Miracle-dz/UniFAR-FTUs huggingface dataset:
Dementia Incidence in the Elderly Population of Greece: Results From the HELIAD Study.

OBJECTIVES Recently a declining trend in dementia incidence rates has been reported in high-income countries. We investigated dementia incidence in a representative sample of the Greek population in the age group of 65 years and above. METHODS This research is part of the Hellenic Epidemiological Longitudinal Investigation of Aging and Diet (HELIAD). The incidence cohort consisted of 1072 participants who were reevaluated after a mean period of 3.09 years. RESULTS The incidence rate of dementia was 19.0 cases per 1000 person-years (age-standardized and sex-standardized incidence: 25.4/1000 person-years), of which 16.3 per 1000 person-years were attributable to Alzheimer disease. Each additional year of age increased dementia risk by 19.3% and each additional year of education decreased dementia risk by 12.1%. Apolipoprotein E (APOE)-ε4 homozygous participants were 18 times more likely to be diagnosed with dementia. A baseline diagnosis of mild cognitive decline (MCI) resulted in a risk for dementia increased by 3.7 times compared with the cognitively normal; in participants with MCI at baseline, APOE-ε4 carriage increased dementia risk by 4.5 times. CONCLUSIONS The incidence rate of dementia in people 65 years and above in Greece is generally consistent with recently published rates in Europe and North America. Advancing age, baseline MCI, and APOE-ε4 homozygosity are risk factors, while higher educational attainment seems protective.
Canadian Occupational Therapists’ Use of Technology With Older Adults: A Nationwide Survey

As rehabilitation specialists, occupational therapy practitioners play a gateway role regarding recommendation of various technologies for homecare. However, no study has investigated current occupational therapy practices concerning information and communication technology (ICT) for older adults in Canada. The objective of this study was to identify Canadian occupational therapists’ (OTs) knowledge and practices of ICT with older adults as well as factors associated with its recommendation. A Canada-wide, cross-sectional, online survey was conducted. Of 387 OTs, only 12.4% reported recommending ICT in practice. ICTs supporting communication and cognition were the main types recommended. The reported barriers to use in practice differed between ICT familiar users and nonusers. Multivariate logistic regression analyses showed that clinicians with more years of clinical experience were more likely to recommend ICT. Clinicians’ services, work environments, and client diagnosis were also factors associated with ICT recommendation. Additional research is needed to understand how to overcome barriers to ICT recommendation in OT practice.
PORF-DDPG: Learning Personalized Autonomous Driving Behavior with Progressively Optimized Reward Function

Autonomous driving with artificial intelligence technology has been viewed as promising for autonomous vehicles hitting the road in the near future. In recent years, considerable progress has been made with Deep Reinforcement Learnings (DRLs) for realizing end-to-end autonomous driving. Still, driving safely and comfortably in real dynamic scenarios with DRL is nontrivial due to the reward functions being typically pre-defined with expertise. This paper proposes a human-in-the-loop DRL algorithm for learning personalized autonomous driving behavior in a progressive learning way. Specifically, a progressively optimized reward function (PORF) learning model is built and integrated into the Deep Deterministic Policy Gradient (DDPG) framework, which is called PORF-DDPG in this paper. PORF consists of two parts: the first part of the PORF is a pre-defined typical reward function on the system state, the second part is modeled as a Deep Neural Network (DNN) for representing driving adjusting intention by the human observer, which is the main contribution of this paper. The DNN-based reward model is progressively learned using the front-view images as the input and via active human supervision and intervention. The proposed approach is potentially useful for driving in dynamic constrained scenarios when dangerous collision events might occur frequently with classic DRLs. The experimental results show that the proposed autonomous driving behavior learning method exhibits online learning capability and environmental adaptability.
Structure of the substrate-binding domain of Plasmodium falciparum heat-shock protein 70-x

The 3.25 Å resolution crystallographic structure of the substrate-binding domain of the erythrocyte-exported Hsp70 chaperone from the malaria parasite Plasmodium falciparum was determined. The parasite domain is shown to be highly similar to the equivalent domain of a human Hsp70 chaperone in structure and mode of substrate engagement.
A Home-Based Bilateral Rehabilitation System With sEMG-based Real-Time Variable Stiffness

Bilateral rehabilitation allows patients with hemiparesis to exploit the cooperative capabilities of both arms to promote the recovery process. Although various approaches have been proposed to facilitate synchronized robot-assisted bilateral movements, few studies have focused on addressing the varying joint stiffness resulting from dynamic motions. This paper presents a novel bilateral rehabilitation system that implements a surface electromyography (sEMG)-based stiffness control to achieve real-time stiffness adjustment based on the user's dynamic motion. An sEMG-driven musculoskeletal model that incorporates the muscle activation and muscular contraction dynamics is developed to provide reference signals for the robot's real-time stiffness control. Preliminary experiments were conducted to evaluate the system performance in tracking accuracy and comfortability, which showed the proposed rehabilitation system with sEMG-based real-time stiffness variation achieved fast adaption to the patient's dynamic movement as well as improving the comfort in robot-assisted bilateral training.
Intravenous Zanamivir: A Viable Option for Critically Ill Patients With Influenza

Objective: To review the pharmacology, clinical trial data, and clinical implications for the intravenous formulation of zanamivir. Data Sources: MEDLINE, PubMed, EMBASE, and Google Scholar were searched during November 2019 to July 2020. Search terms zanamivir and neuraminidase inhibitor were used. Study Selection and Data Extraction: All human trials and major reports from compassionate use programs with the intravenous zanamivir (IVZ) formulation were assessed and reviewed here. Data Synthesis: IVZ was found to be similar but not superior to oral oseltamivir in hospitalized patients when studied in populations with very low baseline oseltamivir resistance. IVZ provides an effective alternative for critically ill patients when oral antiviral therapy is not preferred or when oseltamivir resistance is increased. Relevance to Patient Care and Clinical Practice: IVZ was recently authorized for use by the European Medicines Agency, and it is eligible for consideration in emergency use protocols and US stockpile inclusion. It will be of particular interest in critically ill patients especially during influenza seasons with appreciable oseltamivir and peramivir resistance. Conclusions: The available information suggests that the intravenous formulation of zanamivir offers a viable alternative treatment for critically ill patients with influenza, especially when resistance to other agents is present.
Highly Tunable Thiol‐Ene Photoresins for Volumetric Additive Manufacturing

Volumetric additive manufacturing (VAM) forms complete 3D objects in a single photocuring operation without layering defects, enabling 3D printed polymer parts with mechanical properties similar to their bulk material counterparts. This study presents the first report of VAM‐printed thiol‐ene resins. With well‐ordered molecular networks, thiol‐ene chemistry accesses polymer materials with a wide range of mechanical properties, moving VAM beyond the limitations of commonly used acrylate formulations. Since free‐radical thiol‐ene polymerization is not inhibited by oxygen, the nonlinear threshold response required in VAM is introduced by incorporating 2,2,6,6‐tetramethyl‐1‐piperidinyloxy (TEMPO) as a radical scavenger. Tuning of the reaction kinetics is accomplished by balancing inhibitor and initiator content. Coupling this with quantitative measurements of the absorbed volumetric optical dose allows control of polymer conversion and gelation during printing. Importantly, this work thereby establishes the first comprehensive framework for spatial–temporal control over volumetric energy distribution, demonstrating structures 3D printed in thiol‐ene resin by means of tomographic volumetric VAM. Mechanical characterization of this thiol‐ene system, with varied ratios of isocyanurate and triethylene glycol monomers, reveals highly tunable mechanical response far more versatile than identical acrylate‐based resins. This broadens the range of materials and properties available for VAM, taking another step toward high‐performance printed polymers.
Pilot Study: Texture Analysis of PET Imaging Demonstrates Changes in 18F-FDG Uptake of the Brain After Prophylactic Cranial Irradiation

Prophylactic cranial irradiation (PCI) is used to decrease the probability of developing brain metastases in patients with small cell lung cancer and has been linked to deleterious cognitive effects. Although no well-established imaging markers for these effects exist, previous studies have shown that structural and metabolic changes in the brain can be detected with MRI and PET. This study used an image processing technique called texture analysis to explore whether global changes in brain glucose metabolism could be characterized in PET images. Methods: 18F-FDG PET images of the brain from patients with small cell lung cancer, obtained before and after the administration of PCI, were processed using texture analysis. Texture features were compared between the pre- and post-PCI images. Results: Multiple texture features demonstrated statistically significant differences before and after PCI when texture analysis was applied to the brain parenchyma as a whole. Regional differences were also seen but were not statistically significant. Conclusion: Global changes in brain glucose metabolism occur after PCI and are detectable using advanced image processing techniques. These changes may reflect radiation-induced damage and thus may provide a novel method for studying radiation-induced cognitive impairment.
Presenilin-2 and Calcium Handling: Molecules, Organelles, Cells and Brain Networks

Presenilin-2 (PS2) is one of the three proteins that are dominantly mutated in familial Alzheimer’s disease (FAD). It forms the catalytic core of the γ-secretase complex—a function shared with its homolog presenilin-1 (PS1)—the enzyme ultimately responsible of amyloid-β (Aβ) formation. Besides its enzymatic activity, PS2 is a multifunctional protein, being specifically involved, independently of γ-secretase activity, in the modulation of several cellular processes, such as Ca2+ signalling, mitochondrial function, inter-organelle communication, and autophagy. As for the former, evidence has accumulated that supports the involvement of PS2 at different levels, ranging from organelle Ca2+ handling to Ca2+ entry through plasma membrane channels. Thus FAD-linked PS2 mutations impact on multiple aspects of cell and tissue physiology, including bioenergetics and brain network excitability. In this contribution, we summarize the main findings on PS2, primarily as a modulator of Ca2+ homeostasis, with particular emphasis on the role of its mutations in the pathogenesis of FAD. Identification of cell pathways and molecules that are specifically targeted by PS2 mutants, as well as of common targets shared with PS1 mutants, will be fundamental to disentangle the complexity of memory loss and brain degeneration that occurs in Alzheimer’s disease (AD).
Alteration of the Fatty Acid Metabolism in the Rat Kidney Caused by the Injection of Serum from Patients with Collapsing Glomerulopathy

Patients with collapsing glomerulopathy (CG) have marked proteinuria that rapidly progresses to chronic renal failure. In this study, we investigated if the nephropathy produced in a rat model by the injection of serum from CG patients induced alterations in fatty acid (FA) metabolism. Twenty-four female Sprague-Dawley rats were divided into four groups of six rats each: Group I, control rats (C); Group II, rats that received injections of 1 mL of 0.9% NaCl saline solution (SS); Group III, rats injected with 25 mg/mL of serum from healthy subjects (HS); and Group IV, rats injected with 25 mg/mL of serum from CG patients. In all groups, the systolic blood pressure (SBP), proteinuria, creatinine clearance (CC), cholesterol and total FA composition in the kidney and serum were evaluated. The administration of serum from CG patients to rats induced glomerular collapse, proteinuria, reduced CC and elevated SBP (p ≤ 0.01) in comparison with the C, SS and HS rats. The FA composition of the serum of rats that received the CG serum showed an increase in palmitic acid (PA) and a decrease in arachidonic acid (AA) when compared to serum from HS (p ≤ 0.02). In rats receiving the CG serum, there was also a decrease in the AA in the kidney but there was an increase in the PA in the serum and kidney (p ≤ 0.01). These results suggest that the administration of serum from CG patients to rats induces alterations in FA metabolism including changes in PA and in AA, which are precursors for the biosynthesis of the prostaglandins that are involved in the elevation of SBP and in renal injury. These changes may contribute to collapsing glomerulopathy disease.
Inhibitor of DNA binding 2 (Id2) Regulates Photic Entrainment Responses in Mice: Differential Responses of the Id2-/- Mouse Circadian System Are Dependent on Circadian Phase and on Duration and Intensity of Light

ID2 is a rhythmically expressed helix–loop–helix transcriptional repressor, and its deletion results in abnormal properties of photoentrainment. By examining parametric and nonparametric models of entrainment, we have started to explore the mechanism underlying this circadian phenotype. Id2-/- mice were exposed to differing photoperiods, and the phase angle of entrainment under short days was delayed 2 h as compared with controls. When exposed to long durations of continuous light, enhanced entrainment responses were observed after a delay of the clock but not with phase advances. However, the magnitude of phase shifts was not different in Id2-/- mice tested in constant darkness using a discrete pulse of saturating light. No differences were observed in the speed of clock resetting when challenged by a series of discrete pulses interspaced by varying time intervals. A photic phase-response curve was constructed, although no genotypic differences were observed. Although phase shifts produced by discrete saturating light pulses at CT16 were similar, treatment with a subsaturating pulse revealed a ~2-fold increase in the magnitude of the Id2-/- shift. A corresponding elevation of light-induced per1 expression was observed in the Id2-/- suprachiasmatic nucleus (SCN). To test whether the phenotype is based on a sensitivity change at the level of the retina, pupil constriction responses were measured. No differences were observed in responses or in retinal histology, suggesting that the phenotype occurs downstream of the retina and retinal hypothalamic tract. To test whether the phenotype is due to a reduced amplitude of state variables of the clock, the expression of clock genes per1 and per2 was assessed in vivo and in SCN tissue explants. Amplitude, phase, and period length were normal in Id2-/- mice. These findings suggest that ID2 contributes to a photoregulatory mechanism at the level of the SCN central pacemaker through control of the photic induction of negative elements of the clock.
Aberrant computational mechanisms of social learning and decision-making in schizophrenia and borderline personality disorder

Psychiatric disorders are ubiquitously characterized by debilitating social impairments. These difficulties are thought to emerge from aberrant social inference. In order to elucidate the underlying computational mechanisms, patients diagnosed with major depressive disorder (N = 29), schizophrenia (N = 31), and borderline personality disorder (N = 31) as well as healthy controls (N = 34) performed a probabilistic reward learning task in which participants could learn from social and non-social information. Patients with schizophrenia and borderline personality disorder performed more poorly on the task than healthy controls and patients with major depressive disorder. Broken down by domain, borderline personality disorder patients performed better in the social compared to the non-social domain. In contrast, controls and major depressive disorder patients showed the opposite pattern and schizophrenia patients showed no difference between domains. In effect, borderline personality disorder patients gave up a possible overall performance advantage by concentrating their learning in the social at the expense of the non-social domain. We used computational modeling to assess learning and decision-making parameters estimated for each participant from their behavior. This enabled additional insights into the underlying learning and decision-making mechanisms. Patients with borderline personality disorder showed slower learning from social and non-social information and an exaggerated sensitivity to changes in environmental volatility, both in the non-social and the social domain, but more so in the latter. Regarding decision-making the modeling revealed that compared to controls and major depression patients, patients with borderline personality disorder and schizophrenia showed a stronger reliance on social relative to non-social information when making choices. Depressed patients did not differ significantly from controls in this respect. Overall, our results are consistent with the notion of a general interpersonal hypersensitivity in borderline personality disorder and schizophrenia based on a shared computational mechanism characterized by an over-reliance on beliefs about others in making decisions and by an exaggerated need to make sense of others during learning specifically in borderline personality disorder.
MiR‐22‐3p inhibits fibrotic cataract through inactivation of HDAC6 and increase of α‐tubulin acetylation

Fibrotic cataract, including posterior capsule opacification (PCO) and anterior subcapsular cataract (ASC), renders millions of people visually impaired worldwide. However, the underlying mechanism remains poorly understood. Here, we report a miRNA‐based regulatory pathway that controls pathological fibrosis of lens epithelium.
Integrating bioinformatics tools to investigate protein phosphorylation

Protein phosphorylation is one of the most important protein post-translational modifications and plays a role in numerous cellular processes including recognition, signaling and degradation. It can be studied experimentally by various methodologies, like employing western blot analysis, site-directed mutagenesis, 2 D gel electrophoresis, mass spectrometry etc. A number of in silico tools have also been developed in order to predict plausible phosphorylation sites in a given protein. In this review, we conducted a benchmark study including the leading protein phosphorylation prediction software, in an effort to determine which performs best. The first place was taken by GPS 2.2, having predicted all phosphorylation sites with a 83% fidelity while in second place came NetPhos 2.0 with 69%.
Isolation and molecular characterizations of canine distemper virus from a naturally infected Korean dog using Vero cells expressing dog signaling lymphocyte activation molecule

Background Canine distemper virus (CDV) infection results in high morbidity and mortality in dogs. There has been no report about isolation of Korean CDV since 1980 in Korea. Objectives To investigate the biological properties and the genetic characterization of Korean CDV. Methods Vero cells expressing dog signaling lymphocyte activation molecule (dSLAM) gene named as Vero/dSLAM were used to isolate CDV using 17 samples. Diagnostic methods such as cytopathic effects, immunofluorescence assay, peroxidase linked assay, electron microscopy, rapid immunodiagnostic assay, and reverse transcription polymerase chain reaction were used to confirm the Korean CDV isolate as a CDV. The genetic analysis was performed through cloning and sequencing of hemagglutinin gene of CDV isolate. Results A virus propagated in Vero/dSLAM cell was confirmed as CDV (CD1901 strain) based on the above methods. The CD1901 strain showed the highest viral titer (105.5 50% tissue culture infectious dose [TCID50]/mL) in the Vero/dSLAM cells at 4 days post inoculation, but did not form a fork on chorioallantoic membrane of 7-day-old egg. Ribavirin, a nucleotide analogue anti-viral agent, inhibits moderately the Korean CDV propagation in the Vero/dSLAM cells. The nucleotide and amino acid sequences of the H gene of CD1901 strain were compared with those of other CDV strains. The CD1901 strain belonged to Asia 1 group and had the highest similarity (99.9%) with the BA134 strain, which was isolated in China in 2008. Conclusions We constructed successfully Vero/dSLAM and isolated one Korean CDV isolate (CD1901 strain) from a naturally infected dog. The CD1901 strain belonged to Asia 1 genotype.
Estrogen receptor β regulates AKT activity through up-regulation of INPP4B and inhibits migration of prostate cancer cell line PC-3

Significance Dysregulation of PI3K/AKT/PTEN signaling is a common characteristic of prostate cancer (PCa). Loss of the tumor suppressor PTEN occurs frequently in PCa and leads to overactive AKT signaling. Complete loss of PTEN is associated with increased metastasis and castration resistance in PCa. However, another tumor suppressor, inositol-polyphosphate 4-phosphatase type II (INPP4B), can partially compensate for the loss of PTEN. INPP4B is up-regulated by the androgen receptor, and androgen deprivation therapy (ADT) would be expected to lead to hyperactive AKT due to concomitant loss of both PTEN and INPP4B. However, the present study shows that ERβ agonists induce expression of INPP4B and down-regulate AKT. This study provides a rationale for further investigations to understand the role of ERβ1 in advanced PCa. Loss of the tumor suppressor, PTEN, is one of the most common findings in prostate cancer (PCa). This loss leads to overactive Akt signaling, which is correlated with increased metastasis and androgen independence. However, another tumor suppressor, inositol-polyphosphate 4-phosphatase type II (INPP4B), can partially compensate for the loss of PTEN. INPP4B is up-regulated by androgens, and this suggests that androgen-deprivation therapy (ADT) would lead to hyperactivity of AKT. However, in the present study, we found that in PCa, samples from men treated with ADT, ERβ, and INPP4B expression were maintained in some samples. To investigate the role of ERβ1 in regulation of INPPB, we engineered the highly metastatic PCa cell line, PC3, to express ERβ1. In these cells, INPP4B was induced by ERβ ligands, and this induction was accompanied by inhibition of Akt activity and reduction in cell migration. These findings reveal that, in the absence of androgens, ERβ1 induces INPP4B to dampen AKT signaling. Since the endogenous ERβ ligand, 3β-Adiol, is lost upon long-term ADT, to obtain the beneficial effects of ERβ1 on AKT signaling, an ERβ agonist should be added along with ADT.