Miracle-dz/UniFAR-FTUs huggingface dataset:
Heparin binding protein in severe COVID-19—A prospective observational cohort study

Background and aims Neutrophil-derived heparin binding protein (HBP; also known as azurocidin or CAP-37) is a key player in bacterial sepsis and a promising biomarker in severe infections. The aims of this study were to assess whether HBP is involved in the pathophysiology of COVID-19 and, if so, whether it can be used to predict severe disease preferably using a point-of-care test. Methods This was a prospective convenience sample study of biomarkers in patients admitted to Skåne University hospital in Sweden with a confirmed COVID-19 diagnosis. Plasma samples and clinical data were collected within 72h after admission, during hospital stay and at discharge. Plasma HBP concentrations samples were measured both with enzyme-linked immunosorbent assay (ELISA) and with a novel dry immunofluorescence analyzer (Joinstar) point-of-care test. Results Thirty-five COVID-19 patients were enrolled in the study. Twenty-nine patients had blood samples taken within 72h after admission. We compared the highest HBP value taken within 72h after admission in patients who eventually developed organ dysfunction (n = 23) compared to those who did not (n = 6), and found that HBP was significantly elevated in those who developed organ dysfunction (25.0 ng/mL (interquartile range (IQR) 16.6–48.5) vs 10.6 ng/mL (IQR 4.8–21.7 ng/mL), p = 0.03). Point-of-care test measurements correlated well with ELISA measurements (R = 0.83). HBP measured by the POC device predicted development of COVID-induced organ dysfunction with an AUC of 0.88 (95% confidence interval (CI) 0.70–1.0). Conclusions HBP is elevated prior to onset of organ dysfunction in patients with severe COVID-19 using a newly developed point-of-care test and hence HBP could be used in a clinical setting as a prognostic marker in COVID-19.
Fecal Microbiome Transplantation from Children with Autism Spectrum Disorder Modulates Tryptophan and Serotonergic Synapse Metabolism and Induces Altered Behaviors in Germ-Free Mice

The relationship between the gut microbiota and ASD is not yet fully understood. Numerous studies have focused on the differences in intestinal microbial and metabolism profiles between TD and ASD children. ABSTRACT To determine the relationship of the gut microbiota and its metabolites with autism spectrum disorder (ASD)-like behaviors and preliminarily explore the potential molecular mechanisms, the fecal microbiota from donors with ASD and typically developing (TD) donors were transferred into germ-free (GF) mice to obtain ASD-FMT mice and TD-FMT mice, respectively. Behavioral tests were conducted on these mice after 3 weeks. 16S rRNA gene sequencing of the cecal contents and untargeted metabolomic analysis of the cecum, serum, and prefrontal cortex were performed. Untargeted metabolomics was also used to analyze fecal samples of TD and ASD children. Western blotting detected the protein expression levels of tryptophan hydroxylase 1 (TPH1), serotonin transporter (SERT), and serotonin 1A receptor (5-HT1AR) in the colon and TPH2, SERT, and 5-HT1AR in the prefrontal cortex of mice. ASD-FMT mice showed ASD-like behavior and a microbial community structure different from that of TD-FMT mice. Tryptophan and serotonin metabolisms were altered in both ASD and TD children and ASD-FMT and TD-FMT mice. Some microbiota may be related to tryptophan and serotonin metabolism. Compared with TD-FMT mice, ASD-FMT mice showed low SERT and 5-HT1AR and high TPH1 expression levels in the colon. In the prefrontal cortex, the expression levels of TPH2 and SERT were increased in the ASD-FMT group relative to the TD-FMT group. Therefore, the fecal microbiome of ASD children can lead to ASD-like behaviors, different microbial community structures, and altered tryptophan and serotonin metabolism in GF mice. These changes may be related to changes in some key proteins involved in the synthesis and transport of serotonin. IMPORTANCE The relationship between the gut microbiota and ASD is not yet fully understood. Numerous studies have focused on the differences in intestinal microbial and metabolism profiles between TD and ASD children. However, it is still not clear if these microbes and metabolites cause the development of ASD symptoms. Here, we collected fecal samples from TD and ASD children, transplanted them into GF mice, and found that the fecal microbiome of ASD children can lead to ASD-like behaviors, different microbial community structures, and altered tryptophan and serotonin metabolism in GF mice. We also demonstrated that tryptophan and serotonin metabolism was also altered in ASD and TD children. Together, these findings confirm that the microbiome from children with ASD may lead to ASD-like behavior of GF mice through metabolites, especially tryptophan and serotonin metabolism.
Interval training versus moderate-intensity continuous training for cardiorespiratory fitness improvements in middle-aged and older adults: a systematic review and meta-analysis

ABSTRACT Interval training has been promoted as a superior, time-efficient exercise strategy for enhancing cardiorespiratory fitness in the ageing population. This study assessed the effectiveness of interval training compared with that of moderate-intensity continuous training (MICT) for improving cardiorespiratory fitness in middle-aged and older adults. Six databases were systematically searched for studies with exercise interventions (minimum 2-week duration). Meta-analyses were conducted for within-group and between-group comparisons of maximal oxygen uptake (VO2max). Sub-group analysis was performed using the nature of interval training (high-intensity interval training [HIIT] and sprint interval training [SIT]). Of 3,257 studies, 14 were included (429 participants). Within–group analyses demonstrated significant VO2max improvements (mL/kg/min) following interval training (mean difference: MD = 2.26; 95% confidence interval [CI] = 1.50–3.02) and MICT (MD = 1.34; 95% CI = 0.45–2.23]. When comparing the modes of training, the gain in VO2max was significantly greater following interval training (MD = 1.10; CI = 0.55-1.64). Sub–group analysis showed that HIIT (MD = 1.04; CI = 0.21–1.88) and SIT (MD = 1.18; CI = 0.60-1.76) resulted in superior VO2max gain than MICT. This study provides evidence synthesis for interval training as a viable exercise strategy to improve cardiorespiratory function in healthy ageing.
Caught on the Fringes of Life: Mothers’ Lived Experiences of Initial Breastfeeding Complications

Becoming a parent changes one’s life, and existential questions arise. Time and being oscillate between joy and powerlessness, vulnerability, and self-confidence, between harmony and unpreparedness. Breastfeeding, one of the first skills new mothers try to master, can be joyful and painful. The aim of this study was to develop a deeper understanding of the phenomenon of initial breastfeeding complications as they are lived and experienced by mothers and how these mothers can be supported. Twelve mothers were interviewed, and a phenomenological lifeworld approach was used. Nourishing an infant and having initial breastfeeding complications can be understood by the essence and its constituents. Expectations are fulfilled, and expectations come to naught when complications are experienced such as wavering between powerlessness and joy and finding solutions through resistance. The results suggest that lifeworld-led caring may lead to deepened acknowledgment and the possibility for mothers to feel supported in their extreme situations.
Charge‐Transfer Excitations: A Challenge for Time‐Dependent Density Functional Theory That Has Been Met

Correctly predicting charge‐transfer states in complex molecules and molecular materials has been a major challenge for first‐principles theory. With the computational cost of accurate ab initio wave‐function methods often being too high for exploring systems of technological relevance, one has to resort to time‐dependent density functional theory (TDDFT). However, for a long time the incorrect description of charge‐transfer excitations has been considered one of the hallmark failures of TDDFT. As charge‐transfer states play an important role in organic solar cells, and generally in many new materials that are aimed at converting sunlight into other forms of energy, the contribution of first principles theory to the field of energy relevant materials was seriously limited. However, in the past years this limitation has been overcome. A new class of nonempirical density functionals can predict charge‐transfer excitations in molecules reliably. The approach by now has been extended to describe molecular solids and solvated systems. The predictive power of TDDFT has thus greatly increased, and computational studies can be expected to give true guidance in material design.
Neurophysiological improvements in speech-in-noise task after short-term choir training in older adults

Perceiving speech in noise (SIN) is important for health and well-being and decreases with age. Musicians show improved speech-in-noise abilities and reduced age-related auditory decline, yet it is unclear whether short term music engagement has similar effects. In this randomized control trial we used a pre-post design to investigate whether a 12-week music intervention in adults aged 50-65 without prior music training and with subjective hearing loss improves well-being, speech-in-noise abilities, and auditory encoding and voluntary attention as indexed by auditory evoked potentials (AEPs) in a syllable-in-noise task, and later AEPs in an oddball task. Age and gender-matched adults were randomized to a choir or control group. Choir participants sang in a 2-hr ensemble with 1-hr home vocal training weekly; controls listened to a 3-hr playlist weekly, attended concerts, and socialized online with fellow participants. From pre- to post-intervention, no differences between groups were observed on quantitative measures of well-being or behavioral speech-in-noise abilities. In the choir group, but not the control group, changes in the N1 component were observed for the syllable-in-noise task, with increased N1 amplitude in the passive condition and decreased N1 latency in the active condition. During the oddball task, larger N1 amplitudes to the frequent standard stimuli were also observed in the choir but not control group from pre to post intervention. Findings have implications for the potential role of music training to improve sound encoding in individuals who are in the vulnerable age range and at risk of auditory decline.
Natural mucosal barriers and COVID-19 in children

BACKGROUND Coronavirus disease 2019 (COVID-19) is more benign in children compared with adults for unknown reasons. This contrasts with other respiratory viruses where disease manifestations are often more severe in children. We hypothesize that a more robust early innate immune response to SARS coronavirus 2 (SARS-CoV-2) protects against severe disease. METHODS Clinical outcomes, SARS-CoV-2 viral copies, and cellular gene expression were compared in nasopharyngeal swabs obtained at the time of presentation to the emergency department from 12 children and 27 adults using bulk RNA sequencing and quantitative reverse-transcription PCR. Total protein, cytokines, and anti–SARS-CoV-2 IgG and IgA were quantified in nasal fluid. RESULTS SARS-CoV-2 copies, angiotensin-converting enzyme 2, and TMPRSS2 gene expression were similar in children and adults, but children displayed higher expression of genes associated with IFN signaling, NLRP3 inflammasome, and other innate pathways. Higher levels of IFN-α2, IFN-γ, IP-10, IL-8, and IL-1β protein were detected in nasal fluid in children versus adults. Children also expressed higher levels of genes associated with immune cells, whereas expression of those associated with epithelial cells did not differ in children versus adults. Anti–SARS-CoV-2 IgA and IgG were detected at similar levels in nasal fluid from both groups. None of the children required supplemental oxygen, whereas 7 adults did (P = 0.03); 4 adults died. CONCLUSION These findings provide direct evidence of a more vigorous early mucosal immune response in children compared with adults and suggest that this contributes to favorable clinical outcomes. FUNDING NIH grants R01 AI134367, UL1 TR002556, T32 AI007501, T32GM007288, P30 AI124414; an Albert Einstein College of Medicine Dean’s COVID-19 Pilot Research Award; and the Eric J. Heyer, MD, PhD Translational Research Pilot Project Award.
Development of a Psychological Intervention to Promote Meaningful Activity in People Living With Mild Dementia: An Intervention Mapping Approach

Abstract Background and Objectives Despite the importance of meaningful activity in mild dementia, only limited data are available on the development of interventions supporting people with mild dementia to engage in meaningful activity. In this article, we describe the development of an intervention that responds to this need. Research Design and Methods Intervention mapping (IM), an evidence-based approach, was used to develop STAYING ACTIVE (STAYing well and active—schedulINg meaninGful and enjoyAble aCTIvities to promote Vitality and wEll-being in mild dementia). The first step, a needs assessment, comprised a literature review, focus groups, and individual interviews with service users. Performance objectives of the intervention were formulated in Step 2, followed by the development of theory-based methods in Step 3. In Step 4, the new intervention was developed based on data collected in previous steps, existing interventions, and pilot testing. Qualitative data were analyzed using framework analysis. Results The needs assessment indicated that people with dementia and their carers view “staying active” as an important part of “enjoying life. ” Adapting to loss through compensation and receiving support were key facilitators of engaging in meaningful activity. Ecological, psychosocial, and activity-oriented theories guided the development of theory-based intervention strategies, which were based on awareness, skills, and addressing barriers of meaningful activity. Discussion and Implications STAYING ACTIVE is grounded on theory, and service user experiences and aims at promoting meaningful activity in mild dementia. The IM framework may be useful in the development of future psychosocial interventions for people with dementia, facilitating transparency when efficacy is evaluated.
New Tmc1 Deafness Mutations Impact Mechanotransduction in Auditory Hair Cells

Transmembrane channel-like protein isoform 1 (TMC1) is a major component of the mechano-electrical transducer (MET) channel in cochlear hair cells and is subject to numerous mutations causing deafness. We report a new dominant human deafness mutation, TMC1 p.T422K, and have characterized the homologous mouse mutant, Tmc1 p.T416K, which caused deafness and outer hair cell (OHC) loss by the fourth postnatal week. MET channels showed decreased Ca2+ permeability and resting open probability, but no change in single-channel conductance or expression. Three adjacent deafness mutations are TMC1 p.L416R, p.G417R, and p.M418K, the last homologous to the mouse Beethoven that exhibits similar channel effects. All substitute a positive for a neutral residue, which could produce charge screening in the channel pore or influence binding of an accessory subunit. Channel properties were compared in mice of both sexes between dominant (Tmc1 p.T416K, Tmc1 p.D569N) and recessive (Tmc1 p.W554L, Tmc1 p.D528N) mutations of residues near the putative pore of the channel. Tmc1 p.W554L and p.D569N exhibit reduced maximum current with no effect on single-channel conductance, implying a smaller number of channels transported to the stereociliary tips; this may stem from impaired TMC1 binding to LHFPL5. Tmc1 p.D528N, located in the pore's narrowest region, uniquely caused large reductions in MET channel conductance and block by dihydrostreptomycin (DHS). For Tmc1 p.T416K and Tmc1 p.D528N, transduction loss occurred between P15 and P20. We propose two mechanisms linking channel mutations and deafness: decreased Ca2+ permeability, common to all mutants, and decreased resting open probability in low Ca2+, confined to dominant mutations. SIGNIFICANCE STATEMENT Transmembrane channel-like protein isoform 1 (TMC1) is thought to be a major component of the mechanotransducer channel in auditory hair cells, but the protein organization and channel structure are still uncertain. We made four mouse lines harboring Tmc1 point mutations that alter channel properties, causing hair cell degeneration and deafness. These include a mouse homolog of a new human deafness mutation pT416K that decreased channel Ca2+ permeability by introducing a positively-charged amino acid in the putative pore. All mutations are consistent with the channel structure predicted from modeling, but only one, p.D528N near the external face of the pore, substantially reduced channel conductance and Ca2+ permeability and virtually abolished block by dihydrostreptomycin (DHS), strongly endorsing its siting within the pore.
Internet-Based Cognitive Behavioral Therapy for Informal Caregivers: Randomized Controlled Pilot Trial

Background Caregiving for a family member can result in reduced well-being for the caregiver. Internet-delivered cognitive behavioral therapy (ICBT) may be one way to support this population. This is especially the case for caregivers in countries with limited resources, but high demand for psychological services. Objective In this study we evaluated the effects of a therapist-guided 8-week-long ICBT intervention for informal caregivers. Methods In total, 63 participants were recruited online and randomized either to the intervention or to the wait-list control group. The main study outcome was the Caregiver Burden Inventory (CBI). Secondary outcomes included measures of caregiver depression, anxiety, stress, and quality of life. Results Moderate between-group effect sizes were observed for the CBI measure, in favor of the intervention group, with a Cohen d=–0.70 for the intention-to-treat analysis. Analyses of the subscales of the CBI showed significant reductions on the subscales of Development and Physical Health. Moderate reductions were found for depression and anxiety scores as indicated by the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) scores. Large between-group effects were observed for reduction in stress and increase in quality of life as indicated by the Perceived Stress Scale-14 (PSS-14), The Brunnsviken Brief Quality of Life Scale (BBQ), and The World Health Organization-Five Well-Being Index (WHO-5). In addition, participants experienced little to no difficulty in using the program and were mostly satisfied with the intervention’s platform and the choice of content. Conclusions This is the first internet intervention study for informal caregivers in Lithuania. The results suggest that therapist-guided ICBT can be effective in reducing caregiver burden, anxiety, depression, stress, and improving quality of life. Trial Registration ClinicalTrials.gov NCT04052724; https://clinicaltrials.gov/ct2/show/NCT04052724
Mindful Self-Care Practice of Nurses in Acute Care: A Multisite Cross-Sectional Survey

Consistent mindful self-care practices mitigate professional burnout and improve resilience to enable nurses provide safe and effective patient care. This study determined the levels and the influencing factors of mindful self-care of nurses in acute care settings. Data were collected from a convenience sample of 258 nurses from seven acute care hospitals using the 36-item Mindful Self-Care Scale. Data were analyzed using descriptive and correlation analyses. Nurses’ mindful self-care scores were low, and female nurses had higher levels of mindful self-care than male nurses. Statistically significant negative correlations were found between nurses’ mindful self-care levels and their age and clinical experience. Nurses’ engagement in mindful self-care is low which may negatively affect their interactions with and care of patients and their families. Therefore, a need exists to develop and evaluate more clinical-based personal and organizational strategies to enhance the mindful self-care practices of nurses.
Evolution and impact of self-efficacy during French COVID-19 confinement: a longitudinal study

Abstract Based on social cognitive theory, we propose that self-efficacy is a personal resource that protects people from the impact of confinement in the context of the COVID-19 pandemic. In a longitudinal study where 197 French citizens were surveyed over 8 weeks of confinement (though only 25 participants responded each of these 8 weeks), we examined the relationships between general self-efficacy and positive affect, negative affect and adaptive performance at work. Consistent with theoretical expectations, self-efficacy was relatively stable during confinement and was positively related to positive affect and negatively related to negative affect. Self-efficacy was also positively correlated with all dimensions of adaptive performance at work during confinement. The role of self-efficacy as a protective factor against depressive risks induced by the stressful COVID-19 pandemic is discussed.
Trajectories of psychological distress among individuals exposed to the 9/11 World Trade Center disaster

Abstract Background Individuals present in lower Manhattan during the 9/11 World Trade Center (WTC) disaster suffered from significant physical and psychological trauma. Studies of longitudinal psychological distress among those exposed to trauma have been limited to relatively short durations of follow-up among smaller samples. Methods The current study longitudinally assessed heterogeneity in trajectories of psychological distress among WTC Health Registry enrollees – a prospective cohort health study of responders, students, employees, passersby, and residents in the affected area (N = 30 839) – throughout a 15-year period following the WTC disaster. Rescue/recovery status and exposure to traumatic events of 9/11, as well as sociodemographic factors and health status, were assessed as risk factors for trajectories of psychological distress. Results Five psychological distress trajectory groups were found: none-stable, low-stable, moderate-increasing, moderate-decreasing, and high-stable. Of the study sample, 78.2% were classified as belonging to the none-stable or low-stable groups. Female sex, being younger at the time of 9/11, lower education and income were associated with a higher probability of being in a greater distress trajectory group relative to the none-stable group. Greater exposure to traumatic events of 9/11 was associated with a higher probability of a greater distress trajectory, and community members (passerby, residents, and employees) were more likely to be in greater distress trajectory groups – especially in the moderate-increasing [odds ratios (OR) 2.31 (1.97–2.72)] and high-stable groups [OR 2.37 (1.81–3.09)] – compared to the none-stable group. Conclusions The current study illustrated the heterogeneity in psychological distress trajectories following the 9/11 WTC disaster, and identified potential avenues for intervention in future disasters.