Miracle-dz/UniFAR-FTUs huggingface dataset:
The Emerging Role of Sestrin2 in Cell Metabolism, and Cardiovascular and Age-Related Diseases

Sestrins (Sesns), including Sesn1, Sesn2, and Sesn3, are cysteine sulfinyl reductases that play critical roles in the regulation of peroxide signaling and oxidant defense. Sesn2 is thought to regulate cell growth, metabolism, and survival response to various stresses, and act as a positive regulator of autophagy. The anti-oxidative and anti-aging roles of Sesn2 have been the focus of many recent studies. The role of Sesn2 in cellular metabolism and cardiovascular and age-related diseases must be analyzed and discussed. In this review, we discuss the physiological and pathophysiological roles and signaling pathways of Sesn2 in different stress-related conditions, such as oxidative stress, genotoxic stress, and hypoxia. Sesn2 is also involved in aging, cancer, diabetes, and ischemic heart disease. Understanding the actions of Sesn2 in cell metabolism and age-related diseases will provide new evidence for future experimental research and aid in the development of novel therapeutic strategies for Sesn2-related diseases.
Sorafenib treatment on Chinese patients with advanced hepatocellular carcinoma

Abstract Sorafenib is of proven efficacy in treating patients of hepatocellular carcinoma (HCC). Our study was aimed to determine the factors influence the sorafenib efficacy. We evaluated data of HCC patients receiving sorafenib from June 2012 to October 2016. All HCC cases were of the Barcelona Clinic Liver Cancer (BCLC) classification stage C. The exclusion criteria: those of BCLC classification stage A or B, with the absence or co-infection of hepatitis B (HBV) and hepatitis C (HCV). The presence of HBV, HCV, macoscopic vascular invasion (MVI) or extrahepatic spread (EHS) was recorded for each patient. Time-to-progression (TTP) and overall survival (OS) were analyzed. Among a total of 90 HCC patients, 48 (53.3%) had HBV infection, 42 (46.7%) had HCV infection, 51 (56.7%) had MVI, and 39 (43.3%) had EHS. Patients with HCV infection showed better TTP and OS than those with HBV infection. Patients with EHS had a longer TTP and OS than those with MVI. For patients with HBV infection, those with EHS had a longer TTP (mean 4.60 vs 2.64 months, P = .002) and OS (mean 6.65 vs 4.53 months, P = .045) compared to those with MVI. Among those with MVI, patients with HBV infection had a poorer TTP (mean 2.64 vs 4.74 months, P = .019) and shorter OS (mean 4.53 vs 7.00 months, P = .059) compared to those with HCV infection. HCC patients with HCV infection or with the presence of EHS showed better sorafenib efficacy.
A systematic review and network meta-analysis

Background:Current research has proved that psoriasis is associated with serum uric acid (SUAC) levels. Our purpose is to clarify SUAC levels and the incidence of hyperuricemia in psoriasis patients, and to compare SUCA levels in different groups’ psoriasis patients. Methods: We plan to search 7 electronic bibliographic databases (PubMed, Embase, Cochrane, and 4 Chinese databases) from inception to August 2019. Literatures selection and data collection will be performed independently by 2 authors. The Newcastle– Ottawascalewill be used to assess themethodologicquality andbias of included studies. Firstly, standardpairwisemeta-analysiswill be used to examine the considered data synthesis. Secondly, if the identified studies appear sufficiently similar within and across the different comparisons between different groups of psoriasis patients, we will estimate SUAC levels using network meta-analysis in different age and ethnicity psoriasis patients. Mean difference, risk ratio, and 95%confidence intervals will be used to assess the SUAC levels and the incidence of hyperuricemia in psoriasis patients. The software of Stata and WinBUGS will be used to calculations. Results: The results will be published in a peer-reviewed journal. Conclusion: Our study will compare SUCA levels in different groups’ psoriasis patients through network meta-analysis, and we believe our job is very meaningful. Ethicsanddissemination:Our study is a secondary study of the existing literature. So, ethical and dissemination approval is not required. Abbreviations: GRADE = Grading of Recommendations Assessment, Development, and Evaluation, MD = mean difference, NOS=Newcastle–Ottawa scale, PRISMA-P= Preferred Reporting Items for Systematic Review andMeta-analysis Protocols, SUAC = serum uric acid.
Risk factors of invasive candidiasis in critical cancer patients after various gastrointestinal surgeries

Abstract For early diagnosis and treatment of invasive candidiasis (IC), the well-known risk factors may not apply in the intensive care unit (ICU). This retrospective study identified the risk factors predicting IC and candidemia in cancer patients under intensive care after gastrointestinal surgery. Enrolled were 229 cancer patients admitted to our oncology surgical ICU after gastrointestinal surgery between January 1, 2010 and October 31, 2014. The most common types of solid gastrointestinal cancers were gastric (49.8%), colon (20.1%), and esophageal (18.3%). The percentage of patients with corrected Candida colonization index (CCI) ≥0.4 was 31.9%. IC was confirmed in 19 patients (8.3%), and the ICU mortality was 15.8%. Candida albicans accounted for 52.6% of the total number of pathogenic Candida isolates. Among patients with CCI ≥0.4, the cancers with the highest prevalence were cardiac (45%) and gastric (36%), with ICU mortalities of 20% and 4.9%, respectively. For the diagnosis of candidemia, (1-3)-β-D-glucan (BDG) ≥80 pg/mL showed a sensitivity and specificity of 25% and 82.7%, respectively, positive and negative predictive values 6.7% and 95.7%, and area under the receiver operating characteristic curve 0.512. CCI ≥0.4 was the only significant predictor of IC, and number of organ failures was the only predictor of candidemia (P = .000 and .026). CCI ≥0.4 was the only significant risk factor predicting IC, with greater prediction of intra-abdominal candidiasis but failure to predict candidemia. Blood culture and BDG detection are recommended to supplement diagnosis. Patients may have multifocal and high-grade Candida colonization after cardiac surgery, and; therefore, are at high risk of IC, which should be taken seriously.
Tube feeding associated postoperative intussusceptions

Abstract Rationale: Postoperative intussusception in adults is a rare but serious complication after gastrointestinal anastomosis surgery. Postoperative intussusception in adults caused by tube feeding was rarely been reported before. The aim of the current study was to summarize the clinical data on a group of patients with tube feeding associated postoperative intussusceptions. The possible etiology and preventive measures will also be discussed. Patient concerns: During the period from May 2013 to January 2018, patients who received gastrointestinal anastomosis in our center were retrospectively reviewed. Preoperative variables including standard demographic and pathological characteristics as well as the treatment and prognosis were also analyzed. Diagnoses: Tube feeding associated postoperative intussusceptions. Interventions: 7 patients were identified with tube feeding associated postoperative intussusceptions with a prevalence of 0.38%. Intussusceptions occurred from 10 to 69 days (median 25.7 days) postoperatively in an acute form. Outcomes: None of the patients had spontaneous reduction and all patients underwent surgery. Antegrade efferent limb intussusceptions were found in all the cases. Intussusception occurred at efferent loop at 23.6 cm (range 15–60) from the gastrointestinal or Braun anastomosis. None of the patients was found recurrence throughout the follow-up period. Lessons: In contrast with other postoperative intussusceptions, the tube feeding associated postoperative intussusceptions have special clinical manifestations. It is more likely to occur in early period of time after the surgery and in an acute form. Surgical correction is recommended for most of patients. Several measures have been proposed to prevent such complications after gastrointestinal surgery, however more research and information are still needed.
A systematic review of observational studies

Objectives:Although there is evidence that aspirin might be able to prevent pancreatic cancer, the findings have been inconsistent. In this paper, we conducted a meta-analysis of observational studies to examine the relationship between aspirin use and the risk of pancreatic cancer. Methods:We identified potential studies by searching the MEDLINE, EMBASE, andWangfang (Chinese database) database (from 1967 to March 2017) and by reviewing the bibliography of relevant publications. Random effects model was used to calculate odds ratio (OR) and 95% confidence interval. The Cochran Q statistic (significance level at P< .1) was used to assess heterogeneity in this study. The author adopted weighted regression method of Egger to assessed publication bias. Results: A total of 12 studies involving 4748 pancreatic cancer cases, were included in the meta-analysis. The study reflected that there was no signification association between aspirin use and mortality risk of pancreatic cancer. Aspirin use might reduce the incidence of pancreatic cancer. Specifically, there was a high signification association between frequent aspirin use and reduced pancreatic cancer incidence, without heterogeneity. In addition, there was a high signification association between duration of aspirin use more than 5 years and reduced pancreatic cancer incidence, without obvious heterogeneity among the original studies. Conclusions: In summary, this meta-analysis suggested that the aspirin use might be negatively related to the incidence risk of pancreatic cancer. Specifically, the frequency and duration of aspirin use might play an important role in decreasing the incidence of pancreatic cancer. Abbreviations: CI= confidence interval, NOS=Newcastle-Ottawa scale, NSAIDs= non-steroidal anti-inflammatory drugs, OR= odds ratio, RR = relative risk.
E3 Ubiquitin Ligase Fbw7 Regulates the Survival of Mature B Cells

Key Points Loss of Fbw7 during B cell development reduces mature B1 and B2 cells. Fbw7 controls survival pathway signaling to prevent apoptosis in mature B cells. Ectopic expression of BCL2 partially overcomes apoptosis upon Fbw7 deficiency. Mature naive B cells expressing BCRs of the IgM and IgD isotypes respond to Ag in secondary lymphoid organs. However, the vast majority of B cells do not undergo productive Ag encounter and have finite life spans dependent on survival signals propagated by the BCR and the BAFFR. In this study, we show that the E3 ubiquitin ligase Fbw7 is required for the maintenance of mature B cell populations in mice. BCR stimulation of B cells induced substantial apoptosis along with proliferative and growth defects upon the loss of Fbw7. Analysis of B cell proteomes revealed aberrant signaling patterns, including lower Bcl2 and diminished NF-κB signaling. Further, excessive accumulation of Fbw7 substrate c-Myc, increased Bim expression, and loss of PI3K signaling mediated apoptosis downstream of BCR signaling. In accordance, strong prosurvival signals delivered through ectopic expression of BCL2 in B cells could largely rescue apoptotic cells in the absence of Fbw7. Overall, this study reveals an unexpected role for Fbw7 in the survival and fitness of mature B cells.
THE EFFECT OF CILOSTAZOL ON SERUM LEVEL OF sICAM-1,sVCAM-1 AND MMP-9 IN PATIENTS WITH UNSTABLE ANGINA

Objective To investigate the effect of cilostazol on serum level of sICAM-1,sVCAM-1,and MMP-9 in patients with unstable angina(UA). Methods This study consisted of 142 patients with confirmed unstable angina in four groups:A,aspirin-treatment group;B,cilostazol-and-aspirin-treatment group;C,aspirin-and-clopidogrel-treatment group;and D,aspirin-cilostazol-and-clopidogrel-treatment group.Twenty-eight age-matched healthy individuals were selected as controls.The serum level of sICAM-1,sVCAM-1 and MMP-9 were compared among them.Therapeutic effect was evaluated.Results Before treatment,the serum sICAM-1,sVCAM-1 and MMP-9 in the patients was higher than that in the controls(P0.05). The serum sICAM-1,sVCAM-1,and MMP-9 decreased in each group after one week or one month of treatment and there was a tendency of decreasing with the extend of duration,in which,group D decreased the most,and group A,the least.The occurrence of adverse effect within one year was seen least in group D,and most in group A.The incidence of side effects among the groups was closed to each other.Conclusion Cilostazol is valuable in clinical application.
Cholecystokinin-Expressing Interneurons of the Medial Prefrontal Cortex Mediate Working Memory Retrieval

Distinct components of working memory are coordinated by different classes of inhibitory interneurons in the PFC, but the role of cholecystokinin (CCK)-positive interneurons remains enigmatic. In humans, this major population of interneurons shows histological abnormalities in schizophrenia, an illness in which deficient working memory is a core defining symptom and the best predictor of long-term functional outcome. Distinct components of working memory are coordinated by different classes of inhibitory interneurons in the PFC, but the role of cholecystokinin (CCK)-positive interneurons remains enigmatic. In humans, this major population of interneurons shows histological abnormalities in schizophrenia, an illness in which deficient working memory is a core defining symptom and the best predictor of long-term functional outcome. Yet, CCK interneurons as a molecularly distinct class have proved intractable to examination by typical molecular methods due to widespread expression of CCK in the pyramidal neuron population. Using an intersectional approach in mice of both sexes, we have succeeded in labeling, interrogating, and manipulating CCK interneurons in the mPFC. Here, we describe the anatomical distribution, electrophysiological properties, and postsynaptic connectivity of CCK interneurons, and evaluate their role in cognition. We found that CCK interneurons comprise a larger proportion of the mPFC interneurons compared with parvalbumin interneurons, targeting a wide range of neuronal subtypes with a distinct connectivity pattern. Phase-specific optogenetic inhibition revealed that CCK, but not parvalbumin, interneurons play a critical role in the retrieval of working memory. These findings shine new light on the relationship between cortical CCK interneurons and cognition and offer a new set of tools to investigate interneuron dysfunction and cognitive impairments associated with schizophrenia. SIGNIFICANCE STATEMENT Cholecystokinin-expressing interneurons outnumber other interneuron populations in key brain areas involved in cognition and memory, including the mPFC. However, they have proved intractable to examination as experimental techniques have lacked the necessary selectivity. To the best of our knowledge, the present study is the first to report detailed properties of cortical cholecystokinin interneurons, revealing their anatomical organization, electrophysiological properties, postsynaptic connectivity, and behavioral function in working memory.
PUMA – pooled uranium miners analysis: cohort profile

Objectives Epidemiological studies of underground miners have provided clear evidence that inhalation of radon decay products causes lung cancer. Moreover, these studies have served as a quantitative basis for estimation of radon-associated excess lung cancer risk. However, questions remain regarding the effects of exposure to the low levels of radon decay products typically encountered in contemporary occupational and environmental settings on the risk of lung cancer and other diseases, and on the modifiers of these associations. These issues are of central importance for estimation of risks associated with residential and occupational radon exposures. Methods The Pooled Uranium Miner Analysis (PUMA) assembles information on cohorts of uranium miners in North America and Europe. Data available include individual annual estimates of exposure to radon decay products, demographic and employment history information on each worker and information on vital status, date of death and cause of death. Some, but not all, cohorts also have individual information on cigarette smoking, external gamma radiation exposure and non-radiological occupational exposures. Results The PUMA study represents the largest study of uranium miners conducted to date, encompassing 124 507 miners, 4.51 million person-years at risk and 54 462 deaths, including 7825 deaths due to lung cancer. Planned research topics include analyses of associations between radon exposure and mortality due to lung cancer, cancers other than lung, non-malignant disease, modifiers of these associations and characterisation of overall relative mortality excesses and lifetime risks. Conclusion PUMA provides opportunities to evaluate new research questions and to conduct analyses to assess potential health risks associated with uranium mining that have greater statistical power than can be achieved with any single cohort.
HAVCR2 mutations are associated with severe hemophagocytic syndrome in subcutaneous panniculitis-like T-cell lymphoma.

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L’archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d’enseignement et de recherche français ou étrangers, des laboratoires publics ou privés. HAVCR2 mutations are associated with severe hemophagocytic syndrome in subcutaneous panniculitis-like T-cell lymphoma Gabrielle Sonigo, Maxime Battistella, Marie Beylot-Barry, Saskia Ingen-Housz-Oro, Nathalie Franck, Stéphane Barète, Serge Boulinguez, Olivier Dereure, Nathalie Bonnet, Pauline Brice, et al.
Patterns of healthcare services utilization associated with intimate partner violence (IPV): Effects of IPV screening and receiving information on support services in a cohort of perinatal women

Background While women experiencing intimate partner violence (IPV) face significant health consequences, their patterns of healthcare services (HCS) utilization are unclear, as are the effects of IPV screening and receiving information on these patterns. Objectives 1. Compare utilization patterns of five HCS (visits to family physician, gynecologist, specialist and emergency room, and hospitalization) in a cohort of perinatal women who reported experiencing versus not experiencing any IPV and IPV types (physical and/or sexual; emotional and/or verbal; social and economic); 2. Examine whether IPV screening, receiving information on support services, or both, affect patterns; and 3. Compare these associations between ethnic groups (Arab and Jewish women). Methods We conducted a prospective study using registry data on HCS utilization obtained from Israel’s largest Health Fund (Clalit) in the year following a 2014–2015 survey of a cohort of 868 perinatal women in Israel (327 Arab minority, 542 Jewish) on their reports of experiencing IPV, IPV screening, and receiving information. Using multivariate analysis, we calculated adjusted odds ratios (AOR) and 95% confidence intervals (CI) for the five HCS utilizations in association with reports of any IPV and IPV types. We adjusted for IPV screening, receiving information about services, and both, in the total sample, and separately among ethnic groups. Results Any IPV and IPV types had significant associations with some HCS utilization variables, with different directions and patterns for the ethnic groups. Experiencing IPV was associated with higher HCS utilization among Arab women, lower utilization in Jewish women. Arab women experiencing IPV were twice as likely to visit a gynecologist than women not experiencing IPV (AOR (95% CI) was 2.00, 1.14–3.51 for any IPV; 2.17, 1.23–3.81 for emotional and/or verbal IPV, and 1.83, 1.04–3.22, for social and economic IPV). Among Jewish women, experiencing any IPV was associated with lower likelihood of emergency-room visits (0.62, 0.41–0.93); and experiencing physical and/or sexual IPV was associated with lower likelihood of family physician visits (OR = 0.20, 0.05–0.82). Both IPV screening and receiving information were associated with lower HCS utilization among Arab women only. Conclusions Different HCS utilization patterns among women who reported experiencing versus not experiencing IPV in different ethnic groups suggest complex relationships that hinge on how HCS address women’s needs, starting with IPV screening and providing information. This might inform tailored programs to tackle IPV at the HCS, particularly for minority women.
Voltage Dependence of Prostanoid Receptors

G protein–coupled receptors (GPCRs) are the largest class of transmembrane receptors and serve as signal mediators to transduce information from extracellular signals such as neurotransmitters, hormones, or drugs to cellular responses. They are exposed to the strong electrical field of the plasma membrane. In the last decade voltage modulation of ligand-induced GPCR activity has been reported for several GPCRs. Using Foerster resonance energy transfer–based biosensors in patch clamp experiments, we discovered a robust voltage dependence of the thromboxane receptor (TP receptor) on the receptor level as well as on downstream signaling. TP receptor activity doubled upon depolarization from −90 to +60 mV in the presence of U46619, a stable analog of prostaglandin H2. Half-maximal effective potential (V0.5) determined for TP receptor was −46 mV, which is within the physiologic range. We identified that depolarization affected the agonist affinity for the TP receptor. Depolarization enhanced responses of several structural analogs of U46619 with modifications to a similar extent all around the molecule, indicating that voltage modulates the general conformation of TP receptor. By means of site direct mutagenesis, we identified TP receptor R2957.40, which showed alteration of voltage sensitivity of TP receptor upon mutation. Voltage sensitivity was not limited to TP receptor because prostaglandin F receptor activated with U46619 and prostaglandin E2 receptor subtype 3 activated with iloprost showed a similar reaction to depolarization as TP receptor. However, prostacyclin receptor activated with iloprost showed no detectable voltage dependence. SIGNIFICANCE STATEMENT Prostanoids mediate many of their physiological effects via transmembrane receptors expressed in the plasma membrane of excitable cells. We found that agonist-mediated activation of prostaglandin F receptors and prostaglandin E2 receptors as well as thromboxane receptors are activated upon depolarization, whereas prostacyclin receptors are not. The voltage-induced modulation of thromboxane receptor activity was observed on the level of receptor conformation and downstream signaling. The range of voltage dependence was restricted by R2957.40 in the agonist-binding pocket.