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Abstract Background Nasal packs are central to nasal surgeries. Primarily, these packs function by controlling bleeding, modulating pain and reducing adhesions postsurgery. However, the major setback of the currently used conventional nasal packs is the unbearable pain the patient undergoes upon removal of these packs. To overcome this shortcoming a variety of biodegradable packs have emerged. This study was aimed at evaluating the safety, efficacy and tolerability of VELNEZ nasal packs. VELNEZ, a patented Datt Mediproducts Pvt. Ltd. nasal pack, is one of its kind biodegradable composite that fragments within a few days of application. Methods Eighty patients were included in an open label, interventional, single arm clinical study using clinical endpoints to investigate the safety and efficacy of nasal pack VELNEZ. The patients were questioned using a visual analog scale from discharge day to 28th postoperative day (9 follow‐up visits) at regular intervals. The standardized questionnaires for hemorrhage control, relief from postoperative pain, moderate obstruction, and pain were used. Results A total of 76 patients were enrolled in the study and 74 patients completed the study. VELNEZ nasal pack played a significant role in controlling hemorrhage and reducing postoperative pain. The average hemorrhage control time was 7.49 ± 3.90 min with only 34.24% of population complaining of pain on the sixth day of surgery (follow‐up 4). Forteen days postsurgery only 10.95% of subject population complained of postoperative pain. This biodegradable composite has an average fragmentation time of 4.7 days in the nasal cavity. In addition, this study did not observe any postoperative adverse events or serious adverse events. Conclusion VELNEZ, a fragmentable nasal pack, is comfortable, safe, and effective against postsurgery bleeding and pain.

Abstract Background Autosomal‐recessive mutations in SPEG (striated muscle preferentially expressed protein kinase) have been linked to centronuclear myopathy with or without dilated cardiomyopathy (CNM5). Loss of SPEG is associated with defective triad formation, abnormal excitation–contraction coupling, calcium mishandling and disruption of the focal adhesion complex in skeletal muscles. To elucidate the underlying molecular pathways, we have utilized multi‐omics tools and analysis to obtain a comprehensive view of the complex biological processes and molecular functions. Methods Skeletal muscles from 2‐month‐old SPEG‐deficient (Speg‐CKO) and wild‐type (WT) mice were used for RNA sequencing (n = 4 per genotype) to profile transcriptomics and mass spectrometry (n = 4 for WT; n = 3 for Speg‐CKO mice) to profile proteomics and phosphoproteomics. In addition, interactomics was performed using the SPEG antibody on pooled muscle lysates (quadriceps, gastrocnemius and triceps) from WT and Speg‐CKO mice. Based on the multi‐omics results, we performed quantitative real‐time PCR, co‐immunoprecipitation and immunoblot to verify the findings. Results We identified that SPEG interacts with myospryn complex proteins CMYA5, FSD2 and RyR1, which are critical for triad formation, and that SPEG deficiency results in myospryn complex abnormalities (protein levels decreased to 22 ± 3% for CMYA5 [P

Abstract Background Down cow syndrome is commonly described in dairy cattle. The diagnosis and treatment of nonambulatory cattle is challenging and prognostic indicators of this condition in beef cattle have not been determined. Objectives Evaluate records of beef cattle (≥2 years of age) presented to 2 referral hospitals for inability to stand and identify prognostic indicators for survival to discharge. Animals Sixty‐three adult beef cattle treated for inability to stand at 2 referral hospitals. Methods Medical records of 63 beef cattle presented for inability to stand between January 2010 and December 2022 were retrospectively analyzed. Continuous and categorical variables were included in univariate and multivariate regression models to evaluate their association with outcome. Results Of 63 animals included in the study, 19% (12/63) were discharged, and the remaining 81% (n = 51) either died (11.1%) or were euthanized (69.8%). The odds of being discharged increased with each additional day of hospitalization (odds ratio [OR], 2.66; 95% confidence interval [CI], 1.39‐6.89) and with each additional flotation therapy session (OR, 2.108; 95% CI, 1.209‐4.219). Down beef cattle with a diagnosis of calving peripheral nerve paralysis and capable of walking out the tank after the first flotation session were 6.66 (95% CI, 1.58‐35.51) and 30 (95% CI, 4.4‐614.98) times more likely to be discharged compared with cattle that had other diagnoses and those that were unable to walk out the tank, respectively. Conclusions and Clinical Importance Treatment of nonambulatory beef cattle carries a poor prognosis. Practitioners can use information from our study as a guide for treatment or euthanasia decisions of nonambulatory beef cattle.

Abstract Efficient and site‐specific delivery of therapeutics drugs remains a critical challenge in cancer treatment. Traditional drug nanocarriers such as antibody‐drug conjugates are not generally accessible due to their high cost and can lead to serious side effects including life‐threatening allergic reactions. Here, these problems are overcome via the engineering of supramolecular agents that are manufactured with an innovative double imprinting approach. The developed molecularly imprinted nanoparticles (nanoMIPs) are targeted toward a linear epitope of estrogen receptor alfa (ERα) and loaded with the chemotherapeutic drug doxorubicin. These nanoMIPs are cost‐effective and rival the affinity of commercial antibodies for ERα. Upon specific binding of the materials to ERα, which is overexpressed in most breast cancers (BCs), nuclear drug delivery is achieved via receptor‐mediated endocytosis. Consequentially, significantly enhanced cytotoxicity is elicited in BC cell lines overexpressing ERα, paving the way for precision treatment of BC. Proof‐of‐concept for the clinical use of the nanoMIPs is provided by evaluating their drug efficacy in sophisticated three‐dimensional (3D) cancer models, which capture the complexity of the tumor microenvironment in vivo without requiring animal models. Thus, these findings highlight the potential of nanoMIPs as a promising class of novel drug compounds for use in cancer treatment.

Objective Treatment guidelines for rheumatoid arthritis (RA) recommend targeting low disease activity or remission and switching therapies for patients not reaching those targets. We evaluated real‐world use of disease activity measures, treatment discontinuation, and switching patterns among patients with RA initiating a first‐line tumor necrosis factor inhibitor (TNFi). Methods Data from adult patients with RA initiating a first‐line TNFi were collected from the American Rheumatology Network (January 2014–August 2021). The proportion of patients with recorded disease activity scores (Clinical Disease Activity Index [CDAI] or Routine Assessment of Patient Index Data 3 [RAPID3]) at TNFi initiation was assessed. Among patients with moderate or severe RA at TNFi initiation, reasons for discontinuation and subsequent advanced therapy were evaluated. Results Among TNFi initiators (n = 15,182), 44.8% recorded a CDAI/RAPID3 score at treatment initiation; of those who did not, 47.0% had recorded a tender and/or swollen joint count or pain score. Among patients with moderate or severe RA (n = 1,651), 52% discontinued their initial TNFi during follow‐up, of which 15%, 46%, 28%, and 12% initiated the same TNFi, another TNFi, a non‐TNFi biologic, or a Janus kinase inhibitor, respectively. The proportion of patients restarting the same TNFi or initiating another TNFi varied according to TNFi discontinuation reason. Conclusion In clinical practice, over half of patients with RA initiating a first‐line TNFi did not have baseline disease activity assessments. Many patients cycled through TNFi despite citing lack of efficacy as the most common reason for discontinuation. Consistent, objective monitoring of treatment response and timely switch to effective therapy is needed in patients with RA.

Abstract This qualitative study describes the development and evaluation of a clinical pathway to facilitate the implementation of catch‐up vaccinations for children with significant needle fear, particularly in children with developmental disabilities. The Specialist Immunization Team, based at a tertiary level teaching children's hospital, participated in process mapping activities using Motivational Interviewing (MI) techniques and reflective discussions. Team members developed a clinical pathway by incorporating parental feedback from semistructured interviews and clinical expertise from within the team, facilitated by colleagues from the Child Development Unit. A process map was developed that included process strengths and touch points with an action plan that was discussed and agreed upon. A repeat process mapping activity was conducted 16 months later. Reports from parental feedback included: positive, efficient, and successful experiences of having their child undergo catch‐up vaccinations. The experience empowered families for further procedures. Team members reported improvements in triaging appropriate children for the pathway, and an increase in confidence to interact and manage behaviors of children with significant anxiety and challenging behaviors. They also reported an increase in successful vaccinations with improved clinical judgment of facilitating the sedation pathway. This study demonstrates that using group facilitation using motivational interviewing in reflective discussions and process mapping utilizing parent and staff feedback in service improvement activities results in efficient and successful service delivery with improved patient outcomes.

Abstract Electroporation, or the use of electric pulses to facilitate the intracellular delivery of DNA, RNA, and other molecules, is a well‐established technique, that has been demonstrated to significantly augment the immunogenicity of DNA/mRNA vaccines and therapeutics. However, the clinical translation of traditional electroporators has been limited due to high costs, large size, complex user operation, and poor tolerability in humans due to nerve stimulation. In prior work, we introduced ePatch: an ultra‐low‐cost, handheld, battery‐free electroporator employing a piezoelectric pulser coupled with a microneedle electrode array that showed enhanced immunogenic responses to an intradermal SARS‐CoV‐2 DNA vaccine in mice. The current study shifts focus from efficacy to tolerability, hypothesizing that ePatch's microneedle array, which localizes the electric field to the superficial skin strata, will minimize nerve stimulation and improve patient comfort. We tested this hypothesis in 14 healthy adults, monitoring pain and other potential adverse effects associated with electroporation. Compared to the insertion of a traditional hypodermic needle, the ePatch was less painful. Adverse effects such as pain, tenderness, erythema and swelling at the application sites were minimal, transient, and statistically indistinguishable between the experimental and placebo ePatch application, suggesting excellent tolerability towards electroporation. In summary, ePatch has a favorable tolerability profile in humans and offers the potential for the safe use of electroporation in a variety of clinical settings, including DNA and mRNA vaccination.

Abstract Introduction The application of host‐derived antibacterial peptides has been highlighted as a potential efficacious and safe tool for the treatment of Huanglongbing (HLB), the most devastating disease of citrus. However, pathogenic bacteria such as HLB‐causing Candidatus liberibacter asiaticus (CLas) often develop resistance against the host antibacterial peptides. We showed that chimeras containing two different host antibacterial peptides not only retain antibacterial activity but also overcome bacterial resistance and enhance plant defence responses. Also, chimeric peptides can have an off‐target impact on the structure and function of plant‐associated microbiomes. However, there is a lack of understanding of the impact of the chimeric peptide therapy on the microbial structure in the citrus phyllosphere while reducing the CLas titre. Here, we aim to evaluate the efficacy of a chimeric peptide (UGK17) to reduce CLas titre, inducing plant defence response and impacting the microbiome associated with the citrus phyllosphere. Material and Method Leaf samples were collected from orange and grapefruit trees in Texas and identified as old and young leaves according to their maturity. We collected three different types of leaves based on their infection and symptoms: healthy, symptomatic (infected with typical symptoms), and asymptomatic (infected without symptoms). In planta assay was performed by dipping the leaves in the 0, 5 and 25 μM of UGK17 solutions for 48 h. The quantifications of CLas titre and pathogenesis‐related (PR) gene expression were done by quantitative polymerase chain reaction (qPCR) and reverse transcription‐qPCR, respectively. Amplicon sequencing was done to evaluate the impact of UGK17 on individual bacterial community structures. In addition, we performed an ex planta assay to assess the effect of UGK17 on the growth of bacterial isolates including Liberibacter crescens instead of unculturable CLas predominant in the phyllosphere. Result The UGK17 treatment reduced the CLas titre in both asymptomatic and symptomatic citrus leaves, regardless of the age of the leaves. The UGK17 application augmented the PR gene expression. In ex planta assay, the growth of L. crescens along with four other strains belonging to the family Rhizobiaceae, was significantly inhibited by the UGK17 while the growth of 74 strains were unaffected. Additionally, there was no statistically significant changes in the microbial community structure with UGK17 treatment. Conclusion Our results suggest that the chimeric peptide therapy is a promising solution to combat HLB by targeting mainly Gram‐negative pathogens and enhancing the plant immune responses without impairing the indigenous microbial community in the citrus phyllosphere.

Abstract Objectives We compared the safety and efficacy of direct oral anticoagulants (DOACs) with those of warfarin in the long‐term (≥6 months) treatment of cerebral venous thrombosis (CVT). Methods We searched electronic databases up to November 2023 to compare the use of DOACs and warfarin in CVT management. Modified Rankin scores (mRS), new intracranial hemorrhage, all‐cause mortality, recurrence and nonrecanalisation events were used to assess outcome. RevMan v5.4 software and the Cochran‐Mantel‐Haenszel method were utilized to analyse data. Results A total of 25 studies involving 2301 patients were identified as having treated CVT with either DOACs or warfarin. Good long‐term mRS scores 0–2 (risk ratio [RR] = 1.01, 95% CI = 0.98–1.03; p = 0.61), new intracranial hemorrhage (RR = 1.00, 95% CI = 0.48–2.08; p = 0.99), all‐cause mortality (RR = 1.00, 95% CI = 0.50–1.98; p = 0.99), nonrecanalisation (RR = 0.95, 95% CI = 0.77–1.18; p = 0.65) and recurrence venous thrombosis events (RR = 0.63, 95% CI = 0.33–1.22; p = 0.17) were similar between the two treatment arms. Subgroup analysis found recurrence of venous thrombosis was lower in the rivaroxaban group compared to warfarin (2.2% vs. 8.5%, RR = 0.33, 95% CI = 0.11–0.98; p = 0.05). Conclusion DOACs and warfarin provide comparable long‐term safety and efficacy profiles. DOACs may be preferred over warfarin due to their ease of clinical management.

Abstract Background and Aims The coronavirus disease 2019 (COVID‐19) pandemic stimulated a paradigm shift in medical and surgical education from in‐person teaching to online teaching. It is unclear whether an in‐person or online approach to surgical teaching for medical students is superior. We aim to compare the outcomes of in‐person versus online surgical teaching in generating interest in and improving knowledge of surgery in medical students. We also aim the quantify the impact of a peer‐run surgical teaching course. Methods A six‐session course was developed by medical students and covered various introductory surgical topics. The first iteration was offered online to 70 UK medical students in March 2021, and the second iteration was in‐person for 20 students in November 2021. Objective and subjective knowledge was assessed through questionnaires before and after each session, and also for the entire course. Data were analyzed from this mixed‐methods study to compare the impact of online versus in‐person teaching on surgical knowledge and engagement. Results Students in both iterations showed significant improvement of 33%–282% across the six sessions in knowledge and confidence after completing the course (p

Abstract Aims Left ventricular filling pressure (LVFP) can be estimated from cardiovascular magnetic resonance (CMR). We aimed to investigate whether CMR‐derived LVFP is associated with signs, symptoms, and prognosis in patients with recently diagnosed heart failure (HF). Methods and results This study recruited 454 patients diagnosed with HF who underwent same‐day CMR and clinical assessment between February 2018 and January 2020. CMR‐derived LVFP was calculated, as previously, from long‐ and short‐axis cines. CMR‐derived LVFP association with symptoms and signs of HF was investigated. Patients were followed for median 2.9 years (interquartile range 1.5–3.6 years) for major adverse cardiovascular events (MACE), defined as the composite of cardiovascular death, HF hospitalization, non‐fatal stroke, and non‐fatal myocardial infarction. The mean age was 62 ± 13 years, 36% were female (n = 163), and 30% (n = 135) had raised LVFP. Forty‐seven per cent of patients had an ejection fraction

Abstract Introduction Plant microbiomes contribute directly to plant health and productivity, but mechanisms that underpin plant microbiome assembly in different compartments (e.g., root, leaf) are not fully understood. Identifying environmental and management factors that affect plant microbiome assembly is important to advance understanding of fundamental ecological processes, and to harness microbiome for improved primary productivity and environmental sustainability. Irrigation and fertilization are two common management practices in Australian tree plantations, but little is known about the effects of these treatments on soil, plant host and their microbiome. Here, we investigated the impact of decade‐long irrigation, fertilization and their combined application on soil, plant traits and microbiome of a Eucalyptus saligna plantation. Materials and Methods Microbial profiling of bulk soil, rhizosphere, root and leaves was performed using amplicon sequencing 16S ribosomal DNA and internal transcribed spacer (ITS) markers for bacteria and fungi, respectively, along with measurements of soil properties and plant traits. Results The results indicated that both management practices significantly affected soil properties and soil and root microbiomes. Irrigation increased but fertilizer treatment reduced microbial alpha diversity. However, neither irrigation nor fertilizer treatment impacted the leaf microbiome. Our findings suggest that management practices impact soil edaphic factors, which in turn influence the below‐ground microbiome (soil and root), but the leaf microbiome remains unaffected. In addition, the leaf microbiome was distinct from soil and root microbiomes, and a source tracker analysis suggested that root and bulk soils only contributed to 53% and 10% operational taxonomic units of the leaf bacterial community, suggesting strong and sequential host selection of the leaf microbiome. In addition, management practices had a limited impact on leaf traits and, consequently, the leaf microbiome maintained its distinct composition. Conclusion These findings provide mechanistic evidence for ecological processes that drive plant microbiome assembly and indicate that host selection plays a more important role than management practices in the leaf microbiome assembly.

Abstract Aims The neutrophil‐to‐lymphocyte ratio (NLR) is a marker of systemic inflammation and plays a critical role in the assessment and prognosis in patients with heart failure. The EMPA‐HEART CardioLink‐6 trial demonstrated that patients with type 2 diabetes (T2D) and coronary artery disease (CAD) treated with a sodium–glucose transport protein 2 inhibitor for 6 months experienced regression in left ventricular mass. Given this, we evaluated the relationship of baseline NLR and cardiac reverse remodelling in the entire cohort of this trial. Methods and results A total of 97 individuals were randomized to receive empagliflozin (10 mg/day) or placebo for 6 months. The primary outcome of the trial was change in left ventricular mass indexed to body surface area (LVMi) from baseline to 6 months as measured by cardiac magnetic resonance imaging. In our analysis, the cohort was stratified above and below an NLR level of 2. To assess the treatment effect on the 6 month change in NLR, we used a linear model adjusting for baseline differences in NLR [analysis of covariance (ANCOVA)] that included an interaction term between the baseline NLR and treatment. To assess the treatment effect on the 6 month change in LVMi in each of the subgroups divided by baseline NLR, we used an ANCOVA adjusting for baseline differences in LVMi that included an interaction term between the subgroups and treatment. The results of the regression models were summarized as adjusted differences with two‐sided 95% confidence intervals (CIs). Patients who exhibited an elevated baseline NLR demonstrated higher LVMi and left ventricular end‐diastolic volume indexed to body surface area than those with a lower NLR. In patients with an NLR

Abstract Aims The duration of type 2 diabetes mellitus (T2DM) is an important determinant of diabetes severity. The EMPA‐HEART CardioLink‐6 trial reported significant left ventricular (LV) mass indexed to body surface area (LVMi) regression in patients treated with the sodium‐glucose cotransporter 2 inhibitor (SGLT2i) empagliflozin for 6 months. This exploratory sub‐analysis of the same trial investigated the association between T2DM duration and LVMi regression. Methods and results A total of 97 individuals with T2DM and coronary artery disease (CAD) were randomly assigned to receive empagliflozin 10 mg daily or placebo. LVMi was measured at the baseline and 6 month visit using cardiac magnetic resonance imaging. The study population was divided into those with a baseline T2DM duration

Abstract Aims Given recent suggestions that serum levels of insulin‐like growth factor‐binding protein 7 (IGFBP7) may identify patients who derive greater cardiorenal benefits from treatment with sodium‐glucose transport 2 inhibitors (SGLT2i), this exploratory sub‐analysis of the EMPA‐HEART CardioLink‐6 randomized controlled trial evaluated the association between serum levels of IGFBP7 and empagliflozin‐mediated left ventricular mass regression. Methods and results The EMPA‐HEART CardioLink‐6 trial used gold‐standard cardiac magnetic resonance imaging to detect change in left ventricular mass indexed to body surface area (LVMi) following 6 months of treatment with empagliflozin or matching placebo in 97 patients with type 2 diabetes and coronary artery disease. Serum samples were collected at baseline and analysed for IGFBP7 using an enzyme‐linked immunosorbent assay. A multivariate linear regression model was used to assess the association between IGFBP7 and baseline LVMi. A linear model adjusting for baseline differences in LVMi was used to test the relationship between baseline IGFBP7 level, change in LVMi over 6 months, and treatment arm. Of the 97 patients enrolled, 74 had complete covariate data and were included in our analysis. No association between baseline IGFBP7 and baseline LVMi was found [baseline LVMi: 0.14 g/m2 (95% CI: −0.29 g/m2 to 0.57 g/m2) per 1 ng/mL higher baseline IGFBP7]. In addition, no difference between patients treated with empagliflozin versus matching placebo was found when evaluating the association between serum IGFBP7, 6 month change in LVMi, and treatment arm [empagliflozin 6 month change in LVMi: 0.25 g/m2 (95% CI: −0.17 g/m2 to 0.67 g/m2) per 1 ng/mL higher IGFBP7 vs. matching placebo 6 month change in LVMi: 0.07 g/m2 (95% CI: −0.21 g/m2 to 0.35 g/m2) per 1 ng/mL higher IGFBP7; Pinteraction = 0.49]. Additional sensitivity analysis assessing IGFBP7 as a categorical variable (above/below the median) showed no significant association between IGFBP7, 6 month change in LVMi, and treatment arm. Conclusions Our study provides insight into the generalizability of IGFBP7 as a surrogate marker of cardiac remodelling in patients with type 2 diabetes and coronary artery disease. Our results suggest that SGLT2i‐mediated reverse cardiac remodelling may be independent of IGFBP7 levels. Further investigations evaluating the association between IGFBP7 and SGLT2i are suggested to understand if and how IGFBP7 levels may modulate benefits received from SLGT2i.

Abstract Dry pea (Pisum sativum) seeds are valuable sources of plant protein, dietary fiber, and starch, but their uses in food products are restricted to some extent due to several off‐flavor compounds. Saponins are glycosylated triterpenoids and are a major source of bitter, astringent, and metallic off‐flavors in pea products. β‐amyrin synthase (BAS) is the entry point enzyme for saponin biosynthesis in pea and therefore is an ideal target for knock‐out using CRISPR/Cas9 genome editing to produce saponin deficient pea varieties. Here, in an elite yellow pea cultivar (CDC Inca), LC/MS analysis identified embryo tissue, not seed coat, as the main location of saponin storage in pea seeds. Differential expression analysis determined that PsBAS1 was preferentially expressed in embryo tissue relative to seed coat and was selected for CRISPR/Cas9 genome editing. The efficiency of CRISPR/Cas9 genome editing of PsBAS1 was systematically optimized in pea hairy roots. From these optimization procedures, the AtU6‐26 promoter was found to be superior to the CaMV35S promoter for gRNA expression, and the use of 37°C was determined to increase the efficiency of CRISPR/Cas9 genome editing. These promoter and culture conditions were then applied to stable transformations. As a result, a bi‐allelic mutation (deletion and inversion mutations) was generated in the PsBAS1 coding sequence in a T1 plant, and the segregated psbas1 plants from the T2 population showed a 99.8% reduction of saponins in their seeds. Interestingly, a small but statistically significant increase (~12%) in protein content with a slight decrease (~5%) in starch content was observed in the psbas1 mutants under phytotron growth conditions. This work demonstrated that flavor‐improved traits can be readily introduced in any pea cultivar of interest using CRISPR/Cas9. Further field trials and sensory tests for improved flavor are necessary to assess the practical implications of the saponin‐free pea seeds in food applications.

This study assessed the hydropower potential of a mountain watershed within the Sunkoshi River basin in Sindhupalchok, Nepal, utilizing geographic information systems (GIS) and the soil and water assessment tool (SWAT) hydrological model. Topographical, soil, land use, meteorological, and discharge data were employed to assess the study area for the appropriateness of hydropower generation. SWAT was utilized to delineate the Sunkoshi basin into 23 distinct subbasins and involved the creation of a detailed river network, incorporating various hydrological attributes including stream links, stream order, stream length, and slope gradient. After that, it was employed to simulate river discharges within these subbasins. The Sequential Uncertainty Fitting Version 2 (SUFI-2) algorithm, integrated within the SWAT Calibration and Uncertainty Program (SWAT-CUP), was employed to calibrate and validate the model. This step involved the adjustment of 25 selected parameters to enhance the model’s accuracy and reliability in representing the hydrological processes of the Sunkoshi basin. Model performance was assessed utilizing three well-established efficiency criteria: coefficient of determination (R2 = 0.79), Nash–Sutcliffe efficiency (NSE = 0.73), and percent bias (PBIAS = 17.59). The study identified 36 sites across streams of order 3, 4, and 5 as having potential for hydropower generation. The hydropower potential at each identified site was evaluated using estimated stream flow and topographical head at various probability of exceedance (PoE) levels (40%, 45%, 50%, and 60%). The aggregate hydropower potential of the basin was quantified, yielding a potential of 371.30 MW at a 40% PoE. The findings suggest that an integrated approach combining SWAT-based hydrological modeling within a GIS can accurately assess a river basin’s hydropower potential and provide insights into further evaluation of the comprehensive environmental assessment of the fragile Himalayan watersheds.

Abstract Amomum subulatum is a popular aromatic and medicinal spice crop being used for centuries to treat a variety of health ailments. The ethnopharmacological use of Amomum subulatum has been described in various medicinal systems including Ayurveda, Unani, and Chinese for its therapeutic properties in mitigating gastrointestinal disorders, lung congestions, respiratory ailments, jaundice, tuberculosis, hyperlipidemia, inflammation, ischemic heart diseases, etc. Literature search using Google Scholar, PubMed, NCBI, Elsevier, Wiley online Library, Springer, Taylor and Francis, Web of Science, Science Direct, Scopus databases was restricted to English‐language articles. Significant information on pharmacological properties of Amomum subulatum, including antioxidant (ROS/RNS pathways), anti‐inflammatory (TNF‐α, IL‐1, IL‐6, COX‐2, NF‐кB, HO‐1, arachidonic acid pathways), antinephrotoxic (urea, creatinine, Cystatin‐C), antihepatotoxic (SGOT, SGPT, and ALP), antidiabetic, etc., was collected for the review. The pharmacological properties of this traditional herb may be attributed to the plethora of secondary metabolites present in it. Preliminary phytochemical screening reported the abundance of flavonoids, terpenoids, steroids, vitamins, minerals, fatty acid esters, etc. 1,8‐cineole (60%–80% of total volatile oil), α‐terpineol, limonene, α‐terpinyl acetate, etc., are the notable phytochemicals reported from Amomum subulatum. However, detailed insights into the molecular mechanistic pathways mediating the beneficial role of this traditional herb on cell/animal models and large‐scale clinical trials are lacking. In the present review, we provide a comprehensive description of the current knowledge on Amomum subulatum, including its phytoconstituents, pharmacological uses, and toxicities, its implication in host health effects, including in vitro/in vivo efficacy, and the potential of these emerging species to suggest areas for future research.

Abstract Background and Aims The effectiveness of coronavirus disease 2019 (COVID‐19) vaccines in reducing symptoms, disease advancement, complications, and mortality in severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection has been well‐established. This case‐control study aimed to compare different blood parameters, and prognostic and survival outcomes of COVID‐19 patients based on vaccination status. Methods We performed a case‐control study that included hospitalized patients with COVID‐19 at Tribhuvan University Teaching Hospital, Kathmandu, Nepal. Individuals who received vaccination were designated as cases and unvaccinated individuals as controls. Demographics, co‐morbidity, clinical data, laboratory data, and disease outcomes were recorded for both groups. Multivariate, Cox, and linear regression were used for analysing blood parameters, hospital admission, survival, and hospital stay, respectively, between cases and controls. Results Out of 100 participants enrolled, 46 were vaccinated, and 54 weren't. At admission, ferritin and erythrocyte sedimentation rate (ESR) were significantly lower in cases. At discharge, cases showed a higher monocyte than controls. Ferritin, ESR, and d‐imer showed excellent performance in determining the severity of symptoms. Significant correlation and regression of ferritin and ESR with the length of hospital stay was observed. Length of hospital stay was significantly lower in cases than in controls. No significant differences between cases and controls were observed in mortality. Conclusion COVID‐19 vaccines effectively reduced hospitalization duration. Ferritin and ESR were significantly lower in vaccinated individuals and showed the best utility in monitoring the disease.

Key Clinical Message Pneumothorax and bronchopleural fistula (BPF) are potentially fatal complications that can occur in patients with COVID‐19 pneumonia. Early detection, appropriate treatment, and consideration of surgical intervention are necessary for optimum outcomes. Abstract Introduction Healthcare professionals face complex challenges as a result of the rare emergence of pneumothorax among the variety of COVID‐19 complications, including severe viral pneumonia. Case History A 57‐year‐old male with multiple comorbidities diagnosed with COVID‐19 pneumonia was admitted to our center and exhibited bilateral crepitations. During hospitalization, the patient developed right‐sided pneumothorax that persisted despite chest tube insertion was linked to the presence of BPF. Discussion The occurrence of pneumothorax in COVID‐19 patients is relatively rare risk factors for which are not yet fully understood, although smoking history may play a role. Conservative management is recommended for asymptomatic cases, while intercostal drainage is necessary for symptomatic patients. Surgical intervention may be required to manage the BPF in some instances. Conclusion Pneumothorax and BPF are rare but potentially life‐threatening complications in patients recovering from COVID‐19 pneumonia. Early recognition, appropriate treatment, and consideration of surgical intervention are crucial for optimizing patient outcomes.

Abstract The recent advent of topological states of matter spawned many significant discoveries. The quantum anomalous Hall (QAH) effect is a prime example due to its potential for applications in quantum metrology, as well as its influence on fundamental research into the underlying topological and magnetic states and into axion electrodynamics. Here, electronic transport studies on a (V,Bi,Sb)2Te3 ferromagnetic topological insulator nanostructure in the QAH regime are presented. This allows access to the dynamics of an individual ferromagnetic domain. The domain size is estimated to be in the 50–100 nm range. Telegraph noise resulting from the magnetization fluctuations of this domain is observed in the Hall signal. Careful analysis of the influence of temperature and external magnetic field on the domain switching statistics provides evidence for quantum tunneling (QT) of magnetization in a macrospin state. This ferromagnetic macrospin is not only the largest magnetic object in which QT is observed, but also the first observation of the effect in a topological state of matter.

Abstract Introduction Citrus greening (aka Huanglongbing, HLB) caused primarily by the bacterial pathogen Candidatus Liberibacter asiaticus (CLas) has devastating effects on the global citrus industry. Agricultural management‐induced changes in microbial communities are hypothesised to contribute toward HLB resistance by reducing pathogen titre and increasing root and soil health. However, we have a limited understanding of the impacts of management practices on the soil microbiome, making the extent of HLB management uncertain. Material and Methods Here we investigated the effect of agricultural management practices on reducing CLas titer via changes in rhizosphere‐associated bacterial communities. Rhizosphere and root samples were collected from two sites in Florida where different management practices (e.g., metalized reflective mulch ground covers, compost application and microbial inoculations) are currently being implemented to prevent HLB. Management‐induced changes in the rhizosphere bacterial community were assessed using amplicon sequencing. qPCR assays were used to quantify the titer of the pathogen CLas in roots. In addition, we measured soil properties and the activities of microbial enzymes involved in soil nutrient cycling. Results Our results indicated that certain management practices lead to shifts in the community structure of rhizosphere bacterial communities that negatively interact with the HLB pathogen. Management practices improved soil quality and reduced CLas titer. Additionally, we found that Actinobacteria were frequently enriched in the successful treatment sites, suggesting that Actinobacteria taxa could be indicators for HLB suppression properties in the soil. Conclusion Our results suggest that microbiome manipulation, either through changes in the management practices or microbial amendment, can increase the suppressive potential of soils, resulting in the reduction in CLas titer and potentially leading to HLB suppression in citrus groves.

Abstract One of the most common issues in renewable energy applications is modelling and regulating grid‐connected PV systems. The model reference adaptive control (MRAC) technique has been analysed in this paper. It's difficult to develop an MRAC that performs well in both transient and steady‐state conditions; hence, the primary goal of this paper is to create a modified MRAC that has excellent steady‐state and transient responses. A modified MRAC scheme has been proposed, where an Ant lion optimisation technique and a well‐known algorithm that is Genetic Algorithm (GA) is used to optimise the controller gain and compared it with each other and also with the conventional MRAC technique. The optimisation techniques are used to tune the controller parameters so that errors should be minimised. The time response analysis of MRAC, MRAC‐GA, and MRAC‐ALO controllers are shown and evaluated using common control criteria such as rising time, settling time, peak overshoot, steady‐state, and error parameters. The simulation findings reveal that the proposed modified MRAC controller, both MRAC‐ALO and MRAC‐GA, outperforms in relation to transient performance and steady‐state performance compared to conventional MRAC controllers.

Abstract Hypertension guidelines recommend measuring blood pressure (BP) in both arms at least once. However, this is seldom done due to uncertainties regarding measurement procedure and the implications of finding a clinically important inter‐arm BP difference (IAD). This study aimed to provide insight into the prevalence of clinically important IADs in a large Indian primary care cohort. A number of 134 678 (37% female) unselected Indian primary care participants, mean age 45.2 (SD 11.9) years, had BP measured in both arms using a standardized, triplicate, automated simultaneous measurement method (Microlife WatchBP Office Afib). On average, there were clinically minor differences in right and left arm BP values: systolic BP 134.4 vs 134.2 mmHg (p

Abstract The soil microbiome response to global change drivers remains largely unclassified, with current studies showing contrasting results to several global change drivers. One such driver, drought, is increasing in severity and frequency due to climate change. Further, legacy effects, or long‐lasting impacts after drought has subsided, could have lasting impacts on the soil microbiome with important consequences for ecosystem functioning. Thus, our study aimed to understand how the soil microbiome responds after a severe, prolonged drought and whether legacy effects persist post‐drought. We measured soil microbial community response in a mesic grassland for two years after a four‐year experimental drought in a native tallgrass prairie. The experimental drought was imposed either (1) chronically by reducing each growing season rainfall event by 66% or (2) intensely by completely eliminating growing season rainfall until an ~45% reduction in mean annual rainfall (climatic average) was achieved. The bacterial community showed no legacies in the first season post‐drought in response to either chronic or intense drought but showed an increased abundance of Verrucomicrobia and decreased richness in both treatments in the second growing season after the drought treatments ended. In the first and second post‐drought growing seasons, we found small differences in beta diversity between the control and intense drought treatment for fungal communities but not for the chronic drought treatment. Further, we found that the two main phyla of fungi, Ascomycota and Basidiomycota, showed reduced relative abundance post‐drought in the intense drought treatment. Overall, few legacies in soil microbial communities persisted after a four‐year experimentally induced drought. However, our results show that the nature of the drought—chronic versus intense—can differentially impact fungal versus bacterial short‐term legacies. These results suggest that the soil microbiome is for the most part drought resistant (responds little during drought) and/or resilient (quickly recovers post‐drought, since a study at the same site found that drought impacted the bacterial community) in this mesic grassland.

Background Ambulatory follow‐up for all patients with heart failure (HF) is recommended within 7 to 14 days after hospital discharge to improve HF outcomes. We examined postdischarge ambulatory follow‐up of patients with comorbid diabetes and HF from a low‐income population in primary and specialty care. Methods and Results Adults with diabetes and first hospitalizations for HF, covered by Alabama Medicaid in 2010 to 2019, were included and the claims analyzed for ambulatory care use (any, primary care, cardiology, or endocrinology) within 60 days after discharge using restricted mean survival time regression and negative binomial regression. Among 9859 Medicaid‐covered adults with diabetes and first hospitalization for HF (mean age, 53.7 years; SD, 9.2 years; 47.3% Black; 41.8% non‐Hispanic White; 10.9% Hispanic/Other [Other included non‐White Hispanic, American Indian, Pacific Islander and Asian adults]; 65.4% women, 34.6% men), 26.7% had an ambulatory visit within 0 to 7 days, 15.2% within 8 to 14 days, 31.3% within 15 to 60 days, and 26.8% had no visit; 71% saw a primary care physician and 12% a cardiology physician. Black and Hispanic/Other adults were less likely to have any postdischarge ambulatory visit (P

Abstract Management of infective endocarditis (IE) in intravenous drug users (IVDUs) can be challenging due to risk of reinfection following surgery. Although complex repair techniques that can be utilized to reconstruct the tricuspid valve after extensive debridement, treatment of active IVDU is incomplete without effective post‐operative harm reduction intervention program.

Abstract Introduction Harnessing synthetic communities (SynCom) of plant growth‐promoting (PGP) microorganisms is considered a promising approach to improve crop fitness and productivity. However, biotic mechanisms that underpin improved plant performance and the effects of delivery mode of synthetic community are poorly understood. These are critical knowledge gaps that constrain field efficacy of SynCom and hence large‐scale adoption by the farming community. Material & Methods In this study, a SynCom of four PGP microbial species was constructed and applied to either as seed dressing (treatment T1, applied at the time of sowing) or to soil (treatment T2, applied in soil at true leaf stage) across five different cotton (Gossypium hirsutum) cultivars. The impact of SynCom on plant growth, rhizosphere microbiome and soil nutrient availability, and how this was modified by plant variety and mode of applications, was assessed. Results Results showed that the seed application of SynCom had the strongest positive impact on overall plant fitness, resulting in higher germination (14.3%), increased plant height (7.4%) and shoot biomass (5.4%). A significant increase in the number of flowers (10.4%) and yield (8.5%) was also observed in T1. The soil nitrate availability was enhanced by 28% and 55% under T1 and T2, respectively. Results further suggested that SynCom applications triggered enrichment of members from bacterial phyla Actinobacteria, Firmicutes and Cyanobacteria in the rhizosphere. A shift in fungal communities was also observed, with a significant increase in the relative abundance of fungi from phyla Chytridiomycota and Basidiomycota in SynCom treatments. A structural equation model suggested that SynCom directly increased crop productivity but also indirectly via impacting the alpha diversity of bacteria. Conclusion Overall, this study provides mechanistic evidence that SynCom applications can shift rhizosphere microbial communities and improve soil fertility, plant growth, and crop productivity, suggesting that their use could contribute toward sustainable increase in farm productivity.

Abstract Objective Evaluation and management of small bowel disorders have always been challenging due to the limitations of the existing technology. Motorized power spiral enteroscopy (PSE) is an innovative new technique that offers easier, faster, and more complete small bowel evaluation with the ability to perform therapeutics. We aimed to evaluate the safety and efficacy of PSE in various indications. Methods Retrospective analysis of prospectively collected data of consecutive patients, who underwent PSE at a tertiary care center. Primary outcome measures were technical success rate, pan‐enteroscopy rate, diagnostic and therapeutic yield, and the secondary outcomes measures were the depth of maximal insertion, median insertion time, and adverse events. Results Fifty‐four patients (mean age of 49.38 ± 16.26 years) underwent PSE for small bowel evaluation. Technical success rate was 95.55% (antegrade route) and 93.10% (retrograde route). Pan‐enteroscopy rate is 46.29% and antegrade enteroscopy to the cecum was achieved in eight patients. Overall diagnostic and therapeutic yields were 85.18% and 30.76%, respectively. The most common findings were ulcero‐stricturing lesions (51.92%) followed by vascular lesions (9.61%). The most common histopathologic diagnosis was Crohn's disease in 29.62%. Median depth of maximal insertion was 400 cm (range 150–550 cm; antegrade route) and 180 cm (range 50–350 cm; retrograde route). The median insertion time to depth of maximal insertion was 70 min (range 30–110 min; antegrade route) and 45 min (range 20–70 min; retrograde route). PSE‐associated major adverse events occurred in one patient and minor adverse events were seen in 48.14%. Conclusion PSE is a safe and effective modality for the evaluation of small bowel disorders with a high diagnostic yield.

Abstract Background and aims Endoscopic ultrasound‐guided gastrojejunostomy (EUS‐GJ) is a therapeutic option for patients with gastric outlet obstruction (GOO), which provides long‐term luminal patency without the risk of tumor ingrowth and/or overgrowth and avoids surgical morbidity. The goal of this study was to assess technical success, clinical success, and adverse events associated with a nasojejunal tube‐assisted EUS‐ GJ technique. Methods This was a retrospective study conducted at a single tertiary care center. The nasojejunal tube (14F) was used to perform the EUS‐GJ (device‐assisted method). During the study period, consecutive GOO patients who underwent EUS‐GJ between August 2018 and December 2021 were included. Technical success was defined as adequate positioning and deployment of the stent. The patient's ability to tolerate a normal oral diet without vomiting was defined as clinical success. Results Thirty patients underwent EUS‐GJ during this study period. Twenty‐six patients had malignant GOO, while four had a benign obstruction. EUS‐GJ was successfully performed in 29 patients, and technical success was 96.67% (29/30). Nasojejunal tube‐assisted EUS‐GJ technique was used in all patients. Clinical success was achieved in all patients who had technical success (29/29, 100%). The adverse events rate was 6.6%. During the procedure, the median procedure time was 25 min (interquartile range 15–42.5), and the average hospitalization was 4.4 days. Normal meals were tolerated by all patients. After 210 days of median follow‐up (range 5–880 days), no recurrence of symptoms was observed. Conclusion The nasojejunal tube‐assisted EUS‐GJ is a safe and effective technique to treat GOO symptoms.

Abstract Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pain disorder causing symptoms of urinary frequency, urgency, and bladder discomfort or pain. Although this condition affects a large population, little is known about its etiology. Genetic analyses of whole exome sequencing are performed on 109 individuals with IC/BPS. One family has a previously reported SIX5 variant (ENST00000317578.6:c.472G>A, p.Ala158Thr), consistent with Branchiootorenal syndrome 2 (BOR2). A likely pathogenic heterozygous variant in ATP2A2 (ENST00000539276.2:c.235G>A, p.Glu79Lys) is identified in two unrelated probands, indicating possible Darier‐White disease. Two private heterozygous variants are identified in ATP2C1 (ENST00000393221.4:c.2358A>T, p.Glu786Asp (VUS/Likely Pathogenic) and ENST00000393221.4:c.989C>G, p.Thr330Ser (likely pathogenic)), indicative of Hailey‐Hailey Disease. Sequence kernel association test analysis finds an increased burden of rare ATP2C1 variants in the IC/BPS cases versus a control cohort (p = 0.03, OR = 6.76), though does not survive Bonferroni correction. The data suggest that some individuals with IC/BPS may have unrecognized Mendelian syndromes. Comprehensive phenotyping and genotyping aid in understanding the range of diagnoses in the population‐based IC/BPS cohort. Conversely, ATP2C1, ATP2A2, and SIX5 may be candidate genes for IC/BPS. Further evaluation with larger numbers is needed. Genetically screening individuals with IC/BPS may help diagnose and treat this painful disorder due to its heterogeneous nature.

Introduction The use of balloon guide catheters (BGC) during endovascular thrombectomy (EVT) has been suggested to lower the risk of distal embolization and improve first pass revascularization rates in patients with acute ischemic stroke. However, a recent large randomized controlled trial suggests there is no significant difference in initial and final revascularization scores among EVT performed with a BGC versus without. We assessed the influence of BGC use during EVT on first pass (FP) and revascularization (RV) success in a historical database from a multi‐hospital health system. Methods Patients with anterior circulation large vessel occlusion undergoing EVT with stent‐retriever or aspiration between 2012 and 2018 at three Kaiser Permanente Southern California (KPSC) region hospitals were identified from the database. BGC use was determined through manual chart review. A chi‐squared test compared the relationship of BGC use with the primary outcomes. The primary outcomes were FP and RV success using a dichotomized TICI score of 2b or greater. Results 218 patients were included in the study. BGC was used in 35/218 (16%) of patients. There was no significant difference in age (p = 0.65), gender (p = 0.92), presenting NIHSS (p = 0.45), hypertension (p = 0.66), diabetes (p = 0.85), atrial fibrillation (p = 0.36), serum glucose (p = 0.43), or pre‐EVT TPA administration (p = 0.36). Among EVT with BGC, FP success was 13/35 (37%) and EVT without BGC had a FP success of 76/183 (42%); p = 0.71. Successful final RV with BGC occurred in 30/35 (86%) while EVT without BGC had a successful final RV of 162/183 (89%); p = 0.78. Because BGC use occurred only with stent‐retriever treatment, subgroup analysis was performed comparing the BGC group (N = 35) with the non‐BGC stent‐retriever (N = 88) and aspiration thrombectomy (N = 95) groups. There was no significant difference in FP (p = 0.88) or RV success (p = 0.42) between the BGC (37% FP and 86% RV), non‐BGC stent‐retriever (42% FP and 92% RV), and aspiration thrombectomy groups (41% FP and 86% RV). Conclusions Among our population, BGC use was not associated with higher first pass or final revascularization success.

Introduction Basilar artery occlusion (BAO) is a life‐threatening condition associated with high morbidity and mortality. The clinical effectiveness of endovascular therapy (EVT) in patients with stroke due to BAO is not well established. The objective of our study is to investigate the role of Posterior circulation Acute Stroke Prognosis Early CT Score (pcASPECTS) in predicting clinical outcome in patients with BAO who undergo EVT. Methods We conducted a retrospective analysis on 45 patients with acute BAO who received EVT from November 2015 to June 2022. Information was collected on demographic variables, medical history, clinical parameters, and CT based pcASPECTS on admission. Functional outcomes were assessed via binarization of the following variables: the modified Rankin scale score on discharge, NIH stroke scale on discharge, and the modified Rankin scale score 90 days following discharge. A series of logistic regression models adjusted for age, gender, atrial fibrillation, systolic blood pressure at admission, tPA receipt, and NIH stroke scale on admission were run to assess the association of pcASPECTS score on admission with binarized outcome measures. Results Among 45 patients (mean age 63.6+11.4 years, 73.3% males), binarized pcASPECTS score on admission (< 7: greater severity, >7: lower severity) was not shown to be significantly associated with functional outcome across a series of logistic regression models. When assessing for binarized modified Rankin scale at discharge (0‐3: good outcome, 4–6: poor outcome), a lower severity of pcASPECTS showed 5.47 times the odds of a good outcome (OR: 5.47; 95% CI: 0.17, 173.25; p‐value: 0.34). When assessing for binarized NIH stroke scale on discharge (0‐15: mild/moderate; >15: severe), a lower severity pcASPECTS showed 6.05 times the odds of a mild/moderate outcome as opposed to a severe outcome (OR: 6.05; 95% CI: 0.32, 114.62; p‐value: 0.23). When assessing for a modified Rankin scale at 90 days post‐discharge, binarized as above, a lower severity pcASPECTS showed 4.36 times the odds of a good outcome (OR: 4.36; 95% CI: 0.27, 69.40; p‐value: 0.30). Conclusions Our study revealed that pcASPECTS on admission may help predict clinical outcomes in patients receiving EVT for BAO and therefore could be used as a guide for medical and endovascular management. These findings have far‐reaching applicability but will require larger studies to confirm significant clinical benefit.

Abstract Low concentrations of natriuretic peptides (NPs) have been associated with greater risk for Type 2 diabetes (T2D). African American individuals (AA) have lower NP levels and are disproportionately burdened by T2D. The purpose of this study was to test the hypothesis that higher post‐challenge insulin in AA adults is associated with lower plasma N‐terminal pro‐atrial natriuretic peptide (NT‐proANP). A secondary purpose was to explore associations between NT‐proANP and adipose depots. Participants were 112 AA and European American (EA) adult men and women. Measures of insulin were obtained from an oral glucose tolerance test and hyperinsulinemic‐euglycemic glucose clamp. Total and regional adipose depots were measured from DXA and MRI. Multiple linear regression analysis was used to assess associations of NT‐proANP with measures of insulin and adipose depots. Lower NT‐proANP concentrations in AA participants was not independent of 30‐min insulin area under the curve (AUC). NT‐proANP was inversely associated with 30‐min insulin AUC in AA participants, and with fasting insulin and HOMA‐IR in EA participants. Thigh subcutaneous adipose tissue and perimuscular adipose tissue were positively associated with NT‐proANP in EA participants. Higher post‐challenge insulin may contribute to lower ANP concentrations in AA adults.

Abstract Understanding the complex tumor microenvironment is key to the development of personalized therapies for the treatment of cancer including colorectal cancer (CRC). In the past decade, significant advances in the field of immunotherapy have changed the paradigm of cancer treatment. Despite significant improvements, tumor heterogeneity and lack of appropriate classification tools for CRC have prevented accurate risk stratification and identification of a wider patient population that may potentially benefit from targeted therapies. To identify novel signatures for accurate prognostication of CRC, we quantified gene expression of 12 immune‐related genes using a medium‐throughput NanoString quantification platform in 93 CRC patients. Multivariate prognostic analysis identified a combined four‐gene prognostic signature (TGFB1, PTK2, RORC, and SOCS1) (HR: 1.76, 95% CI: 1.05–2.95, *p

Delirious mania is an acute neurobehavioral syndrome which can have the features of mania, delirium, psychosis and catatonia. There are no diagnostic and treatment guidelines of delirious mania which can lead to delayed treatment, increasing morbidity and mortality. The primary goal of this report is to raise awareness among healthcare professionals and improve patient outcomes for this potentially life-threatening condition. In this case report, we present an octogenarian female, a case of bipolar disorder, current episode manic, who had impaired orientation, delusion of persecution, and altered sleep–wake cycle. She was treated with a combination of mood stabilizer and antipsychotic and discharged after 24 days of admission.

Levetiracetam (LEV), a second-generation antiepileptic, is used as an adjunct therapy in primary generalized tonic–clonic seizures, refractory partial-onset seizures, and seizure prophylaxis after brain surgery. It is well tolerated, effective and has a convenient dosing regimen. As any other drugs, it has some adverse drug effects, including neuropsychiatric adverse effects ranging from agitation and mood symptoms to psychosis and suicide. Strong diagnostics guidelines are yet to be formulated for LEV-induced psychosis; however, complete recovery from psychotic symptoms after stopping LEV supports the possible adverse reaction from Naranjo’s algorithm and, hence, the diagnosis. This case report presents a 16 years boy with focal onset generalized tonic–clonic seizure, whose drug regimen was switched to LEV, following which he had the delusion of persecution, second-person auditory hallucination, and aggressive behavior, which decreased on the 2nd day of cessation of LEV.

The Omicron variant of concern (VOC) replaced the delta variant rapidly and became the predominant strain due to more mutations in spike protein and receptor-binding domain (RBD) enhancing its infectivity and binding affinity. The severity of the illness is less than that of the delta variant. Omicron is nonsusceptible to REGEN-COV™ and bamlanivimab with etesevimab. Drugs that are effective against the Omicron variant are oral antiviral drugs such as Paxlovid (nirmatrelvir/ritonavir), remdesivir, sotrovimab, and molnupiravir. The potency of sotrovimab is reduced to 3-fold against Omicron, and 8-fold reduction in potency with sotrovimab is found in a particular variant of Omicron with a R346K substitution in spike protein. There are neither clinical trials comparing the efficacy of these 4 therapies with each other nor any data on a combination of two or more therapies. The current recommendation for mild-moderate, nonhospitalized patients who are at a high risk of disease progression is to use Paxlovid as the first-line option. If Paxlovid is not available or cannot be administered due to drug interactions, then the next best choice is sotrovimab. The third choice is remdesivir if sotrovimab is also not available and molnupiravir is to be given if the other three options are not available or cannot be administered. For prevention, 2130 (cilgavimab) in combination with COV2-2196 (tixagevimab) has been effective against BA.2 only. LY-CoV1404 (bebtelovimab) is recently authorized as it is effective against all sublineages of the Omicron variant. Regarding vaccine efficacy (VE), the 3-dose VE with mRNA vaccines at 14–60 days was found to be 71.6%, and after 60 days, it is 47.4%. There is a 34–38-fold reduction of neutralizing activity with prebooster sera and a 19-fold reduction with booster sera for the Omicron variant. This probably explains the reason for worldwide breakthrough infections with the Omicron variant with waning immunity. The neutralizing antibody response against Omicron elicited by the bivalent vaccine is superior to that of the ancestral Wuhan strain, without any safety concerns. For future advances, the ribosome display technology can be applied for the generation of human single-chain fragment variable (scFv) antibodies from B cells of recovered patients against Omicron and other Coronavirus variants as they are easier and faster to produce and have high affinity and high specificity.

Toxoplasma gondii is an intracellular protozoan parasite that causes toxoplasmosis in around one-third of the world population, particularly in pregnant women and immunocompromised individuals. Diabetes mellitus (DM) is one of the most severe global health challenges in the 21st century, and especially, type-2 diabetes mellitus (T2DM) accounts for 90% of the diabetes cases diagnosed globally. In Bangladesh, the rate of T2DM is rising gradually with the improvement in living standards. The aim of this study is to find out the correlation between latent toxoplasmosis and T2DM, emphasizing the pro-inflammatory cytokine immunity. For this, 100 (N=100) patients with T2DM and 100 (N=100) healthy controls were enrolled to determine the seroprevalence of toxoplasmosis using enzyme-linked immunosorbent assay (ELISA). In addition, ELISA was also performed to determine the level of pro-inflammatory cytokine, interleukin (IL)-12, to understand its role in the development of toxoplasmosis. In our study, 39.39% of the T2DM patients were positive with anti-T. gondii Immunoglobulin G by ELISA, whereas the rate of seropositivity in healthy controls was 39.73%. We did not find significant association between T. gondii infection and T2DM, but our data confirmed a high prevalence of chronic toxoplasmosis in Bangladeshi population. From hematology tests, it was found that the T2DM patients had significantly lower levels of total white blood cells (P=0.0015), circulating eosinophils (P=0.0026), and neutrophils (P=0.0128) than the healthy controls. On the other hand, the levels of lymphocytes (P=0.0204) and monocytes (P=0.0067) were significantly higher in patients. Furthermore, T. gondii infected T2DM patients had significantly higher levels of IL-12 than the healthy controls (P=0.026), suggesting a link between parasitic infection and IL-12 secretion. Further studies are to be performed to find out the exact cause of high prevalence of chronic T. gondii infection in Bangladeshi population.

Abstract Traditionally, the management of type B aortic dissection has been the domain of the vascular surgeons. Timing and type of intervention still generate debate. We sought to review our early experience with the treatment of this condition based on a hybrid approach following an aortic multi‐disciplinary team meeting involving close cooperation between cardiac surgeons, vascular surgeons, interventional radiologists, vascular anesthetists, and cardiac anesthetists. Four patients (age 41–56 years; 3 males; 1 female) with type B aortic dissection underwent aortic arch surgery through a hybrid approach: one elective procedure consisting of ascending aorta and hemi‐arch replacement with debranching followed by thoracic endovascular aortic repair (TEVAR); one redo procedure requiring aortic arch replacement with hybrid frozen elephant trunk; two acute presentations (aortic arch replacement and debranching followed by TEVAR; AVR with ascending aorta, arch, and proximal descending thoracic aorta replacement with conventional elephant trunk and debranching). Deep hypothermic circulatory arrest was required in three patients. Despite respiratory complications and slightly prolonged postoperative course, all patients survived without onset of stroke, paraplegia, malperfusion, endoleak, or need for re‐exploration. Follow‐up remains satisfactory. Different factors may affect outcome following complex aortic procedures. Nevertheless, close cooperation between cardiac surgeons, vascular surgeons, and interventional radiologists may reduce potential for complications and address aspects that may not be completely within the domain of individual specialists.

Abstract Aims Recent large randomized controlled trials (RCTs) have demonstrated efficacy of sodium‐glucose cotransporter‐2 inhibitors (SGLT2i) in both preventing and treating heart failure (HF). SGLT2i‐induced reversal of left ventricular remodelling has been proposed as a mechanism contributing to this effect. Methods and results We performed a systematic review and meta‐analysis of RCTs to compare SGLT2i versus placebo (treatment duration >3 months) on cardiac remodelling parameters as measured by cardiac magnetic resonance imaging (cMRI) in patients with HF and/or diabetes. The PubMed and ClinicalTrials.gov databases were searched until 15 June 2021. Our primary outcome was change in absolute left ventricular mass (LVM) from baseline to study endpoint. Secondary outcomes included changes in LVM indexed to body surface area, left ventricular end‐systolic volume (LVESV), left ventricular end‐diastolic volume (LVEDV), and left ventricular ejection fraction (LVEF) from baseline to study endpoint. The Cochrane Collaboration's tool was used to assess risk of bias. Five studies representing 408 patients were included. SGLT2i was associated with greater LVM regression compared to placebo (MD, −5.76 g; 95% CI, −10.87 g to −0.64 g, I2 = 73%; overall effect, P

Abstract The incorporation of Si1−xGex nanowire based metal‐semiconductor‐metal (MSM) Schottky biristor allows the conceptualization and realization of low latch‐up and latch‐down voltages with retained latching window. With the aim of investigating the device governing physics and device performance, mathematical simulation is carried out using exhaustive and calibrated 2D Technology computer‐aided design (TCAD) device simulation. The device performance is investigated with respect to channel doping, electrode work function, channel length, temperature and mole fraction (x) to maximize the latching window size and minimize the latch‐up voltage. The detailed sensitivity analysis is also carried for the proposed device with parametric sweep method.

Abstract Background Cancer emergence is associated with a series of cellular transformations that include acquired drug resistance followed by tumor metastasis. Matrix metalloproteinases (MMPs) and Hsp90 chaperone are implicated in tumor progression, however, they are not studied in the context of drug resistance. Aims In the present study, we aimed at understanding the cross‐talk between acquired drug resistance and tumor progression, linking MMP7 and Hsp90. Methods and results We have developed an in vitro model system for acquired drug resistance and studied the correlation between MMP7 and Hsp90. We demonstrate that enhanced drug efflux activity correlates with the induced expression and activity of MMP7, and enhanced metastatic potential of cells, however, in Hsp90‐dependent manner. The MMP7 overexpression alone could enhance the drug efflux activity marginally, and metastasis significantly. However, challenging these cells with 17AAG has significantly increased the drug efflux activity and, in contrast, decreased the metastatic potential. Evaluating our in vitro findings in mice xenografts revealed that MMP7 overexpression facilitates altered homing properties. However, these cells, in response to 17AAG treatment, exhibited increased localized tumor growth but decreased tumor metastasis. Conclusion We demonstrated a cross‐talk between Hsp90 and MMP7 in regulating the acquired drug resistance and tumor progression. Our findings provide novel insights on targeting drug resistant‐tumors.

Abstract The versatile nature of organic conjugated materials renders their flawless integration into a diverse family of optoelectronic devices with light‐harvesting, photodetection, or light‐emitting capabilities. Classes of materials that offer the possibilities of two or more distinct optoelectronic functions are particularly attractive as they enable smart applications while providing the benefits of the ease of fabrication using low‐cost processes. Here, we develop a novel, multi‐purpose conjugated small molecule by combining boron‐azadipyrromethene (aza‐BODIPY) as electron acceptor with triphenylamine (TPA) as end‐capping donor units. The implemented donor–acceptor–donor (D–A–D) configuration, in the form of TPA‐azaBODIPY‐TPA, preserves ideal charge transfer characteristics with appropriate excitation energy levels, with the additional ability to be used as either a charge transporting interlayer or light‐sensing semiconducting layer in optoelectronic devices. To demonstrate its versatility, we first show that TPA‐azaBODIPY‐TPA can act as an excellent hole transport layer in methylammonium lead triiodide (MAPbI3)‐based perovskite solar cells with measured power conversion efficiencies exceeding 17%, outperforming control solar cells with PEDOT:PSS by nearly 60%. Furthermore, the optical bandgap of 1.49 eV is shown to provide significant photodetection in the wavelength range of up to 800 nm where TPA‐azaBODIPY‐TPA functions as donor in near‐infrared organic photodetectors (OPDs) composed of fullerene derivatives. Overall, the established versatility of TPA‐azaBODIPY‐TPA, combined with its robust thermal stability as well as excellent solubility and processability, provides a new guide for developing highly efficient multi‐purpose electronic materials for the next‐generation of smart optoelectronic devices.

Objective This clinical note describes a patient who presented with acute basilar artery occlusion and a persistent primitive proatlantal artery. Case Presentation We present the case of an 82‐year‐old woman who presented with sudden onset of left‐sided weakness. Cross‐sectional imaging revealed occlusion of the basilar artery with a persistent primitive proatlantal artery. She then underwent successful mechanical thrombectomy. Complete reperfusion was achieved; thereafter, she recovered well from the ischemic stroke and was discharged home. Discharge modified Rankin Scale score was