Miracle-dz/UniFAR-FTUs huggingface dataset:
Emotion Regulation and Depressive Symptoms Mediate the Association Between Schizotypal Personality Traits and Suicidality in Chinese College Students

Abstract Objective The psychological mechanisms underlying the relationship between schizotypal personality traits and suicidality are not understood. This study investigated the association of schizotypal personality traits with suicidality and explored the mediating role of cognitive appraisal and depression in the relationship between those two variables in a sample of Chinese college students. Method Participants (N = 2457) completed the Schizotypal Personality Questionnaire, the Emotional Regulation Questionnaire, the Zung Self-rating Depression Scale, and three questions related to suicidality. Results The cognitive reappraisal score was lower in the students with suicidality than the students without suicidality, whereas scores for depression and schizotypal personality traits were higher in the students with suicidality than the students without suicidality. Schizotypal personality traits and depression were risk factors for suicidality. Depression mediated the association between schizotypal personality traits and suicidality. Cognitive reappraisal negatively affected symptoms of depression and had a significant mediating effect on the association between schizotypal personality traits and suicidality. Conclusions Schizotypal personality traits and depression are risk factors for suicidality. Cognitive reappraisal and depression mediate the association between schizotypal personality traits and suicidality.
In older patients with NSTE-ACS, clopidogrel safely reduced bleeding compared with ticagrelor at 1 year

SOURCE CITATION Gimbel M, Qaderdan K, Willemsen L, et al. Clopidogrel versus ticagrelor or prasugrel in patients aged 70 years or older with non-ST-elevation acute coronary syndrome (POPular AGE): the randomised, open-label, non-inferiority trial. Lancet. 2020;395:1374-81. 32334703.
COVID-19 Shines a Spotlight on the Age-Old Problem of Social Isolation

In the midst of COVID-19, the nation has become increasingly aware of the impact of social isolation on physical, social, spiritual, and psychological health. Older adults, especially those who are nearing the end of life, are already at higher risk of the detrimental effects of social isolation and loneliness. Novel social distancing rules imposed by governments and agencies during the COVID-19 pandemic have caused older adults to experience a degree of social isolation and loneliness that is unprecedented. This article highlights aspects of the social isolation and loneliness literature. Three cases of elderly patients who required medical care during the COVID-19 pandemic are presented. Common themes of factors contributing to social isolation in each of the health care delivery settings are described, and opportunities for creative interventions by health care providers are identified. As the pandemic continues to unfold and evolve, providers should aim to regularly assess patient risk of isolation and be proactive in preventing negative effects. Additionally, what is learned from health care providers' experiences delivering palliative care during a pandemic can be incorporated into daily practice as social isolation and loneliness are long-standing challenges for the elderly population.
Intra‐puparial development in the hoverflies Eristalinus aeneus and Eristalis tenax (Diptera: Syrphidae)

The intra‐puparial development of 150 pupae of Eristalinus aeneus (Scopoli, 1763) and Eristalis tenax (Linnaeus, 1758) was analyzed. Individuals were obtained from the sixth laboratory generation kept under artificial rearing conditions at the facilities of the University of Alicante (Spain). The experiment was conducted at 25 ± 1°C temperature, 50 ± 5% relative humidity, and 12:12 hr (L:D) of photoperiod. Groups of 10 pupae were collected every 6 hr over 48 hr, after that period, pupae were collected daily until the adult emergence. They were fixed in 5% formic acid and preserved in 70% ethanol. Fixed pupae were dissected and photographed. The chronology and morphological changes that take place during the intra‐puparial development in both species were analyzed and compared. Five phases were observed: prepupa, before 6 hr; cryptocephalic pupa, between 6 and 24 hr; phanerocephalic pupa, between 24 and 30 hr; pharate adult, after 30 hr; and the adult imago, restricted to the very end of the development process just before adult emergence. In total, the intra‐puparial development lasted 189 ± 4 hr in E. aeneus and 192 ± 3 hr in E. tenax, with the pharate adult the longest phase (some 81% of the total developmental time). These data can be used to develop accurate cold storage protocols during artificial rearing of both pollinator species, avoiding critical events during the development and increasing survival.
Obesity and diabetes as comorbidities for COVID-19: Underlying mechanisms and the role of viral–bacterial interactions

Obesity and diabetes are established comorbidities for COVID-19. Adipose tissue demonstrates high expression of ACE2 which SARS- CoV-2 exploits to enter host cells. This makes adipose tissue a reservoir for SARS-CoV-2 viruses and thus increases the integral viral load. Acute viral infection results in ACE2 downregulation. This relative deficiency can lead to disturbances in other systems controlled by ACE2, including the renin-angiotensin system. This will be further increased in the case of pre-conditions with already compromised functioning of these systems, such as in patients with obesity and diabetes. Here, we propose that interactions of virally-induced ACE2 deficiency with obesity and/or diabetes leads to a synergistic further impairment of endothelial and gut barrier function. The appearance of bacteria and/or their products in the lungs of obese and diabetic patients promotes interactions between viral and bacterial pathogens, resulting in a more severe lung injury in COVID-19.
Loss of TMEM106B potentiates lysosomal and FTLD‐like pathology in progranulin‐deficient mice

Single nucleotide polymorphisms (SNPs) in TMEM106B encoding the lysosomal type II transmembrane protein 106B increase the risk for frontotemporal lobar degeneration (FTLD) of GRN (progranulin gene) mutation carriers. Currently, it is unclear if progranulin (PGRN) and TMEM106B are synergistically linked and if a gain or a loss of function of TMEM106B is responsible for the increased disease risk of patients with GRN haploinsufficiency. We therefore compare behavioral abnormalities, gene expression patterns, lysosomal activity, and TDP‐43 pathology in single and double knockout animals. Grn−/−/Tmem106b−/− mice show a strongly reduced life span and massive motor deficits. Gene expression analysis reveals an upregulation of molecular signature characteristic for disease‐associated microglia and autophagy. Dysregulation of maturation of lysosomal proteins as well as an accumulation of ubiquitinated proteins and widespread p62 deposition suggest that proteostasis is impaired. Moreover, while single Grn−/− knockouts only occasionally show TDP‐43 pathology, the double knockout mice exhibit deposition of phosphorylated TDP‐43. Thus, a loss of function of TMEM106B may enhance the risk for GRN‐associated FTLD by reduced protein turnover in the lysosomal/autophagic system.
Comparison of dengue case classification schemes and evaluation of biological changes in different dengue clinical patterns in a longitudinal follow-up of hospitalized children in Cambodia

Background The World Health Organization (WHO) proposed guidelines on dengue clinical classification in 1997 and more recently in 2009 for the clinical management of patients. The WHO 1997 classification defines three categories of dengue infection according to severity: dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS). Alternative WHO 2009 guidelines provide a cross-sectional classification aiming to discriminate dengue fever from dengue with warning signs (DWWS) and severe dengue (SD). The primary objective of this study was to perform a comparison of two dengue classifications. The secondary objective was to describe the changes of hematological and biochemical parameters occurring in patients presenting with different degrees of severity during the course of the disease, since progression to more severe clinical forms is unpredictable. Methodology/Principal findings We performed a prospective, monocentric, cross-sectional study of hospitalized children in Cambodia, aged from 2 to 15 years old with severe and non-severe dengue. We enrolled 243 patients with acute dengue-like illness: 71.2% were dengue infections confirmed using quantitative reverse transcription PCR or NS1 antigen capture ELISA, of which 87.2% and 9.0% of DF cases were respectively classified DWWS and SD, and 35.9% of DHF were designated SD using an adapted WHO 2009 classification for SD case definition. Systematic use of ultrasound at patient admission was crucial for detecting plasma leakage. No difference was observed in the concentration of secreted NS1 protein between different dengue severity groups. Lipid profiles were different between DWWS and SD at admission, characterized by a decrease in total cholesterol, HDL cholesterol, and LDL cholesterol, in SD. Conclusions/Significance Our results show discrepancies between the two classifications, including misclassification of severe dengue cases as mild cases by the WHO 1997 classification. Using an adapted WHO 2009 classification, SD more precisely defines the group of patients requiring careful clinical care at a given time during hospitalization.
Sulforaphane Reverses the Amyloid-β Oligomers Induced Depressive-Like Behavior.

BACKGROUND Depression is one of the most common behavioral and psychological symptoms in people with Alzheimer's disease (AD). To date, however, the molecular mechanisms underlying the clinical association between depression and AD remained elusive. OBJECTIVE Here, we study the relationship between memory impairment and depressive-like behavior in AD animal model, and investigate the potential mechanisms. METHODS Male SD rats were administered amyloid-β oligomers (AβOs) by intracerebroventricular injection, and then the depressive-like behavior, neuroinflammation, oxidative stress, and the serotonergic system were measured in the brain. Sulforaphane (SF), a compound with dual capacities of anti-inflammation and anti-oxidative stress, was injected intraperitoneally to evaluate the therapeutic effect. RESULTS The results showed that AβOs induced both memory impairment and depressive-like behavior in rats, through the mechanisms of inducing neuroinflammation and oxidative stress, and impairing the serotonergic axis. SF could reduce both inflammatory factors and oxidative stress parameters to protect the serotonergic system and alleviate memory impairment and depressive-like behavior in rats. CONCLUSION These results provided insights into the biological mechanisms underlying the clinical link between depressive disorder and AD, and offered new drug options for the treatment of depressive symptoms in dementia.
News Frames and News Exposure Predicting Flu Vaccination Uptake: Evidence from U.S. Newspapers, 2011–2018 Using Computational Methods

ABSTRACT Flu remains a prevalent public health issue and the flu vaccine uptake remains low. This study examined the behavioral consequences of first- and second-level agenda setting by testing the effects of exposure to flu-related news coverage and different frames on flu vaccine uptake, while controlling for confounding sociodemographic factors, utilizing computational methods. Findings suggested that the media effects on children and adult influenza vaccine uptake differed. The frame of influenza caused deaths/illnesses stories was the only media frame that positively predicted flu vaccine uptake among children. Four frames, including influenza caused deaths/illnesses stories, flu prevention tips, things to know about flu vaccine, and public accountability positively predicted flu vaccine uptake among adults. Exposure rate negatively predicted flu vaccine uptake among adults. A few sociodemographic factors impacted flu vaccine uptake. Results also revealed the most and least exposed frames and state exposure rates to flu-related news stories.
Identification of genes and pathways associated with subchondral bone in osteoarthritis via bioinformatic analysis

Abstract Osteoarthritis (OA) is a high prevalent musculoskeletal problem, which can cause severe pain, constitute a huge social and economic burden, and seriously damage the quality of life. This study was intended to identify genetic characteristics of subchondral bone in patients with OA and to elucidate the potential molecular mechanisms involved. Data of gene expression profiles (GSE51588), which contained 40 OA samples and 10 normal samples, was obtained from the Gene Expression Omnibus (GEO). The raw data were integrated to obtain differentially expressed genes (DEGs) and were further analyzed with bioinformatic analysis. The protein–protein interaction (PPI) networks were built and analyzed via Search Tool for the Retrieval of Interacting Genes (STRING). The significant modules and hub genes were identified via Cytoscape. Moreover, Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analysis were performed. Totally 235 DEGs were differentially expressed in the subchondral bone from OA patients compared with those of normal individuals, of which 78 were upregulated and 157 were downregulated. Eight hub genes were identified, including DEFA4, ARG1, LTF, RETN, PGLYRP1, OLFM4, ORM1, and BPI. The enrichment analyses of the DEGs and significant modules indicated that DEGs were mainly involved in inflammatory response, extracellular space, RAGE receptor binding, and amoebiasis pathway. The present study provides a novel and in-depth understanding of pathogenesis of the OA subchondral bone at molecular level. DEFA4, ARG1, LTF, RETN, PGLYRP1, OLFM4, ORM1, and BPI may be the new candidate targets for diagnosis and therapies on patients with OA in the future.
The relation between prepregnancy maternal body mass index and total gestational weight gain with the characteristics of the newborns

Abstract Aims To evaluate the relationship between the maternal body mass index (BMI) and total gestational weight gain (GWG) with the characteristics of newborns, taking into consideration the birth weight (BW), weight for age score (WfA), length for age (LfA), and weight for length (WfL), APGAR score, and premature delivery. Methods We conducted a study, from March 2015 to 2016. We included a number of 1218 pregnant women who delivered single babies, from three different hospitals that serve the entire Mures County and who met our inclusion criteria. Results We did not find significant differences regarding weight, length at birth, and gestational age, between girls and boys, neither between total GWG during pregnancy and the measured anthropometric parameters of the newborns, or between maternal GWG and gestational age of the newborns. We found a positive correlation between the mothers’ BMI and the BW of the newborns (p =.03, r = 0.06, 95% CI = 0.0036–0.1169), but not between BMI and the birth length and nor with APGAR score. The statistical analysis showed a positive correlation between BMI and LfA (p = .01, r = 0.07, 95%CI = 0.0141–0.1269), but not with WfA and WfL. Women with higher BMI before getting pregnant showed significantly higher frequency of preterm delivery (p = .0078). We found a statistically significant correlation between GWG and BW (p<.0001). Excessive GWG correlates statistically significant with BW (p < .0001). Conclusions We found a positive correlation between the mothers’ BMI and excessive GWG and the BW of their newborns in women delivering a single baby. Women with higher BMI showed significantly higher frequency of preterm delivery.
The interplay between α7 nicotinic acetylcholine receptors, pannexin‐1 channels and P2X7 receptors elicit exocytosis in chromaffin cells

Pannexin‐1 (Panx1) forms plasma membrane channels that allow the exchange of small molecules between the intracellular and extracellular compartments, and are involved in diverse physiological and pathological responses in the nervous system. However, the signaling mechanisms that induce their opening still remain elusive. Here, we propose a new mechanism for Panx1 channel activation through a functional crosstalk with the highly Ca2+ permeable α7 nicotinic acetylcholine receptor (nAChR). Consistent with this hypothesis, we found that activation of α7 nAChRs induces Panx1‐mediated dye uptake and ATP release in the neuroblastoma cell line SH‐SY5Y‐α7. Using membrane permeant Ca2+ chelators, total internal reflection fluorescence microscopy in SH‐SY5Y‐α7 cells expressing a membrane‐tethered GCAMP3, and Src kinase inhibitors, we further demonstrated that Panx1 channel opening depends on Ca2+ signals localized in submembrane areas, as well as on Src kinases. In turn, Panx1 channels amplify cytosolic Ca2+ signals induced by the activation of α7 nAChRs, by a mechanism that seems to involve ATP release and P2X7 receptor activation, as hydrolysis of extracellular ATP with apyrase or blockage of P2X7 receptors with oxidized ATP significantly reduces the α7 nAChR‐Ca2+ signal. The physiological relevance of this crosstalk was also demonstrated in neuroendocrine chromaffin cells, wherein Panx1 channels and P2X7 receptors contribute to the exocytotic release of catecholamines triggered by α7 nAChRs, as measured by amperometry. Together these findings point to a functional coupling between α7 nAChRs, Panx1 channels and P2X7 receptors with physiological relevance in neurosecretion.
A Novel Recessive Mutation in SPEG Causes Early Onset Dilated Cardiomyopathy

Dilated cardiomyopathy (DCM) is a common cause of heart failure and sudden cardiac death. It has been estimated that up to half of DCM cases are hereditary. Mutations in more than 50 genes, primarily autosomal dominant, have been reported. Although rare, recessive mutations are thought to contribute considerably to DCM, especially in young children. Here we identified a novel recessive mutation in the striated muscle enriched protein kinase (SPEG, p. E1680K) gene in a family with nonsyndromic, early onset DCM. To ascertain the pathogenicity of this mutation, we generated SPEG E1680K homozygous mutant human induced pluripotent stem cell derived cardiomyocytes (iPSC-CMs) using CRISPR/Cas9-mediated genome editing. Functional studies in mutant iPSC-CMs showed aberrant calcium homeostasis, impaired contractility, and sarcomeric disorganization, recapitulating the hallmarks of DCM. By combining genetic analysis with human iPSCs, genome editing, and functional assays, we identified SPEG E1680K as a novel mutation associated with early onset DCM and provide evidence for its pathogenicity in vitro. Our study provides a conceptual paradigm for establishing genotype-phenotype associations in DCM with autosomal recessive inheritance.
Comparative Analysis of Infection by Rickettsia rickettsii Sheila Smith and Taiaçu Strains in a Murine Model

Rocky Mountain spotted fever (RMSF) is a life-threatening tick-borne disease caused by Rickettsia rickettsii, which is widely distributed throughout the Americas. Over 4000 cases of RMSF are recorded annually in the United States, while only around 100 cases are reported in Brazil. Conversely, while case fatality rates in the United States oscillate around 5%, in Brazil they can surpass 70%, suggesting that differences in tick vectoring capacity, population sensitivity, and/or variability in virulence of the rickettsial strains may exist. In this study, we compared the susceptibility of C3H/HeN mice to two highly virulent strains of R. rickettsii, one from the United States (Sheila Smith) and the other from Brazil (Taiaçu). Animals inoculated with the Taiaçu strain succumbed to infection earlier and exhibited severe histological lesions in both liver and spleen sooner than mice infected with the Sheila Smith strain. These differences in survival and signs of the disease are not related to a greater proliferation of the Taiaçu strain, as there were no significant differences in the rickettsial load in mice tissues inoculated with either strain. The present study is the first step to experimentally assess differences in fatality rates of RMSF in two different regions of the American continent.
Wide range of G6PD activities found among ethnic groups of the Chittagong Hill Tracts, Bangladesh

The proportion of Plasmodium vivax malaria among all malarias is increasing worldwide. Treatment with 8-aminoquinolines remain the only radical cure. However, 8-aminoquinolines can cause severe hemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficient patients. The population of the multi-ethnic Chittagong Hill Tracts (CHT) carry the highest malaria burden within Bangladesh. As in many countries the national treatment guidelines recommend 8-aminoquinoline based radical cure without routine G6PD deficiency (G6PDd) testing to guide treatment. Aim of this study was to determine the need for routine testing within a multi-ethnic population by assessing the prevalence of G6PDd among the local population. Participants from 11 ethnicities were randomly selected and malaria status was assessed by microscopy, rapid diagnostic test (RDT) and polymerase chain reaction (PCR). G6PD status was determined by spectrophotometry and G6PD genotyping. The adjusted male median (AMM) was defined as 100% G6PD activity, participants were categorized as G6PD deficient (<30% activity), G6PD intermediate (30% to 70% activity) or G6PD normal (>70% activity). Median G6PD activities between ethnicities were compared and the association between G6PD activity and malaria status was assessed. 1002 participants were enrolled and tested for malaria. G6PD activity was measured by spectrophotometry in 999 participants and host G6PD genotyping undertaken in 323 participants. Seven participants (0.7%) had peripheral parasitaemia detected by microscopy or RDT and 42 by PCR (4.2%). Among 106 participants (32.8%) with confirmed genotype, 99 (93.4%) had the Mahidol variant. The AMM was 7.03U/gHb with 90 (9.0%) G6PD deficient participants and 133 (13.3%) with intermediate G6PD activity. Median G6PD activity differed significantly between ethnicities (p<0.001), proportions of G6PD deficient individuals ranged from 2% to 26% but did not differ between participants with and without malaria. The high G6PDd prevalence and significant variation between ethnicities suggest routine G6PDd testing to guide 8-aminoquinoline based radical in the CHT and comparable settings.
Gating and regulation of KCNH (ERG, EAG, and ELK) channels by intracellular domains

ABSTRACT The KCNH family comprises the ERG, EAG, and ELK voltage-activated, potassium-selective channels. Distinct from other K channels, KCNH channels contain unique structural domains, including a PAS (Per-Arnt-Sim) domain in the N-terminal region and a CNBHD (cyclic nucleotide-binding homology domain) in the C-terminal region. The intracellular PAS domains and CNBHDs interact directly and regulate some of the characteristic gating properties of each type of KCNH channel. The PAS-CNBHD interaction regulates slow closing (deactivation) of hERG channels, the kinetics of activation and pre-pulse dependent population of closed states (the Cole-Moore shift) in EAG channels and voltage-dependent potentiation in ELK channels. KCNH channels are all regulated by an intrinsic ligand motif in the C-terminal region which binds to the CNBHD. Here, we focus on some recent advances regarding the PAS-CNBHD interaction and the intrinsic ligand.