabetes is feasible, will provide earlier, targeted detection of advanced fibrosis, and reduce unnecessary referrals to hepatology outpatients for fibrosis risk assessment. Our study will provide important information about the feasibility of establishing a NAFLD pathway for people with type 2 diabetes in primary care. Ultimately, our findings will help direct spending and resource allocation for NAFLD in a high-risk population. Regular evaluation by stakeholders during implementation will help to create a reliable and sustainable community care pathway and establish a perpetual cycle of learning in primary care.

Trial registration
ANZCTR, ACTRN12621000330842. Registered 23 March 2021.