Miracle-dz/UniFAR-FTUs huggingface dataset:
Humoral immune response following prime and boost BNT162b2 vaccination in people living with HIV on antiretroviral therapy

People living with HIV (PLWH) with low CD4 T‐cell counts may be at a higher risk for severe coronavirus disease 2019 (COVID‐19) outcomes and in need of efficient vaccination. The World Health Organization (WHO) now recommends prioritizing PLHIV for COVID‐19 vaccination. Data on immune responses after messenger RNA (mRNA) vaccination in PLHIV in relation to CD4 counts are scarce. We aimed at assessing the humoral immune response in PLHIV after mRNA vaccination against COVID‐19.
Impact of medical therapies for inflammatory bowel disease on the severity of COVID-19: a systematic review and meta-analysis

Background During COVID-19 pandemic, the safety of medical therapies for inflammatory bowel disease (IBD) in relation to COVID-19 has emerged as an area of concern. This study aimed to evaluate the association between IBD therapies and severe COVID-19 outcomes. Method We performed a systematic review and meta-analysis of all published studies from December 2019 to August 2021 to identify studies that reported severe COVID-19 outcomes in patients on current IBD therapies including 5-aminosalicylic acid (5-ASA), immunomodulators, corticosteroids, biologics, combination therapy, or tofacitinib. Results Twenty-two studies were identified. Corticosteroids (risk ratio (RR) 1.91 (95% CI 1.25 to 2.91, p=0.003)) and 5-ASA (RR 1.50 (95% CI 1.17 to 1.93, p=0.001)) were associated with increased risk of severe COVID-19 outcomes in patients with IBD patients. However, possible confounders for 5-ASA use were not controlled for. Sub-analysis showed that corticosteroids increased the risk of intensive care unit (ICU) admission but not mortality. Immunomodulators alone (RR 1.18 (95% CI 0.87 to 1.59, p=0.28)) or in combination with anti-TNFs ((RR 0.96 (95% CI 0.80 to 1.15, p=0.63)), tofacitinib (RR 0.81 (95% CI 0.49 to 1.33, p=0.40)) and vedolizumab ((RR 1.02 (95% CI 0.79 to 1.31, p=0.89)) were not associated with severe disease. Anti-TNFs (RR 0.47 (95% CI 0.40 to 0.54, p<0.00001)) and ustekinumab (RR 0.55 (95% CI 0.43 to 0.72, p<0.00001)) were associated with decreased risk of severe COVID-19. Conclusion In patients with IBD, the risk of severe COVID-19 is higher among patients receiving corticosteroids. Corticosteroid use was associated with ICU admission but not mortality. The risk is also higher among patients receiving 5-ASAs. However, patient-level data were lacking and insufficient data existed for meta-regression analyses to adjust for confounding. Vedolizumab, tofacitinib, and immunomodulators alone or in combination with anti-TNF were not associated with severe disease. Anti-TNFs, and ustekinumab were associated with favourable outcomes.
Association of Homologous Recombination–DNA Damage Response Gene Mutations with Immune Biomarkers in Gastroesophageal Cancers

The prevalence of homologous recombination–DNA damage response (HR-DDR) genetic alterations is of therapeutic interest in gastroesophageal cancers. This study is a comprehensive assessment of HR-DDR mutation prevalence across gastroesophageal adenocarcinomas and squamous cell carcinomas. Here we investigate the association of HR-DDR mutations with known predictors for immune-checkpoint inhibition [deficiency in mismatch-repair (dMMRP), tumor mutational burden (TMB), and programmed death ligand 1 (PD-L1)]. We confirmed HR-DDR mutations are present in a subset of gastroesophageal adenocarcinomas (23%) and gastroesophageal squamous cell carcinomas (20%). Biomarker expression of dMMRP (18% vs. 1%) and TMB-high with a cutoff of ≥10 mt/MB (27% vs. 9%) was significantly more prevalent in the DDR-mutated cohort compared with the non-DDR-mutated cohort. Mean combined positive score for PD-L1 in the total adenocarcinoma cohort was significantly higher in the DDR-mutated cohort compared with the non–DDR-mutated cohort (10.1 vs. 5.8). We demonstrated that alterations in ARID1A, BRCA2, PTEN, and ATM are correlated with dMMRP, TMB-high, and increased PD-L1 expression in gastroesophageal adenocarcinomas. Our findings show that a subset of gastroesophageal tumors harbor HR-DDR mutations correlated with established immune biomarkers. By better understanding the relationship between HR-DDR mutations and immune biomarkers, we may be able to develop better immunotherapy combination strategies to target these tumors.
Impact of Additives on Heterogeneous Crystallization of Acetaminophen

Introducing foreign substrates or additives is the common way to regulate polymorphism or kinetics of crystallization. Most present studies consider the substrate factor and additive factor separately. Here, the interplay between the additive, crystallizing molecules, and the substrate was investigated. Acetaminophen (APAP) was used as the model compound. 5 wt. % dioctyl sodium sulfosuccinate (AOT), poly(acrylic) acid (PAA), and hydroxypropyl methylcellulose (HPMC) were employed as additives. The interfacial crystal growth rate of APAP in the presence of additives was studied between slides coated with chitosan (CS) film. The crystallization kinetics of the additive/APAP mixture on CS substrate was also investigated. The additive/APAP was characterized by differential scanning calorimetry (DSC), and the interfacial molecular interaction was studied by Fourier transform infrared spectroscopy (FTIR). The results indicate that the additive-substrate interaction can change the interfacial growth behavior observed in the additive-APAP binary system. Nevertheless, crystallizing without confinement, the additive-APAP interaction is more effective at controlling the crystallization of APAP, and the substrates did not have much effect.
The relationship between cognition and mathematics in children with attention-deficit/hyperactivity disorder: a systematic review

ABSTRACT Cognitive processes play an imperative role in children’s mathematics learning. Difficulties in cognitive functioning are a core feature of Attention Deficit Hyperactivity Disorder (ADHD) in children, who also tend to show lower levels of mathematics attainment than their typically developing peers. This review (registration number: CRD42020169708) sought to aggregate findings from studies assessing the relationship between cognition and mathematics in children with a clinical ADHD diagnosis aged 4–12 years. A total of 11,799 studies published between 1992 and August 2020 were screened for eligibility using various database (PsycINFO, PubMed, SCOPUS, EMBASE, ERIC, Web of Science, and additional sources), from which four studies met inclusion criteria. A narrative synthesis was conducted on the correlations between mathematics and cognitive domains, including an evaluation of the risk of bias within the studies. Across four studies meeting inclusion criteria, memory, inhibitory control, and processing speed were assessed. The results showed a positive association between cognition and mathematics performance in this population. The strength of associations across these studies varied as a function of the cognitive domain in question, means by which mathematics performance was assessed, as well as whether confounding factors such as age and IQ were controlled for. Collectively, this review demonstrates a lack of research in this area and points to various methodological considerations for identifying the association between cognition and mathematics performance in ADHD.
Fungi: Friend or Foe? A Mycobiome Evaluation in Children With Autism and Gastrointestinal Symptoms

ABSTRACT Gastrointestinal (GI) symptoms often affect children with autism spectrum disorders (ASD) and GI symptoms have been associated with an abnormal fecal microbiome. There is limited evidence of Candida species being more prevalent in children with ASD. We enrolled 20 children with ASD and GI symptoms (ASD + GI), 10 children with ASD but no GI symptoms (ASD − GI), and 20 from typically developing (TD) children in this pilot study. Fecal mycobiome taxa were analyzed by Internal Transcribed Spacer sequencing. GI symptoms (GI Severity Index [GSI]), behavioral symptoms (Social Responsiveness Scale -2 [SRS-2]), inflammation and fungal immunity (fecal calprotectin and serum dectin-1 [ELISA]) were evaluated. We observed no changes in the abundance of total fungal species (alpha diversity) between groups. Samples with identifiable Candida spp. were present in 4 of 19 (21%) ASD + GI, in 5 of 9 (56%) ASD − GI, and in 4 of 16 (25%) TD children (overall P = 0.18). The presence of Candida spp. did not correlate with behavioral or GI symptoms (P = 0.38, P = 0.5, respectively). Fecal calprotectin was normal in all but one child. Finally, there was no significance in serum dectin-1 levels, suggesting no increased fungal immunity in children with ASD. Our data suggest that fungi are present at normal levels in the stool of children with ASD and are not associated with gut inflammation.
Assessment of Antimicrobial by Nanocomposite of Bacterial Cellulose Loaded with Nanoparticles Sodium Alginate and Chitosan

Antimicrobial membrane disc of BC with sodium alginate and chitosan were fabricated through doping nanoparticles as antibacterial agents. Nanoparticles was densely arrayed inside BC fibers composites as confirmed by field emission scanning electron microscopy (FE-SEM). Fourier transform-infrared (FT-IR) spectra of the BC membranes exhibited characteristic peaks for specific functional groups of ch and sd alg beside swelling test and antimicrobial property of these nanoparticles sodium alginate and Chitosan doped cellulose membrane against E. coli and S. aureus was evaluated by the diffusion disc method. Effects of antimicrobial agent quantity, volume-related properties (nanoparticles) on the antimicrobial activity of cellulose membrane were studied. Antimicrobial activity was observed Chitosan nanoparticles were compared when compared with sodium alginate. Maximum E. coli inhibition 85% was achieved with only 5% of amphetamine from the nanoparticles chitosan in cellulose membrane. The resulting bio composites membrane have high antibiotic activity against Staphylococcus aureus. These membranes can potentially be used in medicine as a wound healing. Keywords: Bacterial cellulose, chitosan, nanoparticles, antibacterial activity, Staphylococcus aureus E. coli .
Innervation of the clavicle: a cadaveric investigation

Background This cadaveric study investigated the innervations of the clavicle and clavicular joints (ie, sternoclavicular and acromioclavicular joints). Methods Twenty cadavers (40 clavicles) were dissected. A skin incision was made to permit exposure of the posterior cervical triangle and infraclavicular fossa. The platysma, sternocleidomastoid, and trapezius muscles were cleaned in order to identify the supraclavicular nerves. Subsequently, the suprascapular and subclavian nerves were localized after removal of the prevertebral layer of the deep cervical fascia. In the infraclavicular region, the pectoralis major and minor muscles were retracted laterally in order to visualize the lateral pectoral nerve. The contribution of all these nerves to the clavicular bone and joints were recorded. Results Along their entire length, all clavicular specimens received contributions from the supraclavicular nerves. The latter innervated the cephalad and ventral aspects of the clavicular bone. The caudal and dorsal aspects of the clavicle were innervated by the subclavian nerve (middle and medial thirds). The lateral pectoral nerve supplied the caudad aspect of the clavicle (middle and lateral thirds). The sternoclavicular joint derived its innervation solely from the supraclavicular nerves whereas the acromioclavicular joint was supplied by the supraclavicular and lateral pectoral nerves. Conclusion The clavicle and clavicular joints are innervated by the subclavian, lateral pectoral, and supraclavicular nerves. Clinical trials are required to determine the relative importance and functional contribution of each nerve.
Adipose-Derived Stem Cells Therapy for Radiation-Induced Skin Injury

Background Radiation-induced skin injuries have been treated with different medical therapies and have shown diverse outcomes. We aim to evaluate the effect of adipose-derived stem cells (ADSCs) therapy on radiation-induced skin injury. Methods We performed a review by querying PubMed, Ovid MEDLINE, and EMBASE databases from inception to April 2020 following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. The MeSH terms “adipose-derived stem cells,” “wound healing,” “radiation,” and synonyms in combinations determined our search strategy. Experimental peer-reviewed articles describing the protocol and comparing the results with controls were included. Non-English studies were excluded. Results Our search recorded a total of 137 articles. Only 8 studies met our inclusion criteria and were included in this review. Five studies evaluated the use of ADSC alone, whereas the others evaluated the efficacy of ADSC seeded in scaffolds. Adipose-derived stem cell–based therapies, either alone or seeded in scaffolds, were shown to improve wound healing in most studies when compared with controls. Conclusions There is evidence supporting the positive benefits from ADSC-based therapies in radiation-induced skin injury. However, further studies are needed to standardize the method of ADSC extraction, radiation-induced skin injury experimental model, and increase the time of follow-up to evaluate the results accurately.
Gene–environment interaction identification via penalized robust divergence

In high‐throughput cancer studies, gene–environment interactions associated with outcomes have important implications. Some commonly adopted identification methods do not respect the “main effect, interaction” hierarchical structure. In addition, they can be challenged by data contamination and/or long‐tailed distributions, which are not uncommon. In this article, robust methods based on γ$\gamma$ ‐divergence and density power divergence are proposed to accommodate contaminated data/long‐tailed distributions. A hierarchical sparse group penalty is adopted for regularized estimation and selection and can identify important gene–environment interactions and respect the “main effect, interaction” hierarchical structure. The proposed methods are implemented using an effective group coordinate descent algorithm. Simulation shows that when contamination occurs, the proposed methods can significantly outperform the existing alternatives with more accurate identification. The proposed approach is applied to the analysis of The Cancer Genome Atlas (TCGA) triple‐negative breast cancer data and Gene Environment Association Studies (GENEVA) Type 2 Diabetes data.
Insights into T‐cell dysfunction in Alzheimer's disease

T cells, the critical immune cells of the adaptive immune system, are often dysfunctional in Alzheimer's disease (AD) and are involved in AD pathology. Reports highlight neuroinflammation as a crucial modulator of AD pathogenesis, and aberrant T cells indirectly contribute to neuroinflammation by secreting proinflammatory mediators via direct crosstalk with glial cells infiltrating the brain. However, the mechanisms underlying T‐cell abnormalities in AD appear multifactorial. Risk factors for AD and pathological hallmarks of AD have been tightly linked with immune responses, implying the potential regulatory effects of these factors on T cells. In this review, we discuss how the risk factors for AD, particularly Apolipoprotein E (ApoE), Aβ, α‐secretase, β‐secretase, γ‐secretase, Tau, and neuroinflammation, modulate T‐cell activation and the association between T cells and pathological AD hallmarks. Understanding these associations is critical to provide a comprehensive view of appropriate therapeutic strategies for AD.
Green synthesis and evaluation of silver nanoparticles for antimicrobial and biochemical profiling in Kinnow (Citrus reticulata L.) to enhance fruit quality and productivity under biotic stress.

Green synthesis of silver nanoparticles (AgNPs) by utilising plant extract is an emerging class of nanotechnology. It revolutionizes all the field of biological sciences by synthesizing chemical free AgNPs. In the present study, AgNPs were synthesised by utilising Moringa oleifera leaves as the main reducing and stabilising agent and characterised through UV-visible spectroscopy, zeta analyser, X-ray diffraction spectroscopy (XRD), energy dispersive X-ray (EDX), and scanning electron microscopy (SEM). The different concentrations of biosynthesised AgNPs (10, 20, 30, and 40 ppm) were exogenously applied on the already infected plants (canker) of Citrus reticulata at different day intervals. The AgNPs at a concentration of 30 ppm was found to be most suitable concentration for creating the resistance against canker disease in Citrus reticulata. The enzymatic activities were also explored and it was found that 30 ppm concentration of biosynthesised AgNPs significantly reduced the biotic stress. Fruit quality and productivity parameters were also assessed and it was found that fruit quality and productivity were significant in response to 30 ppm concentration of biosynthesised AgNPs. The present work highlights the potent role of biosynthesised AgNPs, which can be used as biological control of citrus diseases and ultimately improving the quality and productivity of Citrus.
Sex Differences in Long-term Outcomes After Group B Streptococcal Infections During Infancy in Denmark and the Netherlands: National Cohort Studies of Neurodevelopmental Impairments and Mortality

Abstract Background Male infants have a higher incidence of invasive group B Streptococcus disease (iGBS) compared with female infants; however, data on sex differences in mortality and long-term outcomes after iGBS are lacking. We assessed whether a child’s sex influences the effects of iGBS on mortality and risk of neurodevelopmental impairments (NDIs). Methods We used Danish and Dutch registry data to conduct a nationwide cohort study of infants with a history of iGBS. A comparison cohort, children without a history of iGBS, was randomly selected and matched on relevant factors. Effect modification by sex was assessed on additive and multiplicative scales. Results Our analyses included data from children with a history of iGBS in Denmark (period 1997 -2017; n = 1432) and the Netherlands (2000 -2017; n = 697) and from 21 172 children without iGBS. There was no clear evidence of between-sex heterogeneity in iGBS-associated mortality. Boys had a higher risk of NDI, with evidence for effect modification on additive scale at the age of 5 years for any NDI (relative excess risk due to interaction = 1.28; 95% confidence interval [CI], -0.53 to 3.09 in Denmark and 1.14; 95% CI, -5.13 to 7.41 in the Netherlands). A similar pattern was observed for moderate/severe NDI at age 5 years in Denmark and age 10 years in the Netherlands. Conclusion Boys are at higher risk of NDI ; our results suggest this is disproportionally increased in those who develop iGBS. Future studies should investigate mechanisms of this effect modification by sex.
Luminescent PLGA Nanoparticles for Delivery of Darunavir to the Brain and Inhibition of Matrix Metalloproteinase-9, a Relevant Therapeutic Target of HIV-Associated Neurological Disorders

Human immunodeficiency virus (HIV) can independently replicate in the central nervous system (CNS) causing neurocognitive impairment even in subjects with suppressed plasma viral load. The antiretroviral drug darunavir (DRV) has been approved for therapy of HIV-infected patients, but its efficacy in the treatment of HIV-associated neurological disorders (HAND) is limited due to the low penetration through the blood–brain barrier (BBB). Therefore, innovations in DRV formulations, based on its encapsulation in optically traceable nanoparticles (NPs), may improve its transport through the BBB, providing, at the same time, optical monitoring of drug delivery within the CNS. The aim of this study was to synthesize biodegradable polymeric NPs loaded with DRV and luminescent, nontoxic carbon dots (C-Dots) and investigate their ability to permeate through an artificial BBB and to inhibit in vitro matrix metalloproteinase-9 (MMP-9) that represents a factor responsible for the development of HIV-related neurological disorders. Biodegradable poly(lactic-co-glycolic) acid (PLGA)-based nanoformulations resulted characterized by an average hydrodynamic size less than 150 nm, relevant colloidal stability in aqueous medium, satisfactory drug encapsulation efficiency, and retained emitting optical properties in the visible region of the electromagnetic spectrum. The assay on the BBB artificial model showed that a larger amount of DRV was able to cross BBB when incorporated in the PLGA NPs and to exert an enhanced inhibition of matrix metalloproteinase-9 (MMP-9) expression levels with respect to free DRV. The overall results reveal the great potential of this class of nanovectors of DRV for an efficacious treatment of HANDs.
Hemodynamic Responses to Crystalloid and Colloid Fluid Boluses during Noncardiac Surgery

Background: Colloids are thought to sustain blood pressure and cardiac index better than crystalloids. However, the relative effects of intraoperative hydroxyethyl starch and crystalloid administration on the cardiac index and blood pressure remain unclear. This study therefore tested in this subanalysis of a previously published large randomized trial the hypothesis that intraoperative goal-directed colloid administration increases the cardiac index more than goal-directed crystalloid administration. Further, the effects of crystalloid and colloid boluses on blood pressure were evaluated. Methods: This planned subanalysis of a previous trial analyzed data from 973 patients, of whom 480 were randomized to colloids and 493 were randomized to crystalloids. Fluid administration was guided by esophageal Doppler. The primary outcome was the time-weighted average cardiac index during surgery between the colloid and crystalloid group. The secondary outcomes were the cardiac index just after bolus administration, time elapsed between boluses, and the average real variability during surgery. The study recorded cardiac index, corrected flow time, and blood pressure at 10-min intervals, as well as before and after each bolus. Results: Time-weighted average of cardiac index over the duration of anesthesia was only slightly greater in patients given colloid than crystalloid, with the difference being just 0.20 l · min–1 · m–2 (95% CI, 0.11 to 0.29; P < 0.001). However, the hazard for needing additional boluses was lower after colloid administration (hazard ratio [95% CI], 0.60 [0.55 to 0.66]; P < 0.001) in a frailty time-to-event model accounting for within-subject correlation. The median [quartiles] number of boluses per patient was 4 [2, 6] for colloids and 6 [3, 8] for crystalloids, with a median difference (95% CI) of –1.5 (–2 to –1; P < 0.001). The average real mean arterial pressure variability did not differ significantly between the groups (difference in means [95% CI] of –0.03 (–0.07 to 0.02) mmHg, P = 0.229). Conclusions: There were not clinically meaningful differences in the cardiac index or mean pressure variability in patients given goal-directed colloid and crystalloids. As might be expected from longer intravascular dwell time, the interval between boluses was longer with colloids. However, on a case basis, the number of boluses differed only slightly. Colloids do not appear to provide substantial hemodynamic benefit. The cardiac index was similar in 973 patients randomized to colloid- or crystalloid-based goal-directed fluid management. Fewer colloid boluses were required but not by a clinically meaningful amount. Supplemental Digital Content is available in the text.