A new method has been developed to improve the detection of norovirus (NoV) in complex fecal samples using nanomaterials-based immunoassays. The method involves using multifunctional trimetallic nanoparticles, known as Ag@Fe3O4@Au NPs. These nanoparticles consist of a core of silver (Ag) and a shell of iron oxide (Fe3O4) decorated with isolated gold (Au) nanoparticles. The nanoparticles have enhanced catalytic activity, making them an ideal nanocatalyst for reducing substrate molecules. The developed Ag@Fe3O4@Au NPs-based immunoassay achieved a limit of detection (LOD) of 1.9 pg/mL for norovirus-like particles (NoV-LP) and 6.97 fecal NoV copy number/mL. Achieving a LOD under 10 copy numbers is important for detailed protein analysis. The study also found that heat treatment of fecal suspension at 65°C was necessary to prevent the degradation of the target analyte for sensitive NoV detection. This work successfully combined multifunctional nanocatalysts for advanced immunoassays, which could contribute to developing nano-biosensing platforms.

Unexpected non-steroidal anti-inflammatory drugs-induced systemic hypersensitivity reaction in a pediatric patient unveiling Systemic Lupus ErythematosusKeywords : pediatric systemic lupus erythematosus (SLE); systemic autoimmune diseases; adverse drug reactions (ADR); non-steroidal anti-inflammatory drugs (NSAID); systemic NSAID hypersensitivity reactions.Word count: 1183Number of figures: 1To the Editor,Systemic Lupus Erythematosus (SLE) is a complex autoimmune disorder characterized by a broad spectrum of clinical manifestations affecting multiple organ systems. While the etiology of SLE remains elusive, it is widely acknowledged that both genetic predisposition and environmental factors play pivotal roles in its pathogenesis1. SLE diagnosis is often challenging due to the vast heterogeneity of clinical manifestations, and it is often called ”the great imitator”2.We present a case of severe non-steroidal anti-inflammatory drugs (NSAID)-induced systemic hypersensitivity in a female Chinese adolescent patient, otherwise healthy except for autoimmune thyroiditis on replacement therapy, who developed clinical and serological features consistent with SLE. A 15-year-old female adolescent presented to our pediatric emergency room (ER) due to urticarial rash and facial edema (Figure 1A ), low-grade fever, dyspnea, abdominal pain, and nausea two hours after taking ketoprofen (40 mg) for migraine. The girl has previously taken ibuprofen (400 mg twice daily) for 11 days, then acetaminophen 1000 mg for two days, associated with 80 mg ketoprofen, and finally, on the same day of admission to the ER, ibuprofen 400 mg together with 40 mg ketoprofen due to diffuse arthralgia and migraine. Anaphylaxis was suspected in the ER, and intramuscular epinephrine, intravenous corticosteroid therapy, and intravenous antihistamines were administered. During observation, for persistent hypotension not responsive to epinephrine, fluid resuscitation with saline was initiated. Empirical broad-spectrum antibiotic therapy was initiated due to suspected sepsis, although subsequent blood cultures were negative. Considering the poor clinical response, the patient was transferred to the intensive care unit. During hospitalization, serum inflammatory markers [C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin, and ferritin] increased. The urticarial rash on the face evolved into a malar rash with vesiculo-bullous lesions, and oral aphthae were observed (Figure 1 B-C ). Instrumental exams revealed pleural, pericardial, and peritoneal effusions. The increased inflammatory markers, the hematologic profile observed since admission (leukopenia, anemia, and thrombocytopenia), and the characteristic clinical manifestations raised suspicion of a possible connective tissue disease (CTD).Further hematological investigations revealed antinuclear antibodies (ANA) titer of 1:320 with a speckled pattern of large granules, positive anti-dsDNA antibodies (enzyme immunoassay: 116 IU/ml, normal values < 10 IU/ml; immunofluorescence: 1:160, normal values < 1:10), and complement fraction (C3, C4) consumption. Based on the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) 2019 criteria3, a diagnosis of SLE was made. High-dose intravenous steroid therapy (steroid pulses 1 g for three consecutive days, followed by gradual tapering) and oral hydroxychloroquine (200 mg daily) were initiated, with clinical improvement (Figure 1D ).Among the above-mentioned environmental factors involved in SLE pathogenesis, drug-induced lupus erythematosus (DILE) represents a distinct subset of SLE triggered by certain medications. DILE typically shares clinical and serological features with idiopathic SLE but is often reversible upon discontinuing the offending agent. Several medications can produce positive results on an ANA test with or without evidence of clinical lupus4.Nonetheless, DILE is not the only drug-related manifestation of SLE. In particular, NSAIDs are associated with a wide spectrum of manifestations in SLE patients. To date, only a few cases of systemic hypersensitivity reaction to ibuprofen have been described in SLE patients. Finch et al. in 1979 first described a NSAID-induced systemic hypersensitivity acute reaction in three young adult women with SLE presenting with profound hypotension, fever, and headaches developed within hours of reinstitution of therapy after voluntarily discontinuation of long-term treatment for arthritis5. Agus et al. identified among 33 patients with ibuprofen hypersensitivity several patients with rheumatological disorders (52% SLE, 12% mixed CTD, 6% undifferentiated CTD, 3% Juvenile Idiopathic Arthritis)6. Ibuprofen is also known to be the causative agent of aseptic meningitis in patients with SLE. Lortholary et al. reported a case of aseptic meningoencephalitis induced by ibuprofen in a 24-year-old woman, revealing unrecognised underlying SLE7. However, limited evidence is available regarding NSAID-induced systemic hypersensitivity acute reaction in the pediatric population. In 2005, Mou et al. described the only pediatric case reported to date of an 11-year-old Thai male who presented with fever, rash, altered mental status, and hypotension after oral administration of ibuprofen, leading to the diagnosis of SLE 8.ADR are heterogeneous and multifactorial diseases due to an exaggerated immune-mediated reaction, not fully described by models of immunologic mechanisms (mainly based on Gell and Coombs classification), which is why several classifications including pseudoallergic reactions and drug hypersensitivity reaction endotypes have been advanced in recent years. In addition, various cofactors such as viral infections, HLA haplotypes, and altered drug metabolism must be considered9. Systemic hypersensitivity reaction to ibuprofen syndrome in patients with known CTD generally consists of fever, gastrointestinal symptoms, myalgia, aseptic meningitis, and, in some, profound hypotension. The mechanism has yet to be discovered. Many of the described symptoms can be explained by a histamine-mediated anaphylactoid reaction, for which patients with CTD, especially SLE, seem to have a higher susceptibility5. All reported cases occurred after prior exposure to the drug.Nevertheless, Schoenfeld et al. reported an in vitro study describing specific cell-mediated immunity to ibuprofen in SLE, suggesting that even without prior exposure to ibuprofen, patients with SLE may exhibit sensitization to this drug10. Severe systemic reactions to ibuprofen can occur in patients with SLE, potentially occurring at any time, even after years of using the drug. The reaction is reproducible within hours of re-exposure11. Indeed, most patients who have developed ibuprofen hypersensitivity have tolerated other NSAIDs without difficulty.Moreover, autoantibodies belonging to the IgE class have been described in various autoimmune contexts, including SLE12. Recently, two studies have focused on IgE ANA in SLE, showing the presence of IgE ANA in 31.5% 13 and 65%14 of SLE patients. Numerous papers have proved that mast cells play a significant role in the pathogenesis of SLE, and it has been speculated that IgE and anti-IgE antibodies, and FcεRI and anti‐FcεRI antibodies activate mast cells through autoimmune pathways and participate in the disease process of SLE. The level of FcεRIα in the serum of patients with SLE was significantly higher than that in healthy controls, with the autoimmune result of FcεRIα and anti‐FcεRI antibody triggering tissue inflammatory damage caused by mast cell activation15.Few cases of systemic hypersensitivity to ibuprofen in adults with systemic inflammatory connective tissue disease are reported in the literature, with only one case in the pediatric population, in which the mechanism of reaction is unknown. The patient presented here represents the second case of ibuprofen severe systemic hypersensitivity reaction as onset manifestation of pediatric-SLE, and the first one after multiple (triple) NSAIDs co-administration occurred without discontinuation of drugs and therefore without a period of sensitization. In addition, our patient also presented with severe hypotension at onset (only 7 cases described in the literature), which was refractory to infusion therapy, the reason why she required amine therapy and admission to the intensive care unit.We aimed to highlight the clinical presentation, diagnostic challenges, and management strategies associated with this unusual drug-induced systemic hypersensitivity reaction in a patient with SLE. We also wanted to underscore the importance of considering underlying systemic autoimmune conditions in patients with severe and uncommon drug-induced reactions, emphasizing the significance of a comprehensive medication history and vigilant monitoring for ADR.Ivan Taietti1,2, M.D., https://orcid.org/0000-0002-0372-523X,Daniele Veraldi1,2 M.D.,Silvia Maria Elena Caimmi2, M.D., https://orcid.org/0000-0003-0515-524X,Elisabetta De Sando2, M.D.,Valeria Brazzelli3,4, M.D., https://orcid.org/0000-0001-5898-6448,Grazia Bossi2, M.D., https://orcid.org/0000-0001-8287-9757,Gian Luigi Marseglia1,2,M.D., https://orcid.org/0000-0003-3662-0159,Amelia Licari1,2, M.D., https://orcid.org/0000-0002-1773-6482,Riccardo Castagnoli1,2, M.D., PhD, https://orcid.org/0000-0003-0029-9383Pediatric Unit, Department of Clinical, Surgical, Diagnostic, and Pediatric Sciences, University of Pavia, Pavia, ItalyPediatric Clinic, Fondazione IRCCS Policlinico San Matteo, Pavia, ItalyInstitute of Dermatology, Department of Clinical, Surgical, Diagnostic, and Pediatric Sciences, University of Pavia, Pavia, ItalyInstitute of Dermatology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy*Correspondence:Riccardo CastagnoliPediatric Unit, Department of Clinical, Surgical, Diagnostic, and Pediatric Sciences, University of Pavia, Pavia, Italy.Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.Piazzale Golgi, 19 27100 Pavia.

Objective: This study aims to enhance the management of Epstein-Barr Virus (EBV) infections by analyzing the correlation between laboratory indicators and clinical manifestations in children, thereby proposing more precise diagnostic and treatment strategies. Methods: In this retrospective study included 163 pediatric patients with EBV infections treated at the Children’s Hospital of Soochow University from December 2017 to December 2019. Data collected through retrospective analysis included gender, age, clinical symptoms, signs, liver function tests, T-cell subset distribution, EBV-DNA copy numbers in plasma and whole blood, and treatment outcomes. Patients were grouped based on EBV copy numbers and hospital stay duration to compare clinical indicators across different groups. Results: The dichotomous results of EBV plasma level showed that the two groups of children were significantly different in the number of days of fever (p= 0.0373), platelet count (p= 0.018), ALT (p= 0.0299), immunoglobulin IgM (p= 0.0323), IgG (p= 0.0299), TBiL (p= 0.0037), LDH (p< 0.001), number of CD19+ cells (p= 0.0204) and length of hospital stay (p< 0.001) were significantly different, indicating that EBV plasma levels may be correlated with these characteristic variables.The dichotomous results of the length of hospital stay showed that the two groups were significantly increased in tonsil enlargement (p= 0.0024), platelet count (p= 0.00449), LDH (p= 0.0394), CD3+ cell count (p= 0.0383), and ferritin (p= 0.0106) and EBV plasma levels (p< 0.001) were significantly different, This suggests a potential correlation between EBV plasma levels and these clinical indicators. Conclusion: Variations in platelet counts and lactate dehydrogenase (LDH) levels in children with EBV infections may serve as indicators of clinical outcomes.

Foot-and-mouth disease virus (FMDV) causes an acute and highly contagious viral disease in cloven-hoofed animals and uses integrin αvβ1, αvβ3, αvβ6, αvβ8, and heparan sulfate proteoglycans (HSPGs) receptors to enter the host cell. Although heparan sulfates have been observed to play a role in binding many viruses to the host cell surface, there is no information in the literature about which member of this polysaccharide family is involved in FMDV binding. Syndecan-1 (SDC1), a member of the heparan sulfate proteoglycan family, exhibits a close association with the integrin family of receptors. In this study, FMDV-insensitive SW480 cells were sensitized by human SDC1 gene transfection. Integrin αvβ6 was used as a positive control group. The SW480 cell line was separately transfected with SDC1, integrin β6, and control plasmids. Following the transfection, the gene expression levels of SDC1 and integrin β6 were quantified using qPCR. In the final stage of the study, the sensitivity to FMDV was examined by monitoring the cytopathic effect (CPE) after the virus inoculation of the gene-transfected cells. This study demonstrated an increase in the expression of the SDC1 gene and the integrin β6 gene post-transfection in SW480 cells. Moreover, FMDV CPE was detected in wells containing cells transfected with both the β6 gene and SDC1, although the effect was higher in the wells transfected with the β6 gene. In conclusion, the in vitro evidence suggests that the SDC1 transmembrane protein could serve as a potential cellular receptor candidate for FMDV.

Salinity is one of the major problems in crop production, especially in Mediterranean territories of the world. There is a universal curiosity in understanding the scenarios for agricultural land degradation due to several factors. The application of co-composted biochar has significantly augmented agriculture during the last era. We conducted a far-reaching review on the influence of co-composed biochar as an organic amendment for cultivating the most expensive spice, Crocus sativus L. (saffron), in saline soil under arid climatic conditions. We explored the positive influences on their production in dry regions where salinity is a limiting factor. Sustainable Agricultural techniques, including consumption and production, must be followed from an integrated and universal perspective. The key inputs for crop production are healthy soil, land, irrigation, and natural plant resources. As these resources are becoming increasingly scarce in different parts of the world, managing and using them sustainably becomes crucial. Improving and managing techniques on existing agricultural lands, such as refurbishing damaged lands via sound agrarian methods, would reduce the pressure to clear forests for agricultural production (SDG GOAL-2, 5). Though several investigations focused on co-composted biochar production and application so far need to be more comprehensive, there is adequate evidence to enlighten their significance in supporting environmental safety and sustainable farming. Based on the review, we recommended upcoming research to comprehend the mechanism of co-composted biochar practices better to stimulate an understanding of its function over time.

Abtract not needed for a response to a Letter to the Editor

Climate change can influence populations of monogamous species by affecting pair-bond dynamics. This study examined the impact of climate on widowhood and divorce, and the subsequent effects on individual vital rates and life-history outcomes over 54 years in a snow petrel (Pagodroma nivea) population. We found that environmental conditions can affect pair-bond dynamics both directly and indirectly. Divorce was adaptive, occurring more frequently after breeding failure and leading to improved breeding success. Divorce probabilities also increased under severe climatic conditions, regardless of prior breeding success, supporting the ”Habitat-mediated” mechanisms. Generally, pair-bond disruptions reduced subsequent vital rates and lifetime outcomes. Climate forecasts from an Atmosphere-Ocean General Circulation Model projected increased male widowhood rates due to decreased sea ice negatively affecting female survival, despite considerable uncertainty. These findings highlight the importance of environmentally induced changes in demographic and pair-bond disruption rates as crucial factors shaping demographic responses to climate change.

Objective: To develop a deep learning (DL) model for carotid plaque detection based on CTA images and to evaluate the model’s precision and clinical application feasibility. Methods: We retrospectively collected data from patients with carotid atherosclerotic plaques who underwent continuous CTA examinations of the head and neck at a tertiary hospital from October 2020 to October 2022. The model combined ResUNet with the Pyramid Scene Parsing Network (PSPNet) to enhance plaque segmentation. Patient plaques were divided into training, validation, and testing sets in a ratio of 7:1.5:1.5. We analyzed recall (lesion-level sensitivity), sensitivity (patient-level), and precision to evaluate the model’s diagnostic performance for carotid plaques. The two stepwise early-stage clinical validation study (Comparison study and Model-human study) was used to simulate real clinical plaque diagnostic scenarios. Results: In total, 647 patients were included in the dataset, including 457 for training, 86 for validation, and 86 for testing. The DL model based on CTA images showed good precision in plaque diagnosis (validation set: precision=80.49%, sensitivity=90.70%, recall=84.62%; test set: precision=78.37%, sensitivity=91.86%, recall=84.58%). In addition, subgroup analysis of the plaque was carried out in the test set, and the precision of the model was evaluated based on plaque location (front, back, inside, and outside) and plaque morphology (smooth and non-smooth). The results showed that the recall of the plaque location was 83.72%, 76.32%, 89.25%, and 83.02%, respectively, and that for plaque morphology was 86.03% and 79.17%, respectively. The model had high accuracy in identifying plaques at different locations and with different morphologies. In the clinical application scenario analysis, the model’s diagnostic results for plaques were found to be higher than those of four out of six radiologists (p < 0.001). Furthermore, the use of this model was found to improve the recall rate of radiologists’ plaque diagnostic results. Additionally, the model’s diagnostic time for plaques (6s) was found to be significantly shorter than that of doctors (p < 0.001). Conclusion: Our research results indicate that the DL model for carotid plaque detection based on CTA images has high accuracy and clinical feasibility. The accuracy of plaque diagnosis is improved through model assisted diagnosis. Besides, the plaque detection time is significantly shortened, which has clinical value in reducing the workload of radiologists and improving the plaque detection rate.

Objective The study investigates spatiotemporal trends in rabies incidence, mortality, and DALYs across Indian states and union territories from 1990-2021. It aims to assess current control measures and identify areas needing intervention, informing strategies to achieve zero rabies deaths by 2030. Results India showed significant declining trend over this period for age-standardized incidence rate (AAPC: -5.22; 95%, CI: -5.32 to -5.11; p < 0.05) with the highest decline observed during the period 2007-2010 (APC: -10.12; 95%CI: -10.91 to -8.21; p < 0.05). The highest reductions were observed in Andhra Pradesh (AAPC: -8.08, 95% CI: -8.21 to -7.94), and Bihar (AAPC: -7.10, 95% CI: -7.38 to -6.82). Mortality trends mirrored incidence declines. Total DALYs decreased significantly from 760,115 in 1990 to 12,803 in 2021, primarily due to a reduction in Years of Life Lost (YLL). The age-standardized DALYs per 100,000 persons decreased by -50.22% over the study period. Despite these improvements, rabies remains a critical concern, with 4,023 deaths recorded in 2021. Conclusion Significant declines in rabies incidence, mortality, and DALYs were observed across the time. State-specific multifaceted approach integrating public health, accessible PEP, one health approach and humane management of stray dogs is essential.

The incidence of multiple primary malignancies (MPMs) associated with colorectal cancer (CRC) varies, ranging from 3.0% to 17.0%, with synchronous MPMs occurring at rates of 1.0% to 4.41%. The incidence of MPMs was found to be higher in male and older CRC patients. However, age-related findings are inconsistent, with some studies indicating a higher risk in younger CRC patients, possibly linked to genetic aberrations and carcinogen exposure. The field cancerization theory, chemotherapy, and radiotherapy demonstrated associations with the occurrence of MPMs. Genetic analyses emphasizing microsatellite instability (MSI), CpG island methylation phenotype (CIMP), chromosomal translocations, and p53 mutations as potential contributors to the development of MPMs associated with CRC. Prognostically, MPMs associated with CRC, especially synchronous cases, are linked to lower survival rates, primarily attributed to postoperative complications.

Background Study on the effect of hydroxychloroquine (HCQ) in treating children with chronic immune thrombocytopenia (ITP) is limited. The association between ANA positivity and its efficacy is not clear. Methods This was a retrospective cohort study on chronic ITP children. We compared the clinical characteristics of patients who received HCQ with those who didn’t, as well as patients who responded to HCQ at 3 months with those who didn’t. Mixed-effects models were performed to assess the effect of HCQ on platelet counts and the association between ANA and its efficacy. Records of side effects associated with HCQ were reviewed. Results A total of 191 children with chronic ITP were included in this study, involved 42 patients who received HCQ. In patients who received HCQ, 69.0% of patients achieved complete response /response at the last follow-up, with a higher frequency than in patients who didn’t (69.0% vs. 48.3%). The overall response rate was 56.8% at 3 months and 40.5% at 1 year. Our results showed no difference in ANA positivity between patients with response to HCQ and those without. HCQ was effective for increasing platelet counts (mean difference: 23.82×109/L; 95% CI: 7.44 ~ 40.21), but the association between ANA positivity and its efficacy was not found. Side effects were recorded in 6 of 42 patients (14.3%). Conclusions HCQ was associated with increased platelet counts in chronic ITP children. The baseline ANA level was not found to have an interaction effect on this efficacy. Side effects of HCQ should be concerned.

The notion that adaptive evolution markedly shapes species distribution probabilities has pushed for genomics-informed species distribution models (gSDMs). These models account for intraspecific variation and gene flow to enhance the accuracy of species range projections. Yet, gSDMs remain encumbered by limitations stemming from substantial sequencing costs and from a global change mindset skewed towards climate warming, likely resulting in an overly narrow view on genomic vulnerability. Current developments in sequencing methodologies are paving the way for gSDMs that transcend spatial and temporal constraints. Specifically, the ability to quantify genome-wide standing genetic variation across species’ ranges unlocks bottom-up gSDM, where range projections are shaped by the intrinsic ability of populations to evolve in response to a wide array of environmental stressors. By integrating range-wide variation in dispersal, drift, demographic history and overall adaptive potential, bottom-up gSDMs promise greater realism and robustness in addressing the full spectrum of environmental threats.

Pan-tilt-zoom (PTZ) cameras, which dynamically adjust their field of view (FOV), are pervasive in large-scale scenes, such as train stations, squares, and airports. In real scenarios, PTZ cameras are required to quickly make decisions informed about where to direct its focus through contextual cues from the surrounding environment. To achieve this goal, some researches project camera videos into three-dimensional (3D) models or panoramas and allow operators to perceive spatial relationships. However, these works face several challenges in terms of real-time processing, localization accuracy, and realistic reference. To address this problem, we propose a visual expansion and real-time calibration for PTZ cameras assisted by panoramic models. We attempt to meet the demand for real-time processing with a motion estimation model for a PTZ camera, to improve calibration performance of PTZ images with only two feature point pairs, and to provide a realistic environmental context through a panoramic model. We verify our methods on both public and our self-built test scene. It can be seen from the experimental results that our method can exhibit impressive accuracy and efficiency.

The distribution of the species Corydoras cf. garbei in the Pajeú river basin is restricted to certain specific habitats and, therefore, it is necessary to understand the distribution of the species in this important river basin. The objective of this study was to detect the species C. cf. garbei using the eDNA method. For this, we performed a targeted approach using two pairs of primers (universal and species-specific) in a conventional PCR for detection of the target species. eDNA samples for eight sampling points were amplified using two pairs of primers and the presence of the target species was confirmed only at one sampling point. We conclude that the conventional PCR approach was considered effective in monitoring the target-species, but improvements in the standardization of the eDNA are necessary for continued use in the semiarid region of the Caatinga biome.

Background and aim: The reflux symptoms score -12 (RSS-12) is a validated questionnaire with good sensitivity and specificity for diagnosing laryngopharyngeal reflux disease (LPRD). However, the correlation between RSS-12 and reflux finding score (RFS) in patients with clinical symptoms suggestive of LPR has not been investigated. In this study, we examined such correlation. Patients and methods: We conducted cohort cross sectional study over 6 months duration in total of 105 patients with typical gastroesophageal reflux disease (GERD ) symptoms associated with LPR symptoms based on RSS-12.We excluded patients with any medical problems or lifestyle habits that could induce similar symptoms. The study participants underwent a telescopic laryngeal examination and the RFS was calculated. Results: The prevalence of LPRD (RFS > 7) in patients with clinical symptoms of GERD and LPR was 14.2% (15 patients). Laryngoscopic abnormalities unrelated to LPRD were present in 16 patients (15.2%). RSS-12 had strong positive correlation with RFS. Conclusion: In patients with clinical symptoms of LPR, RSS-12 strongly predicts the diagnosis of LPRD.

Objectives In laryngopharyngeal reflux (LPR) gold standard in diagnostics is still lacking. A proton pump (PPI) trial is often completed but the effect and diagnostic accuracy in LPR is disputed and not only acid refluxes are considered having impact in LPR. Therefor further diagnostic evaluations may be needed. Earlier, 24h pH-measuring including a proximal probe was most often performed, but combined 24h pH-impedance monitoring (24h pH-MII) is now considered superior to the traditional method. The main aim of this study is to investigate if we find more persons with pre-conditions of LPR evaluated by 24h-pH-MII compared to conventional 24h-pH measuring including a high probe. Design Retrospectively, we included 24h pH-MII measurements performed December 2016 - December 2019 concerning LPR as the issue of question. In total 82 measurements were included and analyzed. The measuring was considered positive if at least one proximal regurgitation occurred during the 24h. Results Based on the 24h pH-measurings, 38% of the subjects had ≥1 proximal regurgitation, compared to 98% in the 24h pH-MII measuring. This results in percent agreement of 39.5% Negative proximal impedance was found in only one subject. This could possibly be due to a too low limit for considering the measurement positive. LPR is on the other hand, according to the available epidemiological data, common and possibly only the most severe cases get referrals for further diagnostic evaluations. Conclusion The present study gives further evidence of 24h pH-MII being superior to conventional 24h pH-measuring in LPR diagnostics.

Change in river basins due to the natural flow alteration is largely attributable to hydropower dam operations worldwide. The amount, duration, and degree of flow change brought about by Nepal’s recent explosion in hydropower production in Marsyangdi and Trisuli Rivers which are near to load centers of Nepal, have seen severe impact on these river ecosystems. The present study attempts to calculate hydrological alteration in the Marsyangdi and Trisuli Rivers near Kaligandaki Basin using Indicators of Hydrological Alteration (IHA) model. Thirty-three ecological parameters were assessed using range of variability approach to determine how electric dams affect rivers downstream. This study compared flow data from hydrological stations of two rivers spanning more than 20 years period, taking into consideration of pre- and post- dam impact periods into account, with a focus on hydrological alteration caused by dam influence. With HA values of 35.41 and 35.55, past a hydropower construction, the results demonstrate the mild influences of the dam in Marsyangdi and Trisuli Rivers, respectively. Of the 33 parameters analyzed, two and seven parameters have altered highly in Marsyangdi and Trisuli River, respectively. The hydrological modifications caused by dams on both rivers may have detrimental effects on aquatic ecosystems. The study’s findings may help Nepal’s hydropower policy makers, who are finding it difficult to comprehend the dynamic effects of dams on rivers.

A transdiagnostic continuum model of psychopathology predicts that ontological insecurity (the propensity toward self-fragmentation) will mediate the relationship between ideal self-discrepancy (perceived discrepancy between actual and ideal self) and depression, anxiety, and subclinical psychotic-like experiences (PLEs). A community sample of 142 participants completed a modified version of the Self-Discrepancy Scale (S-DS), the Ontological Insecurity Scale (OIS-34), the Depression and Anxiety subscales of the DASS-21, and the Positive subscale of the Community Assessment of Psychic Experiences (CAPE-P15). Hierarchical multiple regression analyses demonstrated that the distress arising from the ideal self-discrepancy significantly and positively predicted depression, anxiety, and PLEs. These relationships ceased to be significant once ontological insecurity entered the regression equation in the final step. In line with the transdiagnostic continuum model, ontological insecurity fully mediated the relationship between ideal self-discrepancy distress and all measures of psychopathology. The findings suggest that future research and psychological interventions might profit more by focusing on the distress arising from self-discrepancy and ontological insecurity than on self-discrepancy itself.

MCC950 is a specific nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome inhibitor that has neuroprotective properties in nervous system disorders. In this study, we investigated its cerebroprotective mechanism in sepsis-associated encephalopathy. We randomly divided 104 Sprague–Dawley rats into sham, sepsis-associated encephalopathy, and sepsis-associated encephalopathy+MCC950 groups. Hematoxylin–eosin and terminal deoxynucleotidyl transferase dUTP nick end labeling staining were employed to observe pathological changes in brain tissue and detect neuronal apoptosis, respectively. Western blotting was employed to detect the expression and intensity of apoptosis-related spot-like proteins and inflammatory factors. Compared to the sham group, all other groups exhibited significant increases in serum tumor necrosis factor alpha, interleukin-1β, interleukin-18, neuron-specific enolase, and S100β (P < 0.05) levels. The apoptosis rate of hippocampus in the sepsis-associated encephalopathy+MCC950 group was significantly lower than that in the sepsis-associated encephalopathy group at 48h and 72h (P < 0.05). The severity of hippocampal tissue lesions in the sepsis-associated encephalopathy+MCC950 group was reduced at 24 h, 48 h, and 72 h compared to the sepsis-associated encephalopathy group, but not at 6 h. Compared to the sepsis-associated encephalopathy group, the sepsis-associated encephalopathy+MCC950 group exhibited significant differences in the level and intensity of protein expression in rat hippocampal tissue at various time points (P < 0.05). Thus, MCC950 exerted cerebroprotective and ameliorative effects in sepsis-associated encephalopathy rats by inhibiting inflammatory responses and pyroptosis mediated by the nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome.

The term “root exudates” encompasses a range of inorganic ions and compounds that plants release into the soil through their roots during the growth stage. It serves as a vital conduit for the exchange of material, energy, and information between plants and the soil. Root exudates represents an essential mechanism through which plants can respond to external stressors. This paper presents a synthesis of existing studies on the components and functions of plant root exudates, the factors influencing their composition, and the response mechanisms of root exudates to abiotic stresses, including drought, salt, high temperature, and heavy metal stresses. Abiotic stresses can alter the composition and content of plant root exudates. Different types of stress elicit the secretion of specific substances, primarily amino acids, organic acids, and sugars, which enter the rhizosphere microenvironment to assist plants in resisting adversity stress. The prospective direction of metabolomics is to investigate the interaction mechanism between plants and rhizosphere microorganisms, which is mediated by root exudates. Furthermore, the collection methods and detection techniques of root exudates are to be enhanced. It is recommended that comprehensive research be conducted on field and field experiments under multiple stress factors. Furthermore, it is advised that the composition and content of root exudates of field plants be monitored dynamically through the use of in-situ intelligence technology. This will facilitate a more comprehensive understanding of the mechanism of root exudate-mediated plant stress resistance under different stress combinations.

cyber resilience is an interdisciplinary topic of study that aims to maintain security and stability in digital environments. This paper examines the increasing complexity and vulnerability of socio-technical systems to assaults, underscoring the necessity for robust cyber resilience strategies. The study highlights the need of cybersecurity for business resilience due to the increasing security risks posed by digital transformation and emerging technologies like big data, block chain, and artificial intelligence. It explores the fundamental concepts of operational and organizational resilience in addition to the stages of the cyber resilience cycle. The paper also delves into data resiliency and data recovery, emphasizing their importance in mitigating the impact of data breaches, natural disasters, and human errors. Key strategies for resilient data recovery are outlined, including automated backups, encryption, continuous data protection, and the integration of Disaster Recovery as a Service (DRaaS). A disaster recovery model for CRM using cloud computing and SaaS is proposed, addressing latency and data loss issues while ensuring continuous service availability. The study underscores the significance of proactive data security measures and collaboration between IT teams and executives to safeguard organizational data and maintain business continuity.

Viral accessory proteins play critical roles in viral escape form host innate immune responses and in viral inflammatory pathogenesis. Here we show that the SARS-CoV-2 accessory protein, ORF9b, but not other SARS-CoV-2 accessory proteins (ORF3a, ORF3b, ORF6, ORF7, ORF8, ORF9c, ORF10), strongly activates inflammasome-dependent caspase-1 in A549 lung carcinoma cells and THP-1 monocyte-macrophage cells. Exposure to lipopolysaccharide (LPS) and ATP additively enhanced the activation of caspase-1 by ORF9b, suggesting that ORF9b and LPS follow parallel pathways in the activation of the inflammasome and caspase-1. Following rational in silico approaches, we have designed small molecules capable of inhibiting the homodimerization of ORF9b, which experimentally inhibited ORF9b-ORF9b homotypic interactions, caused mitochondrial eviction of ORF9b, inhibited ORF9b-induced activation of caspase-1 in A549 and THP-1 cells, cytokine release in THP-1 cells, and restored type I interferon (IFN-I) signaling suppressed by ORF9b in both cell models. These small molecules are first-in-class compounds targeting a viral accessory protein critical for viral-induced exacerbated inflammation and escape from innate immune responses, with the potential of mitigating the severe immunopathogenic damage induced by highly pathogenic coronaviruses and restoring antiviral innate immune responses curtailed by viral infection.

Worry and rumination are common forms of perseverative cognition (PC) and repetitive negative thinking towards stressors. PC can generate psychophysiological stress before or after exposure to stressors and is linked to chronic stress, diseases, and adverse health outcomes. PC has been associated with vagally-mediated heart rate variability (vmHRV). In the present meta-analytic review, effect sizes for the relationship between PC and vmHRV were computed for baseline, stressor, and recovery conditions vmHRV among studies using within-subject and between-subject analyses. A total of 55 effect sizes were extracted from 24 eligible articles (17 for baseline, 15 for reactivity, 8 for recovery). Small to medium effect sizes were observed for the correlations between PC and baseline vmHRV (g = .40, SE = .10), within-subject reactivity vmHRV (g = .27, SE = .07), and between-subject recovery vmHRV (g = .44, SE = .18). The other meta-analyses did not yield statistically significant effect sizes. High heterogeneity was detected across the meta-analyses and statistical tests suggested the absence of publication biases. Overall, PC in laboratory studies was observed to differentially associate with baseline, reactivity, and recovery vmHRV. The scarcity of vmHRV recovery studies was discussed.

IntroductionTuberculosis (TB), which is caused by bacteria of the Mycobacterium tuberculosis complex, is one of the oldest diseases known to affect humans and a leading cause of death worldwide (1).Approximately one-third of the global population is infected with a lifetime risk of 10% for developing tuberculosis (TB) disease. In 2017, there were 10.4 million reported cases of TB worldwide, corresponding to an incidence rate of 133 cases per 100,000 individuals. Among these cases, 90% were adults over the age of 15, and 64% were male. (2).Iran is considered a high-burden country for tuberculosis, with a notable incidence rate. The endemicity of TB in this region increases the pretest probability of the disease in patients presenting with compatible symptoms and radiological findings (3). Pulmonary TB is usually a disease having a gradual onset. Fever is the most common observed constitutional symptom which characteristically develops in the late afternoon. There may be other manifestations in up to 75% of cases of pulmonary TB, such as malaise, weakness, unusual fatigue, headache, night sweats and weight loss. This is usually accompanied by caseous necrosis and concomitant caseous liquefaction and cough and purulent sputum which is often associated with mild hemoptysis (4).Sputum smear microscopy and culture are commonly used for the diagnosis of pulmonary TB. However, it’s essential to recognize the limitations of these tests (5, 6). Smear microscopy has a sensitivity ranging from 36.9% to 55.6% and specificity of around 99%, while culture has higher sensitivity (approximately 80-90%) but takes longer for results (7, 8). Importantly, negative smear and culture results do not exclude the diagnosis of TB, especially in cases of paucibacillary disease or extrapulmonary involvement (8).