Miracle-dz/UniFAR-FTUs huggingface dataset:
Cultural Engagement and Incidence of Cognitive Impairment: A 6-year Longitudinal Follow-up of the Japan Gerontological Evaluation Study (JAGES)

Background Active engagement in intellectually enriching activities reportedly lowers the risk of cognitive decline; however, few studies have examined this association, including engagement in traditional cultural activities. This study aimed to elucidate the types of cultural engagement associated with lower risk of cognitive impairment. Methods We examined the association between cultural engagement and cognitive impairment using Cox proportional hazards models in a cohort of 44,985 participants (20,772 males and 24,213 females) aged 65 years or older of the Japan Gerontological Evaluation Study from 2010 to 2016. Intellectual activities (eg, reading books, magazines, and/or newspapers), creative activities (eg, crafts and painting), and traditional cultural activities (eg, poetry composition [haiku], calligraphy, and tea ceremony/flower arrangement) were included among cultural engagement activities. Results Over a follow-up period of 6 years, incident cognitive disability was observed in 4,198 respondents (9.3%). After adjusting for potential confounders, such as depression and social support, intellectual activities were protectively associated with the risk of cognitive impairment (hazard ratio [HR] for those who read and stated that reading was their hobby, 0.75; 95% confidence interval [CI] 0.66–0.85 and HR for those who read but did not consider reading a hobby, 0.72; 95% CI, 0.65–0.80). Engagement in creative activities was also significantly correlated with lower risk of cognitive impairment (crafts: HR 0.71; 95% CI, 0.62–0.81 and painting: HR 0.80; 95% CI, 0.66–0.96). The association between traditional cultural activities and the risk of cognitive impairment was not statistically significant. Conclusions Engagement in intellectual and creative activities may be associated with reduced risk of dementia.
The effects of the COVID-19 pandemic on levels of physical fitness.

INTRODUCTION The COVID-19 pandemic, caused by infections from a novel human coronavirus, has been reported since December 2019 in China but was only made official in March 2020. Since then, it has had an impact worldwide, both due to its aggressiveness and its fast propagation. Society has been facing this pandemic by following the recommendations and determinations of the WHO and the strategies deployed by governmental institutions. Among these, social isolation has been shown to be the most important, because when isolating, society tends to move less, with a consequent increase in physical inactivity and sedentary behavior, affecting its levels of physical fitness. The objectives of this review were: to review the most important effects of physical inactivity and sedentary behavior on the physical fitness levels of the population during the COVID-19 pandemic. CONCLUSION The role of a regular practice of activities on the levels of physical fitness is fundamental to define the balance of quality of life during a COVID-19.
The clinicopathological characteristics and genetic alterations between younger and older gastric cancer patients with curative surgery

Few reports have investigated different genetic alterations according to age in various cancers. In total, 1749 GC patients receiving curative surgery were enrolled. The clinicopathological features, and prognoses were compared between younger (<65 years) and older (≥65 years) patients. Genetic mutations were analyzed using mass spectrometric single nucleotide polymorphism genotyping technology, including 68 validated mutations within eight genes (TP53, ARID1A, BRAF, and the PI3K/AKT pathway) previously reported in relation to age. Younger patients were more likely to be female and have poor cell differentiation, diffuse-type tumors, less lymphovascular invasion, fewer liver metastases, and better 5-year overall survival (OS) (68.0% vs. 54.6%, P<0.001) and disease-free survival (DFS) (65.4% vs. 53.0%, P<0.001) rates than older patients. Regarding the genetic alterations, older patients had more microsatellite instability-high (MSI-H) tumors and more ARID1A mutations than younger patients. Younger patients had significantly better OS and DFS rates than older patients for each pathological Tumor, Node, Metastasis (TNM) stage. Older patients had a significantly higher non-cancer related death rate than younger patients (36.2% vs. 12.3%, P<0.001). Age was an independent prognostic factor in GC. In conclusion, age was associated with different clinicopathological features and genetic alterations in GC with curative surgery.
Chelicerata sDscam isoforms combine homophilic specificities to define unique cell recognition

Significance Neuronal self-avoidance is a conserved process in vertebrates and invertebrates. In Drosophila, self-avoidance is mediated by the Down syndrome cell adhesion molecule (Dscam1) gene that encodes tens of thousands of proteins through alternative splicing. In vertebrates, an analogous function is performed by ∼60 clustered protocadherins (cPcdh) through promoter choice. Here we use cell aggregation assays to study the binding preferences of ∼100 sDscam protein in scorpion. We report that while related in sequence to the fly Dscam, the scorpion sDscam adopts a strategy that is similar to that of vertebrate cPcdhs, of combined specificity when coexpressed. Our findings identify sDscams as likely candidates to mediate neuronal self-avoidance in Chelicerata, as well as provide a remarkable example of convergent evolution. Thousands of Down syndrome cell adhesion molecule (Dscam1) isoforms and ∼60 clustered protocadhrein (cPcdh) proteins are required for establishing neural circuits in insects and vertebrates, respectively. The strict homophilic specificity exhibited by these proteins has been extensively studied and is thought to be critical for their function in neuronal self-avoidance. In contrast, significantly less is known about the Dscam1-related family of ∼100 shortened Dscam (sDscam) proteins in Chelicerata. We report that Chelicerata sDscamα and some sDscamβ protein trans interactions are strictly homophilic, and that the trans interaction is meditated via the first Ig domain through an antiparallel interface. Additionally, different sDscam isoforms interact promiscuously in cis via membrane proximate fibronectin-type III domains. We report that cell–cell interactions depend on the combined identity of all sDscam isoforms expressed. A single mismatched sDscam isoform can interfere with the interactions of cells that otherwise express an identical set of isoforms. Thus, our data support a model by which sDscam association in cis and trans generates a vast repertoire of combinatorial homophilic recognition specificities. We propose that in Chelicerata, sDscam combinatorial specificity is sufficient to provide each neuron with a unique identity for self–nonself discrimination. Surprisingly, while sDscams are related to Drosophila Dscam1, our results mirror the findings reported for the structurally unrelated vertebrate cPcdh. Thus, our findings suggest a remarkable example of convergent evolution for the process of neuronal self-avoidance and provide insight into the basic principles and evolution of metazoan self-avoidance and self–nonself discrimination.
Consecutive changes in serum alkaline phosphatase isoenzyme 3 activities in Holstein heifers during the first 18 months of life

This study investigated consecutive fluctuations in serum activities of bone-specific alkaline phosphatase (ALP) isoenzyme 3 (ALP3) in 11 clinically healthy Holstein heifers during the first 18 months of life. ALP3 activities at the first sampling time point after weaning (3 months) were significantly lower than those at multiple time points during the pre-weaning period. Those activities increased from a minimum at 3 months to a peak at 6 months during the post-weaning period. In the anthropometric data, daily body weight and wither height gains appeared to be below the public data at 4 months and 4–5 months, respectively. The data suggested that serum ALP3 activity can be used to monitor skeletal growth of heifers at weaning.
Functional analysis and cryo-electron microscopy of Campylobacter jejuni serine protease HtrA

ABSTRACT Campylobacter jejuni is a predominant zoonotic pathogen causing gastroenteritis and other diseases in humans. An important bacterial virulence factor is the secreted serine protease HtrA (HtrA Cj ), which targets tight and adherens junctional proteins in the gut epithelium. Here we have investigated the function and structure of HtrA Cj using biochemical assays and cryo-electron microscopy. Mass spectrometry analysis identified differences and similarities in the cleavage site specificity for HtrA Cj by comparison to the HtrA counterparts from Helicobacter pylori and Escherichia coli. We defined the architecture of HtrA Cj at 5.8 Å resolution as a dodecamer, built of four trimers. The contacts between the trimers are quite loose, a fact that explains the flexibility and mobility of the dodecameric assembly. This flexibility has also been studied through molecular dynamics simulation, which revealed opening of the dodecamer to expose the proteolytically active site of the protease. Moreover, we examined the rearrangements at the level of oligomerization in the presence or absence of substrate using size exclusion chromatography, which revealed hexamers, dodecamers and larger oligomeric forms, as well as remarkable stability of higher oligomeric forms (> 12-mers) compared to previously tested homologs from other bacteria. Extremely dynamic decay of the higher oligomeric forms into lower forms was observed after full cleavage of the substrate by the proteolytically active variant of HtrA Cj . Together, this is the first report on the in-depth functional and structural analysis of HtrA Cj , which may allow the construction of therapeutically relevant HtrA Cj inhibitors in the near future.
Re-evaluation of the discriminative stimulus effects of lysergic acid diethylamide with male and female Sprague-Dawley rats

Recent discoveries from clinical trials with psychedelic-assisted therapy have led to a resurgence of interest in the psychopharmacology of lysergic acid diethylamide (LSD). Preclinical drug discrimination is an invaluable tool to investigate the neurochemical mechanisms underlying subjective drug effects. The current study extends previous drug discrimination research by including both sexes. Adult female (n = 8) and male (n = 8) Sprague-Dawley rats were trained to discriminate 0.08 mg/kg LSD from saline under a fixed ratio 20 schedule of food reinforcement. Substitution tests were conducted with several substances, including other serotonergic hallucinogens, psychostimulants, mixed psychedelic-stimulants and synthetic cathinones. Stimulus antagonist tests were conducted with selected serotonin and dopamine antagonists. LSD-substitution with serotonergic hallucinogens was comparable between sexes. Modest but intriguing differences were observed between male and female rats in the extent of partial substitution by 3,4-methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine enantiomers and the synthetic cathinones, 3,4-methylenedioxypyrovalerone and 4-methylmethcathinone. Dopamine antagonists failed to block the LSD cue in both sexes and exerted stronger rate suppressant effects in male rats. The 5-hydroxytryptamine antagonist, (R)-(+)-a-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl) ethyl]-4-piperidinemethanol (MDL 100 907) blocked LSD discrimination in both sexes, although complete blockade was evident at lower doses in male rats. These results support previous findings regarding the prominent role of serotonergic activities underlying LSDs discriminative stimulus effects in male rats and generalize these findings to female rats. In consideration of the rising popularity in psychedelic-assisted psychotherapy, further research may be warranted to evaluate possible sex differences in the behavioral and subjective effects of LSD.
Klebsiella Cluster Endophthalmitis following Intravitreal Bevacizumab: Role of Early Detection, Pars Plana Vitrectomy, and Intracameral Moxifloxacin

ABSTRACT Aim To report the clinical profile, outcomes of early vitrectomy for cluster endophthalmitis developing after intravitreal Bevacizumab (IVB), and discuss the role of prophylactic intracameral moxifloxacin for eyes undergoing combined cataract surgery with IVB. Methods Single center, retrospective analysis of 35 consecutive eyes developing post-IVB inflammation. Results Of the 35 eyes that were administered IVB (27 eyes ‘IVB alone’ and 8 eyes ‘IVB with cataract surgery’). Endophthalmitis developed in 28 eyes, 6 eyes were managed with Intravitreal antibiotic (IVAB) alone, while 22 eyes required early vitrectomy. Only one eye undergoing a combined phacoemulsification with IVB developed endophthalmitis. Majority(26/28) of the eyes achieved visual acuity equal to/greater than pre-IVB injection vision over a period of 3.15 ± 3.2 months. Conclusion Early detection and prompt PPV were effectual for achieving good functional outcomes in our cluster of post-IVB Klebsiella endophthalmitis. Intracameral moxifloxacin was protective in cases undergoing combined cataract surgery with IVB.
Perceptions of who is in the healthcare team? A content analysis of social media posts during COVID-19 pandemic

ABSTRACT Social media posts can be used to explore public perceptions of interprofessional teams and healthcare professionals. The aim of this study was to use social listening technique to explore unfiltered public perceptions of the professionals involved in healthcare teams during the COVID-19 pandemic, in a naturalistic online setting, and to elaborate on the emotional reactions in response to an online social media post. A cross-sectional retrospective review of comments on a specific social media post was conducted between 15 March and 28 April 2020 using summative content analysis. One image that was widely circulated on social media platforms with two questions: ‘Who society thinks works at hospital? versus who really works at hospitals? ’ was selected. Three platforms were searched, Facebook®, Twitter®, and LinkedIn®. Only publicly available posts were included. Out of the initial 40 posts identified, 21 posts which had 1759 comments were analysed and 1576 were included for coding. Of the emerging nine themes, perceptions of who is in the team was the largest (40.5%, n = 639), followed by agreement (23.1%, n = 364) and feeling excluded (16.2%, n = 255). Of emotional expressions, 42.1% were positive and 57.9% negative. The most frequent emotions were frustration (54.4%, n = 857) followed by gratitude (16.3%, n = 257) and relief (15.9%, n = 250). The post brought considerable attention to the role of the interprofessional team and generated many feelings of frustration and exclusion. For this reason, the response to this social media post is very important and not to be overlooked. Healthcare professionals need to work together to strengthen their presence as an interprofessional team, united to deliver safe effective quality care for patients. The current COVID-19 pandemic and the media attention should be taken as an opportunity by the interprofessional community to work together to combat negative media stereotypes. Further research is warranted on public perceptions of the healthcare team.
Factors affecting the distribution, abundance and diversity of rock-pool fishes on the Cape Peninsula, South Africa

A quantitative description of the fish communities inhabiting rock pools on the Cape Peninsula, South Africa, and the relationships between the physical characteristics of the pools and the distribution, abundance and diversity of the resident fish fauna are given.A total of 1 541 fish, representing 21 species, were collected from 84 rock pools using the ichthyocide Rotenone. The mean density was 7,42 fish m−2 (49,60 gm−2) of pool area or 0,58 fish m−2 (3,67 gm−2) of the whole intertidal zone in which the pools were situated. Clinus superciliosus, C. cottoides and Chorisochismus dentex were the most abundant species, together comprising 75% of the biomass and 60% of the number of fish caught.The number of species, number of individuals and biomass of fish in the pools all correlated significantly (P < 0,01) with pool size and the amount of rock cover available. In addition, the number of species decreased up the shore. These three environmental factors in combination accounted for between 58% and 88% of t.
Sophoricoside ameliorates cardiac hypertrophy by activating AMPK/mTORC1-mediated autophagy

Abstract Aim: The study aims to evaluate protective effects of sophoricoside (Sop) on cardiac hypertrophy. Meanwhile, the potential and significance of Sop should be broadened and it should be considered as an attractive drug for the treatment of pathological cardiac hypertrophy and heart failure. Methods: Using the phenylephrine (PE)-induced neonatal rat cardiomyocytes (NRCMs) enlargement model, the potent protection of Sop against cardiomyocytes enlargement was evaluated. The function of Sop was validated in mice received transverse aortic coarctation (TAC) or sham surgery. At 1 week after TAC surgery, mice were treated with Sop for the following 4 weeks, the hearts were harvested after echocardiography examination. Results: Our study revealed that Sop significantly mitigated TAC-induced heart dysfunction, cardiomyocyte hypertrophy and cardiac fibrosis. Mechanistically, Sop treatment induced a remarkable activation of AMPK/mTORC1-autophagy cascade following sustained hypertrophic stimulation. Importantly, the protective effect of Sop was largely abolished by the AMPKα inhibitor Compound C, suggesting an AMPK activation-dependent manner of Sop function on suppressing pathological cardiac hypertrophy. Conclusion: Sop ameliorates cardiac hypertrophy by activating AMPK/mTORC1-mediated autophagy. Hence, Sop might be an attractive candidate for the treatment of pathological cardiac hypertrophy and heart failure.
Overnight switch from rasagiline to safinamide in Parkinson's disease patients with motor fluctuations: a tolerability and safety study

When switching between monoamine oxidase type B (MAO‐B) inhibitors, a 15‐day suspension period is a precautionary measure to avoid a serotonin syndrome and hypertensive crisis. However, this indication results in a major inconvenience for parkinsonian patients because of the worsening of their clinical condition. In routine clinical practice, neurologists often perform a substitution of these two drugs without solution of continuity (i.e. overnight), to avoid worsening of fluctuations and prolonged OFF periods. Therefore, a safety open label study was performed to investigate the possible risks of switching overnight from rasagiline to safinamide.
RNAemia Corresponds to Disease Severity and Antibody Response in Hospitalized COVID-19 Patients

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents a global health emergency. To improve the understanding of the systemic component of SARS-CoV-2, we investigated if viral load dynamics in plasma and respiratory samples are associated with antibody response and severity of coronavirus disease 2019 (COVID-19). SARS-CoV-2 RNA was found in plasma samples from 14 (44%) out of 32 patients. RNAemia was detected in 5 out of 6 fatal cases. Peak IgG values were significantly lower in mild/moderate than in severe (0.6 (interquartile range, IQR, 0.4–3.2) vs. 11.8 (IQR, 9.9–13.0), adjusted p = 0.003) or critical cases (11.29 (IQR, 8.3–12.0), adjusted p = 0.042). IgG titers were significantly associated with virus Ct (Cycle threshold) value in plasma and respiratory specimens ((ß = 0.4, 95% CI (confidence interval, 0.2; 0.5), p < 0.001 and ß = 0.5, 95% CI (0.2; 0.6), p = 0.002). A classification as severe or a critical case was additionally inversely associated with Ct values in plasma in comparison to mild/moderate cases (ß = −3.3, 95% CI (−5.8; 0.8), p = 0.024 and ß = −4.4, 95% CI (−7.2; 1.6), p = 0.007, respectively). Based on the present data, our hypothesis is that the early stage of SARS-CoV-2 infection is characterized by a primary RNAemia, as a potential manifestation of a systemic infection. Additionally, the viral load in plasma seems to be associated with a worse disease outcome.
A rise in left atrial pressure detected by the V‐LAP™ system for patients with heart failure during the coronavirus disease 2019 pandemic

During the coronavirus disease 2019 (COVID‐19) pandemic, many patients refrained from inpatient medical care. For those inflicted with heart failure (HF), the risk of repeat hospitalizations is particularly high in case of infection. This presents an important opportunity for remote monitoring of haemodynamic data for these patients, in order to detect and treat accordingly. The aim of the present case is to report of the first measurements of a novel wireless left atrial pressure (LAP) monitoring system, the V‐LAP™ (Vectorious Medical Technologies, Ltd), during the COVID‐19 pandemic. The V‐LAP™ Left Atrium Monitoring systEm for Patients With Chronic sysTOlic & Diastolic Congestive heart Failure (VECTOR‐HF) is a first‐in‐man clinical study assessing the safety and feasibility of the V‐LAP™ monitoring system. Our first patient, a 59‐year‐old man with severe ischaemic cardiomyopathy (left ventricular ejection fraction −30%) was enrolled prior to the COVID‐19 outbreak. As per protocol, both the patient and the medical team were blinded to the results in the first 3 months after implantation. We were able to witness the LAP during the pandemic, as the patient remained undertreated, demonstrating a gradual increase from a mean pressure of 6.56 to 19.4 mmHg, as well as prominent V waves, before the data became available to the medical team and the patient was treated accordingly. Thereafter, pressures have returned to low values. This case demonstrated the feasibility of remote monitoring of LAP using the V‐LAP™ system, as well as the potential benefit of remote care of HF patients.
Conserved actin machinery drives microtubule-independent motility and phagocytosis in Naegleria

Naegleria diverged from the “yeast-to-human” lineage >1 billion years ago. Velle and Fritz-Laylin found that Naegleria, which lacks interphase microtubules, has a robust actin cytoskeletal repertoire and uses conserved, Arp2/3–derived actin networks to drive cell crawling and enhance phagocytosis. These findings support an evolutionarily ancient origin for these phenotypes.