bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ventromedial Hypothalamus Activation Aggravates Hypertension Myocardial Remodeling Through the Sympathetic Nervous System
Authors: Zhou Yuyang , Liu Zhihao , Liu Zihan , Zhou Huixin , Xu Xiao , Li Zeyan , Chen Hu , Wang Yuhong , Zhou Zhen , Wang Meng , Lai Yanqiu , Zhou Liping , Zhou Xiaoya , Jiang Hong 
Published: October 2021

Background: The ventromedial hypothalamus (VMH) is an important nuclei in responding to emotional stress, and emotional stress is a risk factor for cardiovascular diseases. However, the role of the VMH in cardiovascular diseases remains unknown. This study aimed to investigate the effects and underlying mechanisms of VMH activation on hypertension related cardiac remodeling in two-kidney-one-clip (2K1C) hypertension (HTN) rats.Methods: Eighteen male Sprague-Dawley rats were injected with AAV-hSyn-hM3D(Gq) into the VMH at 0 weeks and then randomly divided into three groups: (1) sham group (sham 2K1C + saline i.p. injection); (2) HTN group (2K1C + saline i.p. injection); (3) HTN+VMH activation group (2K1C + clozapine-N-oxide i.p. injection). One week later, rats were subjected to a sham or 2K1C operation, and 2 weeks later rats were injected with clozapine-N-oxide or saline for 2 weeks.Results: In the HTN+VMH activation group, FosB expression was significantly increased in VMH sections compared with those of the other two groups. Compared to the HTN group, the HTN+VMH activation group showed significant: (1) increases in systolic blood pressure (SBP); (2) exacerbation of cardiac remodeling; and (3) increases in serum norepinephrine levels and sympathetic indices of heart rate variability. Additionally, myocardial RNA-sequencing analysis showed that VMH activation might regulate the HIF-1 and PPAR signal pathway and fatty acid metabolism. qPCR results confirmed that the relative mRNA expression of HIF-1α was increased and the PPARα and CPT-1 mRNA expression were decreased in the HTN+VMH activation group compared to the HTN group.Conclusions: VMH activation could increase SBP and aggravate cardiac remodeling possibly by sympathetic nerve activation and the HIF-1α/PPARα/CPT-1 signaling pathway might be the underlying mechanism.
Metabolic Consequences of Neuronal HIF1α-Deficiency in Mediobasal Hypothalamus in Mice
Authors: Rozjan Azmat , Shan Weibi , Yao Qiaoling 
Published: October 2021

ObjectiveThis study aims to investigate whether hypoxia-inducible factor 1α (HIF1α) in the neurons of the mediobasal hypothalamus is involved in the regulation of body weight, glucose, and lipid metabolism in mice and to explore the underlying molecular mechanisms.MethodsHIF1αflox/flox mice were used. The adeno-associated virus that contained either cre, GFP and syn, or GFP and syn (controls) was injected into the mediobasal hypothalamus to selectively knock out HIF1α in the neurons of the mediobasal hypothalamus. The body weight and food intake were weighed daily. The levels of blood glucose, insulin, total cholesterol (TC), triglyceride (TG), free fatty acid (FFA), high-density lipoprotein (HDL), and low-density lipoprotein (LDL)were tested. Intraperitoneal glucose tolerance test (IPGTT) was performed. The insulin-stimulated Akt phosphorylation in the liver, epididymal fat, and skeletal muscle were examined. Also, the mRNA expression levels of HIF1α, proopiomelanocortin (POMC), neuropeptide Y (NPY), and glucose transporter protein 4 (Glut4) in the hypothalamus were checked.ResultsAfter selectively knocking out HIF1α in the neurons of the mediobasal hypothalamus (HIF1αKOMBH), the body weights and food intake of mice increased significantly compared with the control mice (p &lt; 0.001 at 4 weeks). Compared with that of the control group, the insulin level of HIF1αKOMBH mice was 3.5 times higher (p &lt; 0.01). The results of the IPGTT showed that the blood glucose level of the HIF1αKOMBH group at 20–120 min was significantly higher than that of the control group (p &lt; 0.05). The serum TC, FFA, HDL, and LDL content of the HIF1αKOMBH group was significantly higher than those of the control group (p &lt; 0.05). Western blot results showed that compared with those in the control group, insulin-induced AKT phosphorylation levels in liver, epididymal fat, and skeletal muscle in the HIF1αKOMBH group were not as significantly elevated as in the control group. Reverse transcription-polymerase chain reaction (RT-PCR) results in the whole hypothalamus showed a significant decrease in Glut4 mRNA expression. And the mRNA expression levels of HIF1α, POMC, and NPY of the HIF1αKOMBH group decreased significantly in ventral hypothalamus.ConclusionsThe hypothalamic neuronal HIF1α plays an important role in the regulation of body weight balance in mice under normoxic condition. In the absence of hypothalamic neuronal HIF1α, the mice gained weight with increased appetite, accompanied with abnormal glucose and lipid metabolism. POMC and Glut4 may be responsible for this effect of HIF1α.
Centralized and Decentralized Delivery of Transgender Health Care Services: A Systematic Review and a Global Expert Survey in 39 Countries
Authors: Koehler Andreas , Strauss Bernhard , Briken Peer , Szuecs Daria , Nieder Timo O. 
Published: October 2021

IntroductionTransgender health care is delivered in both centralized (by one interdisciplinary institution) and decentralized settings (by different medical institutions spread over several locations). However, the health care delivery setting has not gained attention in research so far. Based on a systematic review and a global expert survey, we aim to investigate its role in transgender health care quality.MethodsWe performed two studies. In 2019, we systematically reviewed the literature published in databases (Cochrane, MEDLINE, EMBASE, Web of Science) from January 2000 to April 2019. Secondly, we conducted a cross-sectional global expert survey. To complete the evidence on the question of (de-)centralized delivery of transgender health care, we performed a grey literature search for additional information than the systematic review and the expert survey revealed. These analyses were conducted in 2020.ResultsEleven articles met the inclusion criteria of the systematic review. 125 participants from 39 countries took part in the expert survey. With insights from the grey literature search, we found transgender health care in Europe was primarily delivered centralized. In most other countries, both centralized and decentralized delivery structures were present. Comprehensive care with medical standards and individual access to care were central topics associated with the different health care delivery settings.DiscussionThe setting in which transgender health care is delivered differs between countries and health systems and could influence different aspects of transgender health care quality. Consequently, it should gain significant attention in clinical practice and future health care research.
Hazardous Effects of Sucralose and Its Disinfection Byproducts Identified From an E. coli Whole-Cell Array Analysis
Authors: Zhai Yuanxin , Bai Dan , Yang Heyun , Li Xiaoliang , Zhu Daiwen , Cao Xin , Ma Hao , Li Xiaolin , Zheng Xing 
Published: October 2021

In this study, anE. coliwhole-cell microarray assay was used to evaluate the impact of sucralose (SUC) on 110 selected genes under different exposure concentrations. Furthermore, toxicity caused by SUC under five disinfection processes was explored. Our results revealed detailed transcriptional information for gaining insights into the toxicity mechanism. SUC at lower concentrations tends to induce more protein response, whereas greater DNA damage occurs at higher concentrations. In addition, SUC could induce changes in the expression of various genes, with the DNA damage exhibiting an obvious concentration dependence. As the exposure concentration of SUC increases, stress is transformed from a single-type level to the entire system, which could enhance cellular ability to resist damage and survive. Exposure–recovery tests show that long-term exposure (24 h) to SUC causes irreversible damage, and at SUC concentrations of 103–104 mg/L, short-term exposure (2 h) exerts the same effect. Furthermore, SUC toxicity is enhanced on disinfection, with ultraviolet light causing particularly serious DNA damage.
Degradation of 17 Benzodiazepines by the UV/H2O2 Treatment
Authors: You Wen-Dan , Ye Pu , Yang Bin , Luo Xin , Fang Jie , Mai Zi-Tian , Sun Jian-Liang 
Published: October 2021

Benzodiazepines are one group of psychoactive drugs widely detected in water environments, and their persistence during conventional wastewater treatment has raised great concerns. Here we investigated the degradation of 17 benzodiazepines in water by UV/H2O2 treatment. The results showed that the UV/H2O2 treatment significantly increased the degradation of 17 benzodiazepines in phosphate buffer solutions at pH 7.0. This can be attributed to the high reactivity of hydroxyl radicals (·OH) towards benzodiazepines with second-order rate constants of 3.48 × 109 M−1 s−1–2.44 × 1010 M−1 s−1. The degradation of alprazolam, a typical benzodiazepine, during the UV/H2O2 treatment was increased with the increasing H2O2 dosage. The solution pH influenced the alprazolam degradation significantly, with the highest degradation at pH 7.0. Water matrix, such as anions (Cl−, HCO3−, NO3−) and humic acid, decreased the degradation of alprazolam by UV/H2O2 treatment. Based on the degradation products identified using quadrupole time-of-flight mass spectrometer, the degradation mechanisms of alprazolam by UV/H2O2 treatment were proposed, and hydroxylation induced by ·OH was the main reaction pathway. The degradation of 17 benzodiazepines by UV/H2O2 treatment in wastewater treatment plant effluent and river water was lower than that in phosphate buffer solutions. The results showed that the benzodiazepine psychoactive drugs in natural water can be effectively removed by the UV/H2O2 treatment.
Association Between Eating Speed and Metabolic Syndrome: A Systematic Review and Meta-Analysis
Authors: Yuan Shu-qian , Liu Ying-ming , Liang Wei , Li Fei-fei , Zeng Yuan , Liu Yin-yue , Huang Shu-zhen , He Quan-yuan , Quach Binh , Jiao Jiao , Baker Julien S. , Yang Yi-de 
Published: October 2021

Objective: This review aimed to systematically summarize and meta-analyze the association between eating speed and metabolic syndrome (MetS).Methods: Following the Preferred Reporting Items for Systematic Reviews, and Meta Analyses (PRISMA) guidelines, four electronic databases (PubMed, Web of Science, MEDLINE, and EMBASE) were searched until March 2021 to identify eligible articles based on a series of inclusion and exclusion criteria. Heterogeneity was examined using I2 statistics. Using random-effects models, the pooled odds ratios (ORs), and 95% CIs were calculated to evaluate the association between eating speed with MetS and its components, including central obesity, blood pressure (BP), high-density lipoprotein cholesterol (HDL), triglyceride (TG), and fasting plasma glucose (FPG).Results: Of the 8,500 original hits generated by the systematic search, 29 eligible studies with moderate-to-high quality were included, involving 465,155 subjects. The meta-analysis revealed that eating faster was significantly associated with higher risks of MetS (OR = 1.54, 95% CI: 1.27–1.86), central obesity (OR = 1.54, 95% CI: 1.37–1.73), elevated BP (OR = 1.26, 95% CI: 1.13–1.40), low HDL (OR = 1.23, 95% CI: 1.15–1.31), elevated TG (OR = 1.29, 95% CI: 1.18–1.42), and elevated FPG (OR = 1.16, 95% CI: 1.06–1.27) compared to eating slowly.Conclusions: The results of the review indicated that eating speed was significantly associated with MetS and its components. Interventions related to decreasing eating speed may be beneficial for the management of MetS.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021242213, identifier: CRD42021242213.
Proposed Nutrient Standards for Plant-Based Beverages Intended as Milk Alternatives
Authors: Drewnowski Adam , Henry Christiani Jeyakumar , Dwyer Johanna T. 
Published: October 2021

Background: Plant-based beverages (PBB) that are marketed as alternatives to cow milk are gaining in popularity worldwide. Nutrient quality of PBB can be highly variable.Objective: To develop a set of voluntary or mandatory nutrient standards for the PBB product category in order to assist innovation and guide product development and reformulation.Methods: The present goal was to develop standards for PBB energy content, minimum protein content and quality, maximum content for added fat, sugar, and salt, and to suggest fortification levels for selected vitamins and minerals. The standards were based on dietary recommendations and guidelines and current practices of federal agencies in the US.Results: The proposed energy and nutrient content for PBB milk alternatives are maximum 85–100 kcal energy per 100 g; a minimum for 2.2/100 g of high-quality protein, low content of saturated fat (&lt;0.75/100 g) and added sugar (5.3–6.25/100 g) and consistent fortification with calcium, vitamins A, D, B-2, and B-12 at levels comparable to those found in cow milk (1%). Ideally, the protein content ought to be increased (2.8/100 g) and added sugar content reduced even further (2.7–3.1/100 g) for “best of class” products. These proposed standards were applied to the 641 existing PBB products listed in the 2018 version of the USDA Branded Food Products Database (BFPDB). The standards were met by &lt;5% of the PBB on the US market.Conclusion: Often viewed as equivalent to milk in nutritional value, many PBB are often low in protein and are fortified with varying amounts of calcium, and vitamins A and D. Nutrient standards for this category should be adopted by the food industry, by public health regulatory authorities, and by standardization bodies such as the Codex Alimentarius.
Prognostic Value of CEA, CA19-9, CA125, CA724, and CA242 in Serum and Ascites in Pseudomyxoma Peritonei
Authors: Liang Lei , Fang Jingyang , Han Xuedi , Zhai Xichao , Song Yan , Lu Yiyan , Zhang Qian , Ma Ruiqing 
Published: October 2021

PurposeTo investigate the expression of carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), CA19-9, CA724, and CA242 in serum and ascites of pseudomyxoma peritonei (PMP) patients and evaluate the predictive value of these elevated biomarkers in pathological grade, completeness of cytoreduction (CC), and survival.MethodsFrom May 2009 to October 2019, a total of 512 patients diagnosed with PMP through pathology in Aerospace Center Hospital were enrolled. The serum and ascites tumor biomarkers were obtained. The diagnostic values between serum and ascites biomarkers in pathology and CC were compared by the receiver operating characteristic (ROC) curves. The correlation between pathology, cytoreduction, and biomarkers was calculated by univariate and multivariate logistic regression. The associations between different numbers of elevated biomarkers and survival status were examined using univariate and multivariate backward Cox proportional hazard regression models.ResultsThe results showed that the areas under the ROC curves (AUROC) in the diagnosis of CC were 0.798 (95% CI: 0.760–0.836) and 0.632 (95% CI: 0.588–0.676) in serum and ascites biomarkers, respectively. The elevated serum and ascites biomarkers were independent risk factors for both pathology and CC. The 1-year, 3-year, and 5-year survival rates were 89.07%, 73.22%, and 66.94%, respectively. Longer survival was observed in patients who had less than two elevated serum biomarkers compared with those with 2–3 and 4-5 elevated serum biomarkers (p &lt; 0.001).ConclusionCEA, CA125, CA19-9, CA724, and CA242 in serum and ascites can be used to judge the severity and predict the resectability. Furthermore, different numbers of elevated biomarkers can help determine the prognosis of PMP.
Case Report: Targeted Therapy for Metastatic Solid Pseudopapillary Neoplasm of the Pancreas With CTNNB1 and PTEN Mutations
Authors: Wang Xinbo , Zhu Daojun , Bao Wei , Li Min , Wang Sizhen , Shen Rongxi 
Published: October 2021

BackgroundSolid pseudopapillary neoplasm (SPN) of the pancreas shows an indolent clinical behavior in cases undergoing surgical resection. The efficacy of combination therapy in the metastatic extrapancreatic SPN treatment remains largely unknown and a clinical challenge.Case PresentationWe report a case of a metastatic pancreatic SPN in a 45-year-old woman who presented with an aggressive peritoneal dissemination and hepatic metastases and still showed an indolent clinical course with combination therapy with repeated surgery and targeted therapy. Although the follow-up effect remains to be seen, this is the first report of practical experience of the targeted agents sunitinib and everolimus in metastatic SPN tumors based on the mutation status of PTEN (c.379G&gt;A; p.G127R) and CTNNB1 (c.98C&gt;G; p.S33C). To our knowledge, the PTEN variant identified in this case has not been previously reported in SPN.ConclusionEvidence on variant genetics indicates that future molecular studies may not only help to explain the mechanism of SPN occurrence and development but are also more likely to direct to future precision treatments.
CT-Based Peritumoral and Intratumoral Radiomics as Pretreatment Predictors of Atypical Responses to Immune Checkpoint Inhibitor Across Tumor Types: A Preliminary Multicenter Study
Authors: He Shuai , Feng Yuqing , Lin Qi , Wang Lihua , Wei Lijun , Tong Jing , Zhang Yuwei , Liu Ying , Ye Zhaoxiang , Guo Yan , Yu Tao , Luo Yahong 
Published: October 2021

ObjectiveTo develop and validate a new strategy based on radiomics features extracted from intra- and peritumoral regions on CT images for the prediction of atypical responses to the immune checkpoint inhibitor (ICI) in cancer patients.MethodsIn total, 135 patients derived from five hospitals with pathologically confirmed malignancies receiving ICI were included in this retrospective study. Atypical responses including pseudoprogression (PsP) and hyperprogression disease (HPD) were identified as their definitions. A subgroup of standard progression disease (sPD) in 2018 was also involved in this study. Based on pretreatment CT imaging, a total of 107 features were extracted from intra- and peri-tumoral regions, respectively. The least absolute shrinkage and selection operator (Lasso) algorithm was used for feature selection, and multivariate logistic analysis was used to develop radiomics signature (RS). Finally, a total of nine RSs, derived from intra-tumoral, peri-tumoral, and combination of both regions, were built respectively to distinguish PsP vs. HPD, PsP vs. sPD, and HPD vs. sPD. The performance of the RSs was evaluated with discrimination, calibration, and clinical usefulness.ResultsNo significant difference was found when compared in terms of clinical characteristics of PsP, HPD, and sPD. RS based on combined regions outperformed those from either intra-tumoral or peri-tumoral alone, yielding an AUC (accuracy) of 0.834 (0.827) for PsP vs. HPD, 0.923 (0.868) for PsP vs. sPD, and 0.959 (0.894) for HPD vs. sPD in the training datasets, and 0.835 (0.794) for PsP vs. HPD, 0.919 (0.867) for PsP vs. sPD, and 0.933 (0.842) for HPD vs. sPD in the testing datasets. The combined RS showed good fitness (Hosmer–Lemeshow test p &gt; 0.05) and provided more net benefit than the treat-none or treat-all scheme by decision curve analysis in both training and testing datasets.ConclusionPretreatment radiomics are helpful to predict atypical responses to ICI across tumor types. The combined RS outperformed those from either intra- or peri-tumoral alone which may provide a more comprehensive characterization of atypical responses to ICI.
Tumor-Infiltrating Cytotoxic T Cells and Tumor-Associated Macrophages Correlate With the Outcomes of Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer
Authors: Yang Yuqin , Tian Wenjing , Su Liqian , Li Peiqiu , Gong Xiaohua , Shi Lu , Zhang Qingling , Zhao Bin , Zhao Hong 
Published: October 2021

BackgroundTumor-infiltrating immune cells (TIICs) play a key role in immunoregulatory networks and are related to tumor development. Emerging evidence shows that these cells are associated with sensitivity to chemotherapy and radiotherapy. However, the predictive role of TIICs in the outcomes of neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer (LARC) is unclear.MethodsImaging mass cytometry (IMC) was performed to comprehensively assess the immune status before nCRT in 6 patients with LARC (3 achieved pathological complete response (pCR), 3 did not) with matched clinicopathological parameters. Immunohistochemistry (IHC) for CD8, CD163 and Foxp3 on biopsy samples from 70 patients prior to nCRT and logistic regression analysis were combined to further evaluate its predictive value for treatment responses in an independent validation group.ResultsA trend of increased CD8+ cytotoxic T lymphocytes (CTLs) and decreased CD163+ tumor-associated macrophages (TAMs) and Foxp3+ regulatory T cells (Tregs) in the pCR group was revealed by IMC. In the validation group, CTLs and TAMs were strong predictors of the clinical response to nCRT. High levels of CTLs were positively associated with the pCR ratio (OR=1.042; 95% CI: 1.015~1.070, p=0.002), whereas TAMs were correlated with a poor response (OR=0.969; 95% CI: 0.941~0.998, p=0.036). A high density of TAMs was also associated with an advanced cN stage.ConclusionCTLs in the tumor microenvironment (TME) may improve the response to nCRT, whereas TAMs have the opposite effect. These results suggest that these cells might be potential markers for the clinical outcomes of nCRT and aid in the clinical decision-making of LARC for improved clinical outcomes.