bluuebunny/crossref_metadata_2025_split huggingface dataset:
Opioid prescriptions among the World Trade Center Health Program population
Authors: Liu Ruiling , Calvert Geoffrey M. , Anderson Kristi R. , Malcolm Helen , Cimineri Lauren , Dupont Hannah , Martinez Marisol 
Published: November 2023

Abstract
Background
The World Trade Center Health Program (Program) provides limited health care to those directly affected by the 9/11 terrorist attacks. Because of physical/mental trauma arising from the 9/11 attacks, Program members might be at high risk of opioid use. To prevent prescription opioid overuse, in 2018 the Program implemented various measures to improve opioid prescribing and expand access to non-opioid pain management among Program members. However, the characteristics of opioid prescriptions dispensed among this population has never been described.

Methods
Administrative and claims data from 07/01/2011 to 09/30/2022 were used to describe opioid prescriptions dispensed during 2013–2021.

Results
From 2013–2021, 108,285 members were Program-enrolled for ≥ 10 months, 4,053 (3.7%) had 22,938 outpatient opioid prescriptions, of which, 62.1% were for cancer-related pain, 11.1% for hospice/end of life care, 4.8% for surgery pain, and 9.8% for acute/chronic pain. Among members with Program-paid diagnostic/treatment claims (n = 70,721), the proportion with opioid prescriptions for cancer/hospice/end of life care increased from 0.5% in 2013 to 1.6% in 2018 (p = 0.010), then decreased to 1.1% in 2021 (p = 0.070), and the proportion for non-cancer surgery/acute/chronic pain decreased from 0.6% in 2013 to 0.23% in 2021 (p = 0.0005). Among members prescribed opioids without cancer/hospice/sickle cell disease, the proportion who started with long-acting opioids or had opioid prescriptions from ≥ 4 prescribers were below 6.5% annually; the proportion receiving a high-dose (≥ 90 morphine milligram equivalents per day [MED]), or with concurrent opioids and benzodiazepines use, or who started opioids with MED ≥ 50 or with long duration (≥ 7 days’ supply) were above 10% annually, but decreased since 2017.

Conclusions
Prevalence of outpatient opioid prescriptions paid by the Program was very low and prescriptions were primarily dispensed for cancer/hospice/end of life care. Although Program efforts to improve opioid prescribing coincided with improvements in outcomes, ongoing surveillance is needed.
Drivers of unprofessional behaviour between staff in acute care hospitals: a realist review
Authors: Aunger Justin Avery , Maben Jill , Abrams Ruth , Wright Judy M. , Mannion Russell , Pearson Mark , Jones Aled , Westbrook Johanna I. 
Published: November 2023

Abstract
Background
Unprofessional behaviours (UB) between healthcare staff are rife in global healthcare systems, negatively impacting staff wellbeing, patient safety and care quality. Drivers of UBs include organisational, situational, team, and leadership issues which interact in complex ways. An improved understanding of these factors and their interactions would enable future interventions to better target these drivers of UB.

Methods
A realist review following RAMESES guidelines was undertaken with stakeholder input. Initial theories were formulated drawing on reports known to the study team and scoping searches. A systematic search of databases including Embase, CINAHL, MEDLINE and HMIC was performed to identify literature for theory refinement. Data were extracted from these reports, synthesised, and initial theories tested, to produce refined programme theories.

Results
We included 81 reports (papers) from 2,977 deduplicated records of grey and academic reports, and 28 via Google, stakeholders, and team members, yielding a total of 109 reports. Five categories of contributor were formulated: (1) workplace disempowerment; (2) harmful workplace processes and cultures; (3) inhibited social cohesion; (4) reduced ability to speak up; and (5) lack of manager awareness and urgency. These resulted in direct increases to UB, reduced ability of staff to cope, and reduced ability to report, challenge or address UB. Twenty-three theories were developed to explain how these contributors work and interact, and how their outcomes differ across diverse staff groups. Staff most at risk of UB include women, new staff, staff with disabilities, and staff from minoritised groups. UB negatively impacted patient safety by impairing concentration, communication, ability to learn, confidence, and interpersonal trust.

Conclusion
Existing research has focused primarily on individual characteristics, but these are inconsistent, difficult to address, and can be used to deflect organisational responsibility. We present a comprehensive programme theory furthering understanding of contributors to UB, how they work and why, how they interact, whom they affect, and how patient safety is impacted. More research is needed to understand how and why minoritised staff are disproportionately affected by UB.

Study registration
This study was registered on the international database of prospectively registered systematic reviews in health and social care (PROSPERO): https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021255490.
Beyond the regulatory radar: knowledge and practices of rural medical practitioners in Bangladesh
Authors: Sujon Hasnat , Sarker Mohammad Habibur Rahman , Uddin Aftab , Banu Shakila , Islam Mohammod Rafiqul , Amin Md. Ruhul , Hossain Md. Shabab , Alahi Md. Fazle , Asaduzzaman Mohammad , Rizvi Syed Jafar Raza , Islam Mohammad Zahirul , Uzzaman Md. Nazim 
Published: November 2023

Abstract
Background
Informal and unregulated rural medical practitioners (RMPs) provide healthcare services to about two-thirds of people in Bangladesh, although their service is assumed to be substandard by qualified providers. As the RMPs are embedded in the local community and provide low-cost services, their practice pattern demands investigation to identify the shortfalls and design effective strategies to ameliorate the service.

Methods
We conducted a cross-sectional study in 2015–16 using a convenient sample from all 64 districts of Bangladesh. Personnel practising modern medicine, without any recognized training, or with recognized training but practising outside their defined roles, and without any regulatory oversight were invited to take part in the study. Appropriateness of the diagnosis and the rationality of antibiotic and other drug use were measured as per the Integrated Management of Childhood Illness guideline.

Results
We invited 1004 RMPs, of whom 877 consented. Among them, 656 (74.8%) RMPs owned a drugstore, 706 (78.2%) had formal education below higher secondary level, and 844 (96.2%) had informal training outside regulatory oversight during or after induction into the profession. The most common diseases encountered by them were common cold, pneumonia, and diarrhoea. 583 (66.5%) RMPs did not dispense any antibiotic for common cold symptoms. 59 (6.7%) and 64 (7.3%) of them could identify all main symptoms of pneumonia and diarrhoea, respectively. In pneumonia, 28 (3.2%) RMPs dispensed amoxicillin as first-line treatment, 819 (93.4%) dispensed different antibiotics including ceftriaxone, 721 (82.2%) dispensed salbutamol, and 278 (31.7%) dispensed steroid. In diarrhoea, 824 (94.0%) RMPs dispensed antibiotic, 937 (95.4%) dispensed ORS, 709 (80.8%) dispensed antiprotozoal, and 15 (1.7%) refrained from dispensing antibiotic and antiprotozoal together.

Conclusions
Inappropriate diagnoses, irrational use of antibiotics and other drugs, and polypharmacy were observed in the practising pattern of RMPs. The government and other stakeholders should acknowledge them as crucial partners in the healthcare sector and consider ways to incorporate them into curative and preventive care.
The effect of transformation policies on healthcare providers’ satisfaction in primary healthcare centers: the case of Eastern Saudi Arabia
Authors: Althumairi Arwa Abdulrahman , Bukhari Fatmah Muhammad , Awary Layan Bassam , Aljabri Duaa 
Published: November 2023

Abstract
Background
The Saudi Arabian Vision 2030 encompasses the Health Sector Transformation Program (HSTP), an initiative aimed at enhancing the accessibility, affordability, and quality of healthcare, with a strong emphasis on patient-centered care. To achieve this vision, the government has been providing training to Primary Healthcare (PHC) centers on patient-centered care, recognizing that spending quality time with patients is crucial for making informed clinical decisions. Therefore, it is essential to evaluate provider satisfaction with the quality of services they provide and assess the impact of organizational factors on care quality. This study represents the first comprehensive assessment of job satisfaction among PHC providers in the Eastern region of Saudi Arabia. It seeks to gauge job satisfaction among PHC providers and explore its associated impact on the quality of care they deliver.

Methods
This study employed a quantitative cross-sectional design. Data were collected using a modified version of the Job Satisfaction Survey (JSS), supplemented by three newly added dimensions. Additionally, questions addressing general characteristics were incorporated into the survey instrument. Data analysis involved calculating frequencies and percentages for univariate analysis, employing t-tests for comparisons between two groups, and utilizing ANOVA for comparisons among multiple groups (bivariate analysis).

Results
A total of 143 PHC providers took part in this study. Of these, 48% reported high satisfaction, while the rest were either dissatisfied or neutral. PHC providers were highly satisfied with supervision (17%, N=94). On the other hand, they were dissatisfied with contingent rewards (3%, N=15). There was a significant difference found between the intention to leave the job (yes, no) and job satisfaction scores (mean (SD)= 83.58 (16.174) vs. mean (SD)=101.64 (16.209),
p-value < 0.001). There were also significant relationships between general characteristics and the dimensions such as co-workers, promotion, responsibility, nature of work, operating procedure, and communication (p-value< 0.05).

Conclusion
The main findings of this study suggest that PHC providers working in PHC centers in the Eastern region were satisfied with their work, especially with supervision and patient care. However, the findings also revealed that there are many areas of the job of PHC providers that require planned reform, such as contingent reward and communication. Furthermore, intention to leave the job was significantly related to job satisfaction score and all the dimensions. The study findings will help policymakers and the Ministry of Health to develop an employee engagement and satisfaction program to track the PHC providers' levels of satisfaction.
SCEL regulates switches between pro-survival and apoptosis of the TNF-α/TNFR1/NF-κB/c-FLIP axis to control lung colonization of triple negative breast cancer
Authors: Chan Shih-Hsuan , Kuo Wen-Hung , Wang Lu-Hai 
Published: November 2023

Abstract
Background
Patients with metastatic triple-negative breast cancer (mTNBC) have a higher probability of developing visceral metastasis within 5 years after the initial diagnosis. Therefore, a deeper understanding of the progression and spread of mTNBC is urgently needed.

Methods
The isobaric tag for relative and absolute quantitation (iTRAQ)-based LC–MS/MS proteomic approach was applied to identify novel membrane-associated proteins in the lung-tropic metastatic cells. Public domain datasets were used to assess the clinical relevance of the candidate proteins. Cell-based and mouse models were used for biochemical and functional characterization of the protein molecule Sciellin (SCEL) identified by iTRAQ to elucidate its role and underlying mechanism in promoting lung colonization of TNBC cells.

Results
The iTRAQ-based LC–MS/MS proteomic approach identified a membrane-associated protein SCEL that was overexpressed in the lung-tropic metastatic cells, and its high expression was significantly correlated with the late-stage TNBC and the shorter survival of the patients. Downregulation of SCEL expression significantly impaired the 3D colony-forming ability but not the migration and invasion ability of the lung colonization (LC) cells. Knockdown of SCEL reduced TNF-α-induced activation of the NF-κB/c-FLIP pro-survival and Akt/Erk1/2 growth signaling pathways in the LC cells. Specifically, knockdown of SCEL expression switched TNF-α-mediated cell survival to the caspase 3-dependent apoptosis. Conversely, ectopic expression of SCEL promoted TNF-α-induced activation of NF-κB/c-FLIP pro-survival and Akt/Erk1/2 pro-growth signaling pathway. The result of co-immunoprecipitation (Co-IP) and GST pull-down assay showed that SCEL could interact with TNFR1 to promote its protein stability. The xenograft mouse model experiments revealed that knockdown of SCEL resulted in increase of caspase-3 activity, and decrease of ki67 and TNFR1 expression as well as increase of tumor-associated macrophages in the metastatic lung lesions. Clinically, SCEL expression was found to be positively correlated with TNFR1 in TNBC tissues. Lastly, we showed that blocking TNF-α-mediated cell survival signaling by adalimumab effectively suppressed the lung colonization of the SCEL-positive, but not the SCEL-downregulated LC cells in the tail-vein injection model.

Conclusions
Our findings indicate that SCEL plays an essential role in the metastatic lung colonization of TNBC by promoting the TNF-α/TNFR1/NF-κB/c-FLIP survival and Akt/Erk1/2 proliferation signaling. Thus, SCEL may serve as a biomarker for adalimumab treatment of TNBC patients.

Graphical abstract
GNF-7, a novel FLT3 inhibitor, overcomes drug resistance for the treatment of FLT3‑ITD acute myeloid leukemia
Authors: Xiao Xinhua , Wang Peihong , Zhang Weina , Wang Jiayi , Cai Mansi , Jiang Hua , Wu Yingli , Shan Huizhuang 
Published: November 2023

Abstract
Background
Acute myeloid leukemia (AML) with FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) mutation accounts for a large proportion of AML patients and diagnosed with poor prognosis. Although the prognosis of FLT3-ITD AML has been greatly improved, the drug resistance frequently occurred in the treatment of FLT3 targeting drugs. GNF-7, a multitargeted kinase inhibitor, which provided a novel therapeutic strategy for overriding leukemia. In this study, we explored the antitumor activity of GNF-7 against FLT3-ITD and clinically-relevant drug resistance in FLT3 mutant AML.

Methods
Growth inhibitory assays were performed in AML cell lines and Ba/F3 cells expressing various FLT3 mutants to evaluate the antitumor activity of GNF-7 in vitro. Western blotting was used to examine the inhibitory effect of GNF-7 on FLT3 and its downstream pathways. Molecular docking and cellular thermal shift assay (CETSA) were performed to demonstrate the binding of FLT3 to GNF-7. The survival benefit of GNF-7 in vivo was assessed in mouse models of transformed Ba/F3 cells harboring FLT3-ITD and FLT3-ITD/F691L mutation. Primary patient samples and a patient-derived xenograft (PDX) model were also used to determine the efficacy of GNF-7.

Results
GNF-7 inhibited the cell proliferation of Ba/F3 cells expressing FLT3-ITD and exhibited potently anti-leukemia activity on primary FLT3-ITD AML samples. Moreover, GNF-7 could bind to FLT3 protein and inhibit the downstream signaling pathway activated by FLT3 including STAT5, PI3K/AKT and MAPK/ERK. In vitro and in vivo studies showed that GNF-7 exhibited potent inhibitory activity against FLT3-ITD/F691L that confers resistant to quizartinib (AC220) or gilteritinib. Importantly, GNF-7 showed potent cytotoxic effect on leukemic stem cells, significantly extend the survival of PDX model and exhibited similar therapy effect compared with gilteritinib.

Conclusions
Our results show that GNF-7 is a potent FLT3-ITD inhibitor and may become a promising lead compound applied for treating some of the clinically drug resistant patients.
Colchicine delivered by a novel nanoparticle platform alleviates atherosclerosis by targeted inhibition of NF-κB/NLRP3 pathways in inflammatory endothelial cells
Authors: Tang Juan , Li Tao , Xiong Xiaojing , Yang Qiaoyun , Su Zedazhong , Zheng Minming , Chen Qingwei 
Published: November 2023

AbstractAtherosclerosis, a chronic inflammatory disease characterized by arterial plaque formation, is one of the most prominent causes of cardiovascular diseases. However, the current treatments often do not adequately compromise the chronic inflammation-mediated plaque accumulation and the disease progression. Therefore, a new and effective strategy that blocks atherosclerosis-associated inflammation is urgently needed to further reduce the risk. Colchicine, a potent anti-inflammatory medication, has shown great potential in the treatment of atherosclerosis, but its adverse effects have hampered its clinical application. Herein, we developed a novel delivery nanosystem encapsulated with colchicine (VHPK-PLGA@COL), which exhibited improved biosafety and sustained drug release along with the gradual degradation of PLGA and PEG as confirmed both in vitro and in vivo. Surface modification of the nanoparticles with the VHPK peptide ensured its capability to specifically target inflammatory endothelial cells and alleviate atherosclerotic plaque accumulation. In the ApoE − / − atherosclerotic mouse model, both colchicine and VHPK-PLGA@COL treatment significantly decreased the plaque area and enhanced plaque stability by blocking the NF-κB/NLRP3 pathways, while VHPK-PLGA@COL exhibited enhanced therapeutic effects due to its unique ability to target inflammatory endothelial cells without obvious long-term safety concerns. In summary, VHPK-PLGA@COL has the potential to overcome the key translational barriers of colchicine and open new avenues to repurpose this drug for anti-atherosclerotic therapy.
Single-cell RNA sequencing unveils Lrg1's role in cerebral ischemia‒reperfusion injury by modulating various cells
Authors: Ruan Zhaohui , Cao Guosheng , Qian Yisong , Fu Longsheng , Hu Jinfang , Xu Tiantian , Wu Yaoqi , Lv Yanni 
Published: November 2023

Abstract
Background and purpose
Cerebral ischemia‒reperfusion injury causes significant harm to human health and is a major contributor to stroke-related deaths worldwide. Current treatments are limited, and new, more effective prevention and treatment strategies that target multiple cell components are urgently needed. Leucine-rich alpha-2 glycoprotein 1 (Lrg1) appears to be associated with the progression of cerebral ischemia‒reperfusion injury, but the exact mechanism of it is unknown.

Methods
Wild-type (WT) and Lrg1 knockout (Lrg1−/−) mice were used to investigate the role of Lrg1 after cerebral ischemia‒reperfusion injury. The effects of Lrg1 knockout on brain infarct volume, blood‒brain barrier permeability, and neurological score (based on 2,3,5-triphenyl tetrazolium chloride, evans blue dye, hematoxylin, and eosin staining) were assessed. Single-cell RNA sequencing (scRNA-seq), immunofluorescence, and microvascular albumin leakage tests were utilized to investigate alterations in various cell components in brain tissue after Lrg1 knockout.

Results
Lrg1 expression was increased in various cell types of brain tissue after cerebral ischemia‒reperfusion injury. Lrg1 knockout reduced cerebral edema and infarct size and improved neurological function after cerebral ischemia‒reperfusion injury. Single-cell RNA sequencing analysis of WT and Lrg1−/− mouse brain tissues after cerebral ischemia‒reperfusion injury revealed that Lrg1 knockout enhances blood‒brain barrier (BBB) by upregulating claudin 11, integrin β5, protocadherin 9, and annexin A2. Lrg1 knockout also promoted an anti-inflammatory and tissue-repairing phenotype in microglia and macrophages while reducing neuron and oligodendrocyte cell death.

Conclusions
Our results has shown that Lrg1 mediates numerous pathological processes involved in cerebral ischemia‒reperfusion injury by altering the functional states of various cell types, thereby rendering it a promising therapeutic target for cerebral ischemia‒reperfusion injury.
A retrospective study of laparoscopic, robotic-assisted, and open emergent/urgent cholecystectomy based on the PINC AI Healthcare Database 2017–2020
Authors: Campbell Stephen , Lee Shih-Hao , Liu Yuki , Wren Sherry M. 
Published: November 2023

Abstract
Background
Robotic-assisted cholecystectomy (RAC) is becoming increasingly common, but the outcomes of emergent/urgent robotic-assisted cholecystectomies compared to emergent laparoscopic (LC) and open cholecystectomies (OC) remain understudied.

Methods
The PINC AI Healthcare Database was queried to identify adults who underwent emergent or urgent (Em-Ur) cholecystectomy between January 1, 2017, and December 31, 2020. Immediate postoperative and 30-day outcomes were identified including intraoperative complications, transfusion, conversion, postoperative complication, and hospital length of stay. Propensity score matching was done to compare outcomes between Em-Ur robotic-assisted, laparoscopic, and open cholecystectomies Subgroup analyses were performed comparing RAC done with and without fluorescent imaging as well as comparing RAC and LC performed for patients with class 3 obesity (BMI ≥ 40 kg/m2).

Results
RAC Em-Ur cholecystectomies are being performed with increasing frequency and is the most utilized modality for patients with class 3 obesity. There was no difference in intraoperative complications (0.3%), bile duct injury (0.2%), or postoperative outcomes between RAC and LC. LC had significantly shorter operating room times (96 min (75,128)) compared to RAC (120 min (90,150)). There was a significant lower rate of conversion to open in RAC (1.9%) relative to LC (3.2%) in both the overall population and the class 3 obesity sub-analysis (RAC-2.6% vs. LC-4.4%). There was no difference in outcomes in robotic-assisted cholecystectomies done with and without fluorescent imaging.

Conclusions
A comparison of propensity score-matched cohorts of emergent/urgent robotic-assisted and laparoscopic cholecystectomy indicates that robotic-assisted cholecystectomy is a safe alternative to laparoscopic cholecystectomy, and that both have superior outcomes to open cholecystectomies.