Search Results (105)

Narrative review synthesizes the most current literature on the SARS-CoV-2 XEC variant, focusing on its genomic evolution, immune evasion characteristics, epidemiological dynamics, and public health implications. To achieve this, we conducted a structured search of the literature of peer-reviewed articles, preprints, and official surveillance data from 2023 to early 2025, prioritizing virological, clinical, and immunological reports related to XEC and its parent lineages. Defined by the distinctive spike protein mutations, T22N and Q493E, XEC exhibits modest reductions in neutralization in vitro, although current evidence suggests that mRNA booster vaccines, including those targeting JN.1 and KP.2, retain cross-protective efficacy against symptomatic and severe disease. The XEC strain of SARS-CoV-2 has drawn particular attention due to its increasing prevalence in multiple regions and its potential to displace other Omicron subvariants, although direct evidence of enhanced replicative fitness is currently lacking. Preliminary analyses also indicated that glycosylation changes at the N-terminal domain enhance infectivity and immunological evasion, which is expected to underpin the increasing prevalence of XEC. The XEC variant, while still emerging, is marked by a unique recombination pattern and a set of spike protein mutations (T22N and Q493E) that collectively demonstrate increased immune evasion potential and epidemiological expansion across Europe and North America. Current evidence does not conclusively associate XEC with greater disease severity, although additional research is required to determine its clinical relevance. Key knowledge gaps include the precise role of recombination events in XEC evolution and the duration of cross-protective T-cell responses. New research priorities include genomic surveillance in undersampled regions, updated vaccine formulations against novel spike epitopes, and long-term longitudinal studies to monitor post-acute sequelae. These efforts can be augmented by computational modeling and the One Health approach, which combines human and veterinary sciences. Recent computational findings (GISAID, 2024) point to the potential of XEC for further mutations in under-surveilled reservoirs, enhancing containment challenges and risks. Addressing the potential risks associated with the XEC variant is expected to benefit from interdisciplinary coordination, particularly in regions where genomic surveillance indicates a measurable increase in prevalence. Full article

Articles have recently been circulating in the media around the world, claiming that natural ${\mathrm{CO}}_2$ sinks have “suddenly and unexpectedly” ceased to function. It turned out that these articles were based on a single preprint of a meanwhile published article. Its reasoning is essentially based on the large spike of ${\mathrm{CO}}_2$ concentration growth in 2023 despite constant anthropogenic emissions. However, there are no obvious indications that photosynthesis or oceanic sinks have decreased. In this paper, it is shown that besides the natural sink systems of the land plants and oceans, the variability of natural emissions has to be considered. Based on a previous publication, it is made evident that natural emissions are temperature-dependent. Therefore, the careful analysis of monthly sea surface temperature and ${\mathrm{CO}}_2$-concentration data for 2023 and 2024 gives a consistent explanation for the rise in atmospheric carbon concentration growth without referring to the implausible hypothesis of failing carbon sinks. The temperature dependence of natural ${\mathrm{CO}}_2$ emissions indicates a clear causality from temperature to ${\mathrm{CO}}_2$ concentration. This is confirmed by the time shift between temperature and the subsequent concentration change. This suggests a new component in climate models with implications for climate policies. Full article

Background: There is still debate whether ribavirin should be added to direct-acting antivirals (DAAs) for the management of treatment-experienced individuals with non-genotype-1 hepatitis C. This study compared the efficacy and safety of adding ribavirin to sofosbuvir-based combinations compared to sofosbuvir-based regimens alone in treating non-genotype 1 hepatitis C virus (HCV) in individuals who have been previously treated. Methods: We searched Cochrane CENTRAL, PubMed, SCOPUS, CINAHL and preprint databases from inception to September 2023 for randomized controlled trials (RCTs) that compared sofosbuvir-based regimens with ribavirin to sofosbuvir-based regimens alone in previously treated individuals with non-genotype 1 HCV infection. Data extraction and quality of study assessments were performed by two independent authors, and synthesis was performed using bias-adjusted models, heterogeneity using I2, and publication bias using funnel plots. Results: Eight RCTs compared sofosbuvir-based combinations with and without ribavirin were included. Overall, the addition of ribavirin to sofosbuvir, compared to sofosbuvir alone, did not show a benefit in achieving sustained virological response (SVR) (OR 0.91, 95% CI 0.26–3.17, I2 = 70.0%) with moderate certainty in Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) evidence. In subgroup analysis, there was no benefit of adding ribavirin to sofosbuvir in individuals with non-genotype 1 HCV. The additional ribavirin was associated with increased adverse events (OR 2.03, 95% CI 1.58–2.6, I2 = 8.0%) and treatment discontinuation (OR 1.81, 95% CI 0.78–4.28, I2 = 0.0%). Conclusions: The moderate certainty evidence suggests that adding ribavirin to sofosbuvir-based regimens may not confer benefit in achieving SVR in previously treated individuals with non-genotype 1 HCV but increases the odds of adverse events and treatment discontinuation. More evidence is needed on the effect of additional ribavirin in achieving SVR in individuals with decompensated cirrhosis. Registration: The protocol is registered on the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42022368868). Full article

Pathogenic variants in the KAT6A gene cause KAT6A syndrome, a neurodevelopmental disorder characterised by intellectual disability (ID), developmental delay, speech and language challenges, feeding difficulties, and skeletal abnormalities. This scoping review synthesises current knowledge on KAT6A syndrome, identifies key research themes, and supports the mission of advocacy groups like the KAT6 Foundation. A systematic search of five databases (Ovid MEDLINE, Ovid EMBASE, PubMed, Web of Science, and Scopus) was conducted from 1990 to 2024, including peer-reviewed articles, preprints, and conference abstracts published from 2022 onward. Of 771 citations retrieved, 111 full-text articles were reviewed, with 62 meeting the inclusion criteria. Data were synthesised into six themes: (1) the genotype and phenotype map, revealing a broad phenotypic spectrum with common features like ID, absent speech, and craniofacial dysmorphism, as well as rare features such as severe aplastic anaemia and pancraniosynostosis; (2) the neurodevelopmental profile, detailing communication deficits, sleep disturbances, and impaired adaptive functioning; (3) the epigenetic and developmental roles of KAT6A, highlighting its critical function in histone acetylation, chromatin remodelling, and gene regulation; (4) molecular biomarkers, identifying distinct DNA methylation episignatures and dysregulated cellular pathways; (5) drug discovery, with preliminary studies suggesting that pantothenate and L-carnitine may mitigate mitochondrial dysfunction and histone acetylation deficits, while RSPO2 overexpression reverses cognitive impairment in animal models; (6) phenotypic overlap with Rett syndrome and KAT6B-related disorders. This review underscores the complexity and variability of KAT6A syndrome, highlighting the need for multidisciplinary approaches to improving diagnosis, management, and development of therapies. Future research should focus on longitudinal studies, underrepresented phenotypes, biomarker identification, and robust therapeutic trials to enhance outcomes for affected individuals and their families. Full article

This paper explores articles hosted on the arXiv preprint server with the aim of uncovering valuable insights hidden in this vast collection of research. Employing text mining techniques and through the application of natural language processing methods, I xamine the contents of quantitative finance papers posted in arXiv from 1997 to 2022. I extract and analyze, without relying on ad hoc software or proprietary databases, crucial information from the entire documents, including the references, to understand the topic trends over time and to find out the most cited researchers and journals in this domain. Additionally, I compare numerous algorithms for performing topic modeling, including state-of-the-art approaches. Full article

Introduction: The fruit of the cashew tree, known as cashew, is accompanied by the fleshy extension of its stem, referred to as the cashew nut. Rich in phenolic compounds, such as phenolic acids, anthocyanins, flavonoids, carotenoids, polyphenols, as well as vitamins C and E, the cashew nut exhibits antioxidant properties. Objective: This systematic review investigated the effects of cashew nuts on oxidative stress in rats. Methodology: The study followed PRISMA guidelines and was registered in PROSPERO. Searches were conducted in the Medline (PubMed), EMBASE, BVS, MedRxiv, Science Direct, Scopus, and Web of Science databases. Experimental studies with rats as the target population, evaluating the effects of cashew nut supplementation on oxidative stress, antioxidant enzymatic activities, and inflammatory markers, were included. Exclusion criteria comprised dissertations, reviews, expert opinions, duplicates, and preprints. Results: Five studies published between 2018 and 2022 were included, all utilizing cashew nut supplementation as the intervention. The results demonstrated a significant reduction in oxidative stress, an increase in the activity of antioxidant enzymes, such as SOD and catalase, and a decrease in inflammatory markers, including TNF-α and IL-1β. The most effective dose was 100 mg/kg/day, yielding consistent results across studies. Conclusion: Cashew nuts show potential for reducing oxidative stress, mitigating inflammation, and enhancing antioxidant defenses in rats. However, further clinical studies are required to better explore their benefits in humans, a field that remains less studied compared to other types of nuts. Full article

Background and Aims: There is still uncertainty about the efficacy and safety of subcutaneous compared to intravenous administration of biologics for inflammatory bowel disease (IBD) remission. Methods: In this systematic review and meta-analysis, we searched Cochrane, PubMed, SCOPUS, CINHAL, and preprint archives for trials that compared the efficacy and safety of subcutaneous and intravenous biologics for the induction and maintenance of IBD remission. Meta-analysis was carried out with a subgroup analysis for Crohn’s disease (CD) and Ulcerative Colitis (UC), heterogeneity using I², and publication bias using funnel plots. Results: A total of 14 randomized controlled trials, 9 on CD, 4 on UC, and 1 with data on both were included Subcutaneous, compared to intravenous administration, was less efficacious for the induction of remission; overall (OR 0.68, 95%CI 0.35–1.31, I² = 83%), worse in UC (OR 0.35, 95%CI 0.07–1.79, I² = 91.2%), and showed similar efficacy in CD (OR 0.97, 95%CI 0.73–1.30, I² = 0%). For the maintenance of remission, subcutaneous biologics were almost similar to intravenous biologics; overall (OR 0.97, 95%CI 0.63–1.49, I² = 57.1%), with less efficacy in UC (OR 0.82, 95%CI 0.54–1.23, I² = 52%), but superior efficacy in CD (OR 1.81, 95%CI 1.09–3.01, I² = 0%). Subcutaneous, compared to intravenous biologics, showed slightly higher odds of treatment discontinuation (OR 1.32, 95%CI 1.02–1.71, I² = 14.2%), worse in UC (OR 1.52, 95%CI 1.17–1.98, I² = 13%), and was similar to intravenous for CD (OR 1.03, 95%CI 0.65–1.62, I² = 0%). Conclusion: Subcutaneous administration has lower efficacy for the induction of remission but can achieve almost similar efficacy and safety in maintaining remission in IBD. Subcutaneous injection has better efficacy and safety in CD than in UC. Full article

Background/Objectives: Interleukin 12/23 inhibitors are a newer class of monoclonal antibodies used to induce and maintain remission for Crohn’s disease (CD), a chronic inflammatory bowel disease, when patients do not respond to conventional immunomodulatory drugs or first-line monoclonal antibody therapies. Although biologics are best administered intravenously, subcutaneous administration has been trialed, with mixed results. This research synthesized evidence on the efficacy and safety of subcutaneous compared to intravenous administration of interleukin 12/23 inhibitors for moderate to severe CD. Methods: In this systematic review and meta-analysis, we searched Cochrane, PubMed, SCOPUS, CINHAL, and preprint archives for randomized controlled trials (RCTs) that compared the efficacy and safety of subcutaneous to intravenous interleukin 12/23 inhibitors for the remission of CD. After study quality assessment, a meta-analysis was carried out using a bias-adjusted inverse variance heterogeneity model, heterogeneity was assessed using I², and publication bias was performed using Doi plots. Evidence certainty was assessed using Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). Results: Seven RCTs, with 2179 participants, all with moderate to severe CD, were included. After meta-analysis, subcutaneous compared to intravenous administration showed similar efficacy for the induction of remission (OR 0.77, 95%CI 0.53–1.12), with no-to-low heterogeneity (I² = 0%, p = 0.97). For the maintenance of remission, only two studies had analyzable data, and they showed that subcutaneous interleukin 12/23 inhibitors were equal or better compared to intravenous administration. Further syntheses showed that subcutaneous compared to intravenous administration of interleukin 12/23 inhibitors had almost similar odds of adverse events (OR 0.91, 95%CI 0.63–1.32, I² = 39%), serious adverse events (OR 0.97, 95%CI 0.61–1.53, I² = 0%), and treatment discontinuation (OR 1.06, 95%CI 0.67–1.68, I² = 0%). Conclusions: In individuals with moderate to severe CD, subcutaneous administration has similar efficacy for inducing remission with comparable safety. More RCTs are needed to confirm these findings. Full article

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disorder of the esophagus with rising prevalence. Dupilumab (DUPI), a monoclonal antibody that targets the interleukin-4 receptor α, has shown promise as a treatment option. We conducted a systematic review and network meta-analysis of randomized controlled trials searching the PubMed/Medline database, the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials (CENTRAL), and the medRxiv preprint server up to 31 July 2024, assessing DUPI’s efficacy and optimal dosing in the treatment of EoE. Finally, three randomized-controlled trials comprising 470 participants, including 102 children under 12 years of age, were included in the qualitative synthesis. Both high-exposure (HE-DUPI, 300 mg weekly) and low-exposure (LE-DUPI, 300 mg biweekly) regimens achieved significant histologic remission relative to placebo (OR = 26.88, 95% CI 11.98–60.29 for LE-DUPI; OR = 29.15, 95% CI 13.68–62.12 for HE-DUPI). Although overall adverse events were comparable between groups, HE-DUPI was associated with a notable increase in serious adverse events. These findings suggest that DUPI is effective in promoting histologic remission in EoE, with LE-DUPI emerging as a preferred option for balancing efficacy and safety. This study highlights the efficacy and safety profiles of different dosing regimens and pediatric groups. Further studies are warranted to explore long-term outcomes and identify patient subgroups that may derive the greatest benefit from DUPI therapy. Full article

Background: New strategies for respiratory syncytial virus (RSV) prevention are available and are in development, but their acceptance is crucial to their effectiveness. Objectives: This systematic review aims to summarize current quantitative and qualitative evidence regarding knowledge and attitudes relating to RSV prevention. Methods: Six databases (PubMed, Scopus, APA PsycArticles; APA PsycInfo; CINAHL Complete; Psychology and Behavioral Sciences Collection) and two preprint repositories (medRxiv and Preprints) were searched up until 23 December 2024 (PROSPERO: CRD42024602351). Results: Sixty-one articles were included, focusing on vaccination for the elderly and adults at risk (n = 10) or pregnant people (n = 24, of which 8 also examined preferences for maternal vs. infant immunization) and infant immunization (n = 27, of which 16 focused on palivizumab, with 6 focusing on adherence to its monthly administration). Eighteen articles assessed attitudes in healthcare professionals. Overall, findings showed limited knowledge and awareness of RSV but generally positive attitudes towards prevention strategies and moderate to high intentions and uptake rates. Protection against the disease and perceived severity promoted acceptance, whereas concerns about side effects hindered it. Maternal vaccination was more acceptable than infant immunization. Conclusions: Attitudes towards RSV prevention options were generally favorable. Should more options become available, preferences may depend on which options are available, their characteristics, and how they are framed and presented. These insights highlight the importance of education on RSV grounded in decision-making literature, while recognizing the likely favorable reception of preventive measures across target age-populations. Full article

This comprehensive survey explored the evolving landscape of generative Artificial Intelligence (AI), with a specific focus on the recent technological breakthroughs and the gathering advancements toward possible Artificial General Intelligence (AGI). It critically examined the current state and future trajectory of generative AI, exploring how innovations in developing actionable and multimodal AI agents with the ability scale their “thinking” in solving complex reasoning tasks are reshaping research priorities and applications across various domains, while the survey also offers an impact analysis on the generative AI research taxonomy. This work has assessed the computational challenges, scalability, and real-world implications of these technologies while highlighting their potential in driving significant progress in fields like healthcare, finance, and education. Our study also addressed the emerging academic challenges posed by the proliferation of both AI-themed and AI-generated preprints, examining their impact on the peer-review process and scholarly communication. The study highlighted the importance of incorporating ethical and human-centric methods in AI development, ensuring alignment with societal norms and welfare, and outlined a strategy for future AI research that focuses on a balanced and conscientious use of generative AI as its capabilities continue to scale. Full article

A hypersurface $M^n$ in a real space form ${\mathbf{R}}^{n+1}$, $S^{n+1}$, or $H^{n+1}$ is isoparametric if it has constant principal curvatures. This paper is a survey of the fundamental work of Cartan and Münzner on the theory of isoparametric hypersurfaces in real space forms, in particular, spheres. This work is contained in four papers of Cartan published during the period 1938–1940 and two papers of Münzner that were published in preprint form in the early 1970s and as journal articles in 1980–1981. These papers of Cartan and Münzner have been the foundation of the extensive field of isoparametric hypersurfaces, and they have all been recently translated into English by T. Cecil. The paper concludes with a brief survey of the recently completed classification of isoparametric hypersurfaces in spheres. Full article

Nipah virus (NiV) is a zoonotic pathogen with the potential to cause human outbreaks with a high case fatality ratio. In this systematic review and meta-analysis, available evidence on NiV infections occurring in healthcare workers (HCWs) was collected and critically appraised. According to the PRISMA statement, four medical databases (PubMed, CINAHL, EMBASE, and Scopus) and the preprint repository medRixv were inquired through a specifically designed searching strategy. A total of 2593 entries were identified; of them, 16 studies were included in qualitative and quantitative analysis detailing the outcome of NiV infection on HCWs and estimates of seroprevalence among healthcare professions. All studies reported data from Asian countries: Malaysia, Singapore, Bangladesh, India (States of Kerala and Bengal), and Philippines. Seroprevalence was estimated from seven studies in 0.00% (95%CI 0.00 to 0.10) for IgM-class antibodies and 0.08% (95%CI 0.00 to 0.72) for IgG class-antibodies, but four of the sampled studies did not report any seropositive cases. A case fatality ratio of 73.52% (95%CI 34.01 to 99.74) was calculated from 10 studies. In conclusion, the present study shows that NiV may result in a possible occupational infection among HCWs involved in managing incident cases. As most NiV outbreaks occur in limited resources settings, it is reasonable that even basic preventive measures (i.e., mandatory use of PPE and appropriate isolation of incident cases with physical distancing) may be quite effective in avoiding the occurrence of new infections among HCWs. Full article

Purpose: Bladder cancer is one of the most common malignancies worldwide with over 614,000 new cases and 220,000 deaths annually. Five percent of newly diagnosed patients have metastatic disease. Metastatic urothelial carcinoma (mUC) is primarily treated with cisplatin-based chemotherapy, immunotherapy, targeted therapy, or combinations. Cure from disease is rarely achieved, with the overall survival being between 12 and 15 months, and the 5-year survival in the range of 5–15%. Historically, mUC has been deemed surgically incurable. There are limited data available to assess survival benefit with surgical extirpation of the primary site or metastases. In this review, we summarize findings from previous studies regarding the role of surgery in patients with clinically node-positive bladder cancer or metastatic urothelial carcinoma, focusing on cytoreductive radical cystectomy (RC) and distant metastasectomy. Materials and Methods: A literature search was conducted on The Medical Literature Analysis and Retrieval System Online (Medline), Excerpta Medica dataBASE (Embase), preprints, and ClinicalTrials.gov for studies that discussed the role of surgery in patients with clinically node-positive bladder cancer or mUC, focusing on cytoreductive radical cystectomy (RC) and distant metastasectomy. The keywords used included transitional cell carcinoma, urothelial carcinoma, bladder cancer, bladder carcinoma, bladder metastasis, bladder tumor, lymph node metastasis, metastasis, and muscle-invasive bladder cancer. Results: The final analysis included 21 studies, including 17 retrospective reviews, 2 prospective phase II trials, and 2 meta-analyses. Of the studies that assessed patients with urothelial carcinoma (UC) with nodal involvement, 15 of 17 showed improved survival with chemotherapy followed by radical cystectomy (RC). To our knowledge, few studies have solely assessed surgery in patients with distant metastases. Most studies include patients with both UC with local LN involvement and patients with distant sites of metastasis. Of these studies, 12 of 13 indicated improved survival with metastasectomy. Conclusions: While it remains to be seen whether metastasectomy will have a role in patients with mUC, patient selection is an important factor when assessing the survival benefits. Patient characteristics correlated with improved survival include good performance status, good response to chemotherapy, and single site of metastasis. Further studies of mUC patients are required to clearly assess the survival impact of cytoreductive surgery. Full article

Background: The increased popularity and ubiquitous use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for the treatment of diabetes, heart failure, and obesity has led to significant concern for increased risk for perioperative aspiration, given their effects on delayed gastric emptying. This concern is highlighted by many major societies that have published varying guidance on the perioperative management of these medications, given limited data. We conducted a scoping review of the available literature regarding the aspiration risk and aspiration/regurgitant events related to GLP-1 RAs. Methods: A librarian-assisted search was performed using five electronic medical databases (PubMed, Embase, and Web of Science Platform Databases, including Web of Science Core Collection, KCI Korean Journal Database, MEDLINE, and Preprint Citation Index) from inception through March 2024 for articles that reported endoscopic, ultrasound, and nasogastric evaluation for increased residual gastric volume retained food contents, as well as incidences of regurgitation and aspiration events. Two reviewers independently screened titles, abstracts, and full text of articles to determine eligibility. Data extraction was performed using customized fields established a priori within a systematic review software system. Results: Of the 3712 citations identified, 24 studies met eligibility criteria. Studies included four prospective, six retrospective, five case series, and nine case reports. The GLP-1 RAs reported in the studies included semaglutide, liraglutide, lixisenatide, dulaglutide, tirzepatide, and exenatide. All studies, except one case report, reported patients with confounding factors for retained gastric contents and aspiration, such as a history of diabetes, cirrhosis, hypothyroidism, psychiatric disorders, gastric reflux, Barrett’s esophagus, Parkinson’s disease, dysphagia, obstructive sleep apnea, gastric polyps, prior abdominal surgeries, autoimmune diseases, pain, ASA physical status classification, procedural factors (i.e., thyroid surgery associated with risk for nausea, ketamine associated with nausea and secretions), and/or medications associated with delayed gastric emptying (opioids, anticholinergics, antidepressants, beta-blockers, calcium channel blockers, DPP-IV inhibitors, and antacids). Of the eight studies (three prospective and five retrospective) that evaluated residual contents in both GLP-1 users and non-users, seven studies (n = 7/8) reported a significant increase in residual gastric contents in GLP-1 users compared to non-users (19–56% vs. 5–20%). In the three retrospective studies that evaluated for aspiration events, there was no significant difference in aspiration events, with one study reporting aspiration rates of 4.8 cases per 10,000 in GLP-1 RA users compared to 4.6 cases per 10,000 in nonusers and the remaining two studies reporting one aspiration event in the GLP-1 RA user group and none in the non-user group. In one study that evaluated for regurgitation or reflux by esophageal manometry and pH, there was no significant difference in reflux episodes but a reduction in gastric acidity in the GLP-1 RA user group compared to the non-user group. Conclusions: There is significant variability in the findings reported in the studies, and most of these studies include confounding factors that may influence the association between GLP-1 RAs and an increased risk of aspiration and related events. While GLP-1 RAs do increase residual gastric contents in line with their mechanism of action, the currently available data do not suggest a significant increase in aspiration and regurgitation events associated with their use and the withholding of GLP-1 RAs to reduce aspiration and regurgitation events, as is currently recommended by many major societal guidelines. Large randomized controlled trials (RCTs) may be helpful in further elucidating the impact of GLP-1 RAs on perioperative aspiration risk. Full article