Miracle-dz/UniFAR-FTUs huggingface dataset:
Frailty in older-age European migrants: Cross-sectional and longitudinal analyses of the Survey of Health, Aging and Retirement in Europe (SHARE).

Frailty correlates with morbidity and is superior to chronological age in predicting mortality. Frailty of older migrants has important implications for the demands placed on healthcare systems. Examining 95,635 Europeans in the Survey of Health, Aging and Retirement in Europe, we investigated cross-sectional and long- itudinal associations between migration and frailty at ages>50 years. We examined whether associations di ﬀ ered by countries' level of healthcare coverage and access for migrants and tested mediation by home- ownership and citizenship. Cross-sectionally, ﬁ rst-generation migrants>50 years old were, on average, 16.4% (95% con ﬁ dence interval [CI]: 14.6, 18.2%) frailer than non-migrants after confounder-adjustment. This de- creased to 12.1% (95% CI: 10.1, 14.1%) after adjustment for citizenship. The strength of association between migrant status and frailty was greater in migrants from low-or-middle-income countries, compared with mi- grants from high-income countries. Migrants into Northern, Western and Eastern Europe were 37.3% (95% CI: 33.2, 41.5%), 12.2% (95% CI: 10.0, 14.6%) and 5.0% (95% CI: 0.5, 9.6%) frailer than non-migrants, respec- tively, but migrants into Southern Europe were no frailer than non-migrants. The strength of association between migrant status and frailty was greater in countries with lower healthcare coverage and access for migrants. However, citizenship attenuated this di ﬀ erence. Longitudinally, migrants were frailer than non-migrants at 50 years old and trajectories converged over time until migrants and non-migrants were equally frail by 80 – 90 years. Our work ﬁ nds no evidence of the ‘ healthy migrant e ﬀ ect ’ outside of Southern Europe in older migrants and suggests that acculturation is a key determinant of migrant health.
Distinct metabolic states govern skeletal muscle stem cell fates during prenatal and postnatal myogenesis

ABSTRACT During growth, homeostasis and regeneration, stem cells are exposed to different energy demands. Here, we characterise the metabolic pathways that mediate the commitment and differentiation of mouse skeletal muscle stem cells, and how their modulation can influence the cell state. We show that quiescent satellite stem cells have low energetic demands and perturbed oxidative phosphorylation during ageing, which is also the case for cells from post-mortem tissues. We show also that myogenic fetal cells have distinct metabolic requirements compared to those proliferating during regeneration, with the former displaying a low respiration demand relying mostly on glycolysis. Furthermore, we show distinct requirements for peroxisomal and mitochondrial fatty acid oxidation (FAO) in myogenic cells. Compromising peroxisomal but not mitochondrial FAO promotes early differentiation of myogenic cells. Acute muscle injury and pharmacological block of peroxisomal and mitochondrial FAO expose differential requirements for these organelles during muscle regeneration. Taken together, these observations indicate that changes in myogenic cell state lead to significant alterations in metabolic requirements. In addition, perturbing specific metabolic pathways impacts on myogenic cell fates and the regeneration process. Summary: Distinct energy metabolism pathways act during mouse skeletal muscle stem cell commitment and differentiation in different physiological states.
Akt3 deletion in mice impairs spatial cognition and hippocampal CA1 long long‐term potentiation through downregulation of mTOR

Loss‐of‐function mutation of Akt3 in humans has been associated with microcephaly and cognitive defects. Two Akt isoforms, Akt1 and Akt3, are highly expressed in hippocampal pyramidal cells. We explored the roles of Akt1 and Akt3, respectively, in spatial cognition and underlying mechanisms.
Parietal Representations of Stimulus Features Are Amplified during Memory Retrieval and Flexibly Aligned with Top-Down Goals

In studies of human episodic memory, the phenomenon of reactivation has traditionally been observed in regions of occipitotemporal cortex (OTC) involved in visual perception. However, reactivation also occurs in lateral parietal cortex (LPC), and recent evidence suggests that stimulus-specific reactivation may be stronger in LPC than in OTC. These observations raise important questions about the nature of memory representations in LPC and their relationship to representations in OTC. Here, we report two fMRI experiments that quantified stimulus feature information (color and object category) within LPC and OTC, separately during perception and memory retrieval, in male and female human subjects. Across both experiments, we observed a clear dissociation between OTC and LPC: while feature information in OTC was relatively stronger during perception than memory, feature information in LPC was relatively stronger during memory than perception. Thus, while OTC and LPC represented common stimulus features in our experiments, they preferentially represented this information during different stages. In LPC, this bias toward mnemonic information co-occurred with stimulus-level reinstatement during memory retrieval. In Experiment 2, we considered whether mnemonic feature information in LPC was flexibly and dynamically shaped by top-down retrieval goals. Indeed, we found that dorsal LPC preferentially represented retrieved feature information that addressed the current goal. In contrast, ventral LPC represented retrieved features independent of the current goal. Collectively, these findings provide insight into the nature and significance of mnemonic representations in LPC and constitute an important bridge between putative mnemonic and control functions of parietal cortex. SIGNIFICANCE STATEMENT When humans remember an event from the past, patterns of sensory activity that were present during the initial event are thought to be reactivated. Here, we investigated the role of lateral parietal cortex (LPC), a high-level region of association cortex, in representing prior visual experiences. We find that LPC contained stronger information about stimulus features during memory retrieval than during perception. We also found that current task goals influenced the strength of stimulus feature information in LPC during memory. These findings suggest that, in addition to early sensory areas, high-level areas of cortex, such as LPC, represent visual information during memory retrieval, and that these areas may play a special role in flexibly aligning memories with current goals.
Computer-aided diagnosis of lung nodule classification between benign nodule, primary lung cancer, and metastatic lung cancer at different image size using deep convolutional neural network with transfer learning

We developed a computer-aided diagnosis (CADx) method for classification between benign nodule, primary lung cancer, and metastatic lung cancer and evaluated the following: (i) the usefulness of the deep convolutional neural network (DCNN) for CADx of the ternary classification, compared with a conventional method (hand-crafted imaging feature plus machine learning), (ii) the effectiveness of transfer learning, and (iii) the effect of image size as the DCNN input. Among 1240 patients of previously-built database, computed tomography images and clinical information of 1236 patients were included. For the conventional method, CADx was performed by using rotation-invariant uniform-pattern local binary pattern on three orthogonal planes with a support vector machine. For the DCNN method, CADx was evaluated using the VGG-16 convolutional neural network with and without transfer learning, and hyperparameter optimization of the DCNN method was performed by random search. The best averaged validation accuracies of CADx were 55.9%, 68.0%, and 62.4% for the conventional method, the DCNN method with transfer learning, and the DCNN method without transfer learning, respectively. For image size of 56, 112, and 224, the best averaged validation accuracy for the DCNN with transfer learning were 60.7%, 64.7%, and 68.0%, respectively. DCNN was better than the conventional method for CADx, and the accuracy of DCNN improved when using transfer learning. Also, we found that larger image sizes as inputs to DCNN improved the accuracy of lung nodule classification.
The effects of contemporary selection and dispersal limitation on the community assembly of acidophilic microalgae

Extremophilic microalgae are primary producers in acidic habitats, such as volcanic sites and acid mine drainages, and play a central role in biogeochemical cycles. Yet, basic knowledge about their species composition and community assembly is lacking. Here, we begin to fill this knowledge gap by performing the first large‐scale survey of microalgal diversity in acidic geothermal sites across the West Pacific Island Chain. We collected 72 environmental samples in 12 geothermal sites, measured temperature and pH, and performed rbcL amplicon‐based 454 pyrosequencing. Using these data, we estimated the diversity of microalgal species, and then examined the relative contribution of contemporary selection (i.e., local environmental variables) and dispersal limitation on the assembly of these communities. A species delimitation analysis uncovered seven major microalgae (four red, two green, and one diatom) and higher species diversity than previously appreciated. A distance‐based redundancy analysis with variation partitioning revealed that dispersal limitation has a greater influence on the community assembly of microalgae than contemporary selection. Consistent with this finding, community similarity among the sampled sites decayed more quickly over geographical distance than differences in environmental factors. Our work paves the way for future studies to understand the ecology and biogeography of microalgae in extreme habitats.
A regulatory circuitry comprising TP53, miR-29 family, and SETDB1 in non-small cell lung cancer

Lung cancer is a malignant tumor with high fatality rate and causes great harm to human economic life. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. With the rapid development of epigenetic study in the last decade, the understanding of the pathogenesis of lung cancer and the development of personalized treatment of lung cancer are picking up pace. Previous studies showed that miR-29 family members (miR-29s; miR-29a, -29b, and -29c) are down-regulated in most human cancers, including NSCLC, but their biological roles in tumorigenesis and their regulation mechanism are still not fully elucidated. Herein, we reported that the miR-29a, -29b and, -29c were coincidently down-regulated in NSCLC, and the histone H3K9 methyltransferase SET domain, bifurcated 1 (SETDB1) was directly targetted by miR-29s. Moreover, SETDB1 negatively regulated the expression of TP53 and overexpression of SETDB1 down-regulating the expression of miR-29s, while TP53 positively regulated the expression of miR-29s and overexpression of TP53 down-regulated the expression of SETDB1. On the other side, as a downstream target of TP53, the H3K9 methyltransferase Suv39h1 was also down-regulated by miR-29s via up-regulating TP53 expression. The further detection of H3K9 methylation status after changes in miR-29s expression revealed that they negatively regulated the levels of H3K9 di- and trimethylation in NSCLC. Collectively, our findings highlight a TP53/miR-29s/SETDB1 regulatory circuitry and assign a role of H3K9 methylation regulator to miR-29s, which may be a potential therapeutic target in the treatment of NSCLC.
Increase of Perfusion Index During Vascular Occlusion Test is Paradoxically Associated With Higher Mortality in Septic Shock After Fluid Resuscitation: A Prospective Study

ABSTRACT Microcirculation disturbances imply poor prognosis in septic shock. Microvascular reserve can be assessed by oximetry-derived Perfusion Index (PI) after vascular occlusion test (VOT). We investigated the relationship between PI during VOT, hyperlactatemia and mortality in septic shock and the role of adrenergic stimulus in these findings. The tests were performed in 106 patients within 24 h after admission. PI was evaluated before/after 03-min flow occlusion. Peaks of PI (&Dgr;PI peak) and time-to-peak were evaluated. PI was also evaluated in hyperemic phases derived by mechanosensitive (&Dgr;PI0–60) and metabolic mechanisms (&Dgr;PI60–120). We compared nonsurvivors with survivors and patients with lowest and highest &Dgr;PI peaks, divided by 50th percentile. &Dgr;PI peak was evaluated in presence/absence of hyperlactatemia. A correlation test between &Dgr;PI peaks and noradrenaline doses and an assessment after doses increasing were also performed. The &Dgr;PI peak values were higher in nonsurvivors [79% (47%–169%) vs. 48% (25%–85%); P=0.003] although peaks were reached slower in nonsurvivors. &Dgr;PI0–60 was similar between groups [−12% (−42% to 28%) vs. 01% (−16%–23%); P = 0.211]. However, &Dgr;PI60–120 was higher in nonsurvivors [49% (29%–84%) vs. 31% (12%–65%); P = 0.035]. Additionally, the group with higher &Dgr;PI peaks had higher mortality than those with lower peaks [HR 2.25 (95% CI = 1.32–4.14); P = 0.003]. Mortality was extremely high in the presence of hyperlactatemia. &Dgr;PI peaks were positively correlated with noradrenaline doses and increased after increasing doses. In conclusion, high values of PI during VOT indicate higher mortality in septic shock and are associated with adrenergic stimulus. Additionally, the assessment of PI-VOT appears to improve the predictive value of arterial lactate.
Oxidative Stress and Necrotizing Enterocolitis: Pathogenetic Mechanisms, Opportunities for Intervention, and Role of Human Milk

This review will examine the role of oxidative stress (OS) in the pathogenesis of necrotizing enterocolitis (NEC) and explore potential preventive and therapeutic antioxidant strategies. Preterm infants are particularly exposed to OS as a result of several perinatal stimuli and constitutive defective antioxidant defenses. For this reason, OS damage represents a contributing factor to several complications of prematurity, including necrotizing enterocolitis (NEC). Being NEC a multifactorial disease, OS may act as downstream component of the pathogenetic cascade. To counteract OS in preterm infants with NEC, several antioxidant strategies have been proposed and different antioxidant compounds have been experimented. It is well known that human milk (HM) is an important source of antioxidants. At the same time, the role of an exclusive HM diet is well recognized in the prevention of NEC. However, donor HM (DHM) processing may impair antioxidant properties. As DHM is becoming a common nutritional intervention for high risk PI, the antioxidant status of preterm and DHM and potential ways to preserve its antioxidant capacity may merit further investigation.
Stem Cells in Dentistry: Types of Intra- and Extraoral Tissue-Derived Stem Cells and Clinical Applications

Stem cells are undifferentiated cells, capable of renewing themselves, with the capacity to produce different cell types to regenerate missing tissues and treat diseases. Oral facial tissues have been identified as a source and therapeutic target for stem cells with clinical interest in dentistry. This narrative review report targets on the several extraoral- and intraoral-derived stem cells that can be applied in dentistry. In addition, stem cell origins are suggested in what concerns their ability to differentiate as well as their particular distinguishing quality of convenience and immunomodulatory for regenerative dentistry. The development of bioengineered teeth to replace the patient's missing teeth was also possible because of stem cell technologies. This review will also focus our attention on the clinical application of stem cells in dentistry. In recent years, a variety of articles reported the advantages of stem cell-based procedures in regenerative treatments. The regeneration of lost oral tissue is the target of stem cell research. Owing to the fact that bone imperfections that ensue after tooth loss can result in further bone loss which limit the success of dental implants and prosthodontic therapies, the rehabilitation of alveolar ridge height is prosthodontists' principal interest. The development of bioengineered teeth to replace the patient's missing teeth was also possible because of stem cell technologies. In addition, a “dental stem cell banking” is available for regenerative treatments in the future. The main features of stem cells in the future of dentistry should be understood by clinicians.
Comparison of the Long-Term Outcomes of Endoscopic Papillary Large Balloon Dilation Alone versus Endoscopic Sphincterotomy for Removal of Bile Duct Stones

Background and Aims Endoscopic papillary large balloon dilation (EPLBD) alone is an alternative to endoscopic sphincterotomy (EST) for treatment of common bile duct (CBD) stones. However, limited data exists regarding comparison of the long-term outcomes for these techniques. In this study, we compared the long-term outcomes after EST with those after EPLBD alone for removal of CBD stones. Methods The records of patients with EST or EPLBD alone referred for CBD stones retrieval between June 2008 and July 2015 were retrospectively reviewed. Complete stone clearance, ERCP-related adverse events, and late biliary complications during long-term follow-up were analyzed. Results Basic patient characteristics were similar between the groups that underwent EST (n = 60) and EPLBD alone (n = 161). EPLBD compared with EST resulted in similar outcomes in terms of complete stone clearance (99.4% versus 100%, P = 0.54) and ERCP-related adverse events (6.8% versus 6.7%, P = 1.00). The mean duration of the follow-up was 74.5 months and 71.6 months who underwent EST and EPLBD alone, respectively (P = 0.42). Late biliary complications were occurred frequently in the EST group than in the EPLBD alone group (11 [18.6%] versus 16 [10.2%]), although the difference did not reach statistical significance (P = 0.11). Multivariate analysis showed that mechanical lithotripsy ([OR], 2.815; 95% CI, 1.148–6.902; P = 0.024) was significantly associated with late biliary complications. Conclusion As an alternative to EST, EPLBD has similar efficacy and safety for managing CBD stones. During long-term follow-up, patients who underwent EPLBD alone may have fewer late biliary complications compared with those after EST. In addition, mechanical lithotripsy may be an independent risk factor for late biliary complications.
Steatohepatitis Is Not Associated with an Increased Risk for Fibrosis Progression in Nonalcoholic Fatty Liver Disease

Introduction Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease globally. The majority of NAFLD patients have fatty liver without inflammation (nonalcoholic fatty liver, NAFL), whereas a minority develop steatohepatitis (nonalcoholic steatohepatitis, NASH). Only NASH and not NAFL has been considered to increase the risk for fibrosis progression. The present study investigates risk factors for fibrosis progression in patients with NAFLD, and if fibrosis progression associates with subsequent mortality. Material and Methods All patients with at least two liver biopsies more than a year apart at our hospital between 1971 and 2016 were identified. Data on plausible risk factors for fibrosis progression were collected. Biopsies were scored for the presence of NASH and fibrosis stage. Regression models were used to investigate the association between baseline NASH and fibrosis progression and fibrosis progression with future mortality. Results 60 patients had undergone serial biopsies (median interval between biopsies 8.4 years, range 1–33 years), with 26 patients (43%) having fibrosis progression. We found no significant risk factors for progression of fibrosis except time between biopsies. Among patients with fibrosis progression, 54% had NAFL and 46% had NASH at baseline. There was a trend for an association between fibrosis progression per se and increased mortality (hazard ratio 2.83, 95% CI 1.0–8.1, p = 0.05). Conclusions In this study on NAFLD, baseline steatohepatitis was not associated with an increased risk for fibrosis progression. NAFLD patients without steatohepatitis may develop progressive fibrosis, and those with progressive fibrosis appear to have a higher mortality risk irrespective of baseline NASH status.
CTLA4Ig Improves Murine iTreg Induction via TGFβ and Suppressor Function In Vitro

Blockade of the CD28:CD80/86 costimulatory pathway has been shown to be potent in blocking T cell activation in vitro and in vivo. The costimulation blocker CTLA4Ig has been approved for the treatment of autoimmune diseases and transplant rejection. The therapeutic application of regulatory T cells (Tregs) has recently gained much attention for its potential of improving allograft survival. However, neither costimulation blockade with CTLA4Ig nor Treg therapy induces robust tolerance on its own. Combining CTLA4Ig with Treg therapy would be an attractive approach for minimizing immunosuppression or for possibly achieving tolerance. However, since the CD28 pathway is more complex than initially thought, the question arose whether blocking CD80/86 would inadvertently impact immunological tolerance by interfering with Treg generation and function. We therefore wanted to investigate the compatibility of CTLA4Ig with regulatory T cells by evaluating direct effects of CTLA4Ig on murine Treg generation and function in vitro. For generation of polyclonal-induced Tregs, we utilized an APC-free in vitro system and added titrated doses of CTLA4Ig at different time points. Phenotypical characterization by flow cytometry and functional characterization in suppressor assays did not reveal negative effects by CTLA4Ig. The costimulation blocker CTLA4Ig does not impair but rather improves murine iTreg generation and suppressor function in vitro.
Relationship of Serum Uric Acid Level with Demographic Features, Risk Factors, Severity, Prognosis, Serum Levels of Vitamin D, Calcium, and Magnesium in Stroke

Introduction Stroke is one of the most common neurological disorders with high mortality rates. A large financial burden is imposed on the families and health systems of countries in addition to the problems related to the disabilities caused by the disease for the patients. Extensive research is being conducted on the disease, including studies seeking possible relationships between some biomarkers such as uric acid and stroke. Methods This descriptive-analytic cross-sectional study was conducted on 170 stroke patients at Babol Ayatollah Rohani Hospital during 2015-2016. Serum uric acid (SUA) levels were measured and recorded at admission time. Patients' demographic data as well as the stroke type and some of their risk factors were entered in a checklist. The data were analyzed by SPSS.v. 23 using chi-square and logistic regression tests. P < 0.05 was considered as significant in all analyses. Results Of the total 170 included patients, 57% had normal, 25% had low, and the remaining patients (18%) had high SUA levels. There was no significant difference in SUA levels in different types of stroke in both genders. Diabetic ischemic embolic patients had higher levels of SUA than diabetic ischemic thrombotic cases. Patients with low magnesium levels had higher rate of low levels of SUA in ischemic stroke. Conclusion Serum uric acid levels are not associated with stroke types and gender. Diabetic embolic ischemic stroke cases had high SUA levels than thrombotic types and in ischemic stroke patients with low serum levels of magnesium, SUA levels were also lower.