bluuebunny/crossref_metadata_2025_split huggingface dataset:
Betulinic Acid Inhibits Endometriosis Through Suppression of Estrogen Receptor β Signaling Pathway
Authors: Xiang Dongfang , Zhao Min , Cai Xiaofan , Wang Yongxia , Zhang Lei , Yao Helen , Liu Min , Yang Huan , Xu Mingtao , Li Huilin , Peng Huijuan , Wang Min , Liang Xuefang , Li Ling , Yao Paul 
Published: December 2020

Endometriosis is an inflammatory gynecological disorder characterized by endometrial tissue growth located outside of the uterine cavity in addition to chronic pelvic pain and infertility. In this study, we aim to develop a potential therapeutic treatment based on the pathogenesis and mechanism of Endometriosis. Our preliminary data showed that the expression of estrogen receptor β (ERβ) was significantly increased, while ERα was significantly decreased, in endometriotic cells compared to normal endometrial cells. Further investigation showed that betulinic acid (BA) treatment suppressed ERβ expression through epigenetic modification on the ERβ promoter, while had no effect on ERα expression. In addition, BA treatment suppresses ERβ target genes, including superoxide dismutase 2 (SOD2), nuclear respiratory factor-1 (NRF1), cyclooxygenase 2 (COX2), and matrix metalloproteinase-1 (MMP1), subsequently increasing oxidative stress, triggering mitochondrial dysfunction, decreasing elevated proinflammatory cytokines, and eventually suppressing endometriotic cell proliferation, mimicking the effect of ERβ knockdown. On the other hand, gain of ERβ by lentivirus infection in normal endometrial cells resulted in increased cell proliferation and proinflammatory cytokine release, while BA treatment diminished this effect through ERβ suppression with subsequent oxidative stress and apoptosis. Our results indicate that ERβ may be a major driving force for the development of endometriosis, while BA inhibits Endometriosis through specific suppression of the ERβ signaling pathway. This study provides a novel therapeutic strategy for endometriosis treatment through BA-mediated ERβ suppression.
The Genotype-Phenotype Association of Von Hipple Lindau Disease Based on Mutation Locations: A Retrospective Study of 577 Cases in a Chinese Population
Authors: Qiu Jianhui , Zhang Kenan , Ma Kaifang , Zhou Jingcheng , Gong Yanqing , Cai Lin , Gong Kan 
Published: December 2020

PurposeVon Hippel-Lindau (VHL) disease is a hereditary kidney cancer syndrome, with which patients are more likely to get affected by renal cell carcinoma (RCC), pancreatic cyst or tumor (PCT), central nervous system hemangioblastoma (CHB), retinal angiomas (RA), and pheochromocytoma (PHEO). Mutations of VHL gene located in 3p25 may impair the function of the VHL protein and lead to the disease. It’s unclear why obvious phenotype varieties exist among VHL patients. Here we aimed to ascertain whether the mutation types and locations affect the phenotype.MethodsWe enrolled 577 Chinese VHL patients from 211 families and divided them into three groups and six subgroups according to their mutation types and locations. Cox survival analysis and Kaplan-Meier analysis were used to compare intergroup age-related tumor risks.ResultsPatients with nonsense or frameshift mutations that were located before residues 117 of VHL protein (NoF1 subgroup) hold lower age-related risks of VHL associated tumors (HR = 0.638, 95%CI 0.461–0.883, p = 0.007), CHB (HR = 0.596, 95%CI 0.409–0.868, p = 0.007) or PCT (HR = 0.595, 95%CI 0.368–0.961, p = 0.034) than patients whose mutations were located after residues 117 (NoF2 subgroup). Patients in NoF1 subgroup still had lower age-related risks of CHB (HR = 0.652, 95%CI 0.476–0.893, p = 0.008) and PCT (HR = 0.605, 95%CI 0.398–0.918, p = 0.018) compared with those in combined NoF2 subgroup and other truncating mutation patients. NoF1 subgroup correspondingly had a longer estimated median lifespan (64 vs. 55 year, p = 0.037) than NoF2 subgroup. Among patients with missense mutations of VHL, only a small minority (23 of 286 missense mutations carriers) carried mutations involving neither HIF-α binding region nor elongin C binding region, who were grouped in MO subgroup. MO subgroup seemed to have a higher age-related risk of PHEO. In the whole cohort (n = 577), PHEO was an independent protective factor for CHB (p = 0.001) and survival (p = 0.005). RA and CHB failed to predict the age-related risk of each other.ConclusionThe mutation types and locations of VHL gene are associated with phenotypes. Genetic counselors could predict phenotypes more accurately based on more detailed genotype-phenotype correlations. Further genotype-phenotype studies should focus on the prediction of tumor recurrence, progression, and metastasis. The deep molecular mechanism of genotype-phenotype correlation is worth further exploring.
ACE2 and Furin Expressions in Oral Epithelial Cells Possibly Facilitate COVID-19 Infection via Respiratory and Fecal–Oral Routes
Authors: Zhong Mei , Lin Bingpeng , Pathak Janak L. , Gao Hongbin , Young Andrew J. , Wang Xinhong , Liu Chang , Wu Kaibin , Liu Mingxiao , Chen Jian-ming , Huang Jiangyong , Lee Learn-Han , Qi Cui-ling , Ge Linhu , Wang Lijing 
Published: December 2020

Background: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that mainly transfers from human to human via respiratory and gastrointestinal routes. The S-glycoprotein in the virus is the key factor for the entry of SARS-CoV-2 into the cell, which contains two functional domains: S1 is an angiotensin-converting enzyme 2 (ACE2) receptor binding domain, and S2 is necessary for fusion of the coronavirus and cell membranes. Moreover, it has been reported that ACE2 is likely to be the receptor for SARS-CoV-2. In addition, mRNA level expression of Furin enzyme and ACE2 receptor had been reported in airway epithelia, cardiac tissue, and enteric canals. However, the expression patterns of ACE2 and Furin in different cell types of oral tissues are still unclear.Methods: In order to investigate the potential infective channel of the new coronavirus via the oropharyngeal cavity, we analyze the expression of ACE2 and Furin in human oral mucosa using the public single-cell sequence datasets. Furthermore, immunohistochemistry was performed in mucosal tissue from different oral anatomical sites to confirm the expression of ACE2 and Furin at the protein level.Results: The bioinformatics results indicated the differential expression of ACE2 and Furin on epithelial cells from different oral anatomical sites. Immunohistochemistry results revealed that both the ACE2-positive and Furin-positive cells in the target tissues were mainly positioned in the epithelial layers, partly expressed in fibroblasts, further confirming the bioinformatics results.Conclusions: Based on these findings, we speculated that SARS-CoV-2 could invade oral mucosal cells through two possible routes: binding to the ACE2 receptor and fusion with cell membrane activated by Furin protease. Our results indicated that oral mucosa tissues are susceptible to SARS-CoV-2 that could facilitate COVID-19 infection via respiratory and fecal–oral routes.
Mesenchymal Stromal Cell-Derived Extracellular Vesicles Reduce Neuroinflammation, Promote Neural Cell Proliferation and Improve Oligodendrocyte Maturation in Neonatal Hypoxic-Ischemic Brain Injury
Authors: Kaminski Nicole , Köster Christian , Mouloud Yanis , Börger Verena , Felderhoff-Müser Ursula , Bendix Ivo , Giebel Bernd , Herz Josephine 
Published: December 2020

Background: Neonatal encephalopathy caused by hypoxia-ischemia (HI) is a major cause of childhood mortality and disability. Stem cell-based regenerative therapies seem promising to prevent long-term neurological deficits. Our previous work in neonatal HI revealed an unexpected interaction between mesenchymal stem/stromal cells (MSCs) and the brains' microenvironment leading to an altered therapeutic efficiency. MSCs are supposed to mediate most of their therapeutic effects in a paracrine mode via extracellular vesicles (EVs), which might be an alternative to cell therapy. In the present study, we investigated the impact of MSC-EVs on neonatal HI-induced brain injury.Methods: Nine-day-old C57BL/6 mice were exposed to HI through ligation of the right common carotid artery followed by 1 h hypoxia (10% oxygen). MSC-EVs were injected intraperitoneally 1, 3, and 5 days after HI. One week after HI, brain injury was evaluated by regional neuropathological scoring, atrophy measurements and immunohistochemistry to assess effects on neuronal, oligodendrocyte and vessel densities, proliferation, oligodendrocyte maturation, myelination, astro-, and microglia activation. Immunohistochemistry analyses were complemented by mRNA expression analyses for a broad set of M1/M2- and A1/A2-associated molecules and neural growth factors.Results: While total neuropathological scores and tissue atrophy were not changed, MSC-EVs significantly protected from HI-induced striatal tissue loss and decreased micro- and astroglia activation. MSC-EVs lead to a significant downregulation of the pro-inflammatory cytokine TNFa, accompanied by a significant upregulation of the M2 marker YM-1 and the anti-inflammatory cytokine TGFb. MSC-EVs significantly decreased astrocytic expression of the A1 marker C3, concomitant with an increased expression of neural growth factors (i.e., BDNF, VEGF, and EGF). These alterations were associated with an increased neuronal and vessel density, coinciding with a significant increase of proliferating cells in the neurogenic sub-ventricular zone juxtaposed to the striatum. MSC-EV-mediated neuroprotection went along with a significant improvement of oligodendrocyte maturation and myelination.Conclusion: The present study demonstrates that MSC-EVs mediate anti-inflammatory effects, promote regenerative responses and improve key developmental processes in the injured neonatal brain. The present results suggest different cellular target mechanisms of MSC-EVs, preventing secondary HI-induced brain injury. MSC-EV treatment may be a promising alternative to risk-associated cell therapies in neonatal brain injury.
Forebrain NgR1 Overexpression Impairs DA Release Suggesting Synergy of Local and Global Synaptic Plasticity Mechanisms
Authors: Arvidsson Emma , Gabulya Sarolta , Brodin Alvin Tore , Karlsson Tobias Erik , Olson Lars 
Published: December 2020

Structural synaptic reorganizations needed to permanently embed novel memories in the brain involve complex plasticity-enhancing and plasticity-inhibiting systems. Increased neural activity is linked to rapid downregulation of Nogo receptor 1 (NgR1), needed to allow local structural synaptic plasticity. This local regulation of plasticity is thought to be moderated by global systems, such as the ascending cholinergic and monoaminergic systems, adding significance to locally increased neural activity. Here we address the reverse possibility that the global systems may also be influenced by the status of local plasticity. Using NgR1-overexpressing mice, with impaired plasticity and long-term memory, we measured the ability to release dopamine (DA), implicated in regulating plasticity and memory. In vivo chronoamperometric recording with high temporal and spatial resolution revealed severe impairment of potassium chloride (KCl)-induced increase of extracellular DA in the dorsal striatum of mice overexpressing NgR1 in forebrain neurons. A similar, but lesser, impairment of DA release was seen following amphetamine delivery. In contrast, potassium chloride-evoked DA release in NgR1 knockout (KO) mice led to increased levels of extracellular DA. That NgR1 can impair DA signaling, thereby further dampening synaptic plasticity, suggests a new role for NgR1 signaling, acting in synergy with DA signaling to control synaptic plasticity.Significance Statement:The inverse correlation between local NgR1 levels and magnitude of KCl-inducible amounts of DA release in the striatum reinforces the rule of NgR1 as a regulator of structural synaptic plasticity and suggests synergy between local and global plasticity regulating systems.
Types of Mastectomies and Immediate Reconstructions for Ipsilateral Breast Local Recurrences
Authors: Simon Pauline , Barrou Julien , Cohen Monique , Rua Sandrine , Lambaudie Eric , Houvenaeghel Gilles 
Published: December 2020

Purpose: Ipsilateral-breast-local-recurrence (ILBLR) is a rare event with little data on immediate-breast-reconstruction (IBR). We report post-operative results of different types of mastectomy for ILBLR with or without IBR performed during a period of 40 months in order to analyze post-operative complications as main objective.Methods: We analyzed mastectomies performed for ILBLR after initial breast conservative treatment from January 2016 to April 2019. The characteristics of patients, surgery, complication rate, postoperative hospitalization have been determined.Results: Of the 207 mastectomies, 32.8% had an IBR: 31 nipple-sparing-mastectomy (NSM) and 37 skin-sparing-mastectomy (SSM) with 37 latissimus-dorsi-flap (LDF) IBR and 31 implant-IBR. Few reconstruction was performed for patients with body-mass-index ≥30 (OR = 0.214), infiltrating ductal carcinomas (OR = 0.272) and ASA-3 patients (OR = 0.254). In multivariate analysis, LDF-IBR was more often realized for NSM and for patients with BMI ≥25. The overall complication rate was 37.4%: 45.6 and 33.1% with and without IBR, respectively (p = 0.056). In multivariate analysis, BMI ≥25 (OR 2.02, p = 0.023), IBR (OR 1.9, p = 0.046) and tobacco (OR 2.17, p = 0.055) were correlated with higher risk of complications. There was no difference for Grade 2–3 complications rates for IBR and no IBR, respectively (14.7%: 10/68 and 9.3%: 13/139). In multivariate analysis, overall survival from date of mastectomy for local recurrence was significantly associated with interval time to local recurrence (OR 6.981).Conclusion: Salvage mastectomy and IBR is a good choice for ILBLR, particularly using flap reconstruction. NSM can be considered as a good option in selected patients for ILBLR for NSM and/or LDFR.
Active Switching of Toroidal Resonances by Using a Dirac Semimetal for Terahertz Communication
Authors: Sun Yuanbao , Liao Denggao , Xu Jinjin , Wu Yiping , Chen Lin 
Published: December 2020

The dynamical switching of a toroidal dipole resonance channel is demonstrated by tuning the Fermi level of a Dirac semimetal film sandwiched between the back substrates. As the Fermi level is increased from 30 to 150 meV, the resonance frequency is switched from 0.283 to 0.201 THz because of the transition from toroidal mode to hybrid mode. The hybrid mode is formed by the interaction between the toroidal mode and the plasmonic mode (induced by a Dirac semimetal film with metallic properties). The influence of the sandwiched dielectric layer (between the toroidal metasurface pattern and the Dirac semimetal film) on the switching effect was also investigated. This active dual-channel terahertz switching may have potential applications in advanced terahertz communication.
The Big Three Health Behaviors and Mental Health and Well-Being Among Young Adults: A Cross-Sectional Investigation of Sleep, Exercise, and Diet
Authors: Wickham Shay-Ruby , Amarasekara Natasha A. , Bartonicek Adam , Conner Tamlin S. 
Published: December 2020

BackgroundSleep, physical activity, and diet have been associated with mental health and well-being individually in young adults. However, which of these “big three” health behaviors most strongly predicts mental health and well-being, and their higher-order relationships in predictive models, is less known. This study investigated the differential and higher-order associations between sleep, physical activity, and dietary factors as predictors of mental health and well-being in young adults.MethodIn a cross-sectional survey design, 1,111 young adults (28.4% men) ages 18–25 from New Zealand and the United States answered an online survey measuring typical sleep quantity and quality; physical activity; and consumption of raw and processed fruit and vegetables, fast food, sweets, and soda, along with extensive covariates (including demographics, socioeconomic status, body mass index, alcohol use, smoking, and health conditions) and the outcome measures of depressive symptoms [measured by the Center for Epidemiological Depression Scale (CES-D)] and well-being (measured by the Flourishing Scale).ResultsControlling for covariates, sleep quality was the strongest predictor of depressive symptoms and well-being, followed by sleep quantity and physical activity. Only one dietary factor—raw fruit and vegetable consumption—predicted greater well-being but not depressive symptoms when controlling for covariates. There were some higher-order interactions among health behaviors in predicting the outcomes, but these did not survive cross-validation.ConclusionSleep quality is an important predictor of mental health and well-being in young adults, whereas physical activity and diet are secondary but still significant factors. Although strictly correlational, these patterns suggest that future interventions could prioritize sleep quality to maximize mental health and well-being in young adults.
Self-Reported Illicit Drug Use Among Norwegian University and College Students. Associations With Age, Gender, and Geography
Authors: Heradstveit Ove , Skogen Jens Christoffer , Edland-Gryt Marit , Hesse Morten , Vallentin-Holbech Lotte , Lønning Kari-Jussie , Sivertsen Børge 
Published: December 2020

Background and Aims: Several studies have pointed to relatively high levels of illicit drug use among students in higher education compared to the general population. The aim of the present study was to provide an updated examination of self-reported illicit drug use among Norwegian University and college students.Methods: Data stem from the SHoT study (Students' Health and Well-being Study), a nationwide cross-sectional survey for higher education in Norway including Norwegian full-time students aged 18–35. Self-reported illicit drug use across a range of specified drugs comprised the outcome variables. Information on gender, age, and study location (geographical area) was also collected and used as stratification variables. The SHoT-survey from 2018 (N = 50,054) was used for the analyses of associations between demographical variables and illicit drug use, while trends in illicit drug use were estimated by comparing the 2018-results with data from the SHoT-surveys conducted in 2010 and 2014.Results: The proportion of students reporting having ever tried illicit drugs increased from 2014 to 2018, for both males (30.8 vs. 36.7%) and females (17.5 vs. 24.0%, both p &lt; 0.001), while only minimal changes occurred between 2010 and 2014. The most commonly used illicit drugs during the past 12 months in 2018 were cannabis (15.2%), followed by MDMA (4.0%), cocaine (3.0%), and LSD/psilocybin (2.1%). Illicit drug use showed both linear increase with age, and inverted U-shaped relationships that peaked in the age span from 23 to 28 years of age. Males reported higher illicit drug use compared with females for all drugs. Proportions of illicit drug use varied across geographical areas within the country, with the highest use being reported in the Oslo area (the largest city and capital of Norway).Conclusions: The present study reports an increase from 2010 to 2018 among Norwegian University and college students in the proportion of those reporting to have tried illicit drugs. Despite varying proportions of use across type of drug, age, gender, and geographical location, the overall high levels of illicit drug use past 12 months confirm the need to address illicit drug use in this population.
The Association Between Vaginal Microbiota Dysbiosis, Bacterial Vaginosis, and Aerobic Vaginitis, and Adverse Pregnancy Outcomes of Women Living in Sub-Saharan Africa: A Systematic Review
Authors: Juliana Naomi C. A. , Suiters Meghan J. M. , Al-Nasiry Salwan , Morré Servaas A. , Peters Remco P. H. , Ambrosino Elena 
Published: December 2020

Background: Previous studies have described the association between dysbiosis of the vaginal microbiota (VMB) and related dysbiotic conditions, such as bacterial vaginosis (BV) and aerobic vaginitis (AV), and various adverse pregnancy outcomes. There is limited overview of this association from countries in sub-Saharan Africa (SSA), which bear a disproportionally high burden of both vaginal dysbiotic conditions and adverse pregnancy outcomes. This systematic review assesses the evidence on the association between VMB dysbiosis, BV, and AV, and late adverse pregnancy outcomes in women living in SSA.Methods: The Preferred Reporting Items for Systematic Review and Meta-Analysis Statement (PRISMA) guidelines were followed. Three databases [PubMed, Embase (Ovid), and Cochrane] were used to retrieve observational and intervention studies conducted in SSA that associated VMB dysbiosis, BV, or AV and preterm birth/labor/delivery, preterm rupture of membranes (PROM), low birthweight, small for gestational age, intrauterine growth restriction, intrauterine infection, intrauterine (fetal) death, stillbirth, perinatal death, or perinatal mortality.Results: Twelve studies out of 693 search records from five SSA countries were included. One study identified a positive association between VMB dysbiosis and low birthweight. Despite considerable differences in study design and outcome reporting, studies reported an association between BV and preterm birth (7/9), low birthweight (2/6), PROM (2/4), intrauterine infections (1/1), and small for gestational age (1/1). None of the retrieved studies found an association between BV and pregnancy loss (5/5) or intrauterine growth retardation (1/1). At least two studies support the association between BV and PROM, low birthweight, and preterm birth in Nigerian pregnant women. No reports were identified investigating the association between AV and late adverse pregnancy outcomes in SSA.Conclusion: Two of the included studies from SSA support the association between BV and PROM. The remaining studies show discrepancies in supporting an association between BV and preterm birth or low birthweight. None of the studies found an association between BV and pregnancy loss. As for the role of VMB dysbiosis, BV, and AV during pregnancy among SSA women, additional research is needed. These results provide useful evidence for prevention efforts to decrease vaginal dysbiosis and its contribution to adverse pregnancy outcomes in SSA.
Hubungan Hipertensi Terhadap Kejadian Stroke
Authors: Puspitasari Puti Nadhirah 
Published: December 2020

Latar belakang: Stroke didefinisikan sebagai gangguan suplai darah ke otak.Banyak faktor yang dapat memengaruhi kejadian stroke. Hipertensi merupakan faktor pencetus utama terjadinya kejadian stroke,baik stroke hemoragik ataupun iskemik.Tujuan : Mengetahui lebih lanjut mengenai hubungan hipertensi terhadap kejadian stroke. Metode : Metode yang digunakan adalah studi literatur yang diambil dari berbagai jurnal nasional dan internasional, metode ini berupaya meringkas kondisi pemahaman terkini mengenai suatu topik. Kesimpulan :Terdapat hubungan hipertensi terhadap kejadian stroke