bluuebunny/crossref_metadata_2025_split huggingface dataset:
ANP promotes HTR‐8/SVneo cell invasion by upregulating protein kinase N 3 via autophagy inhibition
Authors: Chu Nan , Tang Yao , Wang Cheng‐Jie , Pei Jiang‐Nan , Luo Shou‐Ling , Yu Yi , Liu Zhen‐Zhen , Liu Hai‐Yan , Qiu Xue‐Min , Wang Ling , Li Da‐Jin , Gu Wei‐Rong 
Published: February 2023

AbstractPreeclampsia is a gestational disease characterized by two major pathological changes‐shallow trophoblast invasion and impaired spiral artery remodeling. Atrial natriuretic peptide (ANP) is a kind of peptide hormone that regulates blood pressure, while the lack of active ANP participates in preeclampsia pathogenesis. However, the underlying mechanism of how ANP modulates trophoblasts function remains unclarified. Here, we performed isobaric tags for relative and absolute quantification (iTRAQ) in ANP‐treated HTR‐8/SVneo cells and identified Protein Kinase 3 (PKN3) as the downstream factor of ANP, which was downregulated in preeclamptic placenta. Chromatin immunoprecipitation analysis and luciferase assays showed that NFYA was one of the transcription factors for the PKN3 promoter, which was also regulated by ANP treatment in HTR‐8/SVneo cells. Transmission electron microscopy and Western Blotting in HTR‐8/SVneo cells indicated that ANP inhibited autophagy via AMPK‐mTORC1 signaling, while excess autophagy was observed in preeclamptic placenta. The increased expression of PKN3 and enhanced cell invasion ability in HTR‐8/SVneo cells induced by ANP could be abolished by autophagy activation or transfection with PKN3 shRNA or NFYA shRNA or NPR‐A shRNA via regulating the invasion‐related genes and the epithelial mesenchymal transition molecules. Our results demonstrated that ANP could enhance trophoblast invasion by upregulating PKN3 via NFYA promotion through autophagy inhibition in an AMPK/mTORC1 signaling‐dependent manner.
Stabilization of nuclear β‐catenin by inhibiting KDM2A mediates cerebral ischemic tolerance
Authors: Zuo Yunyan , Zhan Lixuan , Wen Haixia , Xue Jiahui , Tan Yafu , Sun Weiwen , Xu En 
Published: February 2023

AbstractHypoxic postconditioning (HPC) with 8% oxygen increases nuclear accumulation of β‐catenin through activating the classical Wnt pathway, thereby alleviating transient global cerebral ischemia (tGCI)‐induced neuronal damage in the hippocampal CA1 subregion of adult rats. However, little is understood about the regulatory mechanism of nuclear β‐catenin in HPC‐mediated cerebral ischemic tolerance. Although lysine(K)‐specific demethylase 2A (KDM2A) has been known as a crucial regulator of nuclear β‐catenin destabilization, whether it plays an important role through modulating nuclear β‐catenin in cerebral ischemic tolerance induced by HPC remains unknown. In this study, we explored the molecular mechanism of stabilizing nuclear β‐catenin by inhibiting KDM2A‐mediated demethylation in the HPC‐offered neuroprotection against tGCI. In addition, we confirmed that nuclear methylated‐β‐catenin in CA1 decreased and nuclear β‐catenin turnover increased after tGCI, which were reversed by HPC. The administration with methyltransferase inhibitor AdOx abrogated HPC‐induced methylation and stabilization of nuclear β‐catenin in CA1, as well as the neuroprotection against tGCI. Notably, HPC downregulated the expression of KDM2A in CA1 and reduced the interaction between KDM2A and β‐catenin in the nucleus after tGCI. The knockdown of KDM2A with small‐interfering RNA could upregulate nuclear methylated‐β‐catenin and stabilize β‐catenin, thereby increasing survivin in CA1 and improving the cognitive function of rats after tGCI. Opposite results were observed by the administration of KDM2A‐carried adenovirus vector. Furthermore, we demonstrated that KDM2A mediates the demethylation of nuclear β‐catenin through jumonji C (JmjC) domain of KDM2A in HEK‐293T and SH‐SY5Y cells. Our data support that the inhibition of KDM2A‐mediated demethylation of nuclear β‐catenin contributes to HPC‐induced neuroprotection against tGCI.
The Effect of Rural Underserved Opportunities Program Participation on Medical Graduates’ Decision to Work in Rural Areas
Authors: Dahal Arati , Kardonsky Kim , Cunningham Matthew , Evans David V. , Keys Toby 
Published: February 2023

Purpose
There is a persistent rural physician shortage in the United States. Policies to scale up the health workforce in response to this shortage must include measures to draw and maintain existing and newly trained health care workers to rural regions. Prior studies have found that experience in community medicine in rural practice settings increases the likelihood of medical graduates practicing in those regions but have not accounted for selection bias. This study examined the impact of a community-based clinical immersion program on medical graduates’ decision to work in rural regions, adjusting for covariates to control for selection bias.

Method
Data on sociodemographic characteristics and career interests and preferences for all 1,172 University of Washington School of Medicine graduates between 2009 and 2014 were collected. A logistic model (model 1) was used to evaluate the impact of Rural Underserved Opportunities Program (RUOP) participation on the probability of physicians working in a rural region. Another model (model 2) included the propensity score as a covariate in the regression to control for possible confounding based on differences among those who did and did not participate in the RUOP.

Results
Of the 994 students included in the analysis, 570 (57.3%) participated in RUOP training, and 111 (11.2%) were currently working in rural communities after their training. Regression analysis results showed that the odds of working in a rural region were 1.83 times higher for graduates who participated in RUOP in model 1 (P = .03) and 1.77 times higher in model 2 (P = .04).

Conclusions
The findings of this study emphasize that educational programs and policies are crucial public health interventions that can promote health equity through proper distribution of health care workers across rural regions of the United States.
Current “state of the art” on dendritic cell-based cancer vaccines in melanoma
Authors: Schwarze Julia Katharina , Geeraerts Xenia , Tuyaerts Sandra , Neyns Bart 
Published: February 2023

Purpose of review
Dendritic cells (DCs) are the gatekeepers of our immune system and indispensable in the antitumor immune response. In recent years, their classification has been revised considerably using single-cell sequencing approaches. In this review, we focus on their unique role in cancer and how specific DC subsets can be manipulated to induce an effective and durable antitumor response.

Recent findings:
Historically, due to the ease of their isolation in sufficient cell numbers from peripheral blood, the utility of monocyte-derived DCs as therapeutic cancer vaccines was explored in the clinic. However, it became clear that naturally circulating myeloid DCs (myDC), exerting their physiological role, are a functionally more powerful cellular source of antigen presenting cells. With the advent of immunomagnetic bead technology to isolate naturally circulating DC subsets, the therapeutic value of these myDC subsets is currently being explored. Since DCs are also needed in the tumor microenvironment in order to “relicense” the activity of antitumor T cells, also intratumoral administration routes for DC vaccines are explored. In addition, to circumvent the use of expensive cellular vaccines, approaches to attract DCs to the tumor microenvironment are considered of interest in order to repair a defective cancer-immunity cycle.

Summary
In recent years, the type of DCs used for vaccination and their administration route evolved considerably. Intratumoral vaccination strategies require combination with additional stimuli to ensure proper functioning of DCs in the tumor microenvironment. Moreover, intratumoral administration limits the applicability to patients with accessible lesions.
Estimation of the population, death, and quality of life in Shaanxi Province, western China: a cross-sectional study
Authors: Miao Xinlei , Chen Jun , Wu Qiong , Meng Wen , Ren Lin , Wu Zhiyuan , Guo Xiuhua , Zhang Xiang , Meng Qun 
Published: February 2023

Abstract

Background:
Measuring the health of the population is of great significance to the development of a region. We aimed to estimate the population, probability of death, and quality of life in western China.

Methods:
We calculated the age-specific mortality rate and prevalence rate of diseases and injuries using the Full Population Database and the Home Page of Inpatient Medical Record. We used multiple interpolation methods to insert missing information from the death data and the model of Kannisto to adjust the mortality rate for elderly individuals. The age-specific prevalence rate of diseases and injuries was adjusted according to the standard ratio of age and methods of equal proportional allocation. Life expectancy was calculated by a life table, and the quality of life was estimated using the Sullivan method.

Results:
The total population continued to increase in 2015 to 2019 in the Shaanxi Province, China. The mortality rate of children under 5 has improved, and the mortality rate of people over 65 is decreasing year by year. Life expectancy increased from 74.66 years in 2015 to 77.19 years in 2019. Even with the total risk of disease and injury, the health-adjusted life expectancy increased 1.90 years within 5 years, and the number of unhealthy years significantly improved. Health-adjusted life expectancy increased 1.75 years when only considered the ten major disease systems (tumours; endocrinology, nutrition and metabolism; mental and behavioral disorders; nervous system; sensory diseases; circulatory system; respiratory system; digestive system; genitourinary system; musculoskeletal system and connective tissue), and the number of unhealthy years increased slightly.

Conclusions:
In the past five years, Shaanxi Province has made progress in improving life expectancy and controlling the development of chronic diseases. It is necessary to take specific preventive measures and improve the quality of basic public health services.
Trends in stroke, cardiovascular disease, and medical expenditure under a community-based long-term stroke prevention program
Authors: Yamagishi Kazumasa , Sankai Tomoko , Muraki Isao , Umesawa Mitsumasa , Cui Renzhe , Imano Hironori , Kihara Tomomi , Noda Hiroyuki , Ikeda Ai , Ohira Tetsuya , Tanigawa Takeshi , Kitamura Akihiko , Sato Shinichi , Kiyama Masahiko , Iso Hiroyasu 
Published: February 2023

Background:
Evidence on the effects of preventive measures for noncommunicable disease is urgently needed for low-income and middle-income countries suffering from stroke epidemics along with population aging.

Objectives:
We sought to examine the impact of a community-based stroke prevention program on incidences of stroke and ischemic heart disease, mortality from cardiovascular disease, and medical expenditure.

Methods:
Trends in the incidences of stroke and ischemic heart disease were documented in a Japanese rural community, Kyowa, from 1981 through 2015. Trends in mortality from cardiovascular disease and in medical expenditures were compared between Kyowa and its surrounding municipalities from 1981 through 2004.

Results:
In Kyowa, the age and-sex-adjusted incidences of stroke and of ischemic heart disease decreased by half (from 4.1 to 1.9 and from 1.5 to 0.7 per year/1000 persons, respectively) over the past 35 years. A similar decreasing trend was observed for the age and-sex-adjusted mortality from cardiovascular disease, and this decreasing trend occurred earlier than that in the surrounding municipalities. The medical expenditures for cardiovascular disease became lower in Kyowa than in the surrounding municipalities over time.

Conclusion:
Our study's findings suggest that a community-based stroke prevention program augmented the decline in the incidences of stroke and ischemic heart disease, mortality from cardiovascular disease, and attenuated the increase in medical expenditures for cardiovascular disease.
The relationship between arginine vasopressin gene polymorphisms and plasma copeptin and hypertensive disorders of pregnancy: a nested case-control study
Authors: Sun Yexiu , Guo Ying , Xu He , Zhao Ji , Wu Di , Hu Jianwei , Wang Dandan , Wu Lei , Peng Hao , Li Hongmei 
Published: February 2023

Objectives:
This study aims to explore the relationship between polymorphism of the arginine vasopressin (AVP) gene and plasma copeptin concentration with the occurrence of hypertension in pregnancy.

Methods:
We conducted a matched nested case–control study in Chinese women. The genotypes of rs3729965, rs3761249, rs1410713, rs2740204, and rs2282018 loci of AVP gene and plasma copeptin at 16–20 gestational weeks were detected in 288 patients with gestational hypertension (GH), 82 with preeclampsia (PE), and 14 with chronic hypertension with superimposed preeclampsia (CH-PE) and their healthy matched controls.

Results:
For every natural logarithm unit increment in copeptin, the risks of GH and PE/CH-PE increased by 5.556 (adjusted odds ratio [aOR]: 6.556, 95% confidence interval [CI]: 2.734–15.717) and 3.312 times (aOR: 4.312, 95% CI: 1.168–15.914). Under the dominant model, the genotype CC + CT of rs2282018 and GG + GT of rs3761249 had higher risks of GH than genotype TT, with aORs of 1.757 (95% CI: 1.077–2.867) and 1.814 (95% CI: 1.111–2.963). Allele A of rs3729965 loci had a lower risk of PE/CH-PE than allele G (aOR: 0.441, 95% CI: 0.199–0.978). However, the frequencies of rs1410713 and rs2740204 genotypes were not significantly different between cases and controls. The model of copeptin combined with the AVP gene and traditional factors (TFs) had a higher ability than the TFs model in predicting GH and PE/CH-PE.

Conclusion:
Our study confirms that higher plasma copeptin and AVP gene variants are associated with the occurrence of GH and PE/CH-PE. The detection of copeptin and AVP gene in the early second trimester improves the predictive ability of TFs for GH and PE/CH-PE.
Virtual Physician Assistant Program Interviews: Faculty and Applicant Perspectives
Authors: Loscalzo Carina , Kuriakose Shinu , Timko-Swaim Lynn , L’Eplattenier Mark 
Published: February 2023

Introduction
Many physician assistant (PA) programs converted from traditional in-person admission interviews to virtual interviews during the COVID-19 pandemic. The purpose of this study was to investigate the perceptions of both PA faculty and applicants to PA programs about the virtual interview process. General perceptions, advantages, and disadvantages were explored.

Methods
A mixed-method approach was implemented to collect data using 2 survey instruments: one for PA program applicants and another for PA program faculty. The surveys were created using a combination of previously used and new questions and distributed through email and social media. Descriptive statistics were used to analyze the independent and dependent variables. Chi-square, one-way ANOVA, and Spearman’s rho correlation were conducted to analyze potential relationships between variables. Qualitative data were analyzed using an iterative process and inductive reasoning to identify recurring themes and code responses into common topical categories.

Results
Completed surveys were received from 178 applicants and 325 faculty members. If given the choice, most applicants favored virtual interviews (62.4%), while the majority of faculty preferred in-person interviews (64.0%). The majority of applicants (84.6%) and faculty (64.9%) were comfortable making a decision about the program or applicant, respectively, after the virtual interview process. The top 3 advantages of virtual interviewing for both faculty and applicants included convenience, decreased travel time, and cost savings.

Discussion
Both faculty and applicants perceived the virtual interview process positively, and thus, this modality may have enough advantages to support its use in the future.
68Ga-FAPI PET/CT Imaging of Intracranial Syphilitic Gumma
Authors: Gong Weidong , Qiu Shuang , Zheng Shiyu , Liu Wei , Zhang Chunyin 
Published: February 2023

Abstract
Intracranial syphilitic gumma is a rare neurological disease. We present 68Ga-DOTA-FAPI-04 and 18F-FDG PET/CT findings of intracranial syphilitic gumma in a 46-year-old man with HIV. In this case, 68Ga-DOTA-FAPI-04 PET/CT outperforms 18F-FDG in helping to visualizing syphilitic gumma. Syphilitic gumma can also cause increase FAPI activity. Our findings suggest the potential value of 68Ga-DOTA-FAPI-04 in the diagnosis of syphilis.
68Ga–DOTA–Exendin-4 PET/CT Demonstrated a Higher Detection Efficacy for Double-Primary Insulinomas Than MRI
Authors: Qiu Lin , Lan Lianjun , Cai Liang , Chen Lin , Chen Yue 
Published: February 2023

Abstract
We presented a 20-year-old woman with gradually increasing lethargy and multiple episodes of dizziness for 5 months. The laboratory examination revealed decreasing level of blood glucose and elevated levels of fasting plasma insulin and C-peptide. The MRI identified a focal nodule in the tail of the pancreas. 68Ga–DOTA–exendin-4 PET/CT revealed 2 intense focal tracer uptakes in the tail of the pancreas, one of which corresponded to the lesion revealed on MRI. The immunohistochemical results of resected samples confirmed the diagnosis of double-primary insulinomas. 68Ga–DOTA–exendin-4 PET/CT demonstrated excellent localization and characterization for double-primary insulinomas in the tail of the pancreas.
Solitary Accessory Spleen-Like Metastasis Coexisted With Splenic Infarction Reveled on 18F-FDG PET/CT in a Hepatocellular Carcinoma Patient
Authors: Shao Fuqiang , Xie Peng 
Published: February 2023

Abstract
Solitary parasplenic metastatic carcinoma may be misinterpreted as accessory spleen on CT images. In addition, elevated FDG uptake in the spleen may also mimic metastasis in patient with a history of carcinoma. Here we present a case of parasplenic metastasis coexisted with splenic infarction reveled on 18F-FDG PET/CT in a 51-year-old man with history of hepatocellular carcinoma.
Renal Ischemia–reperfusion Injury Attenuated by Exosomes Extracted From Splenic Ischemic Preconditioning Models
Authors: Liu Hongtao , Shen Ye 
Published: February 2023

Background.
To investigate the protective effects of exosomes extracted from splenic ischemic preconditioning (sIPC) models on renal ischemia–reperfusion injury (IRI).

Methods.
sIPC was conducted on mice before renal IRI, and exosomes derived from sIPC mice were infused into a mouse model of renal IRI. The kidney tissue and serum were collected 24 h later. The morphological changes, inflammation and apoptosis in IR kidneys were determined by hematoxylin–eosin (HE), terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL), and Ki-67 immunohistochemical staining. In addition, the proinflammatory cytokines in serum and cell supernatant were measured with enzyme-linked immunosorbent assays (ELISAs). Then, we administered exosomes to mouse renal epithelial cells. TUNEL assays and flow cytometry were used to evaluate cell apoptosis. Bax and Bcl-2 levels were measured via Western blotting.

Results.
HE staining showed that the renal IRI was attenuated after sIPC. TUNEL results showed that renal tissue apoptosis was greatly reduced after sIPC or injection of exosomes. ELISAs showed that the serum creatinine (sCr), tumor necrosis factor alpha, and interleukin-1 β levels induced by IRI decreased with sIPC. In vitro, exosomes extracted from the hypoxia/reoxygenation (H/R) splenic fibroblast model had the same protective effect. TUNEL and flow cytometry results showed that the exosomes reduced apoptosis. ELISAs showed that tumor necrosis factor alpha and interleukin-1 β were significantly increased in the H/R group but decreased due to the exosomes treated with starvation. WB results showed that Bax expression was increased and Bcl-2 expression was decreased in the H/R group. However, exosomes decreased the Bax level and increased the Bcl-2 level.

Conclusions.
Exosomes extracted from sIPC models exerted a protective effect to attenuate renal IRI.
Restoration of Bile Duct Injury of Donor Livers During Ex Situ Normothermic Machine Perfusion
Authors: de Jong Iris E.M. , Bodewes Silke B. , van Leeuwen Otto B. , Oosterhuis Dorenda , Lantinga Veerle A. , Thorne Adam M. , Lascaris Bianca , van den Heuvel Marius C. , Wells Rebecca G. , Olinga Peter , de Meijer Vincent E. , Porte Robert J. 
Published: February 2023

Background.
End-ischemic ex situ normothermic machine perfusion (NMP) enables assessment of donor livers prior to transplantation. The objective of this study was to provide support for bile composition as a marker of biliary viability and to investigate whether bile ducts of high-risk human donor livers already undergo repair during NMP.

Methods.
Forty-two livers that were initially declined for transplantation were included in our NMP clinical trial. After NMP, livers were either secondary declined (n = 17) or accepted for transplantation (n = 25) based on the chemical composition of bile and perfusate samples. Bile duct biopsies were taken before and after NMP and assessed using an established histological injury severity scoring system and a comprehensive immunohistochemical assessment focusing on peribiliary glands (PBGs), vascular damage, and regeneration.

Results.
Bile ducts of livers that were transplanted after viability testing during NMP showed better preservation of PBGs, (micro)vasculature, and increased cholangiocyte proliferation, compared with declined livers. Biliary bicarbonate, glucose, and pH were confirmed as accurate biomarkers of bile duct vitality. In addition, we found evidence of PBG-based progenitor cell differentiation toward mature cholangiocytes during NMP.

Conclusions.
Favorable bile chemistry during NMP correlates well with better-preserved biliary microvasculature and PBGs, with a preserved capacity for biliary regeneration. During NMP, biliary tree progenitor cells start to differentiate toward mature cholangiocytes, facilitating restoration of the ischemically damaged surface epithelium.
Obinutuzumab Effectively Depletes Key B-cell Subsets in Blood and Tissue in End-stage Renal Disease Patients
Authors: Looney Cary M. , Schroeder Aaron , Tavares Erica , Garg Jay , Schindler Thomas , Vincenti Flavio , Redfield Robert R. , Jordan Stanley C. , Busque Stephan , Woodle E. Steve , Khan Jared , Eastham Jeffrey , Micallef Sandrine , Austin Cary D. , Morimoto Alyssa 
Published: February 2023

Background.
The THEORY study evaluated the effects of single and multiple doses of obinutuzumab, a type 2 anti-CD20 antibody that induces antibody-dependent cell-mediated cytotoxicity and direct cell death, in combination with standard of care in patients with end-stage renal disease.

Methods.
We measured B-cell subsets and protein biomarkers of B-cell activity in peripheral blood before and after obinutuzumab administration in THEORY patients, and B-cell subsets in lymph nodes in THEORY patients and an untreated comparator cohort.

Results.
Obinutuzumab treatment resulted in a rapid loss of B-cell subsets (including naive B, memory B, double-negative, immunoglobulin D+ transitional cells, and plasmablasts/plasma cells) in peripheral blood and tissue. This loss of B cells was associated with increased B cell–activating factor and decreased CXCL13 levels in circulation.

Conclusions.
Our data further characterize the mechanistic profile of obinutuzumab and suggest that it may elicit greater efficacy in indications such as lupus where B-cell targeting therapeutics are limited by the resistance of pathogenic tissue B cells to depletion.