bluuebunny/crossref_metadata_2025_split huggingface dataset:
The influence of cross-regional medical treatment on total medical expenses, medical insurance payments, and out-of-pocket expenses of patients with malignant tumors in Chinese low-income areas
Authors: Zhang Bokai , Wang Haixin , Zhang Hongyu , Tian Guomei , Zhang Ting , Shi Qi , Liu Jian , Xu Jinpeng , Liu Jingchu , Wu Qunhong , Kang Zheng 
Published: July 2022

Abstract
Background
In recent years, due to the increasing number of cross-regional medical patients, countries around the world have issued a series of policies or regulations to reduce their out-of-pocket burden. In this context, this study intended to explore the impact of the Spatio-temporal characteristics of cross-regional medical treatment on total medical expenses, medical insurance payments, and out-of-pocket expenses of patients with malignant tumors in low-income areas.

Methods
This study included 54,904 data of cross-provincial medical treatment of malignant tumor patients insured in Heilongjiang Province, China in 2020. Firstly, Microsoft Excel 2019 and ArcGIS 10.2 were applied to conduct a descriptive analysis of the Spatio-temporal characteristics of their cross-provincial medical treatment. Then, binary and multivariate logistic regression models were used to explore the specific impact of economic level and geographical distance of medical regions on total medical expenses, medical insurance payments, and out-of-pocket expenses.

Results
The number of cross-regional medical patients showed a gradual upward trend from February to December, and fell back in January. They were concentrated in regions with high economic level and short distance from the insured region, where were more likely to form the group with high out-of-pocket expenses (AOR = 3.620, P < 0.001; AOR = 1.882, P < 0.001). While this possibility in middle-distance medical regions were less (AOR = 0.545, P < 0.001). Afterwards, two sensitivity analysis methods showed that the results were robust.

Conclusion
The number of cross-regional medical patients with malignant tumors in low-income areas is affected by seasonal factors, meanwhile, their total medical expenses, actual medical insurance payment levels, and out-of-pocket expenses are all affected by the economic level and geographical distance of medical regions. And the middle-distance medical regions may be the best choice for patients with planned cross-regional medical treatment. These provide some evidence for policymakers to improve the fairness and sustainability of medical security for cross-regional medical patients and reduce their direct economic burden of disease.
Identifying patterns of immune related cells and genes in the peripheral blood of acute myocardial infarction patients using a small cohort
Authors: Zheng Peng-Fei , Zou Qiong-Chao , Chen Lu-Zhu , Liu Peng , Liu Zheng-Yu , Pan Hong-Wei 
Published: July 2022

Abstract
Background
The immune system plays a vital role in the pathophysiology of acute myocardial infarction (AMI). However, the exact immune related mechanism is still unclear. This research study aimed to identify key immune-related genes involved in AMI.

Methods
CIBERSORT, a deconvolution algorithm, was used to determine the proportions of 22 subsets of immune cells in blood samples. The weighted gene co-expression network analysis (WGCNA) was used to identify key modules that are significantly associated with AMI. Then, CIBERSORT combined with WGCNA were used to identify key immune-modules. The protein–protein interaction (PPI) network was constructed and Molecular Complex Detection (MCODE) combined with cytoHubba plugins were used to identify key immune-related genes that may play an important role in the occurrence and progression of AMI.

Results
The CIBERSORT results suggested that there was a decrease in the infiltration of CD8 + T cells, gamma delta (γδ) T cells, and resting mast cells, along with an increase in the infiltration of neutrophils and M0 macrophages in AMI patients. Then, two modules (midnightblue and lightyellow) that were significantly correlated with AMI were identified, and the salmon module was found to be significantly associated with memory B cells. Gene enrichment analysis indicated that the 1,171 genes included in the salmon module are mainly involved in immune-related biological processes. MCODE analysis was used to identify four different MCODE complexes in the salmon module, while four hub genes (EEF1B2, RAC2, SPI1, and ITGAM) were found to be significantly correlated with AMI. The correlation analysis between the key genes and infiltrating immune cells showed that SPI1 and ITGAM were positively associated with neutrophils and M0 macrophages, while they were negatively associated with CD8 + T cells, γδ T cells, regulatory T cells (Tregs), and resting mast cells. The RT-qPCR validation results found that the expression of the ITGAM and SPI1 genes were significantly elevated in the AMI samples compared with the samples from healthy individuals, and the ROC curve analysis showed that ITGAM and SPI1 had a high diagnostic efficiency for the recognition of AMI.

Conclusions
Immune cell infiltration plays a crucial role in the occurrence and development of AMI. ITGAM and SPI1 are key immune-related genes that are potential novel targets for the prevention and treatment of AMI.
hUC-EVs-ATO reduce the severity of acute GVHD by resetting inflammatory macrophages toward the M2 phenotype
Authors: Su Yan , Sun Xueyan , Liu Xiao , Qu Qingyuan , Yang Liping , Chen Qi , Liu Fengqi , Li Yueying , Wang Qianfei , Huang Bo , Huang Xiao-Jun , Zhang Xiao-Hui 
Published: July 2022

AbstractBackgroundBoth extracellular vesicles from mesenchymal stromal cell-derived human umbilical cords (hUC-EVs) and arsenic trioxides (ATOs) have been demonstrated to treat acute graft-versus-host disease (aGVHD) via immunomodulation. Apart from immunomodulation, hUC-EVs have a unique function of drug delivery, which has been proposed to enhance their efficacy. In this study, we first prepared ATO-loaded hUC-EVs (hUC-EVs-ATO) to investigate the therapeutic effect and potential mechanisms of hUC-EVs-ATO in a mouse model of aGVHD after allogeneic hematopoietic stem cell transplantation (HSCT).MethodsAn aGVHD model was established to observe the therapeutic effects of hUC-EVs-ATO on aGVHD. Target organs were harvested for histopathological analysis on day 14 after transplantation. The effects of hUC-EVs-ATO on alloreactive CD4+were evaluated by flow cytometry in vivo and in vitro. Flow cytometry, RT-PCR, immunofluorescence colocalization analysis and Western blot (Wb) analysis were performed to examine macrophage polarization after hUC-EV-ATO treatment. The cytokines in serum were measured by a cytometric bead array (CBA). TEM, confocal microscopy and Wb were performed to observe the level of autophagy in macrophages. A graft-versus-lymphoma (GVL) mouse model was established to observe the role of hUC-EVs-ATO in the GVL effect.ResultsThe clinical manifestations and histological scores of aGVHD in the hUC-EVs-ATO group were significantly reduced compared with those in the ATO and hUC-EVs groups. The mice receiving hUC-EVs-ATO lived longer than the control mice. Notably, hUC-EVs-ATO interfering with alloreactive CD4+T cells differentiation were observed in aGVHD mice but not in an in vitro culture system. Additional studies showed that depletion of macrophages blocked the therapeutic effects of hUC-EVs-ATO on aGVHD. Mechanistically, hUC-EVs-ATO induced autophagic flux by inhibiting mammalian target of rapamycin (mTOR) activity to repolarize M1 to M2 macrophages. Additionally, using a murine model of GVL effects, hUC-EVs-ATO were found not only to reduce the severity of aGVHD but also to preserve the GVL effects. Taken together, hUC-EVs-ATO may be promising candidates for aGVHD treatment.ConclusionshUC-EVs-ATO enhanced the alleviation of aGVHD severity in mice compared with ATO and hUC-EVs without weakening GVL activity. hUC-EVs-ATO promoted M1 to M2 polarization via the mTOR-autophagy pathway. hUC-EVs-ATO could be a potential therapeutic approach in aGVHD after allo-HSCT.
Mitochondria dysfunction in CD8+ T cells as an important contributing factor for cancer development and a potential target for cancer treatment: a review
Authors: Zhang Lu , Zhang Wen , Li Ziye , Lin Shumeng , Zheng Tiansheng , Hao Bingjie , Hou Yaqin , Zhang Yanfei , Wang Kai , Qin Chenge , Yue Liduo , Jin Jing , Li Ming , Fan Lihong 
Published: July 2022

AbstractCD8+ T cells play a central role in anti-tumor immunity. Naïve CD8+ T cells are active upon tumor antigen stimulation, and then differentiate into functional cells and migrate towards the tumor sites. Activated CD8+ T cells can directly destroy tumor cells by releasing perforin and granzymes and inducing apoptosis mediated by the death ligand/death receptor. They also secrete cytokines to regulate the immune system against tumor cells. Mitochondria are the central hub of metabolism and signaling, required for polarization, and migration of CD8+ T cells. Many studies have demonstrated that mitochondrial dysfunction impairs the anti-tumor activity of CD8+ T cells through various pathways. Mitochondrial energy metabolism maladjustment will cause a cellular energy crisis in CD8+ T cells. Abnormally high levels of mitochondrial reactive oxygen species will damage the integrity and architecture of biofilms of CD8+ T cells. Disordered mitochondrial dynamics will affect the mitochondrial number and localization within cells, further affecting the function of CD8+ T cells. Increased mitochondria-mediated intrinsic apoptosis will decrease the lifespan and quantity of CD8+ T cells. Excessively low mitochondrial membrane potential will cause the release of cytochrome c and apoptosis of CD8+ T cells, while excessively high will exacerbate oxidative stress. Dysregulation of mitochondrial Ca2+ signaling will affect various physiological pathways in CD8+ T cells. To some extent, mitochondrial abnormality in CD8+ T cells contributes to cancer development. So far, targeting mitochondrial energy metabolism, mitochondrial dynamics, mitochondria-mediated cell apoptosis, and other mitochondrial physiological processes to rebuild the anti-tumor function of CD8+ T cells has proved effective in some cancer models. Thus, mitochondria in CD8+ T cells may be a potential and powerful target for cancer treatment in the future.
Change of renal function after short-term use of cardioprotective agents in patients with type 2 diabetes is not accurately assessed by the change of estimated glomerular filtration rate: an observational study
Authors: Kolwelter Julie , Striepe Kristina , Bosch Agnes , Kannenkeril Dennis , Ott Christian , Schiffer Mario , Schmieder Roland E. 
Published: July 2022

Abstract
Background
After initiating cardioprotective agents, a fall of estimated glomerular filtration rate (eGFR) has been reported in several studies. Our goal was to evaluate the accuracy of change of Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFR in patients with type 2 diabetes (T2D) after short-term pharmacological intervention with angiotensin-converting enzyme inhibitor, angiotensin-receptor blocker, gliptin or sodium-glucose cotransporter-2 inhibitor.

Methods
We analyzed 190 patients with T2D in the early stage of the disease, having no overt renal impairment by CKD-EPI equation. In each patient, we measured GFR (mGFR) by applying the constant infusion input clearance technique with sinistrin (Inutest; Fresenius, Linz, Austria) at baseline and after short-term (4–12 weeks) pharmacological intervention with cardioprotective agents (ramipril, telmisartan, linagliptin, metformin, empagliflozin) that potentially lead to an alteration of renal function. Simultaneously, a standardized analysis of serum creatinine was performed and eGFR was estimated by the CKD-EPI equation.

Results
Average mGFR was 111 ± 20 ml/min/1.73m2, whereas eGFR was lower with 93 ± 13 ml/min/1.73m2. The ratio eGFR/mGFR in relation to mGFR was almost curvilinear, showing an underestimation of renal function by eGFR in the upper normal range. At baseline only 80 patients (42%) lay within ± 10% of mGFR and the concordance correlation coefficient (CCC) was extremely low (− 0.07). After short-term pharmacological intervention changes in eGFR and mGFR correlated with each other (r = 0.286, p < 0.001). For example, for a given mGFR of 111 ml/min/1.73m2, a change of mGFR by ± 10% corresponded to ± 11 ml/min/1.73m2, but the confidence interval of eGFR was 25 ml/min/1.73m2. The CCC was low (0.22).

Conclusion
The agreement between eGFR by CKD-EPI and mGFR is modest and the change of renal function after short-term pharmacological intervention is not accurately and precisely reflected by the change of eGFR in patients with T2D in the early stage of their disease.
Estimating the pre- and post-diagnosis costs of tuberculosis for adults in Pakistan: household economic impact and costs mitigating strategies
Authors: Razzaq Shama , Zahidie Aysha , Fatmi Zafar 
Published: July 2022

Abstract
Background
Despite free tuberculosis (TB) care in Pakistan, patients still have to bear high costs, which push them into poverty. This study estimated the pre- and post-diagnosis costs households bear for TB care, and investigated coping mechanisms among adults ≥ 18 years in Karachi, Pakistan.

Methods
We conducted a cross-sectional study comprising of 516 TB patients identified with completion of at least one month intensive treatment from four public sector health facilities from two institutes in Karachi, Pakistan. A standardized questionnaire to estimate patient's costs was administered. The study outcomes were direct medical and non-medical costs, and indirect costs. The costs were estimated during pre-diagnostic and post-diagnostic phase which includes diagnostic, treatment, and hospitalization phases. A descriptive analysis including mean and standard deviation (± SD), median and interquartile range (IQR), and frequencies and proportions (%) was employed.

Results
Out of 516 TB patients, 52.1% were female with a mean age of 32.4 (± 13.7) years. The median costs per patient during the pre-diagnostic, diagnostic, treatment and hospitalization periods were estimated at USD63.8/ PKR7,377, USD24/ PKR2,755, USD10.5/ PKR1,217, and USD349.0/ PKR40,300, respectively. The total household median cost was estimated at USD129.2/ PKR14,919 per patient. The median indirect cost was estimated at USD52.0/ PKR5,950 per patient. Of total, 54.1% of patients preferred and consulted private providers in the first place at the onset of symptoms, while, 36% attended public healthcare services, 5% and 4.1% went to dispensary and pharmacy, respectively, as a first point of care.

Conclusions
TB patients bear substantial out-of-pocket costs before they are enrolled in publically funded TB programs. There should be provision of transport and food vouchers, also health insurance for in-patient treatment. This advocates a critical investigation into an existing financial support network for TB patients in Pakistan towards reducing the burden.
Freeze-all policy versus luteal phase support with low dose of human chorionic gonadotrophin for high-responder patients undergoing intracytoplasmic sperm injection on pregnancy outcomes: a retrospective cohort observational study
Authors: ELhelw Ehab Mohamed , El Serour Ahmed Gamal Elden Abou , Rady Mahmoud Salah , Abdeltawab Ahmed 
Published: July 2022

Abstract
Background
The literature has always controversies on the use of freeze-all policy in high-responder women performing intracytoplasmic sperm injection. In this article, we discuss the benefits of freeze-all policy on the incidence of pregnancy outcomes and the complications.

The main body of abstract
Freeze-all policy is applied to the intracytoplasmic sperm injection program by freezing of all embryos and delaying embryo transfer to another subsequent ovarian cycle, to decrease the incidence of ovarian hyperstimulation syndrome, especially in high-responder women. Unfortunately, freeze-all policy is correlated with an increase in the economic costs and more ICSI laboratory effort. Delayed embryo transfer (ET) is correlated with more anxiety among the patients. An alternative strategy is to perform fresh embryo transfer with more intensive luteal phase support to compensate for the negative effect of the GnRH agonist on the endometrial receptivity and luteal phase support.

Short conclusion
The freeze-all policy had better pregnancy rates with less incidence of moderate to severe hyperstimulation syndrome compared with original fresh embryo transfer in high-responder women performing intracytoplasmic sperm injection.
Twenty-Year Benefit From Adjuvant Goserelin and Tamoxifen in Premenopausal Patients With Breast Cancer in a Controlled Randomized Clinical Trial
Authors: Johansson Annelie , Dar Huma , van ’t Veer Laura J. , Tobin Nicholas P. , Perez-Tenorio Gizeh , Nordenskjöld Anna , Johansson Ulla , Hartman Johan , Skoog Lambert , Yau Christina , Benz Christopher C. , Esserman Laura J. , Stål Olle , Nordenskjöld Bo , Fornander Tommy , Lindström Linda S. 
Published: July 2022

PURPOSE To assess the long-term (20-year) endocrine therapy benefit in premenopausal patients with breast cancer. METHODS Secondary analysis of the Stockholm trial (STO-5, 1990-1997) randomly assigning 924 premenopausal patients to 2 years of goserelin (3.6 mg subcutaneously once every 28 days), tamoxifen (40 mg orally once daily), combined goserelin and tamoxifen, or no adjuvant endocrine therapy (control) is performed. Random assignment was stratified by lymph node status; lymph node–positive patients (n = 459) were allocated to standard chemotherapy (cyclophosphamide, methotrexate, and fluorouracil). Primary tumor immunohistochemistry (n = 731) and gene expression profiling (n = 586) were conducted in 2020. The 70-gene signature identified genomic low-risk and high-risk patients. Kaplan-Meier analysis, multivariable Cox proportional hazard regression, and multivariable time-varying flexible parametric modeling assessed the long-term distant recurrence-free interval (DRFI). Swedish high-quality registries allowed a complete follow-up of 20 years. RESULTS In estrogen receptor–positive patients (n = 584, median age 47 years), goserelin, tamoxifen, and the combination significantly improved long-term distant recurrence-free interval compared with control (multivariable hazard ratio [HR], 0.49; 95% CI, 0.32 to 0.75, HR, 0.57; 95% CI, 0.38 to 0.87, and HR, 0.63; 95% CI, 0.42 to 0.94, respectively). Significant goserelin-tamoxifen interaction was observed ( P = .016). Genomic low-risk patients (n = 305) significantly benefitted from tamoxifen (HR, 0.24; 95% CI, 0.10 to 0.60), and genomic high-risk patients (n = 158) from goserelin (HR, 0.24; 95% CI, 0.10 to 0.54). Increased risk from the addition of tamoxifen to goserelin was seen in genomic high-risk patients (HR, 3.36; 95% CI, 1.39 to 8.07). Moreover, long-lasting 20-year tamoxifen benefit was seen in genomic low-risk patients, whereas genomic high-risk patients had early goserelin benefit. CONCLUSION This study shows 20-year benefit from 2 years of adjuvant endocrine therapy in estrogen receptor–positive premenopausal patients and suggests differential treatment benefit on the basis of tumor genomic characteristics. Combined goserelin and tamoxifen therapy showed no benefit over single treatment. Long-term follow-up to assess treatment benefit is critical.
Oxytocin, Vasopressin, and Social Behavior: From Neural Circuits to Clinical Opportunities
Authors: Rigney Nicole , de Vries Geert J , Petrulis Aras , Young Larry J 
Published: July 2022

AbstractOxytocin and vasopressin are peptide hormones secreted from the pituitary that are well known for their peripheral endocrine effects on childbirth/nursing and blood pressure/urine concentration, respectively. However, both peptides are also released in the brain, where they modulate several aspects of social behaviors. Oxytocin promotes maternal nurturing and bonding, enhances social reward, and increases the salience of social stimuli. Vasopressin modulates social communication, social investigation, territorial behavior, and aggression, predominantly in males. Both peptides facilitate social memory and pair bonding behaviors in monogamous species. Here we review the latest research delineating the neural circuitry of the brain oxytocin and vasopressin systems and summarize recent investigations into the circuit-based mechanisms modulating social behaviors. We highlight research using modern molecular genetic technologies to map, monitor activity of, or manipulate neuropeptide circuits. Species diversity in oxytocin and vasopressin effects on social behaviors are also discussed. We conclude with a discussion of the translational implications of oxytocin and vasopressin for improving social functioning in disorders with social impairments, such as autism spectrum disorder.
Framing and understanding the whole aspect of oral sex from social and health perspectives: a narrative review
Authors: Pakpahan Cennikon , Darmadi Darmadi , Agustinus Agustinus , Rezano Andri 
Published: July 2022

Historically, oral sex is part of human sexual behaviour even though some consider it taboo, and its expression is deemed inappropriate. Human rights also stand out as technology becomes more sophisticated, leading to its practice disclosure in the 21st century. The large-scale oral sex discussion in media encourages people to express it, and there is feedback on whether it is right or not. It all depends on each person’s values. We found this sexual behaviour occurs everywhere regardless of religion, culture and race. Pop culture influences this behaviour considerably. It can be seen in music, movies and television programmes that allude to oral sex. Numerous motivations underlying this behaviour include sexual pleasure for the sake of psychological well-being. It is undeniable that this behaviour is still controversial. There is a risk of it causing disease, but it reportedly provides many benefits. Oral sex is not a new behaviour crossing boundaries, according to our theory. It is an old behaviour that has been highlighted because of the factors that support it. This behaviour, still considered taboo, has its disadvantages, such as sexually transmitted disease and oral cancer, but also has benefits, such as preventing preeclampsia.
Living HTA: Automating Health Technology Assessment with R
Authors: Smith Robert A. , Schneider Paul P. , Mohammed Wael 
Published: July 2022

Background: Requiring access to sensitive data can be a significant obstacle for the development of health models in the Health Economics & Outcomes Research (HEOR) setting. We demonstrate how health economic evaluation can be conducted with minimal transfer of data between parties, while automating reporting as new information becomes available. Methods: We developed an automated analysis and reporting pipeline for health economic modelling and made the source code openly available on a GitHub repository. The pipeline consists of three parts: An economic model is constructed by the consultant using pseudo data. On the data-owner side, an application programming interface (API) is hosted on a server. This API hosts all sensitive data, so that data does not have to be provided to the consultant. An automated workflow is created, which calls the API, retrieves results, and generates a report. Results: The application of modern data science tools and practices allows analyses of data without the need for direct access – negating the need to send sensitive data. In addition, the entire workflow can be largely automated: the analysis can be scheduled to run at defined time points (e.g. monthly), or when triggered by an event (e.g. an update to the underlying data or model code); results can be generated automatically and then be exported into a report. Documents no longer need to be revised manually. Conclusions: This example demonstrates that it is possible, within a HEOR setting, to separate the health economic model from the data, and automate the main steps of the analysis pipeline.