bluuebunny/crossref_metadata_2025 huggingface dataset:
The pathways from perceived discrimination to self-rated health among the Chinese diaspora during the COVID-19 pandemic: investigation of the roles of depression, anxiety, and social support
Authors: Chen Youli , Wang Zicong , Dong Weizhen , Xu Jia Huei Chen , Wu Sizhe Ji , Zhang Xiangyang , Chen Chun
Published: August 2021

Background

Research indicates the adverse impacts of perceived discrimination on health, and discrimination inflamed by the COVID-19 pandemic, a type of social exclusion, could affect the well-being of the Chinese diaspora. We analyzed the relationship and pathways of perceived discrimination’s effect on health among the Chinese diaspora in the context of the pandemic to contribute to the literature on discrimination in this population under the global public health crisis.

Methods

We analyzed data from 705 individuals of Chinese descent residing in countries outside of China who participated in a cross-sectional online survey between April 22 and May 9, 2020. This study utilized a structural equation model (SEM) to evaluate both direct and indirect effects of perceived discrimination on self-rated health (SRH) and to assess the mediating roles of psychological distress (namely, anxiety and depression) and social support from family and friends.

Results

This online sample comprised predominantly young adults and those of relatively high socioeconomic status. This study confirmed the total and direct effect of recently perceived discrimination on SRH and found the indirect effect was mainly mediated by depression. Mediating roles of anxiety and social support on the discrimination-health relationship were found insignificant in this SEM.

Conclusions

Our findings suggest discrimination negatively affected the well-being of the Chinese diaspora, and depression acted as a major mediator between the discrimination-health relationship. Therefore, interventions for reducing discrimination to preserve the well-being of the Chinese diaspora are necessary. Prompt intervention to address depression may partially relieve the disease burden caused by the surge of discrimination.
Associations between polyfluoroalkyl substance and organophosphate flame retardant exposures and telomere length in a cohort of women firefighters and office workers in San Francisco
Authors: Clarity Cassidy , Trowbridge Jessica , Gerona Roy , Ona Katherine , McMaster Michael , Bessonneau Vincent , Rudel Ruthann , Buren Heather , Morello-Frosch Rachel
Published: August 2021

Background

Environmental chemical exposures can affect telomere length, which in turn has been associated with adverse health outcomes including cancer. Firefighters are occupationally exposed to many hazardous chemicals and have higher rates of certain cancers. As a potential biomarker of effect, we assessed associations between chemical exposures and telomere length in women firefighters and office workers from San Francisco, CA.

Methods

We measured serum concentrations of polyfluoroalkyl substances (PFAS), urinary metabolites of flame retardants, including organophosphate flame retardants (OPFRs), and telomere length in peripheral blood leukocytes in women firefighters (N = 84) and office workers (N = 79) who participated in the 2014–15 Women Workers Biomonitoring Collaborative. Multiple linear regression models were used to assess associations between chemical exposures and telomere length.

Results

Regression results revealed significant positive associations between perfluorooctanoic acid (PFOA) and telomere length and perfluorooctanesulfonic acid (PFOS) and telomere length among the whole cohort. Models stratified by occupation showed stronger and more significant associations among firefighters as compared to office workers. Among firefighters in models adjusted for age, we found positive associations between telomere length and log-transformed PFOA (β(95%CI) = 0.57(0.12, 1.02)), PFOS (0.44 (0.05, 0.83)), and perfluorodecanoic acid (PFDA) (0.43 (0.02, 0.84)). Modeling PFAS as categories of exposure showed significant associations between perfluorononanoic acid (PFNA) and telomere length among firefighters. Significant associations between OPFR metabolites and telomere length were seen for bis (1,3-dichloro-2-propyl) phosphate (BDCPP) and telomere length among office workers (0.21(0.03, 0.40)) and bis (2-chloroethyl) phosphate (BCEP) and telomere length among firefighters (− 0.14(− 0.28, − 0.01)). For OPFRs, the difference in the direction of effect by occupational group may be due to the disparate detection frequencies and concentrations of exposure between the two groups and/or potential unmeasured confounding.

Conclusion

Our findings suggest positive associations between PFAS and telomere length in women workers, with larger effects seen among firefighters as compared to office workers. The OPFR metabolites BDCPP and BCEP are also associated with telomere length in firefighters and office workers. Associations between chemical exposures and telomere length reported here and by others suggest mechanisms by which these chemicals may affect carcinogenesis and other adverse health outcomes.
Development of a Web GIS for small-scale detection and analysis of COVID-19 (SARS-CoV-2) cases based on volunteered geographic information for the city of Cologne, Germany, in July/August 2020
Authors: Schmidt Fabian , Dröge-Rothaar Arne , Rienow Andreas
Published: August 2021

Background

Various applications have been developed worldwide to contain and to combat the coronavirus disease-19 (COVID-19) pandemic. In this context, spatial information is always of great significance. The aim of this study is to describe the development of a Web GIS based on open source products for the collection and analysis of COVID-19 cases and its feasibility in terms of technical implementation and data protection.

Methods

With the help of this Web GIS, data on this issue were collected voluntarily from the Cologne area. Using house perimeters as a data basis, it was possible to check, in conjunction with the Official Topographic Cartographic Information System object type catalog, whether buildings with certain functions, for example residential building with trade and services, have been visited more frequently by infected persons than other types of buildings. In this context, data protection and ethical and legal issues were considered.

Results

The results of this study show that the development of a Web GIS for the generation and evaluation of volunteered geographic information (VGI) with the help of open source software is possible. Furthermore, there are numerous data protection and ethical and legal aspects to consider, which not only affect VGI per se but also affect IT security.

Conclusions

From a data protection perspective, more attention needs to be paid to the intervention and post-processing of data. In addition, official data must always be used as a reference for the actual spatial consideration of the number of infections. However, VGI provides added value at a small-scale level, so that valid information can also be reliably derived in the context of health issues. The creation of guidelines for the consideration of data protection, ethical aspects, and legal requirements in the context of VGI-based applications must also be considered.

Trial registration The article does not report the results of a health care intervention for human participants
Uncovering cancer vulnerabilities by machine learning prediction of synthetic lethality
Authors: Benfatto Salvatore , Serçin Özdemirhan , Dejure Francesca R. , Abdollahi Amir , Zenke Frank T. , Mardin Balca R.
Published: August 2021

Background

Synthetic lethality describes a genetic interaction between two perturbations, leading to cell death, whereas neither event alone has a significant effect on cell viability. This concept can be exploited to specifically target tumor cells. CRISPR viability screens have been widely employed to identify cancer vulnerabilities. However, an approach to systematically infer genetic interactions from viability screens is missing.

Methods

Here we describe PAn-canceR Inferred Synthetic lethalities (PARIS), a machine learning approach to identify cancer vulnerabilities. PARIS predicts synthetic lethal (SL) interactions by combining CRISPR viability screens with genomics and transcriptomics data across hundreds of cancer cell lines profiled within the Cancer Dependency Map.

Results

Using PARIS, we predicted 15 high confidence SL interactions within 549 DNA damage repair (DDR) genes. We show experimental validation of an SL interaction between the tumor suppressor CDKN2A, thymidine phosphorylase (TYMP) and the thymidylate synthase (TYMS), which may allow stratifying patients for treatment with TYMS inhibitors. Using genome-wide mapping of SL interactions for DDR genes, we unraveled a dependency between the aldehyde dehydrogenase ALDH2 and the BRCA-interacting protein BRIP1. Our results suggest BRIP1 as a potential therapeutic target in ~ 30% of all tumors, which express low levels of ALDH2.

Conclusions

PARIS is an unbiased, scalable and easy to adapt platform to identify SL interactions that should aid in improving cancer therapy with increased availability of cancer genomics data.
Low high-density lipoprotein cholesterol levels are associated with malignant intraductal papillary mucinous neoplasms: A multicenter study
Authors: Wang Cheng , Lin Tingting , Wang Xinru , Yu Zhicheng , Zhuge Xiaoling , Cui Wenjing , Wang Miaomiao , Wang Zhongqiu , Guo Chuangen , Chen Xiao
Published: August 2021

Background

Intraductal papillary mucinous neoplasms (IPMNs) can potentially undergo malignant transformation. Studies have shown that high-density lipoprotein cholesterol (HDL-c) was associated with the risk of cancer. In this study, the association between HDL-c and the incidence of malignancy in IPMNs was investigated.

Materials and methods

226 patients with histologically proven IPMNs who underwent surgery were included in the present study. Patients were assigned to a training group (n = 151) and validation group (n = 75). Patients’ demographic information, clinical data, and histopathological evaluation findings were obtained from medical records. Malignant IPMNs were defined as lesions that showed high grade dysplasia and invasive carcinoma. Logistic regression analyses were used to show the association between HDL-c and malignant IPMNs. Receiver operating characteristic (ROC) curves were generated to analyze predictive performance.

Results

The prevalence of low HDL-c levels was higher in patients with malignant IPMNs than in those with non-malignant IPMNs (P < 0.01) in both the training group and validation group. The prevalence of malignant IPMNs decreased with an increase in HDL-c levels both in patients with all types of IPMNs, as well as in those with branch-duct IPMNs (BD-IPMNs).Logistic analysis showed that low HDL-c levels were associated with malignant IPMNs (odds ratio (OR) = 20.56, 95 % confidence interval (CI): 2.58–163.64, P < 0.01) in all types of IPMNs and BD-IPMNs (OR = 17.6, 95 %CI: 1.16–268.46, P = 0.02 ).The predictive performance of mural nodules plus low HDL-c levels was higher than that of mural nodules alone or mural nodules plus cyst size for the identification of malignant BD-IPMNs.

Conclusions

HDL-c levels may serve a potential biomarker for identifying malignant IPMNs and improve the predictive ability of malignancy in BD-IPMNs.
The role of the electrokinetic charge of neurotrophis-based nanocarriers: protein distribution, toxicity, and oxidative stress in in vitro setting
Authors: Dąbkowska Maria , Ulańczyk Zofia , Łuczkowska Karolina , Rogińska Dorota , Sobuś Anna , Wasilewska Monika , Olszewska Maria , Jakubowska Katarzyna , Machaliński Bogusław
Published: August 2021

Background

The rational chemical design of nanoparticles can be readily controlled and optimized by quantitatively studying protein adsorption at variously charged polymer carriers, determining their fate in biological fluids. We manufactured brain-derived neurotrophic factor (BDNF) -based electrostatic nanocomplexes with a different type of dendrimer core (anionic or cationic), encapsulated or not in polyethylene glycol (PEG), and studied their physicochemical properties and behavior in a biological setting. We investigated whether the electrokinetic charge of dendrimer core influences BDNF loading and desorption from the nanoparticle and serves as a determinant of nanoparticles’ behavior in in vitro setting, influencing mitochondrial dysfunction, lipid peroxidation, and general nanoparticles’ cellular toxicity.

Results

We found that the electrokinetic charge of the dendrimer core influences nanoparticles in terms of BDNF release profile from their surfaces and their effect on cell viability, mitochondrial membrane potential, cell phenotype, and induction of oxidative stress. The electrostatic interaction of positively charged core of nanoparticles with cell membranes increases their cytotoxicity, as well as serious phenotype alterations compared to negatively charged nanoparticles core in neuron-like differentiated human neuroblastoma cells. Moreover, PEG adsorption at nanoparticles with negatively charged core presents a distinct decrease in metabolic cell activity. On the contrary, charge neutralization due to PEG adsorption on the surface of nanoparticles with positively charged core does not reduce their cytotoxicity, makes them less biocompatible with differentiated cells, and presumably shows non-specific toxicity.

Conclusions

The surface charge transformation after adsorption of protein or polyelectrolyte during nanocarriers formulation has an important role not only in designing nanomaterials with potent neuroprotective and neuroregenerative properties but also in applying them in a cellular environment.

Graphic abstract
Bitter melon derived extracellular vesicles enhance the therapeutic effects and reduce the drug resistance of 5-fluorouracil on oral squamous cell carcinoma
Authors: Yang Meng , Luo Qingqiong , Chen Xu , Chen Fuxiang
Published: August 2021

Background

Plant-derived extracellular vesicles (PDEVs) have been exploited for cancer treatment with several benefits. Bitter melon is cultivated as a vegetable and folk medicine with anticancer and anti-inflammatory activities. 5-Fluorouracil (5-FU) is widely used for cancer treatment. However, 5-FU-mediated NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammation activation induced the resistance of oral squamous cell carcinoma (OSCC) cells to 5-FU. In this study, we explored the potential of bitter melon-derived extracellular vesicles (BMEVs) for enhancing the therapeutic efficacy and reduce the resistance of OSCC to 5-FU.

Results

Herein, we demonstrate that bitter melon derived extracellular vesicles (BMEVs), in addition to their antitumor activity against OSCC have intrinsic anti-inflammatory functions. BMEVs induced S phase cell cycle arrest and apoptosis. Apoptosis induction was dependent on reactive oxygen species (ROS) production and JUN protein upregulation, since pretreatment with N-acetyl cysteine or catechin hydrate could prevent apoptosis and JUN accumulation, respectively. Surprisingly, BMEVs significantly downregulated NLRP3 expression, although ROS plays a central role in NLRP3 activation. We further assessed the underlying molecular mechanism and proposed that the RNAs of BMEVs, at least in part, mediate anti-inflammatory bioactivity. In our previous studies, NLRP3 activation contributed to the resistance of OSCC cells to 5-FU. Our data clearly indicate that BMEVs could exert a remarkable synergistic therapeutic effect of 5-FU against OSCC both in vitro and in vivo. Most notably, NLRP3 downregulation reduced the resistance of OSCC to 5-FU.

Conclusions

Together, our findings demonstrate a novel approach to enhance the therapeutic efficacy and reduce the drug resistance of cancer cells to chemotherapeutic agents, which provides proof-of-concept evidence for the future development of PDEVs-enhanced therapy.

Graphic Abstract
Fluorescent carbon-dots enhance light harvesting and photosynthesis by overexpressing PsbP and PsiK genes
Authors: Wang Yuhui , Xie Zhuomi , Wang Xiuhua , Peng Xin , Zheng Jianping
Published: August 2021

Background

Fluorescent carbon-dots (CDs) with multifaceted advantages have provided hope for improvement of crop growth. Near infrared (NIR) CDs would be more competitive and promising than short-wavelength emissive CDs, which are not directly utilized by chloroplast. The molecular targets and underlying mechanism of these stimulative effects are rarely mentioned.

Results

NIR-CDs with good mono-dispersity and hydrophily were easily prepared by a one-step microwave-assisted carbonization manner, which showed obvious UV absorptive and far-red emissive properties. The chloroplast-CDs complexes could accelerate the electron transfer from photosystem II (PS II) to photosystem I (PS I). NIR-CDs exhibited a concentration-dependent promotion effect on N. benthamiana growth by strengthening photosynthesis. We firstly demonstrated that potential mechanisms behind the photosynthesis-stimulating activity might be related to up-regulated expression of the photosynthesis and chloroplast synthesis related genes, among which PsbP and PsiK genes are the key regulators.

Conclusion

These results illustrated that NIR-CDs showed great potential in the applications to increase crop yields through ultraviolet light harvesting and elevated photosynthesis efficiency. This work would provide a theoretical basis for the understanding and applications of the luminescent nanomaterials (not limited to CDs) in the sunlight conversion-related sustainable agriculture.

Graphic abstract
Patient-reported outcomes in coronary artery disease: the relationship between the standard, disease-specific set by the International Consortium for Health Outcomes Measurement (ICHOM) and the generic health-related quality of life instrument 15D
Authors: Lappalainen Laura , Stenvall Harriet , Lavikainen Piia , Miettinen Heikki , Martikainen Janne , Sintonen Harri , Tolppanen Anna-Maija , Roine Risto P. , Hartikainen Juha
Published: August 2021

Background

Patient-reported outcome (PRO) instruments measure health gains, including changes in health-related quality of life (HRQoL). Previous studies have assessed the reliability and relationship of multiple HRQoL instruments in search of the optimal instrument for feasible measurement of PROs. Although the 15D instrument was shown to have the best sensitivity and construct validity among cardiac patients, it is unknown how well it captures relevant disease-specific information scores compared to instruments included in the International Consortium for Health Outcomes Measurement (ICHOM) standard set. The aim of this study was to investigate whether the disease-specific PRO instruments and a generic HRQoL instrument capture disease related symptoms in coronary artery disease (CAD) patients.

Methods

Health status and HRQoL were assessed with the instruments included in the ICHOM standard set: Seattle Angina Questionnaire short-form (SAQ-7), Rose Dyspnea Scale (RDS), two-item Patient Health Questionnaire (PHQ-2), and with the 15D HRQoL instrument at baseline and 1 year from the treatment in a university hospital setting. Spearman correlation and explanatory factor analysis were used to assess the relationship of baseline scores and 1-year change in scores of 297 patients.

Results

At baseline, the overall 15D score and SAQ-physical limitation (SAQ-PL), 15D “breathing” and SAQ-PL, as well as “breathing” and RDS showed moderately strong correlations. The factor interpreted to reflect “Breathing-related physical activity”, based on high loadings of “breathing”, RDS, SAQ-PL, “mobility”, “vitality”, and “usual activities”, explained 19.2% of the total variance. Correlations between 1-year changes in scores were fair. The factor of “Breathing-related physical activity”, with significant loading of RDS, SAQ-PL, “breathing, “usual activities”, “vitality”, “sexual activity”, “mobility”, and disease-specific quality of life explained 20.5% of the total variance in 1-year change in scores. The correlation of angina frequency measured by SAQ-7 and the 15D instrument was poor.

Conclusions

The 15D detects dyspnea and depression similarly to RDS and PHQ-2 but not angina similarly to the SAQ-7. This may call for supplementing the 15D instrument with a disease-specific instrument when studying CAD patients.
A novel nomogram based on cardia invasion and chemotherapy to predict postoperative overall survival of gastric cancer patients
Authors: Mo Hanjun , Li Pengfei , Jiang Sunfang
Published: August 2021

Background

We aimed to establish and externally validate a nomogram to predict the 3- and 5-year overall survival (OS) of gastric cancer (GC) patients after surgical resection.

Methods

A total of 6543 patients diagnosed with primary GC during 2004–2016 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. We grouped patients diagnosed during 2004–2012 into a training set (n = 4528) and those diagnosed during 2013–2016 into an external validation set (n = 2015). A nomogram was constructed after univariate and multivariate analysis. Performance was evaluated by Harrell’s C-index, area under the receiver operating characteristic curve (AUC), decision curve analysis (DCA), and calibration plot.

Results

The multivariate analysis identified age, race, location, tumor size, T stage, N stage, M stage, and chemotherapy as independent prognostic factors. In multivariate analysis, the hazard ratio (HR) of non-cardia invasion was 0.762 (P < 0.001) and that of chemotherapy was 0.556 (P < 0.001). Our nomogram was found to exhibit excellent discrimination: in the training set, Harrell’s C-index was superior to that of the 8th American Joint Committee on Cancer (AJCC) TNM classification (0.736 vs 0.699, P < 0.001); the C-index was also better in the validation set (0.748 vs 0.707, P < 0.001). The AUCs for 3- and 5-year OS were 0.806 and 0.815 in the training set and 0.775 and 0.783 in the validation set, respectively. The DCA and calibration plot of the model also shows good performance.

Conclusions

We established a well-designed nomogram to accurately predict the OS of primary GC patients after surgical resection. We also further confirmed the prognostic value of cardia invasion and chemotherapy in predicting the survival rate of GC patients.
Histopathological validation of safe margin for nephron-sparing surgery based on individual tumor growth pattern
Authors: Li Gang , Xiao Tengfei , Wang Keruo , Zhang Renya , Wang Aixiang , Yan Chengzhi , Wang Chunhui
Published: August 2021

Background

To evaluate the clinicopathologic value of morphological growth patterns of small renal cell carcinoma (sRCC) and determine the actual demand for taking a rim of healthy parenchyma to avoid positive SM.

Methods

Data was collected from 560 sRCC patients who underwent laparoscopic surgeries from May 2010 to October 2017. One hundred forty-nine cases received nephron-sparing surgery (NSS) and others received radical nephrectomy (RN). All specimens were analyzed separately by two uropathologists, and three morphological growth patterns were identified. The presence of pseudocapsule (PC), surgical margins (SM), and other routine variables were recorded. The relationship between growth patterns and included variables was measured by the χ2 test and Fisher’s exact probability test. Survival outcomes were evaluated by Kaplan-Meier method and the log-rank test.

Results

The median age of patients was 63.2 years old and the mean tumor diameter was 3.0 cm. Four hundred eighty (85.7%) cases were clear cell RCC and 541 (96.6%) cases were at the pT1a stage. Peritumoral PC was detected in 512 (92.5%) specimens, and the ratio of tumor invasion in PC in infiltration pattern increased obviously than that of the other growth patterns. Similarly, the pT stage was significantly correlated with the infiltration pattern as well. One hundred forty-nine patients underwent NSS and 3 (2.0%) of them showed positive SM after operation. Statistical differences of the 5-year overall survival (OS) and the cancer-specific survival (CSS) existed between different morphological growth patterns, PC status, and pT stages.

Conclusions

Morphological growth patterns of sRCC might be used as a potential biomarker to help operate NSS to avoid the risk of positive SM. How to distinguish different morphological growth patterns before operation and the effectiveness of the growth pattern as a novel proposed parameter to direct NSS in sRCC patients deserves further exploration.
Dimethyl fumarate inhibits antibody-induced platelet destruction in immune thrombocytopenia mouse
Authors: Tong Huan , Ding Yangyang , Gui Xiang , Sun Zengtian , Wang Guozhang , Zhang Sixuan , Xu Zhengqing , Wang Xiamin , Xu Xiaoqi , Ju Wen , Li Yue , Li Zhenyu , Zeng Lingyu , Xu Kailin , Qiao Jianlin
Published: August 2021

Background

Immune thrombocytopenia (ITP) is an autoimmune disease characterized as a low platelet count resulting from immune-mediated platelet destruction. Dimethyl fumarate (DMF) is widely applied for the treatment of several autoimmune diseases with immunosuppressive effect. However, whether it ameliorates ITP is unclear. This study aims to evaluate whether DMF has a preventive effect on ITP in mice.

Methods

DMF (30, 60 or 90 mg/kg body weight) was intraperitoneally injected into mice followed by injection of rat anti-mouse integrin GPIIb/CD41antibody to induce ITP. Peripheral blood was isolated to measure platelet count and spleen mononuclear cells were extracted to measure Th1 and Treg cells along with detecting the levels of IFN-γ, and TGFβ-1 in plasma and CD68 expression in spleen by immuohistochemical staining. Additionally, macrophage cell line RAW264.7 was cultured and treated with DMF followed by analysis of cell apoptosis and cycle, and the expression of FcγRI, FcγRIIb and FcγRIV mRNA.

Results

DMF significantly inhibited antiplatelet antibody-induced platelet destruction, decreased Th1 cells and the expression of T-bet and IFN-γ, upregulated Treg cells and the expression of Foxp3 and TGF-β1 as well as reduced CD68 expression in the spleen of ITP mouse. DMF-treated RAW264.7 cells showed S-phase arrest, increased apoptosis and downregulated expression of FcγRI and FcγRIV. Meanwhile, in vitro treatment of DMF also decreased the expression of cyclin D1 and E2, reduced Bcl-2 level and increased Bax expression and caspase-3 activation.

Conclusions

In conclusion, DMF prevents antibody-mediated platelet destruction in ITP mice possibly through promoting apoptosis, indicating that it might be used as a new approach for the treatment of ITP.
Application of the Ultra-Poverty Graduation Model in understanding community health volunteers’ preferences for socio-economic empowerment strategies to enhance retention: a qualitative study in Kilifi, Kenya
Authors: Nyanja Njeri , Nyamu Nelson , Nyaga Lucy , Chabeda Sophie , Lusambili Adelaide , Temmerman Marleen , Mantel Michaela , Ngugi Anthony
Published: August 2021

Background

A significant shortage of healthcare workforce exists globally. To achieve Universal Healthcare coverage, governments need to enhance their community-based health programmes. Community health volunteers (CHVs) are essential personnel in achieving this objective. However, their ability to earn a livelihood is compromised by the voluntary nature of their work; hence, the high attrition rates from community-based health programmes. There is an urgent need to support CHVs become economically self-reliant. We report here on the application of the Ultra-Poverty Graduation (UPG) Model to map CHVs’ preferences for socio-economic empowerment strategies that could enhance their retention in a rural area in Kenya.

Methods

This study adopted an exploratory qualitative approach. Using a semi-structured questionnaire, we conducted 10 Focus Group Discussions with the CHVs and 10 Key Informant Interviews with County and Sub-county Ministry of Health and Ministry of Agriculture officials including multi-lateral stakeholders’ representatives from two sub-counties in the area. Data were audio-recorded and transcribed verbatim and transcripts analysed in NVivo. Researcher triangulation supported the first round of analysis. Findings were mapped and interpreted using a theory-driven analysis based on the six-step Ultra-Poverty Graduation Model.

Results

We mapped the UPG Model’s six steps onto the results of our analyses as follows: (1) initial asset transfer of in-kind goods like poultry or livestock, mentioned by the CHVs as a necessary step; (2) weekly stipends with consumption support to stabilise consumption; (3) hands-on training on how to care for assets, start and run a business based on the assets transferred; (4) training on and facilitation for savings and financial support to build assets and instil financial discipline; (5) healthcare provision and access and finally (6) social integration. These strategies were proposed by the CHVs to enhance economic empowerment and aligned with the UPG Model.

Conclusion

These results provide a user-defined approach to identify and assess strategic needs of and approaches to CHVs’ socio-economic empowerment using the UPG model. This model was useful in mapping the findings of our qualitative study and in enhancing our understanding on how these needs can be addressed in order to economically empower CHVs and enhance their retention in our setting.
Real wage growth in the U.S. health workforce and the narrowing of the gender pay gap
Authors: Barry Janis
Published: August 2021

Background

Healthcare has been identified as a job engine during recent recessions in the U.S. Whether the healthcare sector provides better than average pay remains a question. This study investigates if wages grew with the expanding demand for healthcare workers between 2001 and 2017. Wage growth in the (1) physicians and surgeons, (2) nurse, (3) healthcare practitioner and technical, (4) healthcare support, and (5) direct patient care jobs are examined. The gender pay gap in each occupation is investigated.

Methods

The American Community Survey (ACS) public use microdata sample (PUMS) for 2001, 2004, 2008, 2013, and 2017 were used to derive hourly wages for full-time, full-year workers aged 18–75. The cumulative percent change in unadjusted, median hourly wages between 2001 and 2017 was calculated for each occupation. Quantile regression estimates predicted a median hourly wage for men and women by year and job after adjusting for differences in demographics, industry, and hours worked.

Results

Unadjusted median wage growth was 9.92% for nurses, 5.68% for healthcare practitioners, and 37.6% for physicians between 2001 and 2017. These rates are roughly above the estimated national rate of wage growth at the 50th wage percentile. In healthcare support and direct patient care occupations, workers experienced either stagnant or negative wage growth. Women had lower occupational wages than men.

Conclusion

The slow or negative median wage growth in all but the physician occupation between 2004–2008 and 2008–2013 confirms that healthcare wages in the U.S. are not recession-proof, unlike healthcare employment. Generally, women's earnings grew at rates that were higher or less negative than rates for men. This trend contributed to narrowing the gender pay gap in every occupation except for nurse.
Comparison of cost effectiveness between video-assisted thoracoscopic surgery (vats) and open lobectomy: a retrospective study
Authors: Chen Wei , Yu Zhanwu , Zhang Yichen , Liu Hongxu
Published: August 2021

Background

Lung cancer is highly prevalent in Chinese population. The association of operative approach with economic burden in these patients remains unknown.

Objectives

This institution-level cohort study aimed to compare the cost-related clinical outcomes and health care costs among patients undergoing video-assisted thoracoscopic surgery (VATS) and open lobectomy, and to investigate the factors associated with the costs.

Methods

This retrospective cohort study included patients who underwent VATS or open lobectomy in a provincial referral cancer center in China in 2018. Propensity score matching (PSM) method was applied to balance the baseline characteristics in VATS lobectomy and open lobectomy group. Clinical effectiveness measures included post-operative blood transfusion, lung infection, and length of stay (LOS). Hospitalization costs were extracted from hospital information system to assess economic burden. Multivariable generalized linear model (GLM) with gamma probability distribution and log-link was used to analyze the factors associated with total costs.

Results

After PSM, 376 patients were selected in the analytic sample. Compared to open lobectomy group, the VATS lobectomy group had a lower blood transfusion rate (2.13% vs. 3.19%, P = 0.75), lower lung infection rate (21.28% vs. 39.89%, P < 0.001) and shorter post-operative LOS (9.4 ± 3.22 days vs. 10.86 ± 4.69 days, P < 0.001). Total hospitalization costs of VATS lobectomy group and open lobectomy were similar: Renminbi (RMB) 84398.03 ± 13616.13, RMB 81,964.92 ± 16748.11, respectively (P = 0.12). Total non-surgery costs were significantly lower in the VATS lobectomy group than in the open lobectomy group: RMB 41948.40 ± 7747.54 vs. RMB 45752.36 ± 10346.42 (P < 0.001). VATS approach, lung infection, longer post-operative length of stay, health insurance coverage, and lung cancer diagnosis were associated with higher total hospitalization costs (P < 0.05).

Conclusions

VATS lobectomy has a lower lung infection rate, and shorter post-operative LOS than open lobectomy. Future studies are needed to investigate other aspects of clinical effectiveness and the economic burden from a societal perspective.
Sex-specific plasma lipid profiles of ME/CFS patients and their association with pain, fatigue, and cognitive symptoms
Authors: Nkiliza Aurore , Parks Megan , Cseresznye Adam , Oberlin Sarah , Evans James E. , Darcey Teresa , Aenlle Kristina , Niedospial Daniel , Mullan Michael , Crawford Fiona , Klimas Nancy , Abdullah Laila
Published: August 2021

Background

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex illness which disproportionally affects females. This illness is associated with immune and metabolic perturbations that may be influenced by lipid metabolism. We therefore hypothesized that plasma lipids from ME/CFS patients will provide a unique biomarker signature of disturbances in immune, inflammation and metabolic processes associated with ME/CFS.

Methods

Lipidomic analyses were performed on plasma from a cohort of 50 ME/CFS patients and 50 controls (50% males and similar age and ethnicity per group). Analyses were conducted with nano-flow liquid chromatography (nLC) and high-performance liquid chromatography (HPLC) systems coupled with a high mass accuracy ORBITRAP mass spectrometer, allowing detection of plasma lipid concentration ranges over three orders of magnitude. We examined plasma phospholipids (PL), neutral lipids (NL) and bioactive lipids in ME/CFS patients and controls and examined the influence of sex on the relationship between lipids and ME/CFS diagnosis.

Results

Among females, levels of total phosphatidylethanolamine (PE), omega-6 arachidonic acid-containing PE, and total hexosylceramides (HexCer) were significantly decreased in ME/CFS compared to controls. In males, levels of total HexCer, monounsaturated PE, phosphatidylinositol (PI), and saturated triglycerides (TG) were increased in ME/CFS patients compared to controls. Additionally, omega-6 linoleic acid-derived oxylipins were significantly increased in male ME/CFS patients versus male controls. Principal component analysis (PCA) identified three major components containing mostly PC and a few PE, PI and SM species—all of which were negatively associated with headache and fatigue severity, irrespective of sex. Correlations of oxylipins, ethanolamides and ME/CFS symptom severity showed that lower concentrations of these lipids corresponded with an increase in the severity of headaches, fatigue and cognitive difficulties and that this association was influenced by sex.

Conclusion

The observed sex-specific pattern of dysregulated PL, NL, HexCer and oxylipins in ME/CFS patients suggests a possible role of these lipids in promoting immune dysfunction and inflammation which may be among the underlying factors driving the clinical presentation of fatigue, chronic pain, and cognitive difficulties in ill patients. Further evaluation of lipid metabolism pathways is warranted to better understand ME/CFS pathogenesis.
Attenuating vascular stenosis-induced astrogliosis preserves white matter integrity and cognitive function
Authors: Liu Qian , Bhuiyan Mohammad Iqbal H. , Liu Ruijia , Song Shanshan , Begum Gulnaz , Young Cullen B. , Foley Lesley M. , Chen Fenghua , Hitchens T. Kevin , Cao Guodong , Chattopadhyay Ansuman , He Li , Sun Dandan
Published: August 2021

Background

Chronic cerebral hypoperfusion (CCH) causes white matter damage and cognitive impairment, in which astrogliosis is the major pathology. However, underlying cellular mechanisms are not well defined. Activation of Na+/H+ exchanger-1 (NHE1) in reactive astrocytes causes astrocytic hypertrophy and swelling. In this study, we examined the role of NHE1 protein in astrogliosis, white matter demyelination, and cognitive function in a murine CCH model with bilateral carotid artery stenosis (BCAS).

Methods

Sham, BCAS, or BCAS mice receiving vehicle or a selective NHE1 inhibitor HOE642 were monitored for changes of the regional cerebral blood flow and behavioral performance for 28 days. Ex vivo MRI-DTI was subsequently conducted to detect brain injury and demyelination. Astrogliosis and demyelination were further examined by immunofluorescence staining. Astrocytic transcriptional profiles were analyzed with bulk RNA-sequencing and RT-qPCR.

Results

Chronic cerebral blood flow reduction and spatial working memory deficits were detected in the BCAS mice, along with significantly reduced mean fractional anisotropy (FA) values in the corpus callosum, external capsule, and hippocampus in MRI DTI analysis. Compared with the sham control mice, the BCAS mice displayed demyelination and axonal damage and increased GFAP+ astrocytes and Iba1+ microglia. Pharmacological inhibition of NHE1 protein with its inhibitor HOE642 prevented the BCAS-induced gliosis, damage of white matter tracts and hippocampus, and significantly improved cognitive performance. Transcriptome and immunostaining analysis further revealed that NHE1 inhibition specifically attenuated pro-inflammatory pathways and NADPH oxidase activation.

Conclusion

Our study demonstrates that NHE1 protein is involved in astrogliosis with pro-inflammatory transformation induced by CCH, and its blockade has potentials for reducing astrogliosis, demyelination, and cognitive impairment.
Derivation and characterization of an HIV-1 mutant that rescues IP6 binding deficiency
Authors: Poston Daniel , Zang Trinity , Bieniasz Paul
Published: August 2021

Background

A critical step in the HIV-1 replication cycle is the assembly of Gag proteins to form virions at the plasma membrane. Virion assembly and maturation are facilitated by the cellular polyanion inositol hexaphosphate (IP6), which is proposed to stabilize both the immature Gag lattice and the mature capsid lattice by binding to rings of primary amines at the center of Gag or capsid protein (CA) hexamers. The amino acids comprising these rings are critical for proper virion formation and their substitution results in assembly deficits or impaired infectiousness. To better understand the nature of the deficits that accompany IP6 binding deficiency, we passaged HIV-1 mutants that had substitutions in IP6 coordinating residues to select for compensatory mutations.

Results

We found a mutation, a threonine to isoleucine substitution at position 371 (T371I) in Gag, that restored replication competence to an IP6-binding-deficient HIV-1 mutant. Notably, unlike wild-type HIV-1, the assembly and infectiousness of resulting virus was not impaired when IP6 biosynthetic enzymes were genetically ablated. Surprisingly, we also found that the maturation inhibitor Bevirimat (BVM) could restore the assembly and replication of an IP6-binding deficient mutant. Moreover, using BVM-dependent mutants we were able to image BVM-induced assembly of individual HIV-1 particles assembly in living cells.

Conclusions

Overall these results suggest that IP6-Gag and Gag-Gag contacts are finely tuned to generate a Gag lattice of optimal stability, and that under certain conditions BVM can rescue IP6 deficiency. Additionally, our work identifies an inducible virion assembly system that can be utilized to visualize HIV-1 assembly events using live cell microscopy.
The high dose of vitamin D supplementation combined with yoga training improve the leukocytes cell survival-related gene expression in breast cancer survivors
Authors: Khedmati Zare Vahid , Javadi Maedeh , Amani-shalamzari Sadegh , Kaviani Mojtaba
Published: August 2021

Background

This study aimed to examine the effect of yoga training combined with vitamin D supplementation on the expression of survival-related genes in leukocytes and psycho-physical status in breast cancer survivors.

Methods

Thirty breast cancer survivor women (age, 48 ± 8 yrs) were randomly assigned into three groups: high dose (4000 IU) of vitamin D supplementation (HD) (n = 10); yoga training with a high dose of vitamin D (Y + HD); (n  = 10); yoga training with a low dose (2000 IU) of vitamin D (Y + LD) (n = 10). Participants performed the Hatha yoga style twice a week. Blood samples and a battery of psychological and physical tests were taken before and after the completion of interventions. Expression of p53, NF-κB, Bcl2, and Bax genes was measured in leukocytes.

Results

Body fat percentage (ηp2 = 0.36), shoulder flexibility (ηp2 = 0.38), Rockport walk tests (ηp2 = 0.49), and anxiety (ηp2 = 0.52) were significantly improved in both the Y + HD and Y + LD groups compared to the HD group (p < 0.05). P53 was significantly over-expressed in the Y + HD group while Bcl2 upregulated in both the Y + HD and Y + LD groups. NF-κB and Bax expression downregulated in all groups but were not statistically significant.

Conclusion

yoga training combined with low and high doses of VD improved physical fitness and psychological measures while only in combination with a high dose of VD positively modified the leukocytes cell survival-related gene expression.
The World Health Organization and the global standardization of medical training, a history
Authors: Weisz George , Nannestad Beata
Published: August 2021

Background

This article presents a history of efforts by the World Health Organization and its most important ally, the World Federation for Medical Education, to strengthen and standardize international medical education. This aspect of WHO activity has been largely ignored in recent historical and sociological work on that organization and on global health generally.

Methods

Historical textual analysis is applied to the digitalized archives and publications of the World Health Organization and the World Federation for Medical Education, as well as to publications in the periodic literature commenting on the standardization of international medical training and the problems associated with it.

Results

Efforts to reform medical training occurred during three distinct chronological periods: the 1950s and 1960s characterized by efforts to disseminate western scientific norms; the 1970s and 1980s dominated by efforts to align medical training with the WHO’s Primary Healthcare Policy; and from the late 1980s to the present, the campaign to impose global standards and institutional accreditation on medical schools worldwide. A growing number of publications in the periodic literature comment on the standardization of international medical training and the problems associated with it, notably the difficulty of reconciling global standards with local needs and of demonstrating the effects of curricular change.
Prognostic significance of the aberrant expression of neuroendocrine markers in melanomas
Authors: Wu Yan , Lai Yumei , Zhang Miao , Li Zhongwu
Published: August 2021

Background

Melanoma is a highly malignant tumor with diverse histopathological morphology and frequent aberrant expression of immunohistochemical markers. An occasionally reported phenomenon is the abnormal expression of neuroendocrine markers. Awareness of this situation is essential because such tumors need to be differentiated from neuroendocrine tumors because of their significant therapeutic and prognostic implications.

Methods

We retrospectively analyzed the expression of chromogranin A (CgA), synaptophysin (Syn) and CD56 as neuroendocrine markers in 308 cases with melanomas. Kaplan-Meier curves and Cox regression analyses were used for overall survival (OS) and progression-free survival (PFS) evaluation and comparison between neuroendocrine markers expression status in all melanoma cases or stage I–II cases.

Results

The expression of neuroendocrine markers in melanomas is not uncommon. CgA was positive in 6/304 (2.0%) cases, Syn in 26/304 (8.6%), and CD56 in 56/189 (29.6%). None of the cases co-expressed all the three markers. Focal or weak expression of at least one neuroendocrine marker was identified in 70/188 (37.2%) cases. The expression of CgA was correlated with age (p = 0.019), while the positive expression of Syn and CD56 showed borderline significance (p = 0.078 and 0.083, respectively), but not for any neuroendocrine marker expression. The expression of any neuroendocrine marker showed borderline significance with staging (p = 0.066). The expression of CgA, Syn, CD56, or any neuroendocrine marker did not correlate with clinicopathological features including sex, specimen type, origin, location, and histology subtype. Survival analyses revealed that the expression of neuroendocrine markers was not associated with OS or PFS.

Conclusions

Our study confirms that neuroendocrine marker expression is a common phenomenon in melanomas, but it has no prognostic significance. Nevertheless, awareness can avoid misdiagnosis in cases of melanomas with unusual morphology and immunophenotypes.
A mixed-methods longitudinal study of Marshallese infant feeding beliefs and experiences in the United States: a study protocol
Authors: Ayers Britni L. , Bogulski Cari A. , Haggard-Duff Lauren , Selig James P. , McElfish Pearl A.
Published: August 2021

Background

Arkansas has the largest population of Marshallese Pacific Islanders residing in the continental United States. Marshallese are disproportionately burdened by poorer maternal and infant health outcomes. Exclusive breastfeeding can prevent or help mitigate maternal and infant health disparities. However, exclusive breastfeeding among United States Marshallese communities remains disproportionately low, and the reasons are not well documented. This paper describes the protocol of a mixed-methods concurrent triangulation longitudinal study designed to explore the beliefs and experiences that serve as barriers and/or facilitators to exclusive breastfeeding intention, initiation, and duration among Marshallese mothers in northwest Arkansas.

Methods

The mixed-methods design collects qualitative and quantitative data during simultaneous data collection events, at third trimester, six weeks postpartum, and six months postpartum. Quantitative and qualitative data will be analyzed separately and then synthesized during the interpretation phase. The research team will disseminate results to study participants, research stakeholders, the broader Marshallese community, and fellow researchers.

Discussion

Findings and results will be presented in subsequent manuscripts upon completion of the study. This study will be an important first step to better understand beliefs and experiences to exclusive breastfeeding intention, initiation, and duration in this community and will inform tools and interventions to help improve health outcomes. The study will also aid in filling the gap in research and providing essential information on the infant feeding beliefs and barriers among a Marshallese community in Arkansas.