Miracle-dz/UniFAR-FTUs huggingface dataset:
Older Women’s Loneliness and Depression Decreased by a Reminiscence Program in Times of COVID-19

The confinement caused by the current COVID-19 pandemic protects physical health, but in turn, has a long-lasting and far-reaching negative psychosocial impact; anxiety, stress, fear and depressive symptoms. All of these have a particular impact on vulnerable older people, putting them at serious risk of loneliness. Women report feeling lonelier than men, affecting women to a greater extent. The present study aims to analyze the efficacy of an integrative reminiscence intervention in older women living in nursing homes to reduce the effects of loneliness and depression after COVID-19. 34 older women living in nursing homes are included into study and were divided into intervention group (N = 14) and control group (N = 20). Results showed a significant reduction in perception of loneliness, depression and better positive affects, after the intervention. The pandemic has not yet finished and the most affected group has been the people living in nursing homes. These results show the need for evidence of interventions that can help the recovery of these people who have been so affected. The effects of loneliness during confinement and its psychological effects can be mitigated through such programs.
Raw and Cooked Vegetable Consumption and Risk of Cardiovascular Disease: A Study of 400,000 Adults in UK Biobank

Objectives Higher levels of vegetable consumption have been associated with a lower risk of cardiovascular disease (CVD), but the independent effect of raw and cooked vegetable consumption remains unclear. Methods From the UK Biobank cohort, 399,586 participants without prior CVD were included in the analysis. Raw and cooked vegetable intakes were measured with a validated dietary questionnaire at baseline. Multivariable Cox regression was used to estimate the associations between vegetable intake and CVD incidence and mortality, adjusted for socioeconomic status, health status, and lifestyle factors. The potential effect of residual confounding was assessed by calculating the percentage reduction in the likelihood ratio (LR) statistics after adjustment for the confounders. Results The mean age was 56 years and 55% were women. Mean intakes of raw and cooked vegetables were 2.3 and 2.8 tablespoons/day, respectively. During 12 years of follow-up, 18,052 major CVD events and 4,406 CVD deaths occurred. Raw vegetable intake was inversely associated with both CVD incidence (adjusted hazard ratio (HR) [95% CI] for the highest vs. lowest intake: 0.89 [0.83–0.95]) and CVD mortality (0.85 [0.74–0.97]), while cooked vegetable intake was not (1.00 [0.91–1.09] and 0.96 [0.80–1.13], respectively). Adjustment for potential confounders reduced the LR statistics for the associations of raw vegetables with CVD incidence and mortality by 82 and 87%, respectively. Conclusions Higher intakes of raw, but not cooked, vegetables were associated with lower CVD risk. Residual confounding is likely to account for much, if not all, of the observed associations. This study suggests the need to reappraise the evidence on the burden of CVD disease attributable to low vegetable intake in the high-income populations.
The Amino Terminal Domain and Modulation of Connexin36 Gap Junction Channels by Intracellular Magnesium Ions

Electrical synapses between neurons in the mammalian CNS are predominantly formed of the connexin36 (Cx36) gap junction (GJ) channel protein. Unique among GJs formed of a number of other members of the Cx gene family, Cx36 GJs possess a high sensitivity to intracellular Mg2+ that can robustly act to modulate the strength of electrical synaptic transmission. Although a putative Mg2+ binding site was previously identified to reside in the aqueous pore in the first extracellular (E1) loop domain, the involvement of the N-terminal (NT) domain in the atypical response of Cx36 GJs to pH was shown to depend on intracellular levels of Mg2+. In this study, we examined the impact of amino acid substitutions in the NT domain on Mg2+ modulation of Cx36 GJs, focusing on positions predicted to line the pore funnel, which constitutes the cytoplasmic entrance of the channel pore. We find that charge substitutions at the 8th, 13th, and 18th positions had pronounced effects on Mg2+ sensitivity, particularly at position 13 at which an A13K substitution completely abolished sensitivity to Mg2+. To assess potential mechanisms of Mg2+ action, we constructed and tested a series of mathematical models that took into account gating of the component hemichannels in a Cx36 GJ channel as well as Mg2+ binding to each hemichannel in open and/or closed states. Simultaneous model fitting of measurements of junctional conductance, gj, and transjunctional Mg2+ fluxes using a fluorescent Mg2+ indicator suggested that the most viable mechanism for Cx36 regulation by Mg2+ entails the binding of Mg2+ to and subsequent stabilization of the closed state in each hemichannel. Reduced permeability to Mg2+ was also evident, particularly for the A13K substitution, but homology modeling of all charge-substituted NT variants showed only a moderate correlation between a reduction in the negative electrostatic potential and a reduction in the permeability to Mg2+ ions. Given the reported role of the E1 domain in Mg2+ binding together with the impact of NT substitutions on gating and the apparent state-dependence of Mg2+ binding, this study suggests that the NT domain can be an integral part of Mg2+ modulation of Cx36 GJs likely through the coupling of conformational changes between NT and E1 domains.
Revamping of Chronic Respiratory Diseases in Low- and Middle-Income Countries

Low- and middle-income countries (LMICs) endure an asymmetrically high burden of worldwide disease and death caused by chronic respiratory diseases (CRDs), i.e., asthma, emphysema, bronchiectasis, and post-tuberculosis lung disease (PTLD). CRDs are firmly related with indigence, infectious diseases, and other non-communicable diseases (NCDs) and add to complex multi-disease with great impact on the lives and livelihood of those affected. The pertinence of CRDs to health and demographic wellbeing is relied upon to increment in the long time ahead, as expectations of life rise and the contending dangers of right on time youth mortality and irresistible infections level. The WHO has distinguished the counteraction and control of NCDs as an earnest improvement issue and crucial for the sustainable development goals (SDSs) by 2030. In this review, we center on CRDs in LMICs. We examine the early life roots of CRDs, challenges in their avoidance, identification and administration in LMICs, and the pathways to resolve for accomplish valid widespread wellbeing inclusion.
Effect of Early Pathogenic Escherichia coli Infection on the Intestinal Barrier and Immune Function in Newborn Calves

We studied the effect of early pathogenic Escherichia coli infection on newborn calves’ intestinal barrier and immune function. A total of 64 newborn Holstein male calves (40–43 kg) were divided into two groups: normal (NG) and test (TG), each with 32 heads. At the beginning of the experiment, the TG calves were orally administered pathogenic E. coli O1 (2.5 × 1011 CFU/mL, 100 mL) to establish a calf diarrhea model. In contrast, the NG calves were given the same amount of normal saline. During the 30 d trial period, the feeding and management of the two groups remained constant. Enzyme-linked immunosorbent assay, quantification PCR, and high-throughput 16S rRNA sequencing technology were used to detect indicators related to the intestinal barrier and immune function in the calf serum and tissues. Pathogenic E. coli O1 had a significant effect on calf diarrhea in the TG; it increased the bovine diamine oxidase (P < 0.05) and endotoxin levels in the serum and decreased (P < 0.05) the intestinal trefoil factor (P < 0.05), Occludin, Claudin-1, and Zonula Occludens 1 (ZO-1) levels in the colon tissue, as well as downregulated the mRNA expression of Occludin, Claudin-1,and ZO-1 in the colon mucosa, leading to increased intestinal permeability and impaired intestinal barrier function. Additionally, pathogenic E. coli had a significant impact on the diversity of colonic microbial flora, increasing the relative abundance of Proteobacteria at the phylum level and decreasing the levels of Firmicutes and Bacteroides. At the genus level, the relative abundance of Escherichia and Shigella in the TG increased significantly (P < 0.05), whereas that of Bacteroides, Butyricicoccus, Rikenellaceae_RC9_gut_group, Blautia, and Lactobacillus was significantly decreased (P < 0.05). In addition, the level of IL-6 in the serum of the TG calves was significantly increased (P < 0.05), whereas the IL-4 and IL-10 levels were significantly decreased (P < 0.05), compared to those in the NG calves. Thus, pathogenic E. coli induced diarrhea early in life disrupts intestinal barrier and impairs immune function in calves.
Baicalein—A Potent Pro-Homeostatic Regulator of Microglia in Retinal Ischemic Injury

Retinal ischemia is a common cause of many retinal diseases, leading to irreversible vision impairment and blindness. Excessive neuroinflammation, including microglial activation and T-cell responses, has been identified as a critical factor associated with neurodegeneration in retinal ischemia. Baicalein is a natural flavonoid reported to have broad anti-inflammatory and neuroprotective bioactivities. Herein, the effects of baicalein on microglia activation in vitro and in vivo were investigated. We found that baicalein exhibited robust anti-inflammatory effect on cultured human and mouse microglia, as demonstrated by decreased induction of pro-inflammatory cytokines and the phosphorylation of phosphoinositide 3-kinase (PI3K) and nuclear factor kappa B (NFκB). Proteomic analysis further unraveled baicalein’s effect on modulating IL-17 signaling pathways and its upstream regulator IL-1β. Intravitreal administration of baicalein in the mouse model of retinal ischemia/reperfusion (I/R) injury attenuated microglial activation and retinal T-cell infiltration, particularly the T helper 17 cells. Additionally, baicalein was shown to exert neuroprotective effects by significantly reducing the retinal ganglion cell (RGC) loss after I/R injury, leading to an improved retinal function and spatial vision. These results suggest that baicalein, a natural flavonoid, acts as a negative regulator of activated microglia and immune responses both in vitro and in vivo, effectively alleviating neurodegeneration in retinal I/R injury. This finding indicates that baicalein could be a potential therapeutic agent against currently incurable degenerative retinal diseases.
Breast Cancer; Discovery of Novel Diagnostic Biomarkers, Drug Resistance, and Therapeutic Implications

Breast cancer is the second most reported cancer in women with high mortality causing millions of cancer-related deaths annually. Early detection of breast cancer intensifies the struggle towards discovering, developing, and optimizing diagnostic biomarkers that can improve its prognosis and therapeutic outcomes. Breast cancer-associated biomarkers comprise macromolecules, such as nucleic acid (DNA/RNA), proteins, and intact cells. Advancements in molecular technologies have identified all types of biomarkers that are exclusively studied for diagnostic, prognostic, drug resistance, and therapeutic implications. Identifying biomarkers may solve the problem of drug resistance which is a challenging obstacle in breast cancer treatment. Dysregulation of non-coding RNAs including circular RNAs (circRNAs) and microRNAs (miRNAs) initiates and progresses breast cancer. The circulating multiple miRNA profiles promise better diagnostic and prognostic performance and sensitivity than individual miRNAs. The high stability and existence of circRNAs in body fluids make them a promising new diagnostic biomarker. Many therapeutic-based novels targeting agents have been identified, including ESR1 mutation (DNA mutations), Oligonucleotide analogs and antagonists (miRNA), poly (ADP-ribose) polymerase (PARP) in BRCA mutations, CDK4/6 (cell cycle regulating factor initiates tumor progression), Androgen receptor (a steroid hormone receptor), that have entered clinical validation procedure. In this review, we summarize the role of novel breast cancer diagnostic biomarkers, drug resistance, and therapeutic implications for breast cancer.
The Distance Between the Cranial Nerve IX-X Root Entry/Exit Zone and the Pontomedullary Sulcus: MR Imaging Study in Patients With Hemifacial Spasm

Subject To quantitatively describe the distance between the cranial nerve (CN) IX-X root entry/exit zone (REZ) and the pontomedullary sulcus in patients with hemifacial spasm (HFS). Methods A total of 215 outpatients with HFS were recruited. Finally, 108 patients who yielded high-quality images were enrolled in the study. MRIs were reconstructed to measure the distance between the bilateral CN IX-X REZs and the corresponding pontomedullary sulcus. Results Among the 108 patients, the ratio of males to females was 39/69, and the mean age was 57.9 ± 6.5 years. The ratio of left to right HFS involvement was 47/61. The average height was 1.62 ± 0.07 m, and the average body mass index (BMI) was 24.65 ± 2.97 kg/m2. The distance between the cephalic end of the CN IX-X REZ and the pontomedullary sulcus was 2.7 ± 0.9 mm. The distance between the caudal end of the CN IX-X REZ and the pontomedullary sulcus was 7.6 ± 1.1 mm. No monotonic relationship was found between distance and height or BMI in the scatter diagrams. Conclusions The CN IX-X REZ is closely related to the pontomedullary sulcus in patients with HFS, and there is no difference between the left and right sides. The distances were not correlated with height or BMI in patients with HFS.
Body Mass Index and Academic Achievement Among Chinese Secondary School Students: The Mediating Effect of Inhibitory Control and the Moderating Effect of Social Support

Based on Embodied Cognition Theory, Inhibitory Decline Theory, and Risk Protective Factors Model, this study verified that body mass index (BMI) affects secondary school students’ academic performance through the mechanism of inhibitory control. In addition, it was verified that the strength of this mechanism depends on the teacher, parent, and peer support received by secondary school students. By using height and weight measurements, the classic stroop task, and the social support scale, 264 secondary school students in Shanxi Province, China, were surveyed and their academic performance was collected. The results showed that students with high BMI had poorer academic performance, and inhibitory control partially mediated the effect between BMI and academic performance, with the inhibitory control mediated effect accounting for 36.68% of the total effect. Support from teachers, parents, and peers can ameliorate the negative effects of BMI on academic performance, with teacher support and parental support also ameliorating the negative effects of BMI on inhibitory control. Thus, high BMI impairs inhibitory control and thus has a negative impact on academic performance, which can be buffered by social support.
Embryonic Hypotaurine Levels Contribute to Strain-Dependent Susceptibility in Mouse Models of Valproate-Induced Neural Tube Defects

Valproic acid (VPA, valproate, Depakote) is a commonly used anti-seizure medication (ASM) in the treatment of epilepsy and a variety of other neurological disorders. While VPA and other ASMs are efficacious for management of seizures, they also increase the risk for adverse pregnancy outcomes, including neural tube defects (NTDs). Thus, the utility of these drugs during pregnancy and in women of childbearing potential presents a continuing public health challenge. Elucidating the underlying genetic or metabolic risk factors for VPA-affected pregnancies may lead to development of non-teratogenic ASMs, novel prevention strategies, or more targeted methods for managing epileptic pregnancies. To address this challenge, we performed unbiased, whole embryo metabolomic screening of E8.5 mouse embryos from two inbred strains with differential susceptibility to VPA-induced NTDs. We identified metabolites of differential abundance between the two strains, both in response to VPA exposure and in the vehicle controls. Notable enriched pathways included lipid metabolism, carnitine metabolism, and several amino acid pathways, especially cysteine and methionine metabolism. There also was increased abundance of ω-oxidation products of VPA in the more NTD-sensitive strain, suggesting differential metabolism of the drug. Finally, we found significantly reduced levels of hypotaurine in the susceptible strain regardless of VPA status. Based on this information, we hypothesized that maternal supplementation with L-carnitine (400 mg/kg), coenzyme A (200 mg/kg), or hypotaurine (350 mg/kg) would reduce VPA-induced NTDs in the sensitive strain and found that administration of hypotaurine prior to VPA exposure significantly reduced the occurrence of NTDs by close to one-third compared to controls. L-carnitine and coenzyme A reduced resorption rates but did not significantly reduce NTD risk in the sensitive strain. These results suggest that genetic variants or environmental exposures influencing embryonic hypotaurine status may be factors in determining risk for adverse pregnancy outcomes when managing the health care needs of pregnant women exposed to VPA or other ASMs.
Sex Difference in Global Burden of Major Depressive Disorder: Findings From the Global Burden of Disease Study 2019

Objectives Globally, major depressive disorder (MDD) is considered to be a leading cause of disability. In this article, we aim to investigate the sex difference in global burden of MDD by year, age, and socioeconomic development, utilizing disability-adjusted life-years (DALYs). Methods Global and national sex-specific DALY estimates caused by MDD from 1990 to 2019 and in different age groups were obtained from the Global Burden of Disease (GBD) Study 2019. Human development index (HDI) was used as an indicator of national socioeconomic development. Spearman correlation and linear regression analyses were performed to explore the relationship between national socioeconomic development and sex difference in MDD burden. Results Sex difference in global burden of MDD persisted between 1990 and 2019, with age-standardized DALY rates being 352 among males vs. 593 among females in 1990 and 354 vs. 564 in 2019. Females had higher burden of MDD than males at the same age. Disability-adjusted life-years numbers and rates among both sexes rapidly increased with age for those aged 10–24 years, along with gradually enlarging sex difference. Age-standardized DALY rates among females were higher than that among males for each HDI-based country group (P < 0.001). National age-standardized DALY rates among both sexes were negatively related to HDI. However, female-to-male age-standardized DALY rate ratios were positively associated with HDI (Spearman r = 0.383, P < 0.001; standardized β = 0.300, P < 0.001). Conclusion Although some improvement in sex difference in global burden of MDD has been achieved, it still persists in the past three decades, with females bearing more burden than males. To reduce sex difference in global MDD burden, more attention should be paid to young people and people in developed countries. The findings highlight the importance of making sex-specific health policy to manage mental impairment caused by MDD.
Predictive Value of Echocardiographic Strain for Myocardial Fibrosis and Adverse Outcomes in Autoimmune Diseases

Background Myocardial fibrosis is an important pathophysiologic mechanism of cardiac involvement that leads to increased mortality in patients with autoimmune diseases (AIDs). The aim of this study was to evaluate the association between myocardial strain from speckle-tracking echocardiography (STE) and fibrosis on cardiovascular magnetic resonance (CMR) and to further explore their prognostic implications in patients with AIDs. Methods We prospectively included 102 AIDs patients with clinically suspected cardiac involvement and 102 age- and sex-matched healthy individuals. Patients underwent CMR for evaluation of myocardial fibrosis by late gadolinium enhancement (LGE) and T1 mapping. A semiquantitative evaluation based on the extent of LGE was used to calculate the total (tLGEs) and segmental (sLGEs) LGE score. Global longitudinal strain (GLS) was evaluated by STE in all subjects. All patients were regularly followed up every 6 months. The primary endpoint was the composite incidence of all-cause death and cardiovascular hospitalization. Results Compared to healthy controls, AIDs patients had impaired GLS (−17.9 ± 5.1% vs. −21.2 ± 2.5%, p < 0.001). LGE was detected in 70% of patients. Patients with LGE presented worse GLS (−17.1 ± 5.3% vs. −19.6 ± 4.1%, p = 0.018) than those without LGE. On multivariate logistic analysis, GLS ≥ −15% was an independent predictor of LGE presence (OR = 4.98, 95%CI 1.35–18.33, p = 0.016). Moreover, a marked and stepwise impairment of segmental longitudinal strain (−19.3 ± 6.6 vs. −14.9 ± 6.5 vs. −8.9 ± 6.3, p < 0.001) was observed as sLGEs increased. During a median follow-up time of 25 months, 6 patients died, and 14 patients were hospitalized for cardiovascular reasons. Both GLS ≥ −15% (HR 3.56, 95%CI 1.28–9.86, p = 0.015) and tLGEs ≥ 6 (HR 4.13, 95%CI 1.43–11.92, p = 0.009) were independently associated with the primary endpoint. Conclusions In AIDs patients, impaired myocardial strain on STE could reflect the presence and extent of myocardial fibrosis and provide incremental prognostic value in addition to LGE in the prediction of adverse outcomes.
Dynamics of Etiolation Monitored by Seedling Morphology, Carotenoid Composition, Antioxidant Level, and Photoactivity of Protochlorophyllide in Arabidopsis thaliana

Although etiolated Arabidopsis thaliana seedlings are widely used as a model to study the de-etiolation process, the etiolation itself at the molecular level still needs elucidation. Here, we monitored the etiolation dynamics for wild type A. thaliana seedlings and lutein-deficient (lut2) mutant between 2 and 12 days of their growth in the absence of light. We analyzed the shape of the apex, the growth rate, the carotenoids and protochlorophyllide (Pchlide) accumulation, and the light-dependent protochlorophyllide oxidoreductase (LPOR) transcripts. Differences concerning the apical hook curvature and cotyledon opening among seedlings of the same age were observed, mostly after day 6 of the culture. We categorized the observed apex shapes and presented quantitatively how distribution among the categories changed during 12 days of seedling growth. The Pchlide654/Pchlide633 ratio, corresponding to the amount of the photoactive Pchlide, was the highest in the youngest seedlings, and decreased with their age. LPORA, LPORB, and LPORC transcripts were detected in etiolated seedlings, and their content decreased during seedling growth. Expression of SAG12 or SAG13 senescence markers, depletion in antioxidants, and excess ion leakage were not observed during the etiolation. Lack of lutein in the lut2 mutant resulted in slow Pchlide accumulation and affected other xanthophyll composition.