bluuebunny/crossref_metadata_2025 huggingface dataset:
Late-life food insecurity and cognition: exploring timing, duration, and mechanisms among older Mexican adults
Authors: Saenz Joseph , Avila Jaqueline C
Published: November 2023

Background

Food insecurity (FI) remains a global public health problem. FI is more prevalent in low-and middle-income countries than high-income countries. FI is related with worse cognitive outcomes including cognitive function, cognitive decline, and cognitive impairment. Few studies have sought to identify how patterns of FI relate with cognitive function in old age and the potential mechanisms underlying this association.

Methods

Data from the 2015 and 2018 waves of the Mexican Health and Aging Study (n = 9,654, age 50+) were used in this study. Reports of FI in 2015 and 2018 were combined to create four patterns of FI groups: “persistently food secure”, “became food secure”, “became food insecure”, and “persistently food insecure”. Linear regression was used to estimate associations between patterns of FI and cognitive task performance. The mediating roles of depressive symptoms, body mass index, and chronic conditions were tested using Karlson, Holm, and Breen methodology.

Results

Approximately half of the sample were persistently food secure, 17% became food secure, 14% became FI, and 15% experienced persistent FI. When adjusting for demographic/socioeconomic confounders, persistent FI related with worse Verbal Learning, Verbal Recall, Visual Scanning, and Verbal Fluency performance compared to the persistently food secure. Becoming FI related with worse Verbal Learning, Visual Scanning, and Verbal Fluency. Mediation analyses provided support for depressive symptoms mediating associations between FI and poorer cognition, where 48% of the association between persistent FI and worse Verbal Recall performance was attributed to higher depressive symptoms. Becoming food secure was not associated with cognitive performance compared to the persistently food secure.

Conclusions

FI may represent an important modifiable risk factor for poorer cognitive outcomes among older adults. Public health efforts should focus on providing stable food access to older adults, especially those living in poverty.
A transfer learning nomogram for predicting prostate cancer and benign conditions on MRI
Authors: Chen Junhao , Feng Bao , Hu Maoqing , Huang Feidong , Chen Yehang , Ma Xilun , Long Wansheng
Published: November 2023

Background

Deep learning has been used to detect or characterize prostate cancer (PCa) on medical images. The present study was designed to develop an integrated transfer learning nomogram (TLN) for the prediction of PCa and benign conditions (BCs) on magnetic resonance imaging (MRI).

Methods

In this retrospective study, a total of 709 patients with pathologically confirmed PCa and BCs from two institutions were included and divided into training (n = 309), internal validation (n = 200), and external validation (n = 200) cohorts. A transfer learning signature (TLS) that was pretrained with the whole slide images of PCa and fine-tuned on prebiopsy MRI images was constructed. A TLN that integrated the TLS, the Prostate Imaging–Reporting and Data System (PI-RADS) score, and the clinical factor was developed by multivariate logistic regression. The performance of the TLS, clinical model (CM), and TLN were evaluated in the validation cohorts using the receiver operating characteristic (ROC) curve, the Delong test, the integrated discrimination improvement (IDI), and decision curve analysis.

Results

TLS, PI-RADS score, and age were selected for TLN construction. The TLN yielded areas under the curve of 0.9757 (95% CI, 0.9613–0.9902), 0.9255 (95% CI, 0.8873–0.9638), and 0.8766 (95% CI, 0.8267–0.9264) in the training, internal validation, and external validation cohorts, respectively, for the discrimination of PCa and BCs. The TLN outperformed the TLS and the CM in both the internal and external validation cohorts. The decision curve showed that the TLN added more net benefit than the CM.

Conclusions

The proposed TLN has the potential to be used as a noninvasive tool for PCa and BCs differentiation.
Clinical value of folate receptor-positive circulating tumor cells in patients with esophageal squamous cell carcinomas: a retrospective study
Authors: Zhou Qiang , He Qiao , He Wenwu , Wang Chenghao , Liu Guangyuan , Wang Kangning , Li Haojun , Li Jialong , Xiao Wenguang , Fang Qiang , Peng Lin , Han Yongtao , Wang Dongsheng , Leng Xuefeng
Published: November 2023

Background

The aim of the study is to explore the role of preoperative folate receptor-positive circulating tumor cell (FR+CTC) levels in predicting disease-free survival (DFS) and overall survival (OS) in patients with esophageal squamous cell carcinomas (ESCC).

Methods

Three ml blood samples were prospectively drawn from ESCC patients, and ligand-targeted polymerase chain reaction (LT-PCR) was used for the quantification of FR+CTCs. Other serum indicators were measured by traditional methods. Clinicopathological characteristics were obtained from the hospital medical record system, DFS and OS data were obtained by follow-up. The correlation between clinico-pathological characteristics, DFS, and OS and FR+CTCs were analyzed, respectively. Risk factors potentially affecting DFS and OS were explored by Cox regression analysis.

Results

there were no significant correlations between FR+CTCs and patient age, sex, albumin, pre-albumin, C-reactive protein (CRP), ferritin and CRP/Albumin ratio, tumor size, grade of differentiation, lymph node metastasis, TNM stage, perineural invasion/vessel invasion (all P > 0.05). Nevertheless, preoperative FR+CTCs were an independent prognostic factor for DFS (HR 2.7; 95% CI 1.31-, P = 0.007) and OS (HR 3.37; 95% CI 1.06-, P = 0.04). DFS was significantly shorter for patients with post-operative FR+CTCs ≥ 17.42 FU/3ml compared with patients < 17.42 FU/3ml (P = 0.0012). For OS, it was shorter for patients with FR+CTCs ≥ 17.42 FU/3ml compared with patients < 17.42 FU/3ml, however, the difference did not reach statistical significance (P = 0.51).

Conclusions

ESCC patients with high FR+CTCs tend to have a worse prognosis. FR+CTCs may monitor the recurrence of cancers in time, accurately assess patient prognosis, and guide clinical decision-making.

Trial registration

The study was approved by the Sichuan Cancer Hospital & Institute Ethics Committee (No. SCCHEC-02-2022-050).
In vivo antiangiogenic effect of nimbolide, trans-chalcone and piperine for use against glioblastoma
Authors: Senrung Anna , Tripathi Tanya , Yadav Joni , Janjua Divya , Chaudhary Apoorva , Chhokar Arun , Aggarwal Nikita , Joshi Udit , Goswami Nidhi , Bharti Alok Chandra
Published: November 2023

Background

Angiogenesis is an important hallmark of Glioblastoma (GBM) marked by elevated vascular endothelial growth factor-A (VEGF-A) and its receptor 2 (VEGFR-2). As previously reported nimbolide (NBL), trans-chalcone (TC) and piperine (PPR) possess promising antiangiogenic activity in several cancers however, their comparative efficacy and mechanism of antiangiogenic activity in GBM against VEGFR-2 has not been elucidated.

Methods

2D and 3D spheroids cultures of U87 (Uppsala 87 Malignant Glioma) were used for evaluation of non-cytotxoic dose for anti-angiogenic activity. The antiangiogenic effect was investigated by the GBM U87 cell line bearing chick CAM model. Excised U87 xenografts were histologically examined for blood vascular density by histochemistry. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect the presence of avian and human VEGF-A and VEGFR-2 mRNA transcripts.

Results

Using 2D and 3D spheroid models, the non-cytotoxic dose of NBL, TC and PPR was ≤ 11 µM. We found NBL, TC and PPR inhibit U87-induced neoangiogenesis in a dose-dependent manner in the CAM stand-alone model as well as in CAM U87 xenograft model. The results also indicate that these natural compounds inhibit the expression of notable angiogenic factors, VEGF-A and VEGFR-2. A positive correlation was found between blood vascular density and VEGF-A as well as VEGFR-2 transcripts.

Conclusion

Taken together, NBL, TC and PPR can suppress U87-induced neoangiogenesis via a reduction in VEGF-A and its receptor VEGFR-2 transcript expression at noncytotoxic concentrations. These phytochemicals showed their utility as adjuvants to GBM therapy, with Piperine demonstrating superior effectiveness among them all.
Methods for quantifying the heterogeneity of psychopathology
Authors: Buss John F. , Watts Ashley L. , Lorenzo-Luaces Lorenzo
Published: November 2023

Objectives

Specifiers for a major depressive disorder (MDE) are supposed to reduce diagnostic heterogeneity. However, recent literature challenges the idea that the atypical and melancholic specifiers identify more homogenous or coherent subgroups. We introduce the usage of distance metrics to characterize symptom heterogeneity. We attempt to replicate prior findings and explore whether symptom heterogeneity is reduced using specifier subgroups.

Methods

We used data derived from the National Epidemiological Survey on Alcohol and Related Conditions (NESARC Wave I; N = 5,749) and the Sequenced Treatment Alternatives to Relieve Depression study (STAR*D; N = 2,498). We computed Hamming and Manhattan distances from study participants’ unique symptom profiles. Distances were standardized from 0-1 and compared by their within- and between-group similarities to their non-specifier counterparts for the melancholic and atypical specifiers.

Results

There was no evidence of statistically significant differences in heterogeneity for specifier (i.e., melancholic or atypical) vs. non-specifier designations (i.e., non-melancholic vs. non-atypical).

Conclusion

Replicating prior work, melancholic and atypical depression specifiers appear to have limited utility in reducing heterogeneity. The current study does not support the claim that specifiers create more coherent subgroups as operationalized by similarity in the number of symptoms and their severity. Distance metrics are useful for quantifying symptom heterogeneity.
Quantifying the benefits of healthy lifestyle behaviors and emotional expressivity in lowering the risk of COVID-19 infection: a national survey of Chinese population
Authors: Miao Yudong , Zhang Wanliang , Li Yi , Wu Jian , Shen Zhanlei , Bai Junwen , Zhu Dongfang , Ren Ruizhe , Zhang Jingbao , Guo Dan , Tarimo Clifford Silver , Li Chengpeng , Dong Wenyong
Published: November 2023

Background

COVID-19 is still prevalent in most countries around the world at the low level. Residents’ lifestyle behaviors and emotions are critical to prevent COVID-19 and keep healthy, but there is lacking of confirmative evidence on how residents’ lifestyle behaviors and emotional expressivity affected COVID-19 infection.

Methods

Baseline study was conducted in August 2022 and follow-up study was conducted in February 2023. Baseline survey collected information on residents’ basic information, as well as their lifestyle behaviors and emotions. Follow-up study was carried out to gather data on COVID-19 infection condition. Binary logistic regression was utilized to identify factors that may influence COVID-19 infection. Attributable risk (AR) was computed to determine the proportion of unhealthy lifestyle behaviors and emotional factors that could be attributed to COVID-19 infection. Sensitivity analysis was performed to test the robustness of the results.

Results

A total of 5776 participants (46.57% males) were included in this study, yielding an overall COVID-19 infection rate of 54.8% (95%CI: 53.5 – 56.0%). The findings revealed that higher stress levels [aOR = 1.027 (95%CI; 1.005–1.050)] and lower frequency in wearing masks, washing hands, and keeping distance [aOR = 1.615 (95%CI; 1.087–2.401)], were positively associated with an increased likelihood of COVID-19 infection (all P < 0.05). If these associations were causal, 8.1% of COVID-19 infection would have been prevented if all participants had normal stress levels [Attributable Risk Percentage: 8.1% (95%CI: 5.9-10.3%)]. A significant interaction effect between stress and the frequency in wearing masks, washing hands, and keeping distance on COVID-19 infection was observed (β = 0.006, P < 0.001), which also was independent factor of COVID-19 infection.

Conclusions

The overall COVID-19 infection rate among residents is at a medium level. Residents’ increasing stress and decreasing frequency in wearing masks and washing hands and keeping distance contribute to increasing risk of infection, residents should increase the frequency of mask-wearing, practice hand hygiene, keep safe distance from others, ensure stable emotional state, minimize psychological stress, providing evidence support for future responses to emerging infectious diseases.
Efficacy and safety of corticosteroids, hyaluronic acid, and PRP and combination therapy for knee osteoarthritis: a systematic review and network meta-analysis
Authors: Qiao Xiaochen , Yan Lei , Feng Yi , Li Xiaoyan , Zhang Kun , Lv Zhi , Xu Chaojian , Zhao Sen , Liu Fengrui , Yang Xihua , Tian Zhi
Published: November 2023

Objective

There are many injectable treatments for knee osteoarthritis with different characteristics and effects, the aim is to understand which one can lead to better and safer results.

Methods

The PRISMA principles were followed when doing the literature search. Web of Science databases, Embase, the Cochrane Library, PubMed, and the Wanfang database were searched to identified randomized controlled trials that assessed the efficacy of corticosteroids (CSC), platelet-rich plasma (PRP), hyaluronic acid (HA), and combination therapy in treating KOA. Risk of bias was assessed using the relevant Cochrane tools (version 1.0). The outcome measure included the visual analog scale (VAS) score, the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) score, and treatment-related adverse events. The network meta-analysis was performed using STATA17 software and a Bayesian stratified random effects model.

Results

Network meta-analysis using the Bayesian random-effects model revealed 35 studies with 3104 participants. PRP showed the best WOMAC score at a 3-month follow-up, followed by PRP + HA, HA, placebo, and CSC; PRP + HA scored the highest VAS, followed by PRP, CSC, HA, and placebo. PRP, CSC, HA, and placebo had the highest WOMAC scores six months following treatment; PRP + HA showed the best VAS scores. PRP showed the best WOMAC score at 12 months, followed by PRP + HA, HA, placebo, and CSC; The best VAS score was obtained with PRP, followed by PRP + HA, HA, and CSC. No therapy demonstrated a rise in adverse events linked to the treatment in terms of safety.

Conclusions

The current study found that PRP and PRP + HA were the most successful in improving function and alleviating pain after 3, 6, and 12 months of follow-up. CSC, HA, PRP, and combination therapy did not result in an increase in the incidence of treatment-related side events as compared to placebo.
The meaning of dignity in care during the COVID-19 pandemic: a qualitative study in acute and intensive care
Authors: Buonaccorso Loredana , De Panfilis Ludovica , Chochinov Harvey Max , Martucci Gianfranco , Massari Marco , Cocchi Monica , Bassi Maria Chiara , Tanzi Silvia
Published: November 2023

Background

The pandemic Era has forced palliative care professionals to use a dignity-in-care approach in different settings from the classic ones of palliative care: acute and intensive care. We explored the meanings of dignity for patients, their family members, and clinicians who have experienced COVID-19 in the acute and intensive care setting.

Methods

A qualitative, prospective study by means of semi-structured interviews with patients hospitalized for COVID-19, family members, and clinicians who care for them.

Findings

Between March 2021 and October 2021, we interviewed 16 participants: five physicians, three nurses, and eight patients. None of the patients interviewed consented for family members to participate: they considered it important to protect them from bringing the painful memory back to the period of their hospitalization. Several concepts and themes arose from the interviews: humanity, reciprocity, connectedness, and relationship, as confirmed by the literature. Interestingly, both healthcare professionals and patients expressed the value of informing and being informed about clinical conditions and uncertainties to protect dignity.

Conclusions

Dignity should be enhanced by all healthcare professionals, not only those in palliative care or end-of-life but also in emergency departments.
Resource Utilization Groups in transitional home care: validating the RUG-III/HC case-mix system in hospital-to-home care programs
Authors: Bolster-Foucault Clara , Holyoke Paul
Published: November 2023

Background

Transitional hospital-to-home care programs support safe and timely transition from acute care settings back into the community. Case-mix systems that classify transitional care clients into groups based on their resource utilization can assist with care planning, calculating reimbursement rates in bundled care funding models, and predicting health human resource needs. This study evaluated the fit and relevance of the Resource Utilization Groups version III for Home Care (RUG-III/HC) case-mix classification system in transitional care programs in Ontario, Canada.

Methods

We conducted a retrospective analysis of clinical assessment data and administrative billing records from a cohort of clients (n = 1,680 care episodes) in transitional home care programs in Ontario. We classified care episodes into established RUG-III/HC groups based on clients’ clinical and functional characteristics and calculated four case-mix indices to describe care relative resource utilization in the study sample. Using these indices in linear regression models, we evaluated the degree to which the RUG-III/HC system can be used to predict care resource utilization.

Results

A majority of transitional home care clients are classified as being Clinically complex (41.6%) and having Reduced physical functions (37.8%). The RUG-III/HC groups that account for the largest share of clients are those with the lowest hierarchical ranking, indicating low Activities of Daily Living limitations but a range of Instrumental Activities of Daily Living limitations. There is notable heterogeneity in the distribution of clients in RUG-III/HC groups across transitional care programs. The case-mix indices reflect decreasing hierarchical resource use within but not across RUG-III/HC categories. The RUG-III/HC predicts 23.34% of the variance in resource utilization of combined paid and unpaid care time.

Conclusions

The distribution of clients across RUG-III/HC groups in transitional home care programs is remarkably different from clients in long-stay home care settings. Transitional care programs have a higher proportion of Clinically complex clients and a lower proportion of clients with Reduced physical function. This study contributes to the development of a case-mix system for clients in transitional home care programs which can be used by care managers to inform planning, costing, and resource allocation in these programs.
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

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

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

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

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

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

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

Atherosclerosis, 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

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

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.
Development and validation of a nomogram for predicting new vertebral compression fractures after percutaneous kyphoplasty in postmenopausal patients
Authors: Zheng Jianhu , Gao Yan , Yu Wenlong , Yu Ning , Jia Zetao , Hao Yanke , Chen Yungang
Published: November 2023

Background

Postmenopausal women face a heightened risk of developing new vertebral compression fractures (NVCFs) following percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fractures (OVCFs). This study aimed to develop and validate a visual nomogram model capable of accurately predicting NVCF occurrence post-PKP to optimize treatment strategies and minimize occurrence.

Methods

This retrospective study included postmenopausal women diagnosed with OVCF who underwent PKP at the Affiliated Hospital of Shandong University of Traditional Chinese Medicine between January 2016 and January 2021. Patient data, including basic information, surgical details, imaging records, and laboratory findings, were collected. The patients were categorized into two groups based on NVCF occurrence within 2 years post-PKP: the NVCF group and the non-NVCF group. Following the utilization of least absolute shrinkage and selection operator (LASSO) regression for feature selection, a nomogram was constructed. Model differentiation, calibration, and clinical applicability were evaluated using receiver operating characteristic (ROC), calibration, and decision (DCA) curve analyses.

Results

In total, 357 patients were included in the study. LASSO regression analysis indicated that cement leakage, poor cement diffusion, and endplate fracture were independent predictors of NVCF. The nomogram demonstrated excellent predictive accuracy and clinical applicability.

Conclusions

This study used LASSO regression to identify three independent predictors of NVCF and developed a predictive model that could effectively predict NVCF occurrence in postmenopausal women. This simple prediction model can support medical decision-making and is feasible for clinical practice.
Effects of the response to the COVID-19 pandemic in chest trauma patients in China: a multicenter retrospective study
Authors: Wang Zhengwei , Li Mi
Published: November 2023

Background

An international pandemic of severe coronavirus disease (COVID-19) has been caused by the novel coronavirus SARS-CoV-2. A large number of patients with chest trauma were infected with COVID-19. The COVID-19 pandemic had a significant impact on the management of chest trauma.

Objective

The present observational study was conducted to evaluate the clinical characteristics and outcomes of chest trauma patients with or without COVID-19 infection.

Methods

A multicenter observational study was performed at three Chinese hospitals between November 1, 2022, and January 31, 2023. All enrolled patients were diagnosed with chest trauma. We analyzed data from existing medical records, including all baseline data and prognostic follow-up data, such as 30-day mortality, hospital stays, hospitalization costs, and complications.

Results

All 375 eligible patients completed the follow-up. There was no significant difference in baseline characteristics between chest trauma combined with COVID-19 (p > 0.05). Chest trauma combined with COVID-19 infection may lead to higher 30-day mortality (16.36% vs. 7.14%, p = 0.005), longer hospital stays (22.5 ± 5.9 vs. 12.8 ± 4.2, p < 0.001), larger hospitalization costs (p < 0.001), and increased hospitalization complications, such as pulmonary embolism (10.30% vs. 4.76%, p = 0.039), deep vein thrombosis (DVT, 33.33% vs. 18.57%, p = 0.001), the incidence of 7-day delirium (69.70% vs. 46.19%, p < 0.001), and respiratory failure (38.18% vs. 24.77%, p = 0.005).

Conclusions

Compared to chest trauma alone, it may lead to higher mortality, larger hospitalization costs, and more complications. To better respond to the future of COVID-19 or other similar virus-borne disease pandemics, it is important to understand the clinical characteristics and complications, such as pulmonary embolism, DVT, and respiratory failure after COVID-19 infection. To guide the future treatment of chest trauma combined with COVID-19 infection or other infectious diseases.
Identification of novel homozygous nonsense SLC10A7 variant causing short stature, amelogenesis imperfecta, and skeletal dysplasia with scoliosis and surgical management of spine
Authors: Zhang Wenyan , Yao Ziming , Guo Ruolan , Cao Jun , Li Wei , Hao Chanjuan , Zhang Xuejun
Published: November 2023

Background

Short stature, amelogenesis imperfecta, and skeletal dysplasia with scoliosis is a rare, autosomal recessive, skeletal disorder first described in 2018. This syndrome starts with pre- and postnatal developmental delay, and gradually presents with variable facial dysmorphisms, a short stature, amelogenesis imperfecta, and progressive skeletal dysplasia affecting the limbs, joints, hands, feet, and spine.

Case presentation

We identified a homozygous novel nonsense mutation in exon 1 of SLC10A7 (NM_001300842.2: c.100G > T / p.Gly34*) segregating with the typical disease phenotype in a Han Chinese family. We reviewed the 12-year surgical treatment history with seven interventions on spine.

Conclusion

To date, only 12 cases of the SLC10A7 mutation have been reported, mainly from consanguineous families. Our patient showed a relatively severe and broad clinical phenotype compared with previously reported cases. In this patient, annual check-ups and timely surgeries led to a good outcome.