Miracle-dz/UniFAR-FTUs huggingface dataset:
Lack of association between TNFA and TNFB polymorphisms and the risk of multiple sclerosis: a meta-analysis from 37 studies

ABSTRACT Background Epidemiological studies about the association between genetic polymorphisms in TNFA, TNFB, and IFNG and the risk for multiple sclerosis (MS) have been performed extensively. However, the results are inconclusive. The purpose of this meta-analysis was to evaluate the contribution of the polymorphisms in TNFA, TNFB, and IFNG to the susceptibility of MS. Methods The PubMed, Web of Science, and China National Knowledge Infrastructure databases were searched to identify relevant studies up to October 2021. A meta-analysis was performed, and pooled odds ratios (OR) and confidence intervals (CI) were computed using fixed or random effects models. Results A marginally significant association of the IFNG +874AT genotype with high risk of MS was observed in a heterozygous comparison (OR = 1.51, 95% CI, 1.02–2.23). However, no significant association between the TNFA (–308 G/A, – 238 G/A, and – 376 G/A) and TNFB +252A/G polymorphisms and MS risk was observed both in overall analysis and in subgroup analysis. Conclusion This meta-analysis provides evidence that the TNFA (–308 G/A, – 238 G/A, and – 376 G/A) and TNFB +252A/G polymorphisms were not risk factors for the occurrence of MS. Further studies with larger samples are necessary to reach the concise results about the contribution of other polymorphisms to the risk of MS.
Thermal Properties of Jatropha Seeds

The thermal properties of Jatropha seeds were investigated for two accessions and in the moisture range of 4 - 16% db. Specific heat was determined using the method of mixtures, bulk thermal diffusivity was determined using the transient method (Dickerson apparatus), while the bulk thermal conductivity was calculated. The results obtained for specific heat ranged from 739.5 – 1560.1J/kg oC for native and 667.4 – 1262.21J/kg oC for improve accessions in the above moisture range. Bulk thermal diffusivity ranged from1.1x10-6 - 1.71x10-6m2/s and 1.29x10-6 m2/s - 1.83X10-6 while bulk thermal conductivity ranged from 0.276 - 0.907 W/moC and 0.283 - 0.797 W/moC for native and improved accessions respectively. ANOVA and means separation (Duncan multiply range test) at 95% confidence level was carried out for specific heat, thermal diffusivity and thermal conductivity. ANOVA showed that moisture had a significant effect on specific heat and bulk thermal conductivity but not on bulk thermal diffusivity. The mean separation shows that for native accession a significant change occured (p<0.05) for specific heat at the moisture contents of 4 and 16%. For the improved accession, the specific heat was significantly different (p<0.05) only at moisture of 8 and 16%. For bulk thermal diffusivity, moisture did not have any significant effect (p<0.05) on either the native accession or the improved accession. Bulk thermal conductivity was significantly affected (at p<0.05) by moisture content only in the native accession but not in the improved accession. The mean separation showed that significant change (p<0.05) in thermal conductivity occurred at the moisture contents of 4 and 16%. This study also shows that increase in moisture content of Jatropha seeds increase all three thermal properties studied irrespective of the accession. Regression analysis shows a high R square grater than 0.9 for all thermal properties studied.
Associations Between Maternal Antenatal Corticosteroid Treatment and Psychological Developmental and Neurosensory Disorders in Children

Key Points Question Is maternal antenatal corticosteroid treatment associated with psychological developmental and neurosensory disorders in children? Findings In this population-based cohort study comprising 670 097 children, exposure to maternal antenatal corticosteroid treatment, compared with nonexposure, was associated with significantly higher rates of psychological developmental and neurosensory disorders in children. Meaning The findings suggest that the risks and benefits to the offspring of maternal antenatal corticosteroids should be carefully considered when deciding on treatment.
Early childhood developmental vulnerability associated with parental mental disorder comorbidity

Objectives: Parental mental health has a profound influence on the mental health and well-being of their offspring. With comorbid mental disorders generally the rule rather than the exception, increased knowledge of the impact of parental mental disorder comorbidity on early child development may facilitate improved targeting and delivery of early intervention for vulnerable offspring. Methods: Participants were 66,154 children and their parents in the New South Wales Child Development Study – a prospective, longitudinal, record-linkage study of a population cohort of children born in NSW between 2002 and 2004. Early childhood developmental vulnerability was assessed at age ~5 years using the Australian Early Development Census, and information on parental mental disorders was obtained from administrative health records. Binomial and multinomial logistic regression were used to assess the relationship between parental mental disorders and early childhood developmental vulnerability on emotional and behavioural domains, as well as membership of latent developmental risk classes reflecting particular classes of vulnerability. Results: Multiple diagnoses of mental disorders in mothers and fathers were associated with an increased likelihood of early childhood emotional and behavioural developmental vulnerability in offspring, relative to parents without mental disorder. The likelihood of offspring vulnerability increased with the number of parental comorbidities, particularly maternal comorbidities. Conclusion: Early childhood developmental vulnerability was strongly associated with parental mental ill-health, with the strength of associations increasing in line with a greater number of mental disorder diagnoses among mothers and fathers. New and expectant parents diagnosed with multiple mental disorders should be prioritised for intervention, including attention to the developmental well-being of their offspring.
The adaptation of academics to the Covid-19 crisis in terms of work time allocation

Academics have seen their work environment and routines severely affected by the Covid19 pandemic. This topic has been analyzed by the literature, mostly from personal and descriptive perspectives, that highlight the challenging transitions and adaptations that academics have endured concerning their work and life-balance. This research complements those studies, by using a sample of university academics working all around the world in all disciplinary fields and focuses on a longitudinal perspective of workload and task time allocation of academic work. The findings show that academics which in general had long working hours, further increased their time of the week dedicated to work leading possibly to the reported cases in the literature of increasing stress and burnout during the pandemic. These effects were found to be similar to all academics, independently of their gender and disciplinary field. More concerning is that this increased number of hours worked per week appears to have established itself as part of the new normal. The main driver for the increased workload is associated with teaching, and to a lesser extent with administrative duties.
Novel polymorphism of the HMGCR gene related to the risk of diabetes in premature triple‐vessel disease patients

Coronary heart disease and diabetes are highly interrelated and complex diseases. We proposed to investigate the association of genetic polymorphisms of the lipoprotein important regulatory genes Niemann‐Pick C1‐like 1 (NPC1L1) and 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase (HMGCR) in patients with premature triple‐vessel coronary disease (PTVD) with diabetes, blood glucose and body mass index.
Comparing dual‐hormone and single‐hormone automated insulin delivery systems on nocturnal glucose management among children and adolescents with type 1 diabetes: A pooled analysis

Department of Medicine, Division of Experimental Medicine, McGill University, Montreal, Canada Montreal Clinical Research Institute, Montreal, Canada Department of Nutrition, Faculty of Medicine, Université de Montréal, Montreal, Canada Endocrinology Division, Centre Hospitalier Université de Montréal (CHUM), Montreal, Canada McGill University Health Centre, Montreal Children's Hospital, Montreal, Canada
Molecular mechanisms and clonal lineages of colistin‐resistant bacteria across the African continent: a scoping review

Colistin (also known as polymyxin E), a polymyxin antibiotic discovered in the late 1940s, has recently reemerged as a last‐line treatment option for multidrug‐resistant infections. However, in recent years, colistin‐resistant pathogenic bacteria have been increasingly reported worldwide. Accordingly, the presented review was undertaken to identify, integrate and synthesize current information regarding the detection and transmission of colistin‐resistant bacteria across the African continent, in addition to elucidating their molecular mechanisms of resistance. PubMed, Google Scholar and Science Direct were employed for study identification, screening and extraction. Overall, based on the developed literature review protocol and associated inclusion/exclusion criteria, 80 studies published between 2000 and 2021 were included comprising varying bacterial species and hosts. Numerous mechanisms of colistin resistance were reported, including chromosomal mutation(s) and transferable plasmid‐mediated colistin resistance (encoded by mcr genes). Perhaps unexpectedly, mcr‐variants have exhibited rapid emergence and spread across most African regions. The genetic variant mcr‐1 is predominant in humans, animals and the natural environment, and is primarily carried by IncHI2‐ type plasmid. The highest number of studies reporting the dissemination of colistin‐resistant Gram‐negative bacteria were conducted in the North African region.
Analysis of Retinal Microvasculature Features in Amblyopic Eyes: A Meta-Analysis

Background: Amblyopia is a common cause of visual disorder with several changes in retinal structure and vessel. To date, alterations in retinal microvasculature features in amblyopia have yielded inconsistent results. Objectives: This meta-analysis aimed to evaluate retinal vessel density (VD) in amblyopic patients using optical coherence tomography angiography (OCTA). Methods: PubMed, Web of Science, Embase, and Cochrane Library databases were systematically searched for published articles comparing retinal microvasculature characteristics in patients with amblyopia and controls. Continuous variable outcomes were assessed using the mean difference (MD) with a 95% confidence interval. Review Manager Version 5.30 was used for the analysis. Results: Thirteen qualified articles were pooled in this meta-analysis. Compared with controls, the foveal whole en face VD of superficial capillary plexus (SCP) and deep capillary plexus (DCP) of patients as measured by 3 × 3-mm scans were significantly lower in amblyopia eyes (MD: −1.37, p = 0.0003; MD: 1.70, p < 0.00001, respectively). Similarly, in the 6 × 6-mm scans, foveal whole en face VD of the SCP and DCP were remarkably lower in amblyopia eyes than in controls (MD: −2.24, p = 0.03; MD: −5.08, p = 0.04, respectively). The parafoveal VD of SCP in 3 × 3-mm scans (MD: −1.96, p < 0.00001) was also lower in amblyopic patients than in controls. Similarly, in 6 × 6-mm scans, amblyopia eyes showed a significant decrease and a trending decrease in the parafoveal VD of the SCP (MD: −3.85, p = 0.007) and DCP (MD: −3.03, p = 0.10), respectively. For whole radial peripapillary capillary (RPC), VD was significantly reduced in amblyopic patients compared to controls (MD = −0.83, p < 0.00001). In addition, the deep foveal avascular zone (FAZ) was larger in amblyopic eyes than in the controls (MD = 0.55, p = 0.007). Conclusions: Our data suggest that whole foveal and parafoveal VD and RPC whole VD were reduced in patients with amblyopia. Moreover, our results reveal that the FAZ is larger in amblyopic patients. Consequently, OCTA may have the potential for diagnosing and monitoring patients with amblyopia.
Non-volatile signals and redox mechanisms are required for the responses of Arabidopsis roots to Pseudomonas oryzihabitans

Abstract Soil bacteria promote plant growth and protect against environmental stresses, but the mechanisms involved remain poorly characterized, particularly when there is no direct contact between the roots and bacteria. Here, we explored the effects of Pseudomonas oryzihabitans PGP01 on the root system architecture (RSA) in Arabidopsis thaliana seedlings. Significant increases in lateral root (LR) density were observed when seedlings were grown in the presence of P. oryzihabitans, as well as an increased abundance of transcripts associated with altered nutrient transport and phytohormone responses. However, no bacterial transcripts were detected on the root samples by RNAseq analysis, demonstrating that the bacteria do not colonize the roots. Separating the agar containing bacteria from the seedlings prevented the bacteria-induced changes in RSA. Bacteria-induced changes in RSA were absent from mutants defective in ethylene response factor (ERF109), glutathione synthesis (pad2-1, cad2-1, and rax1-1) and in strigolactone synthesis (max3-9 and max4-1) or signalling (max2-3). However, the P. oryzihabitans-induced changes in RSA were similar in the low ascorbate mutants (vtc2-1and vtc2-2) to the wild-type controls. Taken together, these results demonstrate the importance of non-volatile signals and redox mechanisms in the root architecture regulation that occurs following long-distance perception of P. oryzihabitans.
Coherent Precipitates with Strong Domain Wall Pinning in Alkaline Niobate Ferroelectrics

High‐power piezoelectric applications are predicted to share approximately one‐third of the lead‐free piezoelectric ceramic market in 2024 with alkaline niobates as the primary competitor. To suppress self‐heating in high‐power devices due to mechanical loss when driven by large electric fields, piezoelectric hardening to restrict domain wall motion is required. In the present work, highly effective piezoelectric hardening via coherent plate‐like precipitates in a model system of the (Li,Na)NbO3 (LNN) solid solution delivers a reduction in losses, quantified as an electromechanical quality factor, by a factor of ten. Various thermal aging schemes are demonstrated to control the average size, number density, and location of the precipitates. The established properties are correlated with a detailed determination of short‐ and long‐range atomic structure by X‐ray diffraction and pair distribution function analysis, respectively, as well as microstructure determined by transmission electron microscopy. The impact of microstructure with precipitates on both small‐ and large‐field properties is also established. These results pave the way to implement precipitate hardening in piezoelectric materials, analogous to precipitate hardening in metals, broadening their use cases in applications.
Fluids and flows in brain cancer and neurological disorders

Abstract Interstitial fluid (IF) and cerebrospinal fluid (CSF) are an integral part of the brain, serving to cushion and protect the brain parenchymal cells against damage and aid in their function. The brain IF contains various ions, nutrients, waste products, peptides, hormones, and neurotransmitters. IF moves primarily by pressure‐dependent bulk flow through brain parenchyma, draining into the ventricular CSF. The brain ventricles and subarachnoid spaces are filled with CSF which circulates through the perivascular spaces. It also flows into the IF space regulated, in part, by aquaporin channels, removing waste solutes through a process of IF‐CSF mixing. During disease development, the composition, flow, and volume of these fluids changes and can lead to brain cell dysfunction. With the improvement of imaging technology and the help of genomic profiling, more information has been and can be obtained from brain fluids; however, the role of CSF and IF in brain cancer and neurobiological disease is still limited. Here we outline recent advances of our knowledge of brain fluid flow in cancer and neurodegenerative disease based on our understanding of its dynamics and composition. This article is categorized under: Cancer > Biomedical Engineering Neurological Diseases > Biomedical Engineering
Safety Evaluation of Geometric Design Criteria: Horizontal Curve Radius and Side Friction Demand on Rural, Two-Lane Highways

AASHTO’s A Policy on Geometric Design of Highways and Streets, 6thEdition, provides design criteria for horizontal curve elements based on the point-mass model. The model equates the centripetal force needed to navigate a horizontal curve of a specific radius traveling at the design speed to the combination of superelevation rate and side friction needed to achieve that force. Few researchers have examined the safety impacts of horizontal curve radius, superelevation rate, and design speed through crash-based research. None of the research reviewed included the effects of design speed or superelevation rate in the crash modification factors (CMFs) or functions. This research explored these factors using a negative binomial regression modeling approach based on data collected from the SHRP 2 RID 2.0 for 889 horizontal curves on rural two-lane highways in Indiana and Pennsylvania, which resulted in roadway departure crash modification functions for horizontal curve radius and side friction demand. The crash modification function for side friction demand includes an interactive component of horizontal curve radius and speed and a direct effect of superelevation rate on roadway departure crashes. The results showed that roadway departure crashes are expected to increase for decreasing curve radius, increasing posted speed limit, and decreased superelevation rate. Furthermore, curve-related CMFs were sensitive to the curve radii used in their development. CMFs developed from curves with larger radii tended to result in larger CMFs. Sample applications are provided for computing the effects of changing the horizontal curve radius, posted speed limit, or both on proposed alternatives.
Reply to Ze‐Hu Liu

We are pleased that our case report entitled, “A rare presentation of herpes simplex virus encephalitis occurring in a pediatric patient on dupilumab for atopic dermatitis,” stimulated conversation by Shi and colleagues regarding the potential association of systemic herpes simplex virus infection in the setting of dupilumab administration. Our decision to present this case was motivated by the expanding off-label use of dupilumab and pending priority review by the FDA for use in patients greater than 6 months of age. Dupilumab is an integral therapy in the treatment of atopic dermatitis, but physician comfort level and favorable side effect profile have led to the expanding use of the medication in younger patients. Wellpowered data in patients less than 6 years of age are limited and we do not yet have a lengthy open-label follow-up in this cohort. This case serves as a cautionary tale as our understanding of dupilumab and immune system interactions in infants and preschoolers is still nascent. Our patient was a previously healthy patient without comorbidities and without evidence of either immunologic deficiency or abnormalities in functional immune assays. While an immunologic etiology may still be elucidated in this case, it is very reasonable to consider a similar immunologic predisposition exists in an age-matched population that may not be easily screened for. It remains unclear at this time if dupilumab contributed to a possible “two-hit phenomena” and further genetic analysis may be instructive. Of note, however, pooled analysis of SOLO 1, SOLO 2, and AD-1021 did reveal a slight increase in herpes-related infections with dupilumab. Lastly, there are limitations to our understanding of in vivo TH1/TH2 maturation in children and dupilumab interaction at such early ages. While inhibition of IL-4 & IL-13 cytokines theoretically should decrease inhibition of TH1-mediated response and improve viral immunity, this has not been clinically proven in children on dupilumab. Case reports citing verruca and molluscum clearance secondary to dupilumab in adults may be secondary to skin barrier improvement and spontaneous resolution rather than enhanced antiviral activity. Conversely, there have been case reports of rapid dissemination of cutaneous molluscum after dupilumab start. Ultimately, this is a case report; only time and increased use of dupilumab in this atopic dermatitis cohort will determine association. It remains unchanged that our duty as dermatologists is to stay alert to possible new drug associations and weigh the risks and benefits of systemic medications in very young atopic dermatitis patients.
Randomized, Double-Blind, Placebo-Controlled, Global Phase III Trial of Talimogene Laherparepvec Combined With Pembrolizumab for Advanced Melanoma

PURPOSE The combination of talimogene laherparepvec (T-VEC) and pembrolizumab previously demonstrated an acceptable safety profile and an encouraging complete response rate (CRR) in patients with advanced melanoma in a phase Ib study. We report the efficacy and safety from a phase III, randomized, double-blind, multicenter, international study of T-VEC plus pembrolizumab (T-VEC-pembrolizumab) versus placebo plus pembrolizumab (placebo-pembrolizumab) in patients with advanced melanoma. METHODS Patients with stage IIIB-IVM1c unresectable melanoma, naïve to antiprogrammed cell death protein-1, were randomly assigned 1:1 to T-VEC-pembrolizumab or placebo-pembrolizumab. T-VEC was administered at ≤ 4 × 106 plaque-forming unit (PFU) followed by ≤ 4 × 108 PFU 3 weeks later and once every 2 weeks until dose 5 and once every 3 weeks thereafter. Pembrolizumab was administered intravenously 200 mg once every 3 weeks. The dual primary end points were progression-free survival (PFS) per modified RECIST 1.1 by blinded independent central review and overall survival (OS). Secondary end points included objective response rate per mRECIST, CRR, and safety. Here, we report the primary analysis for PFS, the second preplanned interim analysis for OS, and the final analysis. RESULTS Overall, 692 patients were randomly assigned (346 T-VEC-pembrolizumab and 346 placebo-pembrolizumab). T-VEC-pembrolizumab did not significantly improve PFS (hazard ratio, 0.86; 95% CI, 0.71 to 1.04; P = .13) or OS (hazard ratio, 0.96; 95% CI, 0.76 to 1.22; P = .74) compared with placebo-pembrolizumab. The objective response rate was 48.6% for T-VEC-pembrolizumab (CRR 17.9%) and 41.3% for placebo-pembrolizumab (CRR 11.6%); the durable response rate was 42.2% and 34.1% for the arms, respectively. Grade ≥ 3 treatment-related adverse events occurred in 20.7% of patients in the T-VEC-pembrolizumab arm and in 19.5% of patients in the placebo-pembrolizumab arm. CONCLUSION T-VEC-pembrolizumab did not significantly improve PFS or OS compared with placebo-pembrolizumab. Safety results of the T-VEC-pembrolizumab combination were consistent with the safety profiles of each agent alone.
The first Australian experience with ward‐based CPAP for COVID19 respiratory failure: A retrospective cohort study

We present the first Australian cohort of patients with COVID‐19 respiratory failure managed with escalating respiratory support including continuous positive airway pressure (CPAP) on a standard medical ward at a tertiary Sydney hospital during the 2021 COVID‐19 Delta variant outbreak. We demonstrate an equivalent mortality to CPAP delivered in intensive care unit and outline our ward structure and management during the pandemic.