Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional Restoration of Exhausted CD8 T Cells in Chronic HIV-1 Infection by Targeting Mitochondrial Dysfunction

CD8 T cell exhaustion is a hallmark of HIV-1 infection, characterized by phenotypic and functional CD8 T cell abnormalities that persist despite years of effective antiretroviral treatment (ART). More recently, the importance of cellular metabolism in shaping T cell antiviral function has emerged as a crucial aspect of immunotherapeutics aimed at re-invigorating exhausted CD8 T cells but remains under-investigated in HIV-1 infection. To gain a better insight into this process and identify new targets for effective CD8 T cell restoration we examined the metabolic profile of exhausted CD8 T cells in HIV-1 infection. We show that relative to HIV-1 elite controllers (EC) and HIV-1 seronegative donors, CD8 T cells from HIV-1 viraemic individuals are skewed toward a PD-1hiEOMEShiT-betlowTIGIT+ phenotype that is maintained during ART. This exhausted signature is enriched in HIV-specific CD8 T cells, compared to CMV-specific CD8 T cell populations, and further delineated by higher expression of the glucose transporter, Glut-1, impaired mitochondrial function and biogenesis, reflecting underlying metabolic defects. A notable improvement in antiviral HIV-specific CD8 T cell function was elicited via mitochondrial antioxidant treatment in combination with pharmacological modulation of mitochondrial dynamics and IL-15 treatment. These findings identify mitochondria as promising targets for combined reconstitution therapies in HIV-1 infection.
Hypertension Subtypes, Mortality Risk, and Differential Effects Between Two Hypertension Guidelines

Aim: To examine which hypertension subtypes are primarily responsible for the difference in the hypertension prevalence and treatment recommendations, and to assess their mortality risk if 2017 American College of Cardiology (ACC)/American Heart Association (AHA) hypertension guideline were adopted among Chinese adults. Methods We used the nationally representative data of China Health and Retirement Longitudinal Study (CHARLS) to estimate the differences in the prevalence of isolated systolic hypertension (ISH), systolic diastolic hypertension (SDH) and isolated diastolic hypertension (IDH) between the 2017 ACC/AHA and the 2018 China Hypertension League (CHL) guidelines. We further assessed their mortality risk using follow-up data from the China Health and Nutrition Survey (CHNS) by the Cox model. Results The increase from the 2017 ACC/AHA guideline on hypertension prevalence was mostly from SDH (8.64% by CHL to 25.59% by ACC/AHA), followed by IDH (2.42 to 6.93%). However, the difference was minuscule in the proportion of people recommended for antihypertensive treatment among people with IDH (2.42 to 3.34%) or ISH (12.00 to 12.73%). Among 22,184 participants with a median follow-up of 6.14 years from CHNS, attenuated but significant associations were observed between all-cause mortality and SDH (hazard ratio 1.56; 95% CI: 1.36,1.79) and ISH (1.29; 1.03,1.61) by ACC/AHA but null association for IDH (1.15; 0.98,1.35). Conclusion Adoption of the 2017 ACC/AHA may be applicable to improve the unacceptable hypertension control rate among Chinese adults but with cautions for the drug therapy among millions of subjects with IDH.
Managerial Networking and Frugal Innovation: Situational Leadership Perspective

This study aimed to examine the integrated relationships of business ties, political ties, sustainable leadership, and frugal innovation. The correlation was assessed with the consideration of social network and situational leadership theories. Data was collected from 363 Small and Medium Enterprises (SMEs) employees in Pakistan with a response rate of 72.60%. Accordingly, the Partial Least Squares-Structural Equation Modeling (PLS-SEM) was employed to examine the validity of the proposed hypotheses. Empirical findings confirmed the significant impact of managerial and business ties on frugal innovation, strengthened by sustainable leadership. However, data analysis negated the positive impact of political ties on frugal innovation, which remains non-significant with the introduction of sustainable leadership among Pakistani SMEs. Hence, future studies are recommended to explore other conditional factors and mediating mechanisms in the relationship between managerial ties and frugal innovation. This idea can bring a deeper insight into the vital role of networking. To the best of the author’s knowledge, no prior study is available about the integrated relationships of managerial ties, frugal innovation, and sustainable leadership. This study enriches the literature in innovation management, especially concerning the social network and situational leadership model.
Contrasting Water Withholding Responses of Young Maize Plants Reveal Link Between Lipid Peroxidation and Osmotic Regulation Corroborated by Genetic Analysis

Linking biochemistry and genetics of tolerance to osmotic stress is of interest for understanding plant adaptations to unfavorable conditions. The aims of this study were to investigate the variability in responses of panel of elite maize inbred lines to water withholding for stress-related traits through association study and to identify pathways linked to detected associations for better understanding of maize stress responses. Densely genotyped public and expired Plant Variety Protection Certificate (ex-PVP) inbred lines were planted in controlled conditions (16-h/8-h day/night, 25°C, 50% RH) in control (CO) and exposed to 10-day water withholding (WW). Traits analyzed were guaiacol peroxidase activity (GPOD), total protein content (PROT), lipid peroxidation (TBARS), hydrogen peroxide accumulation (H2O2), proline accumulation (proline), and current water content (CWC). Proline accumulation was found to be influenced by H2O2 and TBARS signaling pathways acting as an accumulation-switching mechanism. Most of the associations detected were for proline (29.4%) and TBARS (44.1%). Gene ontology (GO) enrichment analysis showed significant enrichment in regulation of integral membrane parts and peroxisomes along with regulation of transcription and polysaccharide catabolism. Dynamic studies involving inbreds with extreme phenotypes are needed to elucidate the role of this signaling mechanism in regulation of response to water deficit.
The Impact of Big Data Management Capabilities on the Performance of Manufacturing Firms in Asian Economy During COVID-19: The Mediating Role of Organizational Agility and Moderating Role of Information Technology Capability

The main purpose of this study is to examine the impact of the big data management capabilities on the performance of manufacturing firms in the Asian Economy during coronavirus disease 2019 (COVID-19). In addition to this, this study is also planned to examine the mediating role of organizational agility in the relationship between the big data management capabilities and the performance of Chinese manufacturing firms during COVID-19. Last, this study has examined the moderating role of information technology capability in the relationship between the big data management capabilities and performance of Chinese manufacturing firms during COVID-19. This study adopted the quantitative method of research with a cross-sectional technique. This study employed a questionnaire to gather the data as a research instrument. This study has used the purposive sampling method by keeping in mind the context of this study. Employees of the Chinese SMEs that were at least 10 years old were the population of this study. The research model was being analyzed by employing the “partial least squares” technique through statistical software the Smart PLS version 3. The results are in line with the proposed hypothesis. This study contributed to the literature by suggesting characteristics that promote or prevent the organization from successfully implementing big data and pointed out that showing resistance in information management system implementation may have different effects on the organization. Besides, the study also discussed the relationship between such information systems and the organization. Findings of these two factors provide insights for the practitioners and researchers in assessing the success or failure of organizations for using big data.
Early Response Assessment in Advanced Stage Melanoma Treated with Combination Ipilimumab/Nivolumab

Background Standard combination ipilimumab/nivolumab (I/N) is given as 4 induction doses for advanced stage melanoma followed by nivolumab single-agent maintenance therapy. While many patients receive less than 4 doses due to immune-related toxicities, it is unclear if fewer doses of I/N may still provide long term clinical benefit. Our aim is to determine if response assessment after 1 or 2 doses of I/N can predict long-term survival and assess if fewer doses of I/N can lead to similar survival outcomes. Methods We performed a retrospective analysis on a cohort of patients with advanced melanoma who w0ere treated with standard I/N. Cox regression of progression-free survival (PFS) and overall survival (OS) models were performed to assess the relationship between response after 1 or 2 doses of I/N and risk of progression and/or death. Clinical benefit response (CBR) was assessed, defined as SD (stable disease) + PR (partial response) + CR (complete response) by imaging. Among patients who achieved a CBR after 1 or 2 doses of I/N, a multivariable Cox regression of survival was used to compare 1 or 2 vs 3 or 4 doses of I/N adjusted by known prognostic variables in advanced melanoma. Results 199 patients were evaluated. Patients with CBR after 1 dose of I/N had improved PFS (HR: 0.16, 95% CI 0.08-0.33; p<0.001) and OS (HR: 0.12, 0.05-0.32; p<0.001) compared to progressive disease (PD). Patients with CBR (vs PD) after 2 doses of I/N also had improved PFS (HR: 0.09, 0.05-0.16; p<0.001) and OS (HR: 0.07, 0.03-0.14; p<0.001). There was no survival risk difference comparing 1 or 2 vs 3 or 4 doses of I/N for PFS (HR: 0.95, 0.37-2.48; p=0.921) and OS (HR: 1.04, 0.22-4.78; p=0.965). Conclusions Early interval imaging with response during induction with I/N may be predictive of long-term survival in advanced stage melanoma. CBR after 1 or 2 doses of I/N is associated with favorable survival outcomes, even in the setting of fewer I/N doses received. Further studies are warranted to evaluate if electively administering fewer combination I/N doses despite tolerance in select patients may balance the benefits of therapy while decreasing toxicities.
Comprehensive Flow Cytometric Characterization of Bronchoalveolar Lavage Cells Indicates Comparable Phenotypes Between Asthmatic and Healthy Horses But Functional Lymphocyte Differences

Equine asthma (EA) is a highly relevant disease, estimated to affect up to 20% of all horses, and compares to human asthma. The pathogenesis of EA is most likely immune-mediated, yet incompletely understood. To study the immune response in the affected lower airways, mixed leukocytes were acquired through bronchoalveolar lavage (BAL) and the cell populations were analyzed on a single-cell basis by flow cytometry (FC). Samples of 38 horses grouped as respiratory healthy or affected by mild to moderate (mEA) or severe EA (sEA) according to their history, clinical signs, and BAL cytology were analyzed. Using FC, BAL cells and PBMC were comprehensively characterized by cell surface markers ex vivo. An increased percentage of DH24A+ polymorphonuclear cells, and decreased percentages of CD14+ macrophages were detected in BAL from horses with sEA compared to healthy horses or horses with mEA, while lymphocyte proportions were similar between all groups. Independently of EA, macrophages in BAL were CD14+CD16+, which contrasts the majority of CD14+CD16- classical monocytes in PBMC. Percentages of CD16-expressing BAL macrophages were reduced in BAL from horses with sEA compared to healthy horses. While PBMC lymphocytes predominantly contain CD4+ T cells, B cells and few CD8+ T cells, BAL lymphocytes comprised mainly CD8+ T cells, fewer CD4+ T cells and hardly any B cells. These lymphocyte subsets’ distributions were similar between all groups. After PMA/ionomycin stimulation in vitro, lymphocyte activation (CD154 and T helper cell cytokine expression) was analyzed in BAL cells of 26 of the horses and group differences were observed (p=0.01–0.11). Compared to healthy horses’ BAL, CD154+ lymphocytes from horses with mEA, and CD4+IL-17A+ lymphocytes from horses with sEA were increased in frequency. Activated CD4+ T helper cells were more frequent in asthmatics’ (mEA, sEA) compared to healthy horses’ PBMC lymphocytes. In summary, FC analysis of BAL cells identified increased polymorphonuclear cells frequencies in sEA as established, while macrophage percentages were mildly reduced, and lymphocyte populations remained unaffected by EA. Cytokine production differences of BAL lymphocytes from horses with sEA compared to healthy horses’ cells point towards a functional difference, namely increased local type 3 responses in sEA.
Systematic Review of Safety and Efficacy of IL-1-Targeted Biologics in Treating Immune-Mediated Disorders

Background The cytokine interleukin (IL)-1 plays a pivotal role in immune-mediated disorders, particularly in autoinflammatory diseases. Targeting this cytokine proved to be efficacious in treating numerous IL-1-mediated pathologies. Currently, three IL-1 blockers are approved, namely anakinra, canakinumab and rilonacept, and two additional ones are expected to receive approval, namely gevokizumab and bermekimab. However, there is no systematic review on the safety and efficacy of these biologics in treating immune-mediated diseases. Objective To evaluate safety and efficacy of anakinra, canakinumab, rilonacept, gevokizumab, and bermekimab for the treatment of immune-mediated disorders compared to placebo, standard-of-care treatment or other biologics. Methods The PRISMA checklist guided the reporting of the data. We searched the PubMed database between 1 January 1984 and 31 December 2020 focusing on immune-mediated disorders. Our PubMed literature search identified 7363 articles. After screening titles and abstracts for the inclusion and exclusion criteria and assessing full texts, 75 articles were included in a narrative synthesis. Results Anakinra was both efficacious and safe in treating cryopyrin-associated periodic syndromes (CAPS), familial Mediterranean fever (FMF), gout, macrophage activation syndrome, recurrent pericarditis, rheumatoid arthritis (RA), and systemic juvenile idiopathic arthritis (sJIA). Conversely, anakinra failed to show efficacy in graft-versus-host disease, Sjögren’s syndrome, and type 1 diabetes mellitus (T1DM). Canakinumab showed efficacy in treating CAPS, FMF, gout, hyper-IgD syndrome, RA, Schnitzler’s syndrome, sJIA, and TNF receptor-associated periodic syndrome. However, use of canakinumab in the treatment of adult-onset Still’s disease and T1DM revealed negative results. Rilonacept was efficacious and safe for the treatment of CAPS, FMF, recurrent pericarditis, and sJIA. Contrarily, Rilonacept did not reach superiority compared to placebo in the treatment of T1DM. Gevokizumab showed mixed results in treating Behçet’s disease-associated uveitis and no benefit when assessed in T1DM. Bermekimab achieved promising results in the treatment of hidradenitis suppurativa. Conclusions This systematic review of IL-1-targeting biologics summarizes the current state of research, safety, and clinical efficacy of anakinra, bermekimab, canakinumab, gevokizumab, and rilonacept in treating immune-mediated disorders. Systematic Review Registration https://www.crd. york.ac. uk/PROSPERO/, identifier CRD42021228547.
Individual and Organizational Factors in Coping With COVID-19 in Soldier Students

The COVID-19 pandemic has posed significant burden across different industrial sectors. Generally, an increase in psychological stress experiences has been reported, while the stress and coping responses of specific, potentially burdened populations have received less attention thus far. Thus, the present study investigated relations between individual (i.e., extraversion, neuroticism, conscientiousness) and organizational (i.e., organizational commitment and study satisfaction) factors, indicators of psychological health (i.e., loneliness, life satisfaction, COVID-19-related stress), and possible mediating effects of four broad coping dimensions (active coping, avoidant coping, social support, positive cognitive restructuring) in a specific sample of soldier students who engage in a double-role being military affiliates and students of non-military subjects. To this end, we assessed data of soldier students at two measurement points (N = 106 at t1 and N = 63 at t2) shortly after the second national lockdown in Germany (20. May 2021 to 11. July 2021) during the COVID-19 pandemic. Personality traits showed expected associations with indicators of psychological health, i.e., positive relations between neuroticism and social loneliness, between extraversion and COVID-19 stress, and negative relations between neuroticism and life satisfaction. Remarkably, organizational variables showed effects above and beyond personality traits on loneliness and life satisfaction. Neither individual, nor organizational factors could predict change in psychological health over time. We found evidence for mediation effects through active coping, avoidant coping, and the use of social support, but not through positive cognitive restructuring. Findings highlight the relative importance of organizational factors besides personality traits for psychological health in a military student sample, holding important implications for designing efficient support systems in the military.
Biobehavioral Implications of Covid-19 for Transplantation and Cellular Therapy Recipients

A growing body of literature has emphasized the importance of biobehavioral processes – defined as the interaction of behavior, psychology, socioenvironmental factors, and biological processes – for clinical outcomes among transplantation and cellular therapy (TCT) patients. TCT recipients are especially vulnerable to distress associated with pandemic conditions and represent a notably immunocompromised group at greater risk for SARS-CoV-2 infection with substantially worse outcomes. The summation of both the immunologic and psychologic vulnerability of TCT patients renders them particularly susceptible to adverse biobehavioral sequelae associated with the Covid-19 pandemic. Stress and adverse psychosocial factors alter neural and endocrine pathways through sympathetic nervous system and hypothalamic-pituitary-adrenal axis signaling that ultimately affect gene regulation in immune cells. Reciprocally, global inflammation and immune dysregulation related to TCT contribute to dysregulation of neuroendocrine and central nervous system function, resulting in the symptom profile of depression, fatigue, sleep disturbance, and cognitive dysfunction. In this article, we draw upon literature on immunology, psychology, neuroscience, hematology and oncology, Covid-19 pathophysiology, and TCT processes to discuss how they may intersect to influence TCT outcomes, with the goal of providing an overview of the significance of biobehavioral factors in understanding the relationship between Covid-19 and TCT, now and for the future. We discuss the roles of depression, anxiety, fatigue, sleep, social isolation and loneliness, and neurocognitive impairment, as well as specific implications for sub-populations of interest, including pediatrics, caregivers, and TCT donors. Finally, we address protective psychological processes that may optimize biobehavioral outcomes affected by Covid-19.
Spatiotemporal Dynamics of Covert vs. Overt Emotional Face Processing in Dysphoria

People at risk of developing clinical depression exhibit attentional biases for emotional faces. To clarify whether such effects occur at an early, automatic, or at a late, deliberate processing stage of emotional processing, the present study used high-density electroencephalography during both covert and overt processing of sad, fearful, happy, and neutral expressions in healthy participants with high dysphoria (n = 16) and with low dysphoria (n = 19). A state-of-the-art non-parametric permutation-based statistical approach was then used to explore the effects of emotion, attentional task demands, and group. Behaviorally, participants responded faster and more accurately when overtly categorizing happy faces and they were slower and less accurate when categorizing sad and fearful faces, independent of the dysphoria group. Electrophysiologically, in an early time-window (N170: 140–180 ms), there was a significant main effect for the dysphoria group, with greater negative voltage for the high vs. low dysphoria group over the left-sided temporo-occipital scalp. Furthermore, there was a significant group by emotional interaction, with the high dysphoria group displaying greater negative amplitude N170 for happy than fearful faces. Attentional task demands did not influence such early effects. In contrast, in an intermediate time-window (EPN: 200–400 ms) and in a late time-window (LPP: 500–750 ms) there were no significant main effects nor interactions involving the dysphoria Group. The LPP results paralleled the behavioral results, with greater LPP voltages for sad and fearful relative to happy faces only in the overt task, but similarly so in the two dysphoria groups. This study provides novel evidence that alterations in face processing in dysphoric individuals can be seen at the early stages of face perception, as indexed by the N170, although not in the form of a typical pattern of mood-congruent attentional bias. In contrast, intermediate (EPN) and late (LPP) stages of emotional face processing appear unaffected by dysphoria. Importantly, the early dysphoria effect appears to be independent of the top-down allocation of attention, further supporting the idea that dysphoria may influence a stage of automatic emotional appraisal. It is proposed that it may be a consequence of a shift from holistic to feature-based processing of facial expressions, or may be due to the influence of negative schemas acting as a negative context for emotional facial processing.
Survival Outcomes of Patients With Stage IB3 Cervical Cancer Who Undergo Abdominal Radical Hysterectomy Versus Radiochemotherapy

Objective This study aimed to compare the survival outcomes among stage IB3 cervical cancer patients who undergo abdominal radical hysterectomy (ARH)+pelvic lymphadenectomy ± para-aortic lymph node dissection versus radiochemotherapy (R-CT). Methods Based on the large number of diagnoses and treatments for cervical cancer in the Chinese database, propensity score matching (PSM) was used to compare the 5-year overall survival (OS) and disease-free survival (DFS) rates of the ARH group and R-CT group. Results There were 590 patients with stage IB3 cervical cancer according to the FIGO 2018 staging system, with 470 patients in the ARH group and 120 patients in the R-CT group. The ARH and R-CT groups showed different 5-year OS and DFS rates in the total study population, and the 5-year OS and DFS rates in the R-CT group (n = 120) were lower than those in the ARH group (n = 470) (OS: 78.1% vs. 92.1%, p < 0.001; DFS: 71.6% vs. 90.3%, p < 0.001). R-CT was associated with a worse 5-year OS rate (hazard ratio [HR] = 3.401; 95% confidence interval [CI] = 1.875–6.167; p < 0.001) and DFS rate (HR = 3.440; 95% CI = 2.075–5.703; p < 0.001) by Cox multivariate analysis. After 1:3 PSM, the 5-year OS and DFS rates in the R-CT group (n = 108) were lower than those in the RH group (n = 280) (OS: 76.4% vs. 94.0%, p < 0.001; DFS: 69.3% vs. 92.6%, p < 0.001, respectively). R-CT was associated with a worse 5-year OS rate (HR = 4.071; 95% CI = 2.042–8.117; p < 0.001) and DFS rate (HR = 4.450; 95% CI = 2.441–8.113; p < 0.001) by Cox multivariate analysis. Conclusion Our study found that for FIGO 2018 stage IB3 cervical cancer patients, ARH resulted in better OS and DFS than R-CT.