Miracle-dz/UniFAR-FTUs huggingface dataset:
The Multi-Partner Consortium to Expand Dementia Research in Latin America (ReDLat): Driving Multicentric Research and Implementation Science

Dementia is becoming increasingly prevalent in Latin America, contrasting with stable or declining rates in North America and Europe. This scenario places unprecedented clinical, social, and economic burden upon patients, families, and health systems. The challenges prove particularly pressing for conditions with highly specific diagnostic and management demands, such as frontotemporal dementia. Here we introduce a research and networking initiative designed to tackle these ensuing hurdles, the Multi-partner consortium to expand dementia research in Latin America (ReDLat). First, we present ReDLat's regional research framework, aimed at identifying the unique genetic, social, and economic factors driving the presentation of frontotemporal dementia and Alzheimer's disease in Latin America relative to the US. We describe ongoing ReDLat studies in various fields and ongoing research extensions. Then, we introduce actions coordinated by ReDLat and the Latin America and Caribbean Consortium on Dementia (LAC-CD) to develop culturally appropriate diagnostic tools, regional visibility and capacity building, diplomatic coordination in local priority areas, and a knowledge-to-action framework toward a regional action plan. Together, these research and networking initiatives will help to establish strong cross-national bonds, support the implementation of regional dementia plans, enhance health systems' infrastructure, and increase translational research collaborations across the continent.
Microbiome Composition and Function in Aquatic Vertebrates: Small Organisms Making Big Impacts on Aquatic Animal Health

Aquatic ecosystems are under increasing stress from global anthropogenic and natural changes, including climate change, eutrophication, ocean acidification, and pollution. In this critical review, we synthesize research on the microbiota of aquatic vertebrates and discuss the impact of emerging stressors on aquatic microbial communities using two case studies, that of toxic cyanobacteria and microplastics. Most studies to date are focused on host-associated microbiomes of individual organisms, however, few studies take an integrative approach to examine aquatic vertebrate microbiomes by considering both host-associated and free-living microbiota within an ecosystem. We highlight what is known about microbiota in aquatic ecosystems, with a focus on the interface between water, fish, and marine mammals. Though microbiomes in water vary with geography, temperature, depth, and other factors, core microbial functions such as primary production, nitrogen cycling, and nutrient metabolism are often conserved across aquatic environments. We outline knowledge on the composition and function of tissue-specific microbiomes in fish and marine mammals and discuss the environmental factors influencing their structure. The microbiota of aquatic mammals and fish are highly unique to species and a delicate balance between respiratory, skin, and gastrointestinal microbiota exists within the host. In aquatic vertebrates, water conditions and ecological niche are driving factors behind microbial composition and function. We also generate a comprehensive catalog of marine mammal and fish microbial genera, revealing commonalities in composition and function among aquatic species, and discuss the potential use of microbiomes as indicators of health and ecological status of aquatic ecosystems. We also discuss the importance of a focus on the functional relevance of microbial communities in relation to organism physiology and their ability to overcome stressors related to global change. Understanding the dynamic relationship between aquatic microbiota and the animals they colonize is critical for monitoring water quality and population health.
Mini Review Immunological Consequences of Immunization With COVID-19 mRNA Vaccines: Preliminary Results

Background: BNT162b2 and mRNA-1273 are the two recently approved mRNA-based vaccines against COVID-19 which has shown excellent safety and efficacy. Preliminary data about specific and neutralizing antibodies is available covering the first 100 days after vaccination. Methods: We reviewed all the publications regarding the immunologic consequences of BNT162b2 and mRNA-1273 vaccination. A summary of specific antibodies concentration and neutralizing antibodies titers elicited by each vaccine is provided. Results: BNT162b2 and mRNA-1273 displayed a reassuring safety and efficacy profile, with the latter above 94%. They can elicit specific antibodies titers and neutralizing antibodies concentrations that are far superior from those observed among COVID-19 human convalescent serum, across a wide span of age, for at least 100 days after vaccination. Moreover, the vaccine-induced T cellular response is oriented toward a TH1 response and no evidence of vaccine-enhanced disease have been reported. Discussion: BNT162b2 and mRNA-1273 can elicit specific antibodies titers and neutralizing antibodies concentrations above those observed among COVID-19 human convalescent serum in the first 100 days after vaccination. Data about vaccine efficacy in those with previous COVID-19 or immunocompromised is still limited.
Steroid Hormone Receptors: Links With Cell Cycle Machinery and Breast Cancer Progression

Progression of cells through cell cycle consists of a series of events orchestrated in a regulated fashion. Such processes are influenced by cell cycle regulated expression of various proteins where multiple families of transcription factors take integral parts. Among these, the steroid hormone receptors (SHRs) represent a connection between the external hormone milieu and genes that control cellular proliferation. Therefore, understanding the molecular connection between the transcriptional role of steroid hormone receptors and cell cycle deserves importance in dissecting cellular proliferation in normal as well as malignant conditions. Deregulation of cell cycle promotes malignancies of various origins, including breast cancer. Indeed, SHR members play crucial role in breast cancer progression as well as management. This review focuses on SHR-driven cell cycle regulation and moving forward, attempts to discuss the role of SHR-driven crosstalk between cell cycle anomalies and breast cancer.
Auto-Regulation Method vs. Fixed-Loading Method in Maximum Strength Training for Athletes: A Systematic Review and Meta-Analysis

The auto-regulation method is a rising training strategy to improve strength and motor performance, and the Autoregulatory Progressive Resistance Exercise (APRE), Rating of Perceived Exertion program (RPE), and Velocity-Based Training (VBT) are the three common auto-regulation programs. However, whether the auto-regulation method is more effective than the traditional strength training (the fixed-loading method) in maximum strength training is still unclear. The present study searched the Pubmed, SPORTDiscus, Web of Science, Embase, EBSCO, Cochrane, CNKI, and CQVIP databases, and included eight related studies published between 2010 and 2020, with a total of 166 subjects including division 1 college players and athletes with at least 1-year training history, and interventions ranging from 5 to 10 weeks. A meta-analysis was performed to check the difference between the two training methods, and analyzed the differences in the existing auto-regulation programs' effectiveness. The overall results showed that the auto-regulation method was more effective than the fixed-loading method in maximum strength training (effect size = 0.64; P < 0.001; I2 = 0%). In specific, the pooled results in subgroup analysis indicated that the auto-regulation method may effectively improve the strength performance in squat (effect size = 4.64; P < 0.05; I2 = 54%) and bench press (effect size = 3.21; P < 0.05; I2 = 62%). Greater benefits of the auto-regulation method on strength improvement could be achieved in an 8-week or even shorter training (effect size = 0.87; P < 0.001; I2 = 0%) compared with those of 8–10 weeks (effect size = 0.32; P < 0.001; I2 = 0%). The APRE is the most effective training program among the three auto-regulation programs (effect size = 0.78; P < 0.001; I2 = 0%). In conclusion, the auto-regulation method could be more effective than the fixed-loading method in maximum strength training. The APRE is a convenient and effective training program that may be considered a practical training program to replace traditional training in athletes.
MicroRNA-935 Directly Targets FZD6 to Inhibit the Proliferation of Human Glioblastoma and Correlate to Glioma Malignancy and Prognosis

MicroRNAs (miRNAs) are involved in human glioblastoma (GB). MiR-935 has been reported to have both tumor-inhibiting and tumorigenesis effects, but its role in GB remains unclear. Because of the high mortality and morbidity associated with the malignancy of GB, a deeper understanding of the molecular crosstalk that occurs in GB is needed to identify new potential targets for treatment. At present, the mechanism of GB at the molecular level is not fully understood. With the aid of bioinformatic analysis, miR-935 was significantly downregulated in GB, and it presented a poorer outcome. In the glioma cell line and in the nude mice model, the miR-935 inhibited cell proliferation by modulating cell circles in vitro and in vivo. Then, the target genes of miR-935 were analyzed by using the online database, and the direct binding was tested with a luciferase analysis. FZD6 was found to be the direct target of miR-935. The effect of miR-935 was recovered by the overexpression of FZD6 in vitro. In addition, the negative correlation of miR-935 and the expression of FZD6 were confirmed in our clinical samples, and the expression of FZD6 has a strong correlation with tumor malignancy and prognosis. This study showed that miR-935 directly inhibited the expression of FZD6 and inhibited the cell proliferation, thereby suppressing the development of GB, suggesting that miR-935 is a cancer suppressor miRNA and may become a prognostic biomarker or a promising potential therapeutic target for human GBs.
Patients With Ankylosing Spondylitis Are Associated With High Risk of Fibromyalgia: A Nationwide Population-Based Cohort Study

Objectives: The main purpose of this retrospective cohort study was to provide an evaluation of Ankylosing spondylitis (AS) patients' fibromyalgia risk in different age and sex subgroups by analyzing large study samples. Methods: Datasets from the National Taiwan Insurance Research Database (NHIRD) were retrieved in this retrospective cohort study. This study was approved by the Institutional Review Board of Chung Shan Medical University (IRB permit number CS15134). Within the Longitudinal Health Insurance Database (LHID), and the subset of NHIRD, we identified AS patients to explore the risk of further fibromyalgia. The exposure cohort included patients with newly-diagnosed AS (ICD-9-CM:720.0) during 2000–2013. After 1:4 age-sex matching and 1:2 propensity score matching, and adjusting potential confounders, individuals without AS were identified as a comparison cohort. The adjusted hazard ratio of subsequent development of fibromyalgia in people with AS was evaluated. Further stratification analyses of different ages and genders were then undertaken to validate the results. Results: In total, 17 088 individuals were included in the present study, including 5,696 patients with AS and 11,392 individuals without AS. Respective incidence rates (per 1,000 person-months) of fibromyalgia was 0.52 (95% CI, 0.46–0.59) in the AS cohort and 0.39 (95% CI, 0.35–0.44) in the non-AS cohort. Compared with the non-AS cohort, aHR of developing fibromyalgia was 1.32 (95% CI, 1.12–1.55) in people with AS. This association was consistent in both statistical models of 1:4 age–sex matching and 1:2 propensity score matching. Conclusion: Patients with AS were associated with a higher risk of fibromyalgia, especially those over 65 years old. In managing patients with AS, clinicians should be aware of this association, which could impact diagnosis, disease activity evaluation, and treatment.
Fractalkine Is Linked to the Necrosome Pathway in Acute Pulmonary Inflammation

Acute pulmonary inflammation affects over 10% of intensive care unit (ICU) patients and is associated with high mortality. Fractalkine (CX3CL1) and its receptor, CX3CR1, have been shown to affect pulmonary inflammation, but previous studies have focused on macrophages. In a murine model of acute pulmonary inflammation, we identified inflammatory hallmarks in C57BL/6J and CX3CR1−/− mice. Pulmonary inflammation was significantly enhanced in the CX3CR1−/− animals compared to the C57BL/6J animals, as assessed by microvascular permeability, polymorphonuclear neutrophil (PMN) migration into lung tissue and alveolar space. The CX3CR1−/− mice showed increased levels of apoptotic PMNs in the lungs, and further investigations revealed an increased activation of necrosome-related receptor-interacting serine/threonine-protein kinases 1 (RIPK1), 3 (RIPK3), and mixed-lineage kinase domain-like pseudokinase (MLKL). Phosphorylated MLKL leads to membrane rupture and damage-associated molecular pattern (DAMP) release, which further enhance inflammation. The release of DAMPs was significantly higher in the CX3CR1−/− mice and led to the activation of various cascades, explaining the increased inflammation. RIPK3 and MLKL inhibition improved the inflammatory response in human PMNs in vitro and confirmed our in vivo findings. In conclusion, we linked CX3CL1 to the necrosome complex in pulmonary inflammation and demonstrated a pivotal role of the necrosome complex in human PMNs.
The Multifaceted Role of Th1, Th9, and Th17 Cells in Immune Checkpoint Inhibition Therapy

During the last decade, immune checkpoint inhibition (ICI) has become a pillar of cancer therapy. Antibodies targeting CTLA-4 or PD-1/PD-L1 have been approved in several malignancies, with thousands of clinical trials currently underway. While the majority of cancer immunotherapies have traditionally focused on enhancing cytotoxic responses by CD8+ or NK cells, there are clear evidences that CD4+ T cell responses can modulate the immune response against tumors and influence the efficacy of ICI therapy. CD4+ T cells can differentiate into several subsets of helper T cells (Th) or regulatory T cells (Treg), with a wide range of effector and/or regulatory functions. Importantly, different Th subsets may have different and sometimes contrasting roles in the clinical response to ICI therapy, which in addition may vary depending on the organ and tumor niche. In this review, we discuss recent evidence that highlights how ICI therapy impacts Th1, Th9, and Th17 cells and vice versa. These data might be important designing better interventions that unleash the full potential of immune response against cancer.
A Large-Scale Sequencing-Based Survey of Plasmids in Listeria monocytogenes Reveals Global Dissemination of Plasmids

The food-borne pathogen Listeria monocytogenes is known for its capacity to cope with multiple stress conditions occurring in food and food production environments (FPEs). Plasmids can provide benefits to their host strains, and it is known that various Listeria strains contain plasmids. However, the current understanding of plasmid frequency and function in L. monocytogenes strains remains rather limited. To determine the presence of plasmids among L. monocytogenes strains and their potential contribution to stress survival, a comprehensive dataset was established based on 1,921 published genomes from strains representing 14 L. monocytogenes sequence types (STs). Our results show that an average of 54% of all L. monocytogenes strains in the dataset contained a putative plasmid. The presence of plasmids was highly variable between different STs. While some STs, such as ST1, ST2, and ST4, contained few plasmid-bearing strains (<15% of the strains per ST), other STs, such as ST121, ST5, ST8, ST3, and ST204, possessed a higher proportion of plasmid-bearing strains with plasmids found in >71% of the strains within each ST. Overall, the sizes of plasmids analyzed in this study ranged from 4 to 170 kbp with a median plasmid size of 61 kbp. We also identified two novel groups of putative Listeria plasmids based on the amino acid sequences of the plasmid replication protein, RepA. We show that highly conserved plasmids are shared among Listeria strains which have been isolated from around the world over the last few decades. To investigate the potential roles of plasmids, nine genes related to stress-response were selected for an assessment of their abundance and conservation among L. monocytogenes plasmids. The results demonstrated that these plasmid genes exhibited high sequence conservation but that their presence in plasmids was highly variable. Additionally, we identified a novel transposon, Tn7075, predicted to be involved in mercury-resistance. Here, we provide the largest plasmid survey of L. monocytogenes to date with a comprehensive examination of the distribution of plasmids among L. monocytogenes strains. Our results significantly increase our knowledge about the distribution, composition, and conservation of L. monocytogenes plasmids and suggest that plasmids are likely important for the survival of L. monocytogenes in food and FPEs.
Single-Pulse TMS to the Temporo-Occipital and Dorsolateral Prefrontal Cortex Evokes Lateralized Long Latency EEG Responses at the Stimulation Site

Introduction Transcranial magnetic stimulation (TMS)–evoked potentials (TEPs) allow for probing cortical functions in health and pathology. However, there is uncertainty whether long-latency TMS-evoked potentials reflect functioning of the targeted cortical area. It has been suggested that components such as the TMS-evoked N100 are stereotypical and related to nonspecific sensory processes rather than transcranial effects of the changing magnetic field. In contrast, TEPs that vary according to the targeted brain region and are systematically lateralized toward the stimulated hemisphere can be considered to reflect activity in the stimulated brain region resulting from transcranial electromagnetic induction. Methods TMS with concurrent 64-channel electroencephalography (EEG) was sequentially performed in homologous areas of both hemispheres. One sample of healthy adults received TMS to the dorsolateral prefrontal cortex; another sample received TMS to the temporo-occipital cortex. We analyzed late negative TEP deflections corresponding to the N100 component in motor cortex stimulation. Results TEP topography varied according to the stimulation target site. Long-latency negative TEP deflections were systematically lateralized (higher in ipsilateral compared to contralateral electrodes) in electrodes over the stimulated brain region. A calculation that removes evoked components that are not systematically lateralized relative to the stimulated hemisphere revealed negative maxima located around the respective target sites. Conclusion TEPs contain long-latency negative components that are lateralized toward the stimulated hemisphere and have their topographic maxima at the respective stimulation sites. They can be differentiated from co-occurring components that are invariable across different stimulation sites (probably reflecting coactivation of peripheral sensory afferences) according to their spatiotemporal patterns. Lateralized long-latency TEP components located at the stimulation site likely reflect activity evoked in the targeted cortex region by direct transcranial effects and are therefore suitable for assessing cortical functions.
The Digital Stressors Scale: Development and Validation of a New Survey Instrument to Measure Digital Stress Perceptions in the Workplace Context

This article reports on the development of an instrument to measure the perceived stress that results from the use and ubiquity of digital technology in the workplace. Based upon a contemporary understanding of stress and a set of stressors that is a substantial update to existing scales, the Digital Stressors Scale (DSS) advances the measurement of digital stress. Initially, 138 items were constructed for the instrument and grouped into a set of 15 digital stressors. Based on a sample of N = 1,998 online questionnaires completed by individuals representative of the US employed population, the scale was refined using exploratory factor analyses (EFA) and PLS-SEM. The resulting and final scale consists of ten stressor categories reflective of one higher-order construct and a total of 50 items. Through a nomological network that includes important outcome variables of digital stress (emotional exhaustion, innovation climate, job satisfaction, user satisfaction) it was then demonstrated that the DSS provides substantial explanatory power, particularly related to emotional exhaustion and user satisfaction. Thus, the DSS constitutes a state-of-the-art self-report instrument to measure the extent of distress appraisal related to digital technologies in the workplace and helps to explain further how and why information and communication technologies can lead to adverse outcomes in individuals, thereby providing the starting point for job related organizational interventions.
SOX9 Knockdown-Mediated FOXO3 Downregulation Confers Neuroprotection Against Ischemic Brain Injury

Background Evidence exists uncovering that SRY-box transcription factor 9 (SOX9) plays a role in ischemic brain injury (IBI). Thus, the current study was conducted to elucidate the specific role of SOX9 and the mechanism by which SOX9 influenced IBI. Methods The IBI-associated regulatory factors were searched by bioinformatics analysis. The rat model of IBI was generated using middle cerebral artery occlusion (MCAO) treatment. Neuronal cells were exposed to oxygen-glucose deprivation (OGD). The expressions of SOX9, forkhead box O3 (FOXO3), transcription of Cbp/p300-interacting transactivator with Glu/Asp-rich carboxy-terminal domain 2 (CITED2), and IκB kinase α (IKKα) in OGD-treated neuronal cells were characterized using reverse transcription quantitative polymerase chain reaction (RT-qPCR) assay. The interaction among CITED2, IKKα, and FOXO3 was identified by chromatin immunoprecipitation (ChIP) and dual luciferase reporter gene assays. Gain- and loss-of-function experiments were performed to verify the relationship among SOX9, FOXO3, CITED2, and IKKα and to investigate their functional effects on apoptosis and the inflammatory response of OGD-treated neuronal cells as well as neurological deficit and infarct area of the rat brain. Results SOX9, FOXO3, CITED2, and IKKα were highly expressed in OGD-treated neuronal cells. Silencing of SOX9 inhibited OGD-induced neuronal apoptosis and inflammatory response and reduced the neurological deficit and infarct area of the brain in the rats, which were caused by MCAO but were reversed by overexpressing FOXO3, CITED2, or IKKα. Conclusion Taken together, our study suggested that upregulation of SOX9 promoted IBI though upregulation of the FOXO3/CITED2/IKKα axis, highlighting a basic therapeutic consideration for IBI treatment.