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Abstract Genome-wide association studies (GWAS) have revolutionized our understanding of the genetic architecture of complex traits and diseases. GWAS summary statistics have become essential tools for various genetic analyses, including meta-analysis, fine-mapping, and risk prediction. However, the increasing number of GWAS summary statistics and the diversity of software tools available for their analysis can make it challenging for researchers to select the most appropriate tools for their specific needs. This systematic review aims to provide a comprehensive overview of the currently available software tools and databases for GWAS summary statistics analysis. We conducted a comprehensive literature search to identify relevant software tools and databases. We categorized the tools and databases by their functionality, including data management, quality control, single-trait analysis, and multiple-trait analysis. We also compared the tools and databases based on their features, limitations, and user-friendliness. Our review identified a total of 305 functioning software tools and databases dedicated to GWAS summary statistics, each with unique strengths and limitations. We provide descriptions of the key features of each tool and database, including their input/output formats, data types, and computational requirements. We also discuss the overall usability and applicability of each tool for different research scenarios. This comprehensive review will serve as a valuable resource for researchers who are interested in using GWAS summary statistics to investigate the genetic basis of complex traits and diseases. By providing a detailed overview of the available tools and databases, we aim to facilitate informed tool selection and maximize the effectiveness of GWAS summary statistics analysis.

Carbon capture and utilization (CCU) has emerged in recent years as a promising decarbonization solution for hard-to-abate industries. Compared to carbon capture and storage (CCS), CCU aims not for the storage of carbon dioxide (CO2) but for its use in the production of synthetic fuels, such as synthetic methanol (MeOH). Synthetic MeOH is produced through CO2 hydrogenation, utilizing green hydrogen (H2). Efficient use of CO2 and H2 feedstocks is essential to maximize the carbon reduction potential and energy efficiency of the process. This study performed an optimization analysis on a small-scale, containerized, and portable CO2 hydrogenation unit with a 5 kg MeOH/h production capacity goal, focusing on carbon conversion efficiency (CCE), MeOH yield, H2 consumption, and MeOH purity. The analysis was conducted using Aspen Plus V12. A single-pass model was used first to evaluate an initial reactor design. The reactor was then re-designed according to the results of the gas hourly space velocity (GHSV). The model was then expanded to include a recycling loop and the final reactor design was validated, aiming to maximize overall efficiency. The effects of the operational parameters including the reactor inlet temperature, reactor pressure, thermal fluid temperature, and condensation temperature were examined. The model was then further expanded to include the MeOH distillation process, and the effect of the distillation temperature was examined. The final product of the analysis was a fully-defined and optimized unit, achieving an 87.97% CCE and an 84.99% MeOH yield, consuming 1.11 kg H2/h for the production of 5.01 kg MeOH/h of 99.86 wt% purity. This study can provide valuable information and guidelines for designing small-scale, containerized, and portable CO2 hydrogenation units, which can serve as alternative solutions to address issues of H2 production and transportation related to large-scale installations.

UNLABELLED: Functional enrichment is the process of identifying implicated functional terms from a given input list of genes or proteins. In this article, we present Flame (v2.0), a web tool which offers a combinatorial approach through merging and visualizing results from widely used functional enrichment applications while also allowing various flexible input options. In this version, Flame utilizes the aGOtool, g: Profiler, WebGestalt, and Enrichr pipelines and presents their outputs separately or in combination following a visual analytics approach. For intuitive representations and easier interpretation, it uses interactive plots such as parameterizable networks, heatmaps, barcharts, and scatter plots. Users can also: (i) handle multiple protein/gene lists and analyse union and intersection sets simultaneously through interactive UpSet plots, (ii) automatically extract genes and proteins from free text through text-mining and Named Entity Recognition (NER) techniques, (iii) upload single nucleotide polymorphisms (SNPs) and extract their relative genes, or (iv) analyse multiple lists of differentially expressed proteins/genes after selecting them interactively from a parameterizable volcano plot. Compared to the previous version of 197 supported organisms, Flame (v2.0) currently allows enrichment for 14 436 organisms. AVAILABILITY AND IMPLEMENTATION: Web Application: http://flame.pavlopouloslab.info. Code: https://github.com/PavlopoulosLab/Flame. Docker: https://hub.docker.com/r/pavlopouloslab/flame.

Critically ill neonates admitted to neonatal intensive care units require specialized pharmacological treatment due to various medical conditions. However, despite the decades of clinical use of some pharmacological agents, there are still significant knowledge gaps surrounding their everyday use. The wide variability of drugs used in neonates, and how they are used in different settings worldwide, precisely reflects this fact. A major factor contributing to this variability is the lack of adequate studies regarding the effectiveness and safety of medications administered to neonates, especially in those born preterm. This is mainly due to inherent difficulties in performing pharmacokinetic, pharmacodynamic, and clinical studies in this age group. In this review, we discuss the existing data on medications most commonly used in the respiratory and cardiovascular care of the sick neonate. Knowledge gaps and future perspectives are highlighted, as well.

Glioblastoma is a highly aggressive brain tumor that has a poor prognosis despite various treatments like surgery, chemotherapy, and irradiation. However, a restricted ketogenic diet (RKD), which has been proven to be effective in treating drug-resistant epilepsy, could be a potential adjunct in the treatment of certain GBM cases. Our study aimed to highlight the existing knowledge, identify collaboration networks, and emphasize the ongoing research based on highly cited studies. During the literature search, we found 119 relevant articles written between 2010 and 2023. Among the top 20 most cited articles, there were seven laboratory and five clinical studies. The works of Olson LK, Chang HT, Schwartz KA, and Nikolai M from the Michigan State University, followed by Seyfried TN and Mukherjee P from Boston College, and Olieman JF, and Catsman-Berrevoets CE from the University Medical Center of Rotterdam, were significant contributions. The laboratory studies showed that RKD had a significant antitumor effect and could prolong survival in mouse glioblastoma models. The clinical studies verified the tolerability, efficacy, and safety of RKD in patients with GBM, but raised concerns about whether it could be used as a single therapy. The current research interest is focused on the efficacy of using RKD as an adjunct in selected chemotherapy regimens and demonstrates that it could provide GBM patients with better treatment options.

AbstractObjective To evaluate the possible association between thyroid function within the euthyroid range and musculoskeletal parameters as well as body composition in a sample of postmenopausal women.Methods This cross-sectional study included 96 postmenopausal women with serum thyroid-stimulating hormone (TSH) within the normal laboratory reference range. Fasting venous blood samples were obtained for biochemical/hormonal assessment. Bone status and body composition were measured using Dual Energy X-ray absorptiometry (DXA). Physical activity was quantified using the International Physical Activity Questionnaire (IPAQ) index.Results Serum TSH correlated with handgrip strength (HGS, r-coefficient = 0.233, p = .025), and total body bone mineral density (BMD) T-score values (r-coefficient = 0.321, p = .003). HGS measures were associated with BMD (r-coefficient = 0.415, p

Available drugs have been used as an urgent attempt through clinical trials to minimize severe cases of hospitalizations with Coronavirus disease (COVID-19), however, there are limited data on common pharmacogenomics affecting concomitant medications response in patients with comorbidities. To identify the genomic determinants that influence COVID-19 susceptibility, we use a computational, statistical, and network biology approach to analyze relationships of ineffective concomitant medication with an adverse effect on patients. We statistically construct a pharmacogenetic/biomarker network with significant drug-gene interactions originating from gene-disease associations. Investigation of the predicted pharmacogenes encompassing the gene-disease-gene pharmacogenomics (PGx) network suggests that these genes could play a significant role in COVID-19 clinical manifestation due to their association with autoimmune, metabolic, neurological, cardiovascular, and degenerative disorders, some of which have been reported to be crucial comorbidities in a COVID-19 patient.

The aim of this study was to evaluate the effect of starvation and refeeding on the growth and food intake of gilthead seabream (Sparus aurata) and seabass (Dicentrarchus labrax) and on the growth and nitrogen uptake of glasswort (Salicornia europaea) in a polyculture aquaponic system under 12 ppt salinity for 75 days. Nine small-scale autonomous aquaponic systems were used, each containing 10 gilthead seabreams (average weight of 6.33 ± 0.73 g and average length of 5.73 ± 0.72 cm) and 10 seabasses (5.82 ± 0.77 g and 6.35 ± 0.45 cm), as well as five glasswort plants. Three fish feeding treatments were performed, a control (A), in which fish were fed daily until satiation, and two fasting treatments for 4 (B) and 7 days (C). Fish growth performance was significantly lower (p

Necrotizing enterocolitis (NEC) is the most prevalent and potentially fatal intestinal injury mainly affecting premature infants, with significant long-term consequences for those who survive. This review explores the scale of the problem, highlighting advancements in epidemiology, the understanding of pathophysiology, and improvements in the prediction and diagnosis of this complex, multifactorial, and multifaced disease. Additionally, we focus on the potential role of metabolomics in distinguishing NEC from other conditions, which could allow for an earlier and more accurate classification of intestinal injuries in infants. By integrating metabolomic data with other diagnostic approaches, it is hoped to enhance our ability to predict outcomes and tailor treatments, ultimately improving care for affected infants.

Background People who have had a stroke or a Transient Ischaemic Attack (TIA) can experience psychological and/or cognitive difficulties. The body of research for psychological and neuropsychological interventions after stroke is growing, however, published systematic reviews vary in scope and methodology, with different types and severity of strokes included, and at times, diverse conclusions drawn about the effectiveness of the interventions evaluated. In this umbrella review, we aim to systematically summarise the existing systematic reviews evaluating psychological interventions for mood and cognition post-stroke/TIA. Methods We will conduct this umbrella review according to the JBI Manual for Evidence Synthesis. The following databases will be searched from inception: Cochrane Database of Systematic Reviews, Database of Reviews of Effects (DARE), MEDLINE, Embase, CINAHL, PsycINFO, and Epistemonikos. Systematic reviews with or without meta-analysis published until the search date will be included. Reviews including psychological interventions addressing mood and/or cognition outcomes for any stroke type or severity will be screened for eligibility. A narrative synthesis, including content analysis, will be used. Each stage of the review will be processed by two independent reviewers and a third reviewer will be considered to resolve disagreements. The methodological quality of the included reviews will be assessed using AMSTAR 2. Discussion Existing systematic reviews provide varied evidence on the effectiveness of psychological interventions post-stroke/TIA. This umbrella review aims to summarise knowledge and evidence on different types of psychological and neuropsychological interventions targeting mood and cognition. Findings will highlight important knowledge gaps and help prioritise future research questions. Systematic Review Registration This protocol was prospectively registered with the International Prospective Register of Systematic Reviews (PROSPERO) on November 15, 2022; PROSPERO CRD42022375947.

Background People who have had a stroke or a Transient Ischaemic Attack (TIA) can experience psychological and/or cognitive difficulties. The body of research for psychological and neuropsychological interventions after stroke is growing, however, published systematic reviews vary in scope and methodology, with different types and severity of strokes included, and at times, diverse conclusions drawn about the effectiveness of the interventions evaluated. In this umbrella review, we aim to systematically summarise the existing systematic reviews evaluating psychological interventions for mood and cognition post-stroke/TIA. Methods We will conduct this umbrella review according to the JBI Manual for Evidence Synthesis. The following databases will be searched from inception: Cochrane Database of Systematic Reviews, Database of Reviews of Effects (DARE), MEDLINE, Embase, CINAHL, PsycINFO, and Epistemonikos. Systematic reviews with or without meta-analysis published until the search date will be included. Reviews including psychological interventions addressing mood and/or cognition outcomes for any stroke type or severity will be screened for eligibility. A narrative synthesis, including content analysis, will be used. Each stage of the review will be processed by two independent reviewers and a third reviewer will be considered to resolve disagreements. The methodological quality of the included reviews will be assessed using AMSTAR 2. Discussion Existing systematic reviews provide varied evidence on the effectiveness of psychological interventions post-stroke/TIA. This umbrella review aims to summarise knowledge and evidence on different types of psychological and neuropsychological interventions targeting mood and cognition. Findings will highlight important knowledge gaps and help prioritise future research questions. Systematic Review Registration This protocol was prospectively registered with the International Prospective Register of Systematic Reviews (PROSPERO) on November 15, 2022; PROSPERO CRD42022375947.

Background People who have had a stroke or a Transient Ischaemic Attack (TIA) can experience psychological and/or cognitive difficulties. The body of research for psychological and neuropsychological interventions after stroke is growing, however, published systematic reviews vary in scope and methodology, with different types and severity of strokes included, and at times, diverse conclusions drawn about the effectiveness of the interventions evaluated. In this umbrella review, we aim to systematically summarise the existing systematic reviews evaluating psychological interventions for mood and cognition post-stroke/TIA. Methods We will conduct this umbrella review according to the JBI Manual for Evidence Synthesis. The following databases will be searched from inception: Cochrane Database of Systematic Reviews, Database of Reviews of Effects (DARE), MEDLINE, Embase, CINAHL, PsycINFO, and Epistemonikos. Systematic reviews with or without meta-analysis published until the search date will be included. Reviews including psychological interventions addressing mood and/or cognition outcomes for any stroke type or severity will be screened for eligibility. A narrative synthesis, including content analysis, will be used. Each stage of the review will be processed by two independent reviewers and a third reviewer will be considered to resolve disagreements. The methodological quality of the included reviews will be assessed using AMSTAR 2. Discussion Existing systematic reviews provide varied evidence on the effectiveness of psychological interventions post-stroke/TIA. This umbrella review aims to summarise knowledge and evidence on different types of psychological and neuropsychological interventions targeting mood and cognition. Findings will highlight important knowledge gaps and help prioritise future research questions. Systematic Review Registration This protocol was prospectively registered with the International Prospective Register of Systematic Reviews (PROSPERO) on November 15, 2022; PROSPERO CRD42022375947.

Summary: LMTK3 is a brain-specific transmembrane serine/threonine protein kinase that acts as a scaffold for protein phosphatase-1 (PP1). Although LMKT3 has been identified as a risk factor for autism and epilepsy, its physiological significance is unknown. Here, we demonstrate that LMTK3 copurifies and binds to KCC2, a neuron-specific K+/Cl− transporter. KCC2 activity is essential for Cl−-mediated hyperpolarizing GABAAR receptor currents, the unitary events that underpin fast synaptic inhibition. LMTK3 acts to promote the association of KCC2 with PP1 to promote the dephosphorylation of S940 within its C-terminal cytoplasmic domain, a process the diminishes KCC2 activity. Accordingly, acute inhibition of LMTK3 increases KCC2 activity dependent upon S940 and increases neuronal Cl− extrusion. Consistent with this, LMTK3 inhibition reduced intrinsic neuronal excitability and the severity of seizure-like events in vitro. Thus, LMTK3 may have profound effects on neuronal excitability as an endogenous modulator of KCC2 activity.

Low-dose computed tomography is being used for lung cancer screening in high-risk groups. Detecting lung cancer at an early stage improves the chance of optimal treatment and increases overall survival. This article compares segmentectomy vs. lobectomy as surgical options, in the case of stage I non-small cell lung carcinoma, ideally IA. To compare the 2 previously referred strategies, data were collected from articles (40 studies were reviewed), reviews, and systematic analyses in PubMed Central, as well as reviewing recent literature. Segmentectomy could be an equal alternative to lobectomy in early-stage NSCLC (tumour < 2 cm). It could be preferred for patients with a low cardiopulmonary reserve, who struggle to survive a lobectomy. As far as early-stage NSCLC is concerned, anatomic segmentectomy is an acceptable procedure in a selective group of patients. For better tumour and stage classification, a systematic lymph node dissection should be performed.

Wormhole solutions, bridges that connect different parts of spacetime, were proposed early in the history of General Relativity. Soon after, it was shown that all wormholes violate classical energy conditions, which are non-negativity constraints on contractions of the stress–energy tensor. Since these conditions are violated by quantum fields, it was believed that wormholes can be constructed in the context of semiclassical gravity. But negative energies in quantum field theory are not without restriction: quantum energy inequalities (QEIs) control renormalized negative energies averaged over a geodesic. Thus, QEIs provide restrictions on the construction of wormholes. This work is a review of the relevant literature, thus focusing on results where QEIs restrict traversable wormholes. Both ‘short’ and ‘long’ (without causality violations) wormhole solutions in the context of semiclassical gravity are examined. A new result is presented on constraints on the Maldacena, Milekhin, and Popov ‘long’ wormhole from the recently derived doubled smeared null energy condition.

Antibiotic, analgesic sedative, and antiseizure medications are among the most commonly used medications in preterm/sick neonates, who are at high risk of nosocomial infections, central nervous system complications, and are exposed to numerous painful/stressful procedures. These severe and potentially life-threatening complications may have serious short- and long-term consequences and should be prevented and/or promptly treated. The reported variability in the medications used in neonates indicates the lack of adequate neonatal studies regarding their effectiveness and safety. Important obstacles contributing to inadequate studies in preterm/sick infants include difficulties in obtaining parental consent, physicians’ unwillingness to recruit preterm infants, the off-label use of many medications in neonates, and other scientific and ethical concerns. This review is an update on the use of antimicrobials (antifungals), analgesics (sedatives), and antiseizure medications in neonates, focusing on current evidence or knowledge gaps regarding their pharmacokinetics, indications, safety, dosage, and evidence-based guidelines for their optimal use in neonates. We also address the effects of early antibiotic use on the intestinal microbiome and its association with long-term immune-related diseases, obesity, and neurodevelopment (ND). Recommendations for empirical treatment and the emergence of pathogen resistance to antimicrobials and antifungals are also presented. Finally, future perspectives on the prevention, modification, or reversal of antibiotic resistance are discussed.

The description of various loading types within the frame of viscoelasticity, such as creep–recovery and stress relaxation in a wide time scale, by means of the same model and similar model parameters is always an interesting topic. In the present work, a viscoelastic model that was analyzed in previous works has been utilized to describe the main standard loading types of viscoelasticity with the same set of model parameters. The relaxation function of this model includes a distribution function followed by the energy barriers that need to be overcome by the molecular domains when a stress field is applied. This distribution function attains a decisive role in the analysis and it was shown that it can be determined on the basis of the loss modulus master curve experimental results. Thereafter, requiring no additional parameters, the creep compliance, the relaxation modulus of poly-lactic acid (PLA) in a wide time scale, as well as creep–recovery at various stresses could be predicted. It was also found that by employing the distribution function associated with the PLA matrix, the creep–recovery experimental data of PLA/hybrid nanocomposites could subsequently be predicted. Therefore, the proposed analysis was shown to be a useful method to predict the material’s viscoelastic response.

Stevia rebaudiana Bertoni, a no-calorie natural sweetener, contains a plethora of polyphenols that exert antioxidant properties with potential medicinal significance. Due to the variety of functional groups, polyphenols exhibit varying solubility depending on the nature of the extraction solvents (water, organic, or their mixtures, defined further on as hydroalcoholic extracts). In the present study, we performed a systematic review, following PRISMA guidelines, and meta-analysis, synthesizing all available data from 45 articles encompassing 250 different studies. Our results showed that the total phenolic content (TPC) of hydroalcoholic and aqueous extracts presents higher values (64.77 and 63.73 mg GAE/g) compared to organic extracts (33.39). Total flavonoid content (TFC) was also higher in aqueous and hydroalcoholic extracts; meta-regression analysis revealed that outcomes in different measuring units (mg QE/g, mg CE/g, and mg RUE/g) do not present statistically significant differences and can be synthesized in meta-analysis. Using meta-regression analysis, we showed that outcomes from the chemical-based ABTS, FRAP, and ORAC antioxidant assays for the same extract type can be combined in meta-analysis because they do not differ statistically significantly. Meta-analysis of ABTS, FRAP, and ORAC assays outcomes revealed that the antioxidant activity profile of various extract types follows that of their phenolic and flavonoid content. Using regression meta-analysis, we also presented that outcomes from SOD, CAT, and POX enzymatic antioxidant assays are independent of the assay type (p-value = 0.905) and can be combined. Our study constitutes the first effort to quantitatively and statistically synthesize the research results of individual studies using all methods measuring the antioxidant activity of stevia leaf extracts. Our results, in light of evidence-based practice, uncover the need for a broadly accepted, unified, methodological strategy to perform antioxidant tests, and offer documentation that the use of ethanol:water 1:1 mixtures or pure water can more efficiently extract stevia antioxidant compounds.