Miracle-dz/UniFAR-FTUs huggingface dataset:
Utilizing Xenogeneic Cells As a Therapeutic Agent for Treating Diseases

The utilization of biologically produced cells to treat diseases is a revolutionary invention in modern medicine after chemically synthesized small molecule drugs and biochemically made protein drugs. Cells are basic units of life with diverse functions in mature and developing organs, which biological properties could be utilized as a promising therapeutic approach for currently intractable and incurable diseases. Xenogeneic cell therapy utilizing animal cells other than human for medicinal purpose has been studied as a new way of treating diseases. Xenogeneic cell therapy is considered as a potential regenerative approach to fulfill current unmet medical needs because xenogeneic cells could be isolated from different animal organs and expanded ex vivo as well as maintain the characteristics of original organs, providing a versatile and plenty cell source for cell-based therapeutics beside autologous and allogeneic sources. The swine species is considered the most suitable source because of the similarity with humans in size and physiology of many organs in addition to the economic and ethical reasons plus the possibility of genetic modification. This review discusses the old proposed uses of xenogeneic cells such as xenogeneic pancreatic islet cells, hepatocytes and neuronal cells as a living drug for the treatment of degenerative and organ failure diseases. Novel applications of xenogeneic mesenchymal stroma cells and urothelial cells are also discussed. There are formidable immunological barriers toward successful cellular xenotransplantation in clinic despite major progress in the development of novel immunosuppression regimens and genetically multimodified donor pigs. However, immunological barriers could be turn into immune boosters by using xenogeneic cells of specific tissue types as a novel immunotherapeutic agent to elicit bystander antitumor immunity due to rejection immune responses. Xenogeneic cells have the potential to become a safe and efficacious option for intractable diseases and hard-to-treat cancers, adding a new class of cellular medicine in our drug armamentarium.
Predictors of Walking App Users With Comparison of Current Users, Previous Users, and Informed Nonusers in a Sample of Dutch Adults: Questionnaire Study

Background The last decade has seen a substantial increase in the use of mobile health apps and research into the effects of those apps on health and health behaviors. In parallel, research has aimed at identifying population subgroups that are more likely to use those health apps. Current evidence is limited by two issues. First, research has focused on broad health apps, and little is known about app usage for a specific health behavior. Second, research has focused on comparing current users and current nonusers, without considering subgroups of nonusers. Objective We aimed to provide profile distributions of current users, previous users, and informed nonusers, and to identify predictor variables relevant for profile classification. Methods Data were available from 1683 people who participated in a Dutch walking event in Amsterdam that was held in September 2017. They provided information on demographics, self-reported walking behavior, and walking app usage, as well as items from User Acceptance of Information Technology, in an online survey. Data were analyzed using discriminant function analysis and multinomial logistic regression analysis. Results Most participants were current walking app users (899/1683, 53.4%), while fewer participants were informed nonusers (663/1683, 39.4%) and very few were previous walking app users (121/1683, 7.2%). Current walking app users were more likely to report walking at least 5 days per week and for at least 30 minutes per bout (odds ratio [OR] 1.44, 95% CI 1.11-1.85; P=.005) and more likely to be overweight (OR 1.72, 95% CI 1.24-2.37; P=.001) or obese (OR 1.49, 95% CI 1.08-2.08; P=.005) as compared with informed nonusers. Further, current walking app users perceived their walking apps to be less boring, easy to use and retrieve information, and more helpful to achieve their goals. Effect sizes ranged from 0.10 (95% CI 0.08-0.30) to 1.58 (95% CI 1.47-1.70). Conclusions The distributions for walking app usage appeared different from the distributions for more general health app usage. Further, the inclusion of two specific subgroups of nonusers (previous users and informed nonusers) provides important information for health practitioners and app developers to stimulate continued walking app usage, including making information in those apps easy to understand and making it easy to obtain information from the apps, as well as preventing apps from becoming boring and difficult to use for goal attainment.
Body in the face of uncertainty: The role of autonomic arousal and interoception in decision-making under risk and ambiguity.

Influential theories posit that bodily responses are important for decision-making under uncertainty. However, the evidence of the role of our ability to perceive subtle bodily changes (interoception) in decision-making under uncertainty is mixed. These differences may arise from the fact that uncertainty, a part of daily decision-making, can be fractionated into risk (known probabilities) and ambiguity (unknown probabilities). Here we examine the role of arousal and interoception in shaping risky and ambiguous decisions. We measured skin conductance responses and heart rate changes while participants (N = 40) made gambling decisions in the context of risky and ambiguous lotteries. Results reveal that the anticipation phase produced the largest arousal responses, suggesting that the anticipation is a major contributor to arousal during gambling behavior, regardless of the uncertainty type. Moreover, physiological responses were higher following positive outcomes than negative outcomes. We did not find any direct relation between interoceptive dimensions and the attitudes toward risk and ambiguity. However, in those with higher interoceptive accuracy, skin conductance responses differentiated between risk and ambiguity as well as between the gamble phases (decision, anticipation, and outcome). Together, our findings demonstrate that decision-making under uncertainty is to some extent associated with individual differences in the ability both to generate and to perceive accurately subtle changes in bodily arousal during the decision-making process. However, these changes seem to be moderately related to the type of uncertainty (risk or ambiguity).
Interaction of tacrolimus through hedgehog signaling pathway: An in vitro evaluation using rat hepatocytes

Tacrolimus (TAC) is the drug of choice in immunosuppressive therapy for organ transplantation; however, adverse effects are still a major concern. The current study aims to decipher the short-term exposure of TAC on rat hepatocytes in relation to activation of hedgehog (HH) signaling pathway. Time dependent study was conducted using primary rat hepatocytes treated with TAC (36 µM) for 6, 12, 24 and 48 h. Western blot analysis was performed using cell lysate in order to analyze the regulation of HH pathway proteins including HHIP, SMO, PTCH, IHH, SHH, and GLI transcription factors. The study revealed change in protein expression of HH signaling molecules with activation of HH pathway, due to downregulation of HHIP, and enrichment of HH ligands with activation of SMO and GLI transcription factors. It is therefore, concluded that short term TAC exposure leads to upregulation of HH pathway in liver, which may initially act to repair the liver damage but can worsen the condition in case of prolonged immunosuppressive therapy. This insight could lead to understand association of off target effects of immunosuppressive drugs and occurrence of other liver diseases in transplant patients when it comes to long term immunosuppressive therapy. These findings also illuminate a novel direction that use of HH inhibitor might provide a therapeutic strategy for immune suppression related liver disorders.
InterEvDock3: a combined template-based and free docking server with increased performance through explicit modeling of complex homologs and integration of covariation-based contact maps

Abstract The InterEvDock3 protein docking server exploits the constraints of evolution by multiple means to generate structural models of protein assemblies. The server takes as input either several sequences or 3D structures of proteins known to interact. It returns a set of 10 consensus candidate complexes, together with interface predictions to guide further experimental validation interactively. Three key novelties were implemented in InterEvDock3 to help obtain more reliable models: users can (i) generate template-based structural models of assemblies using close and remote homologs of known 3D structure, detected through an automated search protocol, (ii) select the assembly models most consistent with contact maps from external methods that implement covariation-based contact prediction with or without deep learning and (iii) exploit a novel coevolution-based scoring scheme at atomic level, which leads to significantly higher free docking success rates. The performance of the server was validated on two large free docking benchmark databases, containing respectively 230 unbound targets (Weng dataset) and 812 models of unbound targets (PPI4DOCK dataset). Its effectiveness has also been proven on a number of challenging examples. The InterEvDock3 web interface is available at http://bioserv.rpbs. univ-paris-diderot.fr/services/InterEvDock3/.
Reciprocal control of translation and transcription in autism spectrum disorder

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and the presence of restricted patterns of interest and repetitive behaviors. ASD is genetically heterogeneous and is believed to be caused by both inheritable and de novo gene variations. Studies have revealed an extremely complex genetic landscape of ASD, favoring the idea that mutations in different clusters of genes interfere with interconnected downstream signaling pathways and circuitry, resulting in aberrant behavior. In this review, we describe a select group of candidate genes that represent both syndromic and non‐syndromic forms of ASD and encode proteins that are important in transcriptional and translational regulation. We focus on the interplay between dysregulated translation and transcription in ASD with the hypothesis that dysregulation of each synthetic process triggers a feedback loop to act on the other, which ultimately exacerbates ASD pathophysiology. Finally, we summarize findings from interdisciplinary studies that pave the way for the investigation of the cooperative impact of different genes and pathways underlying the development of ASD.
Clinical outcomes, management, and treatment patterns in patients with metastatic castration‐resistant prostate cancer treated with radium‐223 in community compared to academic settings

The most common site of disease in metastatic castration‐resistant prostate cancer (mCRPC) is the bone. The ALSYMPCA study demonstrated that radium‐223 significantly improved overall survival (OS) in mCRPC patients with symptomatic bone metastases and without visceral metastases. However, administration requires a multidisciplinary approach and an infrastructure that supports coordination of care, which may differ by practice site. We aimed to evaluate practice patterns and treatment outcomes in patients with mCRPC treated at a community practice (CP) compared with those treated at an academic center (AC).
Condom use and vulnerabilities to sexually transmitted infections in quilombola communities: a descriptive study, Sergipe, Brazil, 2016-2017*

Objective: To analyze frequency of condom use according to vulnerability factors for sexually transmitted infections in quilombola communities in Sergipe state, Brazil. Methods: This was a descriptive cross-sectional study carried out in 2016-2017. A structured questionnaire with sociodemographic and behavioral questions was used; rapid HIV and syphilis tests were performed. Comparisons between categorical variables were performed using Fisher’s exact test. Results: Among the 367 individuals from 14 communities, the majority had low levels of education (72.8%), were not working (59.7%) and had a stable sex partner (90.7%). Lack of access to prevention supplies and information accounted for respondent programmatic vulnerability. There was a higher proportion of inconsistent condom use with a stable partner (90.1%) among individuals who reported lack of access to information (p=0.001) and inconsistent use with a casual partner (p<0.001). Conclusion: Frequency of condom use with a stable partner was significantly proportional to condom use with a casual partner and access to information on prevention.
HBD1 protein with a tandem repeat of two HMG-box domains is a DNA clip to organize chloroplast nucleoids in Chlamydomonas reinhardtii

Significance Compaction of bulky DNA is a universal issue for all DNA-based life forms. Both chloroplasts and mitochondria maintain their own multicopy genomes organized as nucleoids, but the mechanism of DNA compaction remains obscure. Here, we discovered a chloroplast nucleoid protein (HBD1) that is highly similar to major mitochondrial nucleoid proteins transcription factor A, mitochondrial (TFAM), and ARS binding factor 2 protein (Abf2p) in terms of possessing two DNA-binding high mobility group box (HMG-box) domains. Our analyses of HBD1 based on DNA origami/atomic force microscopy showed that HBD1 is capable of compacting DNA by introducing U-turns and cross-strand bridges with the two HMG-box domains, indicating that proteins with two HMG-box domains could compact DNA in both mitochondrial and chloroplast nucleoids. Compaction of bulky DNA is a universal issue for all DNA-based life forms. Chloroplast nucleoids (chloroplast DNA–protein complexes) are critical for chloroplast DNA maintenance and transcription, thereby supporting photosynthesis, but their detailed structure remains enigmatic. Our proteomic analysis of chloroplast nucleoids of the green alga Chlamydomonas reinhardtii identified a protein (HBD1) with a tandem repeat of two DNA-binding high mobility group box (HMG-box) domains, which is structurally similar to major mitochondrial nucleoid proteins transcription factor A, mitochondrial (TFAM), and ARS binding factor 2 protein (Abf2p). Disruption of the HBD1 gene by CRISPR-Cas9–mediated genome editing resulted in the scattering of chloroplast nucleoids. This phenotype was complemented when intact HBD1 was reintroduced, whereas a truncated HBD1 with a single HMG-box domain failed to complement the phenotype. Furthermore, ectopic expression of HBD1 in the mitochondria of yeast Δabf2 mutant successfully complemented the defects, suggesting functional similarity between HBD1 and Abf2p. Furthermore, in vitro assays of HBD1, including the electrophoretic mobility shift assay and DNA origami/atomic force microscopy, showed that HBD1 is capable of introducing U-turns and cross-strand bridges, indicating that proteins with two HMG-box domains would function as DNA clips to compact DNA in both chloroplast and mitochondrial nucleoids.
Impact of heart failure drug therapy on rates of gastrointestinal bleeding in LVAD recipients: An INTERMACS analysis

Introduction: Gastrointestinal bleeding (GIB) remains a common and vexing complication of left ventricular assist device (LVAD) support. Recent single-center analyses suggest that ACE inhibitors (ACEi)/angiotensin receptor blockers (ARB) and digoxin may prevent GIB in LVAD patients. Here we evaluate the effect of guideline-directed medical therapies (GDMT) for heart failure (HF) on rates of GIB through analysis of the INTERMACS registry database. Methods: Thirteen thousand seven hundred thirty-two patients who received a continuous-flow LVAD and were on antiplatelet therapy and anticoagulation with warfarin after 3 months of pump support were included in the analysis. GIB events following implant were assessed based on receipt of ACEi/ARB, beta-blockers (BB), mineralocorticoid receptor antagonist (MRA), amiodarone, digoxin, loop diuretics, and phosphiesterase-5 inhibitors (PDE5). Backwards stepwise cox regression was used to control for confounding of each drug class on each other, as well as for clinical variables like age, gender, renal function, HF etiology, and device strategy. Results: After 3 months of pump support medications used in LVAD patients were BB (65.0%), ACEi/ARB (51.7%), Amio (43.7%), MRA (37.9%), and loop diuretics (70.1%). In patients with available data, PDE and digoxin use were 18.2% and 16.9%, respectively. The overall incidence of GIB was 19.5% at 2 years of support. After adjustment for other clinical variables, loop diuretics (HR 1.274, p < 0.001) and PDE5 (HR 1.241, p < 0.001) use were associated with increased risk of GIB, while use of BB (HR 0.871, p = 0.006) was associated with lower risk of GIB. ACEi/ARB (HR 1.002, p = 0.971), Amio (HR 1.083, p = 0.106), AA (HR 0.967, p = 0.522) or digoxin (HR 1.087, p = 0.169) did not affect GIB rates on LVAD support (Figure). Conclusion: Despite recent reports, ACEi/ARB, MRA, Amio, and digoxin use does not appear to be associated with GIB during LVAD support. The heightened risk seen in those on loop diuretics may reflect venous congestion in these patients, while antiplatelet effects of PDE5 could drive the higher risk of GIB.
Vestibular Function in Older Adults With Cognitive Impairment: A Systematic Review

Supplemental Digital Content is available in the text. Importance: Given the rising prevalence of patients with dementia and those at risk for it, early identification is prioritized. As vestibular dysfunction is associated with Alzheimer’s disease (AD) and may contribute to its onset, vestibular assessment may yield an opportunity in early dementia screening. Objective: This systematic review structures and compares the different raw outcome measures used to assess vestibular function while comparing older adults with preserved cognition to individuals with cognitive impairment, either suffering from mild cognitive impairment (MCI) or AD. Design: Two investigators independently and systematically searched publications performing objectively measured vestibular testing in a patient population consisting of either MCI or AD, compared with a control group of older adults with preserved cognition. No limitations regarding language or publication date were applied. References of the retrieved articles were hand searched for relevant articles. Results: Seven articles were included for analysis. A total of 235 older adults with impaired cognition (150 AD, 85 MCI) were compared with a control group of 481 older adults with preserved cognition. Evaluation of the peripheral vestibular function included video head impulse test (vHIT), videonystagmography (VNG), electronystagmography (ENG) including bithermal caloric irrigation and vestibular evoked myogenic potentials (VEMP). The VEMP test, assessing otolith function and the elicited vestibulocollic reflex (VCR), was able to differentiate subjects with AD and its prodromal stage from healthy controls, with p13 latency (p < 0.05) and amplitude (p < 0.05) having the most discriminating power. No correlation between cognitive decline and vestibulo-ocular reflex measurements in different frequency ranges of the semicircular canals (using vHIT, rotatory chair testing, and caloric irrigation) was found. Because of the limited number of available studies and the large heterogeneity in outcome measures, these results have to be interpreted with caution. Conclusions: Measurements of the VCR, as evoked by the VEMP test, discriminate between patients with cognitive impairment (MCI and AD) and older adults with preserved cognition, whereas measurements of the vestibulo-ocular reflex do not. More studies are needed to further elaborate on these findings.
The mediating role of partner communication on contraceptive use among adolescent girls and young women participating in a small-group intervention in Malawi: A longitudinal analysis

ABSTRACT Though effective reproductive health interventions have been developed for adolescent girls and young women (AGYW) in sub-Saharan Africa, few have explored whether specific components of the interventions are responsible for observed changes in behaviour. Data for this longitudinal mediation analysis come from a quasi-experimental, sexual and reproductive health study conducted among AGYW (age 15–24) in Malawi. We assessed the extent to which the relationship between attending communication-specific small-group sessions and contraceptive use at one-year was mediated by contraceptive communication with partners at six months, using a bootstrapping procedure to estimate indirect effects. Of 358 participants, 44% attended communication-specific small-group sessions, 37% communicated with partners about contraception at six months, and 21% used non-barrier contraception at one-year. Participants who attended communication-specific small-group sessions had increased contraceptive communication with partners at six months (aOR = 1.48, 95% CI: 1.07–2.38) and increased non-barrier contraceptive use at one-year (aOR = 3.53, 95% CI: 1.86–6.69). The relationship between attending communication-specific small-group sessions and non-barrier contraceptive use at one-year was partially mediated by contraceptive communication with partners at six months (indirect effect = 0.04, 95% CI: 0.01–0.07). Our results suggest that contraceptive communication with partners is modifiable through interventions and important for AGYW non-barrier contraceptive uptake.
Vasopressor Discontinuation Order in Septic Shock With Reduced Left Ventricular Function

Background: The optimal vasopressor management for septic patients with left ventricular (LV) dysfunction has not been well established, and current evidence is conflicting regarding the optimal vasopressor discontinuation order. Objective: The objective was to evaluate the impact of LV dysfunction on the hemodynamic management of septic shock by assessing the incidence of clinically significant hypotension after vasopressor discontinuation. Methods: In this single-center, retrospective cohort study, adult patients were included if they met the Sepsis-3 definition of septic shock, had LV dysfunction (defined as an ejection fraction ≤40%), and received norepinephrine and vasopressin as the last vasopressors discontinued. The primary outcome was the incidence of clinically significant hypotension following discontinuation of vasopressin or norepinephrine. Clinically significant hypotension was defined as a MAP less than 60 mmHg and the need for either: 1) the reinstitution of the previously discontinued agent at any dosage, 2) the receipt of at least 500 mL of a crystalloid at a rate of at least 500 mL/hour, 3) or the receipt of at least 25 grams of albumin 5% at a rate of at least 25 gram/hour. Secondary outcomes included intensive care unit (ICU) and hospital lengths of stay, and ICU and hospital mortality. Results: A total of 78 patients met inclusion criteria, with 37 patients having vasopressin discontinued first and 41 having norepinephrine discontinued first. Clinically significant hypotension occurred in 28 patients (76%) following the discontinuation of vasopressin, compared to 28 patients (81%) following the discontinuation of norepinephrine (p = 0.61). ICU length of stay was 9 days in the vasopressin discontinued first cohort, compared to 15 days in the norepinephrine discontinued first cohort (p = 0.01). There was no statistically significant difference in mortality observed. Conclusion: The discontinuation order of norepinephrine and vasopressin did not impact the incidence of clinically significant hypotension in patients with septic shock and LV dysfunction, but may influence ICU length of stay, although other factors may have impacted this finding.