Miracle-dz/UniFAR-FTUs huggingface dataset:
Associations between Healthcare Resources and Healthy Life Expectancy: A Descriptive Study across Secondary Medical Areas in Japan

Japan has the highest life expectancy in the world. However, this does not guarantee an improved quality of life. There is a gap between life expectancy and healthy life expectancy. This study aimed to reveal the features of healthy life expectancy across all secondary medical areas (n = 344) in Japan and examine the relationship among healthcare resources, life expectancy, and healthy life expectancy at birth. Data were collected from Japan’s population registry and long-term insurance records. Differences in healthy life expectancy by gender were calculated using the Sullivan method. Maps of healthy life expectancy were drawn up. Descriptive statistics and correlation analysis were used for analysis. The findings revealed significant regional disparities. The number of doctors and therapists, support clinics for home healthcare facilities and home-visit treatments, and dentistry expenditure per capita were positively correlated with life expectancy and healthy life expectancy (correlation coefficients > 0.2). They also revealed gender differences. Despite controlling for population density, inequalities in healthy life expectancy were observed, highlighting the need to promote social policies to reduce regional disparities. Japanese policymakers should consider optimal levels of health resources to improve life expectancy and healthy life expectancy. The geographical distribution of healthcare resources should also be reconstituted.
Atmospheric Biodetection Part I: Study of Airborne Bacterial Concentrations from January 2018 to May 2020 at Saclay, France

Background: The monitoring of bioaerosol concentrations in the air is a relevant endeavor due to potential health risks associated with exposure to such particles and in the understanding of their role in climate. In this context, the atmospheric concentrations of bacteria were measured from January 2018 to May 2020 at Saclay, France. The aim of the study was to understand the seasonality, the daily variability, and to identify the geographical origin of airborne bacteria. Methods: 880 samples were collected daily on polycarbonate filters, extracted with purified water, and analyzed using the cultivable method and flow cytometry. A source receptor model was used to identify the origin of bacteria. Results: A tri-modal seasonality was identified with the highest concentrations early in spring and over the summer season with the lowest during the winter season. Extreme changes occurred daily due to rapid changes in meteorological conditions and shifts from clean air masses to polluted ones. Conclusion: Our work points toward bacterial concentrations originating from specific seasonal-geographical ecosystems. During pollution events, bacteria appear to rise from dense urban areas or are transported long distances from their sources. This key finding should drive future actions to better control the dispersion of potential pathogens in the air, like persistent microorganisms originating from contaminated areas.
Early Biomarkers of Neurodegenerative and Neurovascular Disorders in Diabetes

Diabetes mellitus (DM) is a common disease worldwide. There is a strong association between DM and neurovascular and neurodegenerative disorders. The first group mainly consists of diabetic retinopathy, diabetic neuropathy and stroke, whereas, the second group includes Alzheimer’s disease, Parkinson’s disease, mild cognitive impairment and dementia. The aforementioned diseases have a common pathophysiological background including insulin resistance, oxidative stress, atherosclerosis and vascular injury. The increasing prevalence of neurovascular and neurodegenerative disorders among diabetic patients has resulted in an urgent need to develop biomarkers for their prediction and/or early detection. The aim of this review is to present the potential application of the most promising biomarkers of diabetes-related neurodegenerative and neurovascular disorders, including amylin, β-amyloid, C-reactive protein (CRP), dopamine, gamma-glutamyl transferase (GGT), glycogen synthase kinase 3β, homocysteine, microRNAs (mi-RNAs), paraoxonase 1, phosphoinositide 3-kinases, tau protein and various growth factors. The most clinically promising biomarkers of neurovascular and neurodegenerative complications in DM are hsCRP, GGT, homocysteine and miRNAs. However, all biomarkers discussed in this review could become a part of the potential multi-biomarker screening panel for diabetic patients at risk of neurovascular and neurodegenerative complications.
Tomographic Task-Related Functional Near-Infrared Spectroscopy in Acute Sport-Related Concussion: An Observational Case Study

Making decisions regarding return-to-play after sport-related concussion (SRC) based on resolution of symptoms alone can expose contact-sport athletes to further injury before their recovery is complete. Task-related functional near-infrared spectroscopy (fNIRS) could be used to scan for abnormalities in the brain activation patterns of SRC athletes and help clinicians to manage their return-to-play. This study aims to show a proof of concept of mapping brain activation, using tomographic task-related fNIRS, as part of the clinical assessment of acute SRC patients. A high-density frequency-domain optical device was used to scan 2 SRC patients, within 72 h from injury, during the execution of 3 neurocognitive tests used in clinical practice. The optical data were resolved into a tomographic reconstruction of the brain functional activation pattern, using diffuse optical tomography. Moreover, brain activity was inferred using single-subject statistical analyses. The advantages and limitations of the introduction of this optical technique into the clinical assessment of acute SRC patients are discussed.
Nettle Tea Inhibits Growth of Acute Myeloid Leukemia Cells In Vitro by Promoting Apoptosis

Urtica dioica (UD), commonly known as “stinging nettle”, is a herbaceous flowering plant that is a widely used agent in traditional medicine worldwide. Several formulations of UD leaf extract have been reported to exhibit anti-inflammatory and antioxidant properties, with anticancer potential. The current study investigated the possible anticancer properties of nettle tea, prepared from Urtica dioica leaves, on acute myeloid leukemia (AML) cell lines, and deciphered the underlying molecular mechanisms. Treatment of AML cell lines (U-937 and KG-1) with UD aqueous leaf extract resulted in a dose- and time-dependent inhibition of proliferation, an increase in apoptotic hallmarks such as phosphatidylserine flipping to the outer membrane leaflet, and DNA fragmentation as revealed by cell-death ELISA and cell-cycle analysis assays. Apoptosis induction in U937 cells involves alterations in the expression of Bax and Bcl-2 upon exposure to nettle tea. Furthermore, the chemical composition of UD aqueous extract indicated the presence of multiple chemical agents, such as flavonoids and phenolics, mainly patuletin, m/p-hydroxybenzoic acid, and caffeic acid, among others, to which the pro-apoptotic and anti-tumor effects may be attributed.
Lysine acetylation of F-actin decreases tropomyosin-based inhibition of actomyosin activity

Recent proteomics studies of vertebrate striated muscle have identified lysine acetylation at several sites on actin. Acetylation is a reversible post-translational modification that neutralizes lysine's positive charge. Positively charged residues on actin, particularly Lys326 and Lys328, are predicted to form critical electrostatic interactions with tropomyosin (Tpm) that promote its binding to filamentous (F)-actin and bias Tpm to an azimuthal location where it impedes myosin attachment. The troponin (Tn) complex also influences Tpm's position along F-actin as a function of Ca2+ to regulate exposure of myosin-binding sites and, thus, myosin cross-bridge recruitment and force production. Interestingly, Lys326 and Lys328 are among the documented acetylated residues. Using an acetic anhydride-based labeling approach, we showed that excessive, nonspecific actin acetylation did not disrupt characteristic F-actin–Tpm binding. However, it significantly reduced Tpm-mediated inhibition of myosin attachment, as reflected by increased F-actin–Tpm motility that persisted in the presence of Tn and submaximal Ca2+. Furthermore, decreasing the extent of chemical acetylation, to presumptively target highly reactive Lys326 and Lys328, also resulted in less inhibited F-actin–Tpm, implying that modifying only these residues influences Tpm's location and, potentially, thin filament regulation. To unequivocally determine the residue-specific consequences of acetylation on Tn–Tpm–based regulation of actomyosin activity, we assessed the effects of K326Q and K328Q acetyl (Ac)-mimetic actin on Ca2+-dependent, in vitro motility parameters of reconstituted thin filaments (RTFs). Incorporation of K328Q actin significantly enhanced Ca2+ sensitivity of RTF activation relative to control. Together, our findings suggest that actin acetylation, especially Lys328, modulates muscle contraction via disrupting inhibitory Tpm positioning.
The Role of Meteorite Impacts in the Origin of Life

The conditions, timing, and setting for the origin of life on Earth and whether life exists elsewhere in our solar system and beyond represent some of the most fundamental scientific questions of our time. Although the bombardment of planets and satellites by asteroids and comets has long been viewed as a destructive process that would have presented a barrier to the emergence of life and frustrated or extinguished life, we provide a comprehensive synthesis of data and observations on the beneficial role of impacts in a wide range of prebiotic and biological processes. In the context of previously proposed environments for the origin of life on Earth, we discuss how meteorite impacts can generate both subaerial and submarine hydrothermal vents, abundant hydrothermal–sedimentary settings, and impact analogues for volcanic pumice rafts and splash pools. Impact events can also deliver and/or generate many of the necessary chemical ingredients for life and catalytic substrates such as clays as well. The role that impact cratering plays in fracturing planetary crusts and its effects on deep subsurface habitats for life are also discussed. In summary, we propose that meteorite impact events are a fundamental geobiological process in planetary evolution that played an important role in the origin of life on Earth. We conclude with the recommendation that impact craters should be considered prime sites in the search for evidence of past life on Mars. Furthermore, unlike other geological processes such as volcanism or plate tectonics, impact cratering is ubiquitous on planetary bodies throughout the Universe and is independent of size, composition, and distance from the host star. Impact events thus provide a mechanism with the potential to generate habitable planets, moons, and asteroids throughout the Solar System and beyond.
CXCR3 and Cognate Ligands are Associated with Immune Cell Alteration and Aggressiveness of Pancreatic Ductal Adenocarcinoma

Purpose: The cytokine milieu in pancreatic ductal adenocarcinoma (PDAC) promotes tumor progression and immune suppression, contributing to the dismal prognosis of patients with PDAC. The roles of many of these cytokines, however, have not been thoroughly investigated in PDAC. Experimental Design: PDAC microarray and The Cancer Genome Atlas datasets were analyzed to identify cytokines and cognate receptors overexpressed in PDAC and associated with survival. Pathway and CIBERSORT analyses were used to elucidate potential mechanisms of altered patient survival. Comparative analysis of cytokine expression in KPC (K-rasG12D; TP53R172H; Pdx-1cre) and KC (K-rasG12D; Pdx-1cre) PDAC models and multicolor immunofluorescence (IF) staining of human PDAC–resected samples were used to validate these findings. Results: CXCL9 and CXCL10 were among the most highly overexpressed cytokines by bioinformatics analyses, while their receptor, CXCR3, was significantly overexpressed by IHC analysis. Higher CXCR3 ligand expression was associated with shorter overall survival, while high CXCR3 expression was associated with better survival. The CXCR3 ligands, CXCL4, 9, and 10, were overexpressed in KPC compared with KC mice. Pathway analysis of CXCR3- and CXCR3 ligand–associated genes showed that CXCR3 is a marker of antitumor immunity, while its ligands may promote immunosuppression. CIBERSORT and IF studies of PDAC tissues demonstrated that high CXCR3 expression was associated with increased CD8+ T-cell and naïve B-cell signatures and loss of plasma cell signatures. CXCR3 ligand expression was associated with increased CD8+ T-cell signatures and loss of natural killer–cell signatures. Conclusions: CXCR3 ligands are overexpressed in PDAC and are associated with poor survival likely related to alterations in tumor immune infiltrate/activity.
Intraoperative Clinical Examination for Assessing Pelvic and Para-Aortic Lymph Node Involvement in Advanced Epithelial Ovarian Cancer: A Systematic Review and Meta-Analysis

After the publication of the Lymphadenectomy in Ovarian Neoplasms (LION) trial results, lymphadenectomy in advanced epithelial ovarian cancer with primary complete cytoreductive surgery is considered indicated only for women with suspicious lymph nodes. The aim of this meta-analysis was to evaluate the diagnostic accuracy of intraoperative clinical examination for detecting lymph node metastases in patients with advanced epithelial ovarian cancer during primary complete cytoreductive surgery. MEDLINE, EMBASE, Web of Science and the Cochrane Library were searched for January 1990 to May 2019 for studies evaluating the diagnostic accuracy of intraoperative clinical examination for detecting lymph node metastases in patients with advanced epithelial ovarian cancer during primary complete cytoreductive surgery, with histology as the gold standard. Methodological quality was assessed by using the QUADAS-2 tool. Pooled diagnostic accuracy was calculated, and hierarchical summary receiver operating curve was constructed. The potential sources of heterogeneity were analyzed by meta-regression analysis. Deek’s funnel plot test for publication bias and Fagan’s nomogram for clinical utility were also used. This meta-analysis included five studies involving 723 women. The pooled sensitivity of intraoperative clinical examination for detecting lymph node metastases was 0.79, 95% CI (0.67–0.87), and its specificity 0.85, 95% CI (0.67–0.94); the area under the hierarchical summary receiver operating curve was 0.86, 95% CI (0.83–0.89). In the meta-regression analysis, patient sample size, mean age, and type of cancer included were significant covariates explaining the potential sources of heterogeneity. Deek’s funnel plot test showed no evidence of publication bias (p = 0.25). Fagan’s nomogram indicated that intraoperative clinical examination increased the post-test probability of lymph node metastases to 79% when it was positive and reduced it to 16% when negative. This meta-analysis shows that the diagnostic accuracy of intraoperative clinical examination during primary complete cytoreductive surgery for detecting lymph node metastases in advanced epithelial ovarian cancer is good.
Cyclic AMP mediates heat stress response by the control of redox homeostasis and ubiquitin-proteasome system.

Heat stress (HS), causing impairment in several physiological processes, is one of the most damaging environmental cues for plants. To counteract the harmful effects of high temperatures, plants activate complex signalling networks, indicated as HS response (HSR). Expression of heat shock proteins (HSPs) and adjustment of redox homeostasis are crucial events of HSR, required for thermotolerance. By pharmacological approaches, the involvement of cAMP in triggering plant HSR has been recently proposed. In this study, to investigate the role of cAMP in HSR signalling, tobacco BY-2 cells overexpressing the "cAMP-sponge", a genetic tool that reduces intracellular cAMP levels, have been used. In vivo cAMP dampening increased HS susceptibility in a HSPs-independent way. The failure in cAMP elevation during HS caused a high accumulation of reactive oxygen species, due to increased levels of respiratory burst oxidase homolog D, decreased activities of catalase and ascorbate peroxidase, as well as down-accumulation of proteins involved in the control of redox homeostasis. In addition, cAMP deficiency impaired proteasome activity and prevented the accumulation of many proteins of ubiquitin-proteasome system (UPS). By a large-scale proteomic approach together with in silico analyses these UPS proteins were identified in a specific cAMP-dependent network of HSR. This article is protected by copyright. All rights reserved.
Interferon-gamma-activated macrophages infected with Burkholderia cenocepacia process and present bacterial antigens to T-cells by class I and II major histocompatibility complex molecules

ABSTRACT Burkholderia cenocepacia is an emerging opportunistic pathogen for people with cystic fibrosis and chronic granulomatous disease. Intracellular survival in macrophages within a membrane-bound vacuole (BcCV) that delays acidification and maturation into lysosomes is a hallmark of B. cenocepacia infection. Intracellular B. cenocepacia induce an inflammatory response leading to macrophage cell death by pyroptosis through the secretion of a bacterial deamidase that results in the activation of the pyrin inflammasome. However, how or whether infected macrophages can process and present B. cenocepacia antigens to activate T-cells has not been explored. Engulfed bacterial protein antigens are cleaved into small peptides in the late endosomal major histocompatibility class II complex (MHC) compartment (MIIC). Here, we demonstrate that BcCVs and MIICs have overlapping features and that interferon-gamma-activated macrophages infected with B. cenocepacia can process bacterial antigens for presentation by class II MHC molecules to CD4+ T-cells and by class I MHC molecules to CD8+ T-cells. Infected macrophages also release processed bacterial peptides into the extracellular medium, stabilizing empty class I MHC molecules of bystander cells. Together, we conclude that BcCVs acquire MIIC characteristics, supporting the notion that macrophages infected with B. cenocepacia contribute to establishing an adaptive immune response against the pathogen.
The Adaptive Potential of the Middle Domain of Yeast Hsp90

Abstract The distribution of fitness effects (DFEs) of new mutations across different environments quantifies the potential for adaptation in a given environment and its cost in others. So far, results regarding the cost of adaptation across environments have been mixed, and most studies have sampled random mutations across different genes. Here, we quantify systematically how costs of adaptation vary along a large stretch of protein sequence by studying the distribution of fitness effects of the same ≈2,300 amino-acid changing mutations obtained from deep mutational scanning of 119 amino acids in the middle domain of the heat shock protein Hsp90 in five environments. This region is known to be important for client binding, stabilization of the Hsp90 dimer, stabilization of the N-terminal-Middle and Middle-C-terminal interdomains, and regulation of ATPase–chaperone activity. Interestingly, we find that fitness correlates well across diverse stressful environments, with the exception of one environment, diamide. Consistent with this result, we find little cost of adaptation; on average only one in seven beneficial mutations is deleterious in another environment. We identify a hotspot of beneficial mutations in a region of the protein that is located within an allosteric center. The identified protein regions that are enriched in beneficial, deleterious, and costly mutations coincide with residues that are involved in the stabilization of Hsp90 interdomains and stabilization of client-binding interfaces, or residues that are involved in ATPase–chaperone activity of Hsp90. Thus, our study yields information regarding the role and adaptive potential of a protein sequence that complements and extends known structural information.
Antenatal Iron-Folic Acid Supplementation Is Associated with Improved Linear Growth and Reduced Risk of Stunting or Severe Stunting in South Asian Children Less than Two Years of Age: A Pooled Analysis from Seven Countries

In South Asia, an estimated 38% of preschool-age children have stunted growth. We aimed to assess the effect of WHO-recommended antenatal iron, and folic acid (IFA) supplements on smaller than average birth size and stunting in South Asian children <2 years old. The sample was 96,512 mothers with their most recent birth within two years, from nationally representative surveys between 2005 and 2016 in seven South Asian countries. Primary outcomes were stunting [length-for-age Z-score (LAZ) < –2], severe stunting [length-for-age Z-score (LAZ) < –3], length-for-age Z score, and perceived smaller than average birth size. Exposure was the use of IFA supplements. We conducted analyses with Poisson, linear and logistic multivariate regression adjusted for the cluster survey design, and 14 potential confounders covering the country of the survey, socio-demographic factors, household economic status, maternal characteristics, and duration of respondent recall. The prevalence of stunting was 33%, severe stunting was 14%, and perceived smaller than average birth size was 22%. Use of antenatal IFA was associated with a reduced adjusted risk of being stunted by 8% (aRR 0.92, 95% CI 0.89, 0.95), of being severely stunted by 9% (aRR 0.91, 95% CI 0.86, 0.96) and of being smaller than average birth size by 14% (aRR 0.86, 95% CI 0.80, 0.91). The adjusted mean LAZ was significantly higher in children whose mothers used IFA supplements. Maternal use of IFA in the first four months gestation and consuming 120 or more supplements throughout pregnancy was associated with the largest reduction in risk of child stunting. Antenatal IFA supplementation was associated with a significantly reduced risk of stunting, severe stunting, and smaller than average perceived birth size and improved LAZ in young South Asian children. The early and sustained use of antenatal IFA has the potential to improve child growth outcomes in South Asia and other low-and-middle-income countries with high levels of iron deficiency in pregnancy.
Children as frequent attenders in primary care: a systematic review

Background Frequent paediatric attendances make up a large proportion of a GP's workload. Currently, there is no systematic review on frequent paediatric attendances in primary care. Aim To identify the sociodemographic and clinical characteristics of children who attend primary care frequently. Design & setting A systematic review. Method The electronic databases MEDLINE, Embase, and PsycINFO were searched up to January 2020, using terms relating to frequent attendance in primary care settings. Studies were eligible if they considered children frequently attending in primary care (aged 0–19 years). Relevant data were extracted and analysed by narrative synthesis. Results Six studies, of fair quality overall, were included in the review. Frequent attendance was associated with presence of psychosocial and mental health problems, younger age, school absence, presence of chronic conditions, and high level of anxiety in their parents. Conclusion Various sociodemographic and medical characteristics of children were associated with frequent attendance in primary care. Research on interventions needs to account for the social context and community characteristics. Integrating GP services with mental health and social care could potentially provide a response to medical and psychosocial needs of frequently attending children and their families.