bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

AbstractBackgroundImmune 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.MethodsDMF (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.ResultsDMF 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.ConclusionsIn 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

AbstractBackgroundA 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.MethodsThis 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.ResultsWe 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.ConclusionThese 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

Abstract
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.