Search Results (1,050)

Various SARS-CoV-2 remdesivir resistance-associated substitutions (RAS) have been reported, but a comprehensive comparison of their resistance levels is lacking. We identified novel RAS and performed head-to-head comparisons with known RAS in Vero E6 cells. A remdesivir escape polyclonal virus exhibited a 3.6-fold increase in remdesivir EC₅₀ and mutations throughout the genome, including substitutions in nsp12 (E796D) and nsp14 (A255S). However, in reverse-genetics infectious assays, viruses harboring both these substitutions exhibited only a slight decrease in remdesivir susceptibility (1.3-fold increase in EC₅₀). The nsp12-E796D substitution did not impair viral fitness (Vero E6 cells or Syrian hamsters) and was reported in a remdesivir-treated COVID-19 patient. In replication assays, a subgenomic replicon containing nsp12-E796D+nsp14-A255S led to a 16.1-fold increase in replication under remdesivir treatment. A comparison with known RAS showed that S759A, located in the active site of nsp12, conferred the highest remdesivir resistance (106.1-fold increase in replication). Nsp12-RAS V166A/L, V792I, E796D or C799F, all adjacent to the active site, caused intermediate resistance (2.0- to 11.5-fold), whereas N198S, D484Y, or E802D, located farther from the active site, showed no resistance (≤2.0-fold). In conclusion, our classification system, correlating replication under remdesivir treatment with RAS location in nsp12, shows that most nsp12-RAS cause moderate resistance. Full article

Madagascar harbors a rich marine biodiversity, yet detailed knowledge of its fish species remains limited. Of the 1689 species listed in 2018, only 22% had accessible cytochrome oxidase I (COI) sequences in public databases. In response to growing pressure on fishery resources, this study aims to strengthen biodiversity monitoring tools. Its objectives were to enrich the COI database for Malagasy marine fishes, create the first 12S reference library, and evaluate the taxonomic resolution of different 12S metabarcodes for eDNA analysis, namely MiFish, Teleo1, AcMDB, Ac12S, and 12SF1/R1. An integrated approach combining morphological, molecular, and phylogenetic analyses was applied for specimen identification of fish captured using various types of fishing gear in Toliara and Ranobe Bays from 2018 to 2023. The Malagasy COI database now includes 2146 sequences grouped into 502 Barcode Index Numbers (BINs) from 82 families, with 14 BINs newly added to BOLD (The Barcode of Life Data Systems), and 133 cryptic species. The 12S library comprises 524 sequences representing 446 species from 78 families. Together, the genetic datasets cover 514 species from 84 families, with the most diverse being Labridae, Apogonidae, Gobiidae, Pomacentridae, and Carangidae. However, the two markers show variable taxonomic resolution: 67 species belonging to 35 families were represented solely in the COI dataset, while 10 species from nine families were identified exclusively in the 12S dataset. For 319 species with complete 12S gene sequences associated with COI BINs (Barcode Index Numbers), 12S primer sets were used to evaluate the taxonomic resolution of five 12S metabarcodes. The MiFish marker proved to be the most effective, with an optimal similarity threshold of 98.5%. This study represents a major step forward in documenting and monitoring Madagascar’s marine biodiversity and provides a valuable genetic reference for future environmental DNA (eDNA) applications. Full article

Background: Several studies have suggested that laparoscopic peritoneal lavage for the treatment of diverticulitis might be associated with an increased event rate. The WSES (World Society of Emergency Surgery) guidelines recommend performing laparoscopic peritoneal lavage only in highly selected patients; however, selection criteria remain poorly described. This study, based on a single-center retrospective cohort of patients presenting with acute diverticulitis and undergoing surgery, aimed to assess the complication and long-term outcomes of the lavage group and to report our experience with the treatment of acute diverticulitis. Methods: Operative management of acute sigmoid diverticulitis was involved, in particular, laparoscopic peritoneal lavage, primary resection, and the Hartmann procedure. Results: Six-month follow-ups showed the occurrence of Clavien–Dindo complications in ≥2 in 21.9% of patients in the sigmoidectomy group versus 61.1% of patients in the lavage group (p = 0.0028). Among the 11 patients with complications after laparoscopic lavage, 9 required a second surgery. After a comparison between the patients with complications and those without who were managed with laparoscopic lavage, descriptive differences were found regarding the BMI (95% CI, 21.7–24.3 vs. 95% CI, 24.7–31.3, p = 0.0419). In analysis, a BMI of ≥27 kg/m² (OR, 16 p = 0.049) was associated with short- and long-term complications in the lavage group. There was no evidence for an association between complications and a BMI of ≥27 kg/m² in the primary resection (OR, 1.61 p = 1) or the Hartmann procedure group (OR, 4.25 p = 0.1438). Perforated colonic diverticulitis treated with laparoscopic peritoneal lavage was associated with a high morbidity rate. Conclusions: The choice of surgical strategy for acute diverticular pathology is complex, influenced by various conditions. BMI could be a prognostic factor for long-term outcomes, including recurrent diverticulitis and the occurrence of abscesses. Full article

Background and Objectives: Evaluating jaw augmentation procedures usually necessitates pre- and postoperative tomographic imaging. Ethical considerations emphasize minimizing radiation exposure. Given that panoramic radiographs (PR, 2D) offer a lower radiation dose compared to cone-beam CT (CBCT, 3D), this study explores the feasibility of estimating tooth root volume from PR, potentially allowing safer clinical assessments with reduced radiation exposure. Materials and Methods: To develop a mathematical approximation method, the 2D tooth root surface in PR was defined as an elliptical model and a cuboid (3D). The true root volume (mm³) was gathered from CBCTs. The missing link for tooth root volume assessment in 2D radiographs is the depth of the root (vestibulo-oral dimension). It was hypothesized that the tooth root surface and its volume are related. A correlation factor “r” corresponding to the tooth roots’ depths was then calculated. Descriptive and inferential statistics were computed (p < 0.05). Results: The mathematical model was performed on 27 molars with an average volume of 472.83 mm³ (±130.25–CBCT). The factor “r” (obtained by dividing the true root volume from CBCT by the total root surface from PR) was computed as 8.04 (±1.90). Using “r” for the volume calculation in the cuboid model, an average volume of 472.37 (±152.92) for the 27 molars was computed. These volumes did not differ significantly. Conclusions: This study demonstrates that a mathematical model using elliptical projections from panoramic radiographs reliably estimates molar root volume, yielding comparable results to CBCT while reducing radiation exposure. Full article

Feline infectious peritonitis (FIP) is caused by mutated feline coronaviruses. Immune-mediated hemolytic anemia (IMHA) arises due to immune-mediated erythrocyte destruction and can be non-associative or associative with diseases such as FIP. Records of cats with FIP were reviewed to find those with associative IMHA based on exclusion of other causes of anemia and a positive saline agglutination test and/or Coombs test. The inclusion criteria were met for 45 cats (26 (58%) cats with effusive and 19 (42%) with non-effusive FIP). Median hematocrit was 18% (interquartile range [IQR] 13–20). Anemia was non-regenerative in 36 (80%) cats and regenerative in 5 (11%) cats; 4 (9%) cats had no reticulocyte count available. Concurrent thrombocytopenia was present in 18 (40%) cats. All 45 cats were treated with nucleoside analogs, and 44 (98%) cats with glucocorticoids; in 5 (11%) cats, glucocorticoids were added after starting antiviral treatment due to persistent anemia. Median follow-up was 72 days (IQR 14–246); at the time of last follow-up 33 (73%) cats had survived while 12 (27%) had died or were euthanized. Of the 33 surviving cats, 17 achieved remission of both FIP and IMHA. In three cats, FIP remission was achieved, but IMHA relapsed; in one of these, IMHA relapsed twice. FIP relapsed without IMHA in two cats, and both FIP and IMHA relapsed in one cat. In 9 cats the antiviral and glucocorticoid treatment is still ongoing at the time of the publication. Although FIP is likely an uncommon cause of associative IMHA, as more cats with FIP are treated with antiviral therapy, it is important to consider IMHA as a possible cause of anemia in cats with FIP. Full article

Background: The guidelines proposed by the World Society for Emergency Surgery (WSES) in 2020 for the management of Acute Diverticulitis (AD) emphasize the safety of non-operative management (NOM) in selected patients and recommend sigmoid resection (SR) with primary anastomosis (PA) as the surgical technique of choice. Aim: To analyze the clinical outcomes following the implementation of an evidence-based clinical pathway developed by an Acute Care Surgery Unit (ACSu) at a reference center. Methods: For analysis, patients were divided into two groups: pre-guidelines (2018–2019) and post-guidelines (2020–2023), following the May 2020 WSES publication. Patients were classified according to the WSES classification. Results: NOM failure and PA after SR rates by groups were as follows (NOM failure not applicable to III–IV): 0-IA, 2.7% and 94.7%; IB–IIA, 16% and 85.2%; IIB, 7.1% and 50%; III–IV, 75.6%. The global stoma-free rate was 78.8%, with a 15.7% anastomotic leak rate and 14.2% significant morbidity, with an increased rate of anastomosis in unstable patients thanks to Damage Control Surgery (DCS). A logistic regression model was performed to identify factors associated with postoperative morbidity. Patients who underwent primary anastomosis had a lower risk of postoperative morbidity compared to those treated with Hartmann’s procedure (OR = 0.22 (0.04–1.25), p = 0.088). Conclusions: Excellent outcomes in AD healthcare may be achieved if evidence-based recommendations are followed. The ACSu plays a key role in designing and promoting these protocols. Full article

Water, the lifeblood of our planet, sustains ecosystems, economies, and communities. However, climate change and increasing hydrological variability have exacerbated global water scarcity, threatening livelihoods and economic stability. According to the United Nations, over 2 billion people currently live in water-stressed regions, a figure expected to rise significantly by 2030. To address this urgent challenge, this study proposes an AI-driven anomaly detection framework for smart water metering networks (SWMNs) using machine learning (ML) techniques and data resampling methods to enhance water conservation efforts. This research utilizes 6 years of monthly water consumption data from 1375 households from Location A, Windhoek, Namibia, and applies support vector machine (SVM), decision tree (DT), random forest (RF), and k-nearest neighbors (kNN) models within ensemble learning strategies. A significant challenge in real-world datasets is class imbalance, which can reduce model reliability in detecting abnormal patterns. To address this, we employed data resampling techniques including random undersampling (RUS), SMOTE, and SMOTEENN. Among these, SMOTEENN achieved the best overall performance for individual models, with the RF classifier reaching an accuracy of 99.5% and an AUC score of 0.998. Ensemble learning approaches also yielded strong results, with the stacking ensemble achieving 99.6% accuracy, followed by soft voting at 99.2% and hard voting at 98.1%. These results highlight the effectiveness of ensemble methods and advanced sampling techniques in improving anomaly detection under class-imbalanced conditions. To the best of our knowledge, this is the first study to explore and evaluate the combined use of ensemble learning and resampling techniques for ML-based anomaly detection in SWMNs. By integrating artificial intelligence into water systems, this work lays the foundation for scalable, secure, and efficient smart water management solutions, contributing to global efforts in sustainable water governance. Full article

Background/Objectives: Direct comparative data for infliximab and vedolizumab are limited due to lack of head-to-head trials. This systematic review and meta-analysis compared the efficacy and safety of infliximab and vedolizumab as intravenous or subcutaneous maintenance treatments for adults with moderately to severely active Crohn’s disease or ulcerative colitis. Methods: Medical databases, PubMed, Embase, and the Cochrane Library were systematically searched from January 2010 to May 2024 to identify Phase 1 to 3 randomized controlled trials. The primary and co-primary outcomes were the proportions of patients achieving clinical remission and clinical response at one year, respectively. Safety was also analyzed (PROSPERO CRD42023483599). Data for each outcome were pooled using a two-sided random-effects model in separate analyses for Crohn’s disease and ulcerative colitis. Results: Seven eligible Crohn’s disease trials and eight eligible ulcerative colitis trials contributed data for 1910 and 2372 patients, respectively. For Crohn’s disease, higher proportions of infliximab-treated patients achieved clinical remission (0.64 [95% confidence interval: 0.60–0.68]) and/or clinical response (0.71 [0.67–0.75]) at one year compared with vedolizumab-treated patients (0.40 [0.35–0.46] and 0.47 [0.43–0.51], respectively). For ulcerative colitis, similar proportions of infliximab- and vedolizumab-treated patients achieved clinical remission (0.54 [0.38–0.71] vs. 0.40 [0.35–0.44]) and/or clinical response (0.52 [0.45–0.58] vs. 0.58 [0.51–0.65]) at one year. Safety results showed no significant differences. Conclusions: An indirect comparison of maintenance treatment with infliximab and vedolizumab demonstrated that infliximab yields significantly better efficacy than vedolizumab in Crohn’s disease, whereas both agents yielded similar efficacy in ulcerative colitis. Full article

Fins are extended surfaces designed to increase heat dissipation from hot sources to their surroundings. Heat transfer is improved by utilising fins of different geometrical shapes. Fins are extensively used in automobile parts, solar panels, electrical equipment, computer CPUs, refrigeration systems, and superheaters. Motivated by these applications, this study investigates the incorporation of magnetic fields and porosity into a convective–radiative triangular fin to enhance heat transfer performance. The shooting technique is applied to study thermal profile and efficiency of the fin. It is found that the magnetic number (Hartmann number), porosity, convective, and radiative parameters reduce the thermal profile, while the Peclet number and ambient temperature increase it. Moreover, the efficiency increases with an increase in the magnetic number, porosity, convective, and radiative parameters, whereas it declines with an increase in the Peclet number and ambient temperature. Increasing the magnetic number from $0.1$ to $0.7$ leads to a $4\%$ reduction in the temperature profile. Similarly, raising the porosity parameter within the same range results in an approximate $3\%$ decrease in the thermal profile. An increase in the convective parameter from $0.1$ to $0.7$ causes about an $8\%$ decline in the thermal profile, while an elevation in the radiative parameter within the same range reduces it by approximately $2\%$. In contrast, enhancing the Peclet number from $0.1$ to $0.7$ increases the thermal profile by nearly $2\%$, and a rise in the ambient temperature within this range leads to an approximate $4\%$ enhancement in the thermal profile. Magnetised triangular fins are observed to have higher thermal transfer ability and efficiency than non-magnetised triangular fins. It is found that the incorporation of a magnetic field into a triangular fin, in conjunction with the porosity, improves the performance and efficiency of the triangular fin. Full article

Background: Vertical alveolar ridge augmentation (ARA) > 3 mm is associated with increased surgical complexity and higher complication rates. Despite the availability of various ARA techniques and graft materials, robust comparative clinical data remain limited. This retrospective multicenter study aimed to evaluate and compare surgical and patient-relevant outcomes across seven established vertical ARA techniques. Methods: This retrospective multicenter study included 70 cases of vertical ARA > 3 mm using seven different techniques (10 cases each): an iliac crest graft (ICG), intraoral autogenous bone block (IBB), allogeneic bone block (ABB), CAD/CAM ABB, CAD/CAM titanium mesh (CAD/CAM TM), magnesium scaffold (MS), and the allogeneic shell technique (ST). The outcome parameters included harvesting and insertion time, bone gain (vertical and horizontal, after a minimum of one year), graft resorption (after one year), donor site morbidity, dehiscence rate, need for material removal, and biological and general financial costs. Results: Harvesting time significantly varied among the different ARA techniques (p = 0.0025), with the longest mean durations in ICGs (51.6 ± 5.8 min) and IBBs (36.5 ± 10.8 min), and no harvesting was required for the other techniques. Insertion times also significantly differed between the different ARA techniques (p < 0.0001) and were longest in IBBs (50.1 ± 7.5 min) and the ST (47.3 ± 13.9 min). ICGs achieved the highest vertical and horizontal bone gain (5.6 ± 0.4 mm), while ABBs and CAD/CAM ABBs showed the lowest (~3.0 mm). Resorption rates significantly differed between the different ARA techniques (p < 0.0001) and were highest for ICGs (25.9 ± 3.9%) and lowest for MSs (5.1 ± 1.5%). Donor site morbidity was 100% in ICGs and 50% in IBBs, with no morbidity in the other groups. Dehiscence rates were 10% in most techniques but 30% in CAD/CAM TMs. Removals were required in all techniques except MSs. Biological and financial costs were high for ICGs and CAD/CAM ABBs and low for MSs. Conclusions: Vertical ARA techniques significantly differ regarding harvesting and insertion time, bone gain, graft resorption, donor site morbidity, dehiscence rates, removals, and costs. While ICGs achieved the highest bone volume, less invasive techniques, such as CAD/CAM-based or resorbable scaffolds, reduced biological costs and complication risks. Technique selection should be individualized based on defects, patients, and reconstructive goals. Full article

The composition of the gut microbiome, defined by environmental factors, significantly affects research outcomes, with variations observed across animal facilities. Efforts to standardize led to the definition of the ‘Altered Schaedler flora’ (ASF), comprising eight bacterial groups. Our data highlights the variability of ASF under pathogen contact. Feces from two wild-type strains (C57Bl/6J and Balb/c mice) with and without proven infection was collected in two different animal facilities and analyzed. The data show a significant difference in the quantity (either reduction or increase) of the eight ASF bacterial groups when comparing infected and non-infected mice across different housing areas (SPF-specific pathogen-free, quarantine, and conventional-experimental areas) within a facility, as well as in comparison to another facility. Furthermore, strain-specific differences are also evident, with certain ASF groups showing a reduction in quantity at one facility but an increase at the other, comparing the same housing area. Comparative studies across facilities confirmed the necessity of baseline determination for accurate ASF analysis. Performing ASF analysis, facilitated by in-house qPCR (quantitative polymerase chain reaction) kits, offers prompt and precise microbiome profiling, enhancing experimental accuracy and health monitoring in animal research settings. Full article

Background: Finding the optimal amount of fluid is a major challenge in burn shock. Although there is evidence that a restrictive fluid regime is beneficial, current practice shows fluid resuscitation still well above recommendations. The extent of trauma, pre-hospital care and the patient’s pre-existing conditions influence requirements. Methods: We analysed outcomes and influencing factors of fluid regimes in a retrospective cohort study including 90 severely burnt patients resuscitated with the same protocol. Results: The mean amount of fluids in the first 24 h was 6.5 mL/kg bodyweight (BW)/% total burn surface area (TBSA). A total of 14% received restrictive (<4), 34% received liberal (4–6) and 51% received excessive (>6) mL/kgBW/%TBSA fluids. There was no difference regarding mortality, age, complications, organ failure, inhalation injury or full-thickness burns in the groups. Patients with excessive fluid therapy had a significantly lower ABSI score (9 vs. 11, p = 0.05) and TBSA (35 vs. 51%, p < 0.001), while patients with a restrictive fluid therapy needed fewer incidences of surgery to cover burn wounds (3.5 vs. 9.0 vs. 7.0, p = 0.008). History of liver disease or alcohol abuse tended to indicate excessive fluid administration. Patients with pre-existing heart failure received restrictive fluid therapy (23 vs. 3 vs. 4%, p = 0.03). Conclusions: Individualised, timely therapy monitoring is as essential as identifying patients with a higher or lower fluid requirement. Excessive fluid resuscitation had fewer deleterious consequences in complications than expected but seems to influence wound healing. Awareness of circumstances that prompt deviations from recommended fluid rates remains elementary. Full article

Atmospheric turbulence introduces distortions to the wavefront of propagating optical radiation. It causes image resolution degradation in astronomical telescopes and significantly reduces the power density of radiation on the target in focusing applications. The impact of turbulence fluctuations on the wavefront can be investigated under laboratory conditions using either a fan heater (roughly tuned), a phase plate, or a deformable mirror (finely tuned) as a turbulence-generation device and a wavefront sensor as a wavefront-distortion measurement device. We designed and developed a software simulator and an experimental setup for the reconstruction of atmospheric turbulence-phase fluctuations as well as an adaptive optical system for the compensation of induced aberrations. Both systems use two 60 mm, 92-channel, bimorph deformable mirrors and two tip-tilt correctors. The wavefront is measured using a high-speed Shack–Hartmann wavefront sensor based on an industrial CMOS camera. The system was able to achieve a 500 Hz correction frame rate, and the amplitude of aberrations decreased from 2.6 μm to 0.3 μm during the correction procedure. The use of the tip-tilt corrector allowed a decrease in the focal spot centroid jitter range of 2–3 times from ±26.5 μm and ±24 μm up to ±11.5 μm and ±5.5 μm. Full article

Nucleocytoplasmic transport is crucial for neuronal cell physiology and defects are involved in neurodegenerative diseases like amyotrophic lateral sclerosis and Alzheimer’s disease, but also in ageing. Recent studies have suggested, that the classic nuclear import factor adapters KPNA3 (also named importin alpha4) and KPNA4 (also named importin alpha3) could be associated with the development of motor neuron diseases, a condition specifically affecting the neurons projecting from brain to spinal cord or from spinal cord to the muscles. Here we set out to analyze the neuronal function of mice deficient in KPNA3 (Kpna3-KO) or KPNA4 (Kpna4-KO). The motoric abilities and locomotion at different time points in ageing were tested to study the role of these two genes on motor neuron function. While we did not find deficits related to motor neurons in both mouse models, we discovered a hypermotoric phenotype in KPNA4-deficient mice. Attention deficit/hyperactivity disorder (ADHD) is caused by a combination of genetic, environmental and neurobiological factors and a number of genes have been suggested in genome-wide association studies to contribute to ADHD, including KPNA4. Here we provide supportive evidence for KPNA4 as a candidate pathogenic factor in ADHD, by analysing Kpna4-KO mice which show ADHD-like symptoms. Full article

Feline infectious peritonitis (FIP) caused by feline coronavirus (FCoV) is a fatal disease in cats characterized by variable manifestations. Myocarditis represents a less commonly described pathology within the clinical spectrum of FIP. No research has described the successful treatment of FIP-induced myocarditis. In this study, 40 cats were included and treated with 15 mg/kg of GS-441524 every 24 h orally. All cats were diagnosed with FIP by reverse transcription quantitative PCR in effusion in combination with typical clinical and laboratory changes. Echocardiography was performed in all cats, and myocarditis was suspected in 4/40 cats. Equivocal wall thickness was diagnosed in 2/4 cats, while systolic dysfunction with biatrial dilation was diagnosed in the other 2/4 cats. One cat also presented with ventricular ectopy. A severe increase in cardiac troponin I was seen in all four cats (median 1.82 ng/mL (1.20–5.84 ng/mL)). Cardiac dimensions and electrocardiographic abnormalities completely normalized in all four cats during treatment with GS-441524 and remained stable after treatment discontinuation during a one-year follow-up period. Myocarditis can be a clinical feature of FIP and present with different cardiologic manifestations. FIP-induced myocarditis can be cured with GS-441524 in combination with symptomatic cardiovascular treatment including pimobendan, clopidogrel, furosemide, or atenolol, depending on the clinical presentation. Full article