Miracle-dz/UniFAR-FTUs huggingface dataset:
Elevated Adenosine Deaminase Levels in the Cerebrospinal Fluid in Immune Checkpoint Inhibitor-induced Autoimmune Encephalitis

Immune checkpoint inhibitors (ICIs) are promising drugs for various cancers. However, immune activation by ICIs can lead to immune-related adverse events (irAEs). Autoimmune encephalitis is a rare irAE, and its clinical features remain unknown. We herein report two patients with ICI-associated autoimmune encephalitis who, saliently, showed elevated adenosine deaminase (ADA) levels in the cerebrospinal fluid (CSF). This is the first report of increased ADA levels in the CSF of patients with ICI-induced autoimmune encephalitis. Although the mechanism of the ADA increase is poorly understood, elevated ADA in the CSF may be informative in the diagnosis of this rare disorder.
Persons with Dementia Living at Home or in Nursing Homes in Nine Swedish Urban or Rural Municipalities

The methodology from the “RightTimePlaceCare” study of dementia care was tested locally in terms of relevance, acceptability and attrition. Comparing persons with dementia (PwDs) receiving home care (HC) with PwDs living in nursing homes (NHs), in urban versus rural areas, regarding their health conditions and informal caregiver burden was also done. Standardized measurements regarding sociodemographic, and physical and mental health was used. Questions related to legal guardianship were added. Interviews were conducted with PwDs and their caregivers in HC (n = 88) and in NHs (n = 58). Bivariate and multivariate logistic regression analysis was used. The attrition rate was higher in HC. In the bivariate regression model, for HC and NH, living at home was significantly associated with more severe neuropsychiatric symptoms (p ≤ 0.001) and being cared by a spouse (p = 0.008). In NH, the informal caregivers were significantly younger (p = 0.003) and living in rural areas (p = 0.007) and more often in paid work (p ≤ 0.001). In the multivariate regression model, informal caregivers were significantly younger (p = 0.007) when caring for a PwD in an NH and caregiver burden was significantly higher in HC and in urban areas (p = 0.043). Legal guardianship was very low. Professionals should acknowledge that PwDs in HC have more behavioural problems and caregivers in urban areas report higher caregiver burden.
Can trophectoderm RNA analysis predict human blastocyst competency?

ABSTRACT A systematic review of the literature showed that trophectoderm biopsy could assist in the selection of healthy embryos for uterine transfer without affecting implantation rates. However, previous studies attempting to establish the relationship between trophectoderm gene expression profiles and implantation competency using either microarrays or RNA sequencing strategies, were not sufficiently optimized to handle the exceptionally low RNA inputs available from biopsied material. In this pilot study, we report that differential gene expression in human trophectoderm biopsies assayed by an ultra-sensitive next generation RNA sequencing strategy could predict blastocyst implantation competence. RNA expression profiles from isolated human trophectoderm cells were analysed with established clinical pregnancy being the primary endpoint. Following RNA sequencing, a total of 47 transcripts were found to be significantly differentially expressed between the trophectoderm cells from successfully implanted (competent) versus unsuccessful (incompetent) blastocysts. Of these, 36 transcripts were significantly down-regulated in the incompetent blastocysts, including Hydroxysteroid 17-Beta Dehydrogenase 1 (HSD17B1) and Cytochrome P450 Family 11 Subfamily A Member 1 (CYP11A1), while the remaining 11 transcripts were significantly up-regulated, including BCL2 Antagonist/Killer 1 (BAK1) and KH Domain Containing 1 Pseudogene 1 (KHDC1P1) of which the latter was always detected in the incompetent and absent in all competent blastocysts. Ontological analysis of differentially expressed RNAs revealed pathways involved in steroidogenic processes with high confidence. Novel differentially expressed transcripts were also noted by reference to a de novo sequence assembly. The selection of the blastocyst with the best potential to support full-term pregnancy following single embryo transfer could reduce the need for multiple treatment cycles and embryo transfers. The main limitation was the low sample size (N = 8). Despite this shortcoming, the pilot suggests that trophectoderm biopsy could assist with the selection of healthy embryos for embryo transfer. A larger cohort of samples is needed to confirm these findings. Abbreviations: AMA: advanced maternal age; ART: assisted reproductive technology; CP: clinical pregnancy; DE: differential expression; FDR: false discovery rate; IVF: in vitro fertilization; LD PCR: long distance PCR; qRT-PCR: quantitative real-time PCR; SET: single embryo transfer; TE: trophectoderm
A NAV2729-sensitive mechanism promotes adrenergic smooth muscle contraction and growth of stromal cells in the human prostate

Voiding symptoms in benign prostatic hyperplasia (BPH) are driven by prostate smooth muscle contraction and prostate growth. Smooth muscle contraction in the prostate and other organs critically depends on activation of the small monomeric GTPase RhoA and probably Rac1. A role of another GTPase, ADP-ribosylation factor 6 (ARF6), for smooth muscle contraction has been recently suggested by indirect evidence but remains to be proven for any organ. Here, we report effects of NAV2729, an inhibitor with assumed specificity for ARF6, in human prostate tissues and cultured prostate stromal cells (WPMY-1). NAV2729 (5 μm) inhibited neurogenic and α1-adrenergic contractions of human prostate tissues. Contractions induced by endothelin-1, by the thromboxane A2 agonist U46619, or by high molar KCl were not inhibited. Correlation analyses suggested up-regulation of prostatic ARF6 expression with increasing degree of BPH, as ARF6 expression increased with the content of prostate-specific antigen (PSA) of prostate tissues. NAV2729 inhibited ARF6 activity but not other GTPases (ARF1, RhoA, Rac1) in prostate tissues and in WPMY-1 cells. Proliferation of WPMY-1 cells was inhibited concentration-dependently by NAV2726, as reflected by decreased viability, 5-ethynyl-2′-deoxyuridine (EdU) assay, colony formation assay, and expression of Ki-67. Silencing of ARF6 expression mimicked effects of NAV2729 on viability and in the EdU assay. Effects of NAV2729 on viability and proliferation were attenuated in cells with silenced ARF6 expression. Our findings suggest that a NAV2729-sensitive mechanism promotes adrenergic contraction and stromal cell growth in the human prostate, which is probably ARF6-mediated. Similar actions in other organs and urodynamic effects of NAV2729 appear possible.
Population data provide evidence against the presence of a set point for hemoglobin levels or tissue oxygen delivery

Hemoglobin levels are believed to be regulated as per a set point model of regulation. This model of regulation, by which specific levels of a parameter are targeted and defended by physiological systems, implies a particular population correlation between the parameter and its controlling hormone. Empirical population correlations of other parameters and their controlling hormones, have denied the presence of such set point‐based regulation. To assess if hemoglobin is regulated according to a set point model we performed a systematic search of PubMed/MEDLINE and Web of Science identifying relevant reports published up to November 2018. Population hemoglobin/erythropoietin level correlations were retrieved, and these empirically derived correlations were compared with the positive correlation implied by a set point model of regulation. Authors of papers containing potentially suitable data were contacted with requests for further analyses, and a meta‐analysis was performed. Twelve correlations between hemoglobin and erythropoietin levels from eleven papers were analyzed. None of these correlations were significantly positive, three, restricted to the normal range of hemoglobin, were significantly negative. All but one of the other correlations showed a negative trend. New analyses of previously published data sets resulted in similar findings. In particular a new analysis of large data sets of males (n = 2417) and females (n = 2592) with normal range hemoglobin levels, revealed significantly negative correlations. A meta‐analysis of our results indicated that the data overall are not consistent with a positive relationship between hemoglobin and erythropoietin (P < 0.0001). Population data indicate that individuals do not have set point levels of hemoglobin.
Predictors of Shoot–Don’t Shoot Decision-Making Performance

Soldiers are required to perform basic combat tasks, such as move, shoot, and communicate, and to make decisions under many environmental stressors, including continuous operations and information-processing tasks driven by C4ISR (Command, Control, Communications, Computers, Intelligence, Surveillance, and Reconnaissance) and other types of information systems. Knowledge requires information processing, and increased processing is usually the root cause of increased error. Friend-or-foe decision-making research has primarily focused on the types of equipment being used and task difficulty levels to examine shoot–don’t shoot errors; however, newer theoretical approaches may enhance cognitive performance research and models focused on decision-making performance. Higher explanatory power and better prediction models may be created using multitheoretical individual factors derived from transactional-stress and information-processing theories. The purpose of this study was to examine multitheoretical individual factor effects of emotional and cognitive predictor variables under dual-task simulated shoot–don’t shoot target scenarios. A quantitative repeated-measures approach was used with a convenience sample of 12 U.S. Army soldiers ages 18 to 34 years.
Liver steatosis is a major predictor of poor outcomes in chronic hepatitis C patients with sustained virological response

Sustained virological response (SVR) results in reduced incidence of hepatocellular carcinoma (HCC) and mortality among chronic hepatitis C (CHC) patients with advanced fibrosis. Since both advanced fibrosis and liver steatosis (LS) may coexist in CHC patients, we evaluated their individual effects on a composite outcome of all‐cause mortality and HCC in CHC patients with SVR following direct‐acting antivirals (DAA) treatment. We retrospectively evaluated inception cohort of 515 CHC patients who achieved SVR following treatment with DAA, with a mean follow‐up of 24 months. Baseline liver fibrosis was assessed by transient elastography, and LS was validated by at least three independent ultrasonographic examinations. 211 of 515 patients (41%) had baseline LS. Patients with LS had a higher cumulative rate of all‐cause mortality and HCC at 2 years of follow‐up compared to patients without LS (15.75% and 2.79%, respectively, P < 0.001), although they did not have increased incidence of advanced fibrosis or cirrhosis. Consistently, multivariate analysis showed that LS was associated with a significant 7.5‐fold increased risk of all‐cause mortality and HCC (HR 7.51, 95% C.I 3.61‐13.36, P < 0.001) even upon adjustment to components of the metabolic syndrome, whereas advanced fibrosis showed only a trend towards statistical significance (HR 2.32, 95% C.I 0.97‐6.59, P = 0.06). In conclusion, LS is a major predictor of all‐cause mortality and HCC in patients who achieved SVR following DAA treatment regardless of fibrosis stage. These patients should be rigorously screened for HCC.
Social identification with animals: Unpacking our psychological connection with other animals.

Our relations with other animals are ubiquitous in human life, yet the psychological structure of our connection with animals is just beginning to receive empirical attention. Drawing on theories of social identification and intergroup relations, we investigate the various ways that people identify with animals. Across 7 studies, we introduce the Identification with Animals Measure (IWAM) and uncover 3 dimensions by which humans identify with animals as a group: solidarity with animals, animal pride, and human-animal similarity. First, we establish the reliability, factorial structure, and predictive validity of the 3-factor IWAM. Next, we find that these factors predict a distinct set of attitudes and behaviors toward animals. Solidarity with animals is defined by feeling connected to other animals and is associated with more contact with animals (i.e., pets) and a greater desire to help animals and to engage in collective actions on their behalf, even if this implies withdrawing privileges to humans. Human-animal similarity is defined by the perception that animals share similarities with humans; this dimension is associated with increased moral concern for their welfare and a greater attribution of typically human traits to other animals. Finally, animal pride is defined by a direct recognition and positive endorsement of the social category that includes all animals, and is associated with viewing humans as more animal-like, and with more competitive and instrumental intergroup relations. The findings confirm that identification with animals is a multidimensional construct that is colored by the unique and complex nature of our relations with nonhuman animals. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Optimization of Timing and Times for Administration of Atorvastatin‐Pretreated Mesenchymal Stem Cells in a Preclinical Model of Acute Myocardial Infarction

Our previous studies showed that the combination of atorvastatin (ATV) and single injection of ATV‐pretreated mesenchymal stem cells (MSCs) (ATV‐MSCs) at 1 week post‐acute myocardial infarction (AMI) promoted MSC recruitment and survival. This study aimed to investigate whether the combinatorial therapy of intensive ATV with multiple injections of ATV‐MSCs has greater efficacy at different stages to better define the optimal strategy for MSC therapy in AMI. In order to determine the optimal time window for MSC treatment, we first assessed stromal cell‐derived factor‐1 (SDF‐1) dynamic expression and inflammation. Next, we compared MSC recruitment and differentiation, cardiac function, infarct size, and angiogenesis among animal groups with single, dual, and triple injections of ATV‐MSCs at early (Early1, Early2, Early3), mid‐term (Mid1, Mid2, Mid3), and late (Late1, Late2, Late3) stages. Compared with AMI control, intensive ATV significantly augmented SDF‐1 expression 1.5∼2.6‐fold in peri‐infarcted region with inhibited inflammation. ATV‐MSCs implantation with ATV administration further enhanced MSC recruitment rate by 3.9%∼24.0%, improved left ventricular ejection fraction (LVEF) by 2.0%∼16.2%, and reduced infarct size in all groups 6 weeks post‐AMI with most prominent improvement in mid groups and still effective in late groups. Mechanistically, ATV‐MSCs remarkably suppressed inflammation and apoptosis while increasing angiogenesis. Furthermore, triple injections of ATV‐MSCs were much more effective than single administration during early and mid‐term stages of AMI with the best effects in Mid3 group. We conclude that the optimal strategy is multiple injections of ATV‐MSCs combined with intensive ATV administration at mid‐term stage of AMI. The translational potential of this strategy is clinically promising. Stem Cells Translational Medicine 2019;8:1068–1083
Betel Chewing: A New Analysis, In Vitro and In Vivo, of the Risk Factors in Oral Cancer.

BACKGROUND Chewing Betel (areca-nut) can cause oral cancer. This happens when its components are in direct contact with the oral epithelium. The aim of this study is to understand this mechanism by analyzing salivary mucins, in vitro, during and after betel chewing. METHODS The in vivo analysis would necessarily involve subtraction of betel to understand its effects. This study analyzed the interaction between mucins and betel in vitro. We added increasing amounts of areca powder, and for comparison an equal amount of pure vine tannin to saliva samples provided by a first volunteer. This study analyzes salivary mucins in two volunteers, one of whom is a regular betel consumer, after chewing the areca-nut, on six saliva samples taken at half-hour intervals. RESULTS In vitro, total precipitation of the salivary mucins occurs after we added 1g of Areca nut (50 mg Tannin equivalent), a concentration five times lower than what is actually present during the chewing period; in vivo, in the first volunteer, there is a statistically significant increase in the mucins after chewing two and half hours: p-value = 0.02034, while for the regular betel consumer there is a significant decrease: p-value = 0.00512. DISCUSSION In vitro, we conclude that the polyphenol content in betel causes total precipitation of mucins and causes poor defense of the oral epithelium. The increase of mucins in the non-routine consumers, show a transient (up to two hours after the end of chewing) inflammatory process. Inflammation can cause keratinization of the oral epithelium because the saliva increases its viscosity for the higher amount of mucins, with its lower adherence and protection of the oral cavity. Subsequent and regular consumption of betel nut, as in the regular betel consumer, can cause chronic fibrosis in the oral epithelium and cut the salivary mucins.
Dendritic cell-associated MAVS is required to control West Nile virus replication and ensuing humoral immune responses

Mitochondrial antiviral signaling protein (MAVS) is a critical innate immune signaling protein that directs the actions of the RIG-I-like receptor (RLR) signaling pathway of RNA virus recognition and initiation of anti-viral immunity against West Nile virus (WNV). In the absence of MAVS, mice die more rapidly after infection with the pathogenic WNV-Texas (TX) strain, but also produce elevated WNV-specific IgG concomitant with increased viral burden. Here we investigated whether there was a B cell intrinsic role for MAVS during the development of protective humoral immunity following WNV infection. MAVS-/- mice survived infection from the non-pathogenic WNV-Madagascar (MAD) strain, with limited signs of disease. Compared to wildtype (WT) controls, WNV-MAD-infected MAVS-/- mice had elevated serum neutralizing antibodies, splenic germinal center B cells, plasma cells and effector T cells. We found that when rechallenged with the normally lethal WNV-TX, MAVS-/- mice previously infected with WNV-MAD were protected from disease. Thus, protective humoral and cellular immune responses can be generated in absence of MAVS. Mice with a conditional deletion of MAVS only in CD11c+ dendritic cells phenocopied MAVS whole body knockout mice in their humoral responses to WNV-MAD, displaying elevated virus titers and neutralizing antibodies. Conversely, a B cell-specific deletion of MAVS had no effect on immune responses to WNV-MAD compared to WT controls. Thus, MAVS in dendritic cells is required to control WNV replication and thereby regulate downstream humoral immune responses.
Phylogenetic and immunoinformatic analysis of VP4, VP7, and NSP4 genes of rotavirus strains circulating in children with acute gastroenteritis in Indonesia

Rotavirus is a major cause of diarrhea in Indonesian children. However, rotavirus vaccines have not been introduced in the national immunization program of Indonesia. Understanding the genetic diversity and conserved antigenic regions of circulating strains are therefore essential to assess the potential efficacy of rotavirus vaccines. We collected fecal samples from hospitalized children less than 5 years of age with acute diarrhea. Rotavirus genotyping was performed by reverse transcriptase polymerase chain reaction, followed by sequencing of the VP4, VP7, and NSP4 genes of representative strains. Phylogenetic analysis was performed to investigate their relationship with globally circulating strains. Conservational analysis, immunoinformatics, and epitope mapping in comparison to vaccine strains were also performed. The sequence analyses showed that differences of multiple amino acid residues existed between the VP4, VP7, and NSP4 antigenic regions of the vaccine strains and the Indonesian isolates. However, many predicted conserved epitopes with higher antigenicity were observed in the vaccine and Indonesian strains, conferring the importance of these epitopes. The identified epitopes showed a higher potential of rotavirus vaccine to be employed in Indonesia. It could also be helpful to inform the design of a peptide vaccine based on the conserved regions and epitopes in the viral proteins.
Characterization of host defense molecules in the human pancreas

ABSTRACT The gut microbiota can play a role in pancreatitis and, likely, in the development of type 1 diabetes (T1D). Anti-microbial peptides and secretory proteins are important mediators of the innate immune response against bacteria but their expression in the human pancreas is not fully known. In this study, immunohistochemistry was used to analyze the expression of seven anti-microbial peptides (Defensin α1, α4, β1-4 and Cathelicidin) and two secretory proteins with known antimicrobial properties (REG3A and GP2) in pancreatic and duodenal biopsies from 10 non-diabetic organ donors and one organ donor that died at onset of T1D. Immunohistochemical data was compared with previously published whole-transcriptome data sets. Seven (Defensin α1, β2, β3, α4, GP2, Cathelicidin, and REG3A) host defense molecules showed positive staining patterns in most non-diabetic organ donors, whereas two (Defensin β1 and β4) were negative in all non-diabetic donors. Two molecules (Defensin α1 and GP2) were restricted to the exocrine pancreas whereas two (Defensin β3, α4) were only expressed in islet tissue. Cathelicidin, β2, and REG3A were expressed in both islets and exocrine tissue. The donor that died at onset of T1D had generally less positivity for the host defense molecules, but, notably, this pancreas was the only one where defensin β1 was found. Neither donor age, immune-cell infiltration, nor duodenal expression correlated to the pancreatic expression of host defense molecules. In conclusion, these findings could have important implications for the inflammatory processes in diabetes and pancreatitis as we find several host defense molecules expressed by the pancreatic tissue.