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Background and Aims: Quality of life in patients with active Crohn's disease may be significantly reduced. We evaluated the effects of upadacitinib induction and maintenance therapy on fatigue, quality of life, and work productivity in the phase 3 trials U-EXCEL, U-EXCEED, and U-ENDURE., Methods: Clinical responders to upadacitinib 45 mg in U-EXCEL and U-EXCEED induction trials were re-randomised 1:1:1 to upadacitinib 30 mg, 15 mg, or placebo for 52 weeks of maintenance in U-ENDURE. Clinically meaningful improvements in Inflammatory Bowel Disease Questionnaire [IBDQ] response, IBDQ remission, Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-Fatigue], and Work Productivity and Activity Impairment were evaluated. Percentages of patients achieving clinically meaningful improvements were assessed at induction Weeks 4 and 12 and maintenance Week 52., Clinical Registration Number: U-EXCEED induction trial [NCT03345836], U-EXCEL induction trial [NCT03345849], U-ENDURE maintenance trial [NCT03345823]., Results: Analysis included 1021 and 502 patients assessed at induction and maintenance, respectively. In U-EXCEL, greater improvements [all p ≤ 0.001] in IBDQ response [71.0% vs 50.2%], IBDQ remission [44.2% vs 23.7%], and FACIT-Fatigue [42.0% vs 27.0%] were observed in upadacitinib-treated patients versus placebo at Week 4. Improvements in IBDQ response, IBDQ remission, and FACIT-Fatigue were similar or greater at Week 12. Clinically meaningful improvement in overall work impairment [52.1% vs 38.1%, p ≤ 0.05] was demonstrated at Week 12. Similar results were observed in U-EXCEED. Improvements were sustained through 52 weeks of upadacitinib maintenance treatment., Conclusions: In patients with active Crohn's disease, upadacitinib treatment relative to placebo significantly improved fatigue, quality of life, and work productivity as early as Week 4. These effects were sustained through 52 weeks of maintenance., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Purpose: The aim of this pilot study was to evaluate the knowledge and perception among dental educators regarding the use of relative value units (RVUs) in medicine, perceived benefits in dentistry, and the relative ranking of the components to define RVUs in dentistry., Methods: A convenience sample of dental educators participating in the American Dental Education Association's Leadership Institute (2023-2024) cohort was surveyed for their knowledge and perception regarding RVUs. The responses were stratified based on experience with RVUs prior to statistical analyses (α = 0.05)., Results: Twenty-six dental educators from 18 different North American dental schools and nine different dental specialties participated in this pilot study. Although not significant, a higher proportion of dental educators with prior experience perceived RVUs as a valuable tool in dental practice for assigning chair time, developing payment models, and tracking student-resident progress in a clinical course. There was a lack of consensus among dental educators regarding the components for determining dental procedural RVUs., Conclusion: This pilot study provides limited evidence that prior knowledge of RVUs may be related to its perceived benefits among dental educators, but a broader study design is needed to draw meaningful conclusions and universally acceptable components for determining RVUs in dentistry., (© 2024 American Dental Education Association.)

To look for the spectrum of infections and the factors predisposing to infection in patients with systemic sclerosis (SSc). In this retrospective study, demographic, clinical features, details of infections, immunosuppressive therapy, and outcomes of patients with SSc attending clinics at department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India from 1990 to 2022 were captured. Multivariable-adjusted logistic regression was applied to identify independent predictors of infection. Data of 880 patients, mean age 35.5 ± 12 years, and female: male ratio 7.7:1, were analyzed. One hundred and fifty-three patients had at least 1 infection with a total of 233 infectious episodes. Infections were most common in lung followed by skin and soft tissue. Tuberculosis was diagnosed in 45 patients (29.4%). Klebsiella was the commonest non-tubercular organism in lung and Escherichia coli in urinary tract infections. In comparison to matched control group, patients with infection had a greater number of admissions due to active disease, odds ratio (OR) 6.27 (CI 3.23-12.18), were receiving immunosuppressive medication OR, 5.05 (CI 2.55-10.00), and had more digital ulcers OR, 2.53 (CI 1.17-5.45). Patients who had infection had more likelihood for death OR, 13.63 (CI 4.75 -39.18). Tuberculosis is the commonest infection and lung remains the major site of infection in patients with SSc. Number of hospital admissions, digital ulcers and immunosuppressive therapy are predictors of serious infection in patients with SSc. Patients with infections had more likelihood of death., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Water-soluble ions, inorganic nitrogen, and stable isotopes in precipitation were assessed from the southern (Koshi Tappu and Khandbari) and northern slopes (Lhasa and SET) of the Himalayas to understand the sources, chemistry of regional precipitation, and climatic processes. Water soluble ions showed distinct seasonal variation, with higher concentrations in the non-monsoon. The concentration of ionic species was highest in Koshi Tappu, followed by Lhasa, SET, and Khandbari. The sources were from the terrigenous (Ca 2+ , HCO 3 - ), marine (Na + and Cl - ), anthropogenic (SO 4 2- , NO 3 - , and NH 4 + ), terrigenous and marine (Mg 2+ ), and biomass-burning (K + ). The southern slope, relative to the northern, was more prone to anthropogenic emissions with higher deposition. Among all sites, inorganic nitrogen deposition at Koshi Tappu was higher than the threshold value (10 kg ha -1 y -1 ). The isotopic composition during the study period was higher in non-monsoon, started declining from June, and depleted in July and August compared to other months, i.e., the monsoon mature phase, along the south-to-north transect. The diminished value of stable isotopes in precipitation with increasing altitude underlines the evidence of the orographic effect in isotopic composition. Our study delineated that the higher/lower d-excess value increased with altitude on the southern/northern slope of the Himalayas. The backward trajectory analysis and the National Centers for Environmental Prediction's Final (NCEP FNL) datasets identified that most of the trajectories arrived from warm and humid low-latitude regions during monsoon and westerlies in non-monsoon. Thus, the chemical characteristics and stable isotopic composition of precipitation differed on the southern and northern slopes of the Himalayas by orographic effect and various sources. This study provides new insights into the atmospheric environment and climatic control of stable isotopes in the Himalayan Tibetan Plateau and facilitates monitoring of transboundary air pollution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The interaction of CD40L and its receptor CD40 on activated T cells and B cells respectively control pro-inflammatory activation in the pathophysiology of autoimmunity and transplant rejection. Previous studies have implicated signaling pathways involving CD40L (interchangeably referred to as CD154), as well as adaptive and innate immune cell activation, in the induction of neuroinflammation in neurodegenerative diseases. This study aimed to assess the safety, tolerability, and impact on pro-inflammatory biomarker profiles of an anti CD40L antibody, tegoprubart, in individuals with amyotrophic lateral sclerosis (ALS)., Methods and Findings: In this multicenter dose-escalating open-label Phase 2A study, 54 participants with a diagnosis of ALS received 6 infusions of tegoprubart administered intravenously every 2 weeks. The study was comprised of 4 dose cohorts: 1 mg/kg, 2 mg/kg, 4 mg/kg, and 8 mg/kg. The primary endpoint of the study was safety and tolerability. Exploratory endpoints assessed the pharmacokinetics of tegoprubart as well as anti-drug antibody (ADA) responses, changes in disease progression utilizing the Revised ALS Functional Rating Scale (ALSFRS-R), CD154 target engagement, changes in pro-inflammatory biomarkers, and neurofilament light chain (NFL). Seventy subjects were screened, and 54 subjects were enrolled in the study. Forty-nine of 54 subjects completed the study (90.7%) receiving all 6 infusions of tegoprubart and completing their final follow-up visit. The most common treatment emergent adverse events (TEAEs) overall (>10%) were fatigue (25.9%), falls (22.2%), headaches (20.4%), and muscle spasms (11.1%). Mean tegoprubart plasma concentrations increased proportionally with increasing dose with a half-life of approximately 24 days. ADA titers were low and circulating levels of tegoprubart were as predicted for all cohorts. Tegoprubart demonstrated dose dependent target engagement associated and a reduction in 18 pro-inflammatory biomarkers in circulation., Conclusions: Tegoprubart appeared to be safe and well tolerated in adults with ALS demonstrating dose-dependent reduction in pro-inflammatory chemokines and cytokines associated with ALS. These results warrant further clinical studies with sufficient power and duration to assess clinical outcomes as a potential treatment for adults with ALS., Trial Registration: Clintrials.gov ID:NCT04322149., Competing Interests: SPE is an employee and Director at Eledon Pharmaceuticals. MR has Honorariums: UCB Pharmaceuticals, Argenx Pharmaceuticals, Alexion Pharmaceuticals. And Grant support: UCB Pharmaceuticals, Argenx Pharmaceuticals, Alexion Pharmaceuticals, Catalyst Pharmaceuticals, Cartesian Therapeutics, Inc., Viela Bio,Momenta Pharmaceuticals, Inc, Seelos Therapeutics, Inc., PTC THERAPEUTICS, INC., Amylyx Pharmaceuticals Inc., Healey Center, NMD Pharma, Janssen Research and Development, Apellis Pharma, MedicinNova Inc, Millennium Pharma, Orion Pharma, Biohaven Pharma, Seikagaku Corporation, Mallinckrodt ARD, Inc, Cytokinetics, Inc, Grifols., (Copyright: © 2024 Perrin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Upadacitinib has demonstrated high and rapid rates of efficacy in adolescent and adult patients with moderate-to-severe atopic dermatitis (AD) as assessed by the Eczema Area and Severity Index (EASI). This post hoc analysis assessed the EASI response in four anatomical regions for patients with moderate-to-severe AD treated with upadacitinib compared to dupilumab over 24 weeks., Methods: Data from patients randomised 1:1 to receive upadacitinib 30 mg extended-release tablet orally once daily or dupilumab 300 mg by subcutaneous injection every 2 weeks after a loading dose of 600 mg in the Heads Up study were analysed for achievement of ≥75%, ≥90%, or 100% reduction of EASI in four body regions: 1) head and neck, 2) trunk (including genitals), 3) upper limbs, and 4) lower limbs (including buttocks) at each study visit through week 24. Patient response data from the Head and Neck Patient Global Impression of Severity (HN-PGIS) were also analysed at each study visit for comparison of upadacitinib to dupilumab., Results: Greater proportions of patients treated with upadacitinib versus dupilumab achieved skin clearance rates of ≥75% (EASI 75) at week 1 and higher clearance rates of ≥90% (EASI 90) or 100% (EASI 100) by week 4 or earlier in all four body regions. This difference was maintained at each visit through week 24 for both EASI 90 and EASI 100. Patient responses on the HN-PGIS indicated that a greater proportion of patients (nominal p-value <0.05) treated with upadacitinib compared to dupilumab reported that AD symptoms in the head and neck region were absent or minimal as early as week 1., Conclusion: Compared to dupilumab, upadacitinib treatment provided higher rates of rapid, sustained efficacy for the head and neck, trunk, upper limbs, and lower limbs for the treatment of moderate-to-severe AD as measured by the EASI and supported by patient responses., (The Author(s). Published by S. Karger AG, Basel.)

Background: Global healthcare and nutrition policies have not eliminated the pressing public health issue of undernutrition, which remains a paramount public health concern in countries like India, coinciding with overweight and obesity, in the form of dual burden of malnutrition. Aim: This study delves into the rural-urban differential in undernutrition among reproductive-aged women in India for targeted policy interventions and to achieve universal health coverage. Methods: Data from the recent iteration of the National Family Health Survey (NFHS-5; 2019-21) were utilized to examine the factors influencing rural-urban differentials in women's undernutrition. A set of logistic regression and Fairlie's decomposition analysis are employed to identify the associated covariates and understand the factors driving these differentials. Results: The analysis reveals that rural women are significantly more vulnerable to undernutrition compared to urban counterparts, with factors such as education, wealth status, age, and dietary diversity playing key roles. The decomposition analysis of the rural-urban gap revealed that the variables considered in the study accounted for approximately 75% of the disparity. The difference in household wealth between rural and urban areas contributed about 63% of the explained gap, followed by educational status (16%), age group (11%), dietary diversity (8%), religion (5%), and media exposure (4%). Conclusion: The findings underscore the importance of targeted interventions addressing socio-economic inequalities to mitigate undernutrition among women in India. Enhancing access to education, improving economic opportunities, promoting dietary diversity, and challenging cultural norms are crucial steps towards achieving equitable nutritional outcomes and reducing the existing rural-urban disparity., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

To systematically identify radiomics features on CT enterography (CTE) scans which can accurately diagnose active Crohn's disease across multiple sources of variation. Retrospective study of CTE scans curated between 2013 and 2015, comprising 164 subjects (65 male, 99 female; all patients were over the age of 18) with endoscopic confirmation for the presence or absence of active Crohn's disease. All patients had three distinct sets of scans available (full and reduced dose, where the latter had been reconstructed via two different methods), acquired on a single scanner at a single institution. Radiomics descriptors from annotated terminal ileum regions were individually and systematically evaluated for resilience to different imaging variations (changes in dose/reconstruction, batch effects, and simulated annotation differences) via multiple reproducibility measures. Multiple radiomics models (by accounting for each source of variation) were evaluated in terms of classifier area under the ROC curve (AUC) for identifying patients with active Crohn's disease, across separate discovery and hold-out validation cohorts. Radiomics descriptors selected based on resiliency to multiple sources of imaging variation yielded the highest overall classification performance in the discovery cohort (AUC = 0.79 ± 0.04) which also best generalized in hold-out validation (AUC = 0.81). Performance was maintained across multiple doses and reconstructions while also being significantly better (p < 0.001) than non-resilient descriptors or descriptors only resilient to a single source of variation. Radiomics features can accurately diagnose active Crohn's disease on CTE scans across multiple sources of imaging variation via systematic analysis of reproducibility measures. Clinical utility and translatability of radiomics features for diagnosis and characterization of Crohn's disease on CTE scans will be contingent on their reproducibility across multiple types and sources of imaging variation., (© 2024. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

Exposure to polycyclic aromatic hydrocarbons (PAHs) in polluted air influences the composition of the skin microbiome, which in turn is associated with altered skin phenotypes. However, the interactions between PAH exposure and viromes are unclear. This study aims to elucidate how PAH exposure affects the composition and function of skin viruses, their role in shaping the metabolism of bacterial hosts, and the subsequent effects on skin phenotype. We analyzed metagenomes from cheek skin swabs collected from 124 Chinese women in our previous study and found that the viruses associated with the two microbiome cutotypes had distinct diversities, compositions, functions, and lifestyles following PAH exposure. Moreover, exposure to high concentrations of PAHs substantially increased interactions between viruses and certain biodegrading bacteria. Under high-PAH exposure, the viruses were enriched in xenobiotic degradation functions, and there was evidence suggesting that the insertion of bacteriophage-encoded auxiliary metabolic genes into hosts aids biodegradation. Under low-PAH exposure conditions, the interactions followed the "Piggyback-the-Winner" model, with Cutibacterium acnes being "winners," whereas under high-PAH exposure, they followed the "Piggyback-the-Persistent" model, with biodegradation bacteria being "persistent." These findings highlight the impact of air pollutants on skin bacteria and viruses, their interactions, and their modulation of skin health. Understanding these intricate relationships could provide insights for developing targeted strategies to maintain skin health in polluted environments, emphasizing the importance of mitigating pollutant exposure and harnessing the potential of viruses to help counteract the adverse effects., (© The Author(s) [2024]. Published by Oxford University Press on behalf of the International Society for Microbial Ecology.)

Herein, we report a supersensitive and specific detection of Salmonella employing nanocatalysis of silver nanoparticle (AgNp). A nanobioprobe was developed employing specific antibody (Ab) that binds to a peptide present in transmembrane protein of Salmonella. We have studied 7 surface-exposed peptide hits from conserved virulence proteins (PagC, ST50, PagN, CdtB and FliC). These peptides were experimentally evaluated by BLI (Bio layer interferometry) for their reactivity towards antisera raised against an admix of major Salmonella serogroups. The most promising peptide was used to generate Ab with binding affinity Kd of 5.6 × 10 -9  M. The Ab exhibited high specificity towards entire Salmonella serotypes prevalent in foods, as illustrated by FACS (Fluorescence-activated cell sorting) study. The Ab-AgNp probe was blocked with a dual layer to prevent non-specific interactions, confirmed by employing BLI and TEM (Transmission electron microscopy). For the electrochemical detection, the autonanocatalysis of AgNp in presence of H 2 O 2 was used to generate numerous Ag +  resulting in an amplified signal that could detect 10 cells/mL. The relative standard deviation (RSD) was observed to be 4.5%. The platform achieved recovery of 100-112% calculated for 10 2  cells/mL. The performance was validated in milk, buffer peptone water (BPW) and tap water by spiking studies. The study highlights the effectiveness of efficiently blocked AgNp-mediated probes for the highly selective and sensitive detection of Salmonella, representing a significant advancement in bacterial sensing., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Iloperidone, a second-generation USFDA approved antipsychotic and BCS class II drug shows poor oral bioavailability of 28%. The present research deals with optimization of transnasal nanoemulsions of Iloperidone using Design Expert (Version 11) and further surface functionalization with chitosan for potentiating nose to brain delivery. Chitosan functionalized transnasal Iloperidone nanoemulsions were developed using oleic acid, charge inducer, Tween 80, Transcutol HP and chitosan using ultrasonication technique and evaluated. Droplet size, polydispersity index and zeta potential of Iloperidone nanoemulsions was found to be 173 ± 0.5 nm, 0.413 ± 0.2 and - 22.5 ± 0.1 mV while that of chitosan functionalized Iloperidone nanoemulsions was 146.4 ± 0.5 nm, 0.291 ± 0.02 and + 23.6 ± 0.3 mV respectively. Ninhydrin assay, TEM and FTIR studies confirmed surface functionalization of Iloperidone nanoemulsion droplets with chitosan. In vitro release of Iloperidone from nanoemulsions and chitosan functionalized nanoemulsions was 90.41 ± 2.1% and 72.02 ± 0.21% while ex vivo permeation of Iloperidone across goat nasal mucosa was 1270.58 ± 0.023 μg/cm 2 and 1096.13 ± 0.043 μg/cm 2 respectively at the end of 8 h. Studies in RPMI 2650 nasal and Neuro2A brain cell line lines indicated safety of chitosan functionalized transnasal Iloperidone nanoemulsions. Studies in Wistar rats showed increased cataleptic effects, reduced cognitive impairment and anxiety-related behaviour with greater brain accumulation indicating promising potential of this approach in nose to brain drug delivery., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Background: High-risk strains of HPV are known to cause cervical cancer. Multiple clinical studies have emphasized that smoking and drinking are critical risk factors for cervical cancer and its high-grade precursors. In this study, we investigated if smoking and/or drinking augment the molecular mechanisms of cervical carcinogenesis and defined a potential therapeutic approach for their attenuation., Methods: The impact of benzo[a]pyrene (B[a]P) and/or ethanol (EtOH) exposure on cervical cancer cells was assessed by measuring changes in their cell migration and invasion characteristics. Expression of HPV16 E6/E7, NF-κB, cytokines, and inflammation mediators was determined using qRT-PCR, immunoblotting, ELISA, luciferase reporter assay, and confocal microscopy. Herein, we used curcumin (Cur), and PLGA nanoparticle formulation of curcumin (PLGA-Cur) and determined effectiveness of free Cur and PLGA-Cur formulation on smoking and drinking activated NF-κB/IL-6 mediated inflammatory signaling pathways using in vitro cervical cancer models., Results: Treatments with B[a]P and/or EtOH altered the expression of HPV16 E6/E7 oncogenes and EMT markers in cervical cancer cells; it also enhanced migration and invasion. In addition, B[a]P and/or EtOH exposure promoted inflammation pathways through TNF-α and NF-κB signaling, leading to IL-6 upregulation and activation of VEGF. The molecular effects caused by B[a]P and/or EtOH exposure were effectively attenuated by curcumin (Cur)/PLGA-Cur treatment., Conclusions: These data suggest a molecular link between smoking, drinking, and HPV infectivity in cervical carcinogenesis. In addition, attenuation of these effects by treatment with Cur/PLGA-Cur treatment, implies the role of curcumin in cervical cancer prevention and treatment., (© 2024. The Author(s).)

Background: Incorporating brentuximab vedotin into the treatment of advanced-stage classic Hodgkin's lymphoma improves outcomes in adult and pediatric patients. However, brentuximab vedotin increases the toxic effects of treatment in adults, more than half of pediatric patients who receive the drug undergo consolidative radiation, and relapse remains a challenge. Programmed death 1 blockade is effective in Hodgkin's lymphoma, including in preliminary studies involving previously untreated patients., Methods: We conducted a phase 3, multicenter, open-label, randomized trial involving patients at least 12 years of age with stage III or IV newly diagnosed Hodgkin's lymphoma. Patients were randomly assigned to receive brentuximab vedotin with doxorubicin, vinblastine, and dacarbazine (BV+AVD) or nivolumab with doxorubicin, vinblastine, and dacarbazine (N+AVD). Prespecified patients could receive radiation therapy directed to residual metabolically active lesions. The primary end point was progression-free survival, defined as the time from randomization to the first observation of progressive disease or death from any cause., Results: Of 994 patients who underwent randomization, 970 were included in the intention-to-treat population for efficacy analyses. At the second planned interim analysis, with a median follow-up of 12.1 months, the threshold for efficacy was crossed, indicating that N+AVD significantly improved progression-free survival as compared with BV+AVD (hazard ratio for disease progression or death, 0.48; 99% confidence interval [CI], 0.27 to 0.87; two-sided P = 0.001). Owing to the short follow-up time, we repeated the analysis with longer follow-up; with a median follow-up of 2.1 years (range, 0 to 4.2 years), the 2-year progression-free survival was 92% (95% CI, 89 to 94) with N+AVD, as compared with 83% (95% CI, 79 to 86) with BV+AVD (hazard ratio for disease progression or death, 0.45; 95% CI, 0.30 to 0.65). Overall, 7 patients received radiation therapy. Immune-related adverse events were infrequent with nivolumab; brentuximab vedotin was associated with more treatment discontinuation., Conclusions: N+AVD resulted in longer progression-free survival than BV+AVD in adolescents and adults with stage III or IV advanced-stage classic Hodgkin's lymphoma and had a better side-effect profile. (Funded by the National Cancer Institute of the National Institutes of Health and others; S1826 ClinicalTrials.gov number, NCT03907488.)., (Copyright © 2024 Massachusetts Medical Society.)

Background/objectives: The aim of this study was to estimate the effect of a 6 months' treatment course of the innate immune modulator NP001 (a pH-adjusted intravenous formulation of purified sodium chlorite), on disease progression, as measured by overall survival (OS) in patients with amyotrophic lateral sclerosis., Methods: Blinded survival data were retrospectively collected for 268 of the 273 patients who had participated in two phase 2 placebo-controlled clinical trials of NP001 (ClinicalTrials.gov: NCT01281631 and NCT02794857) and received at least one dose of either 1 mg/kg or 2 mg/kg of NP001 as chlorite based on actual body weight, or placebo. Kaplan-Meier methods were used on the intent-to-treat population to estimate survival probabilities., Results: In the overall population, the median OS was 4.8 months (2.7 years [95% CI: 2.3, 3.5] in the 2 mg/kg NP001group and 2.3 years [95% CI: 1.8, 2.9] in the placebo group). Hazard ratio (HR): 0.77 (95% CI: 0.57, 1.03), p = 0.073. Among patients aged ≤ 65 years, the median OS for the 2 mg/kg NP001 group was 10.8 months (3.3 years [95% CI: 2.4, 3.8] in the 2 mg/kg NP001 group and 2.4 years [95% CI: 1.7, 3.3] in the placebo group). HR: 0.69 (95% CI: 0.50, 0.95). No differences were observed in the 1 mg/kg NP001 group or in patients aged > 65 years., Conclusions: The findings from this study suggest that a 6 months' treatment course of NP001 resulted in a 4.8-month increase in overall survival in patients with ALS. The findings from this study indicate that targeting inflammation associated with the innate immune system may provide a pathway for new therapeutic options for the treatment of ALS.

Background and Aims: Non-invasive cross-sectional imaging via magnetic resonance enterography [MRE] offers excellent accuracy for the diagnosis of stricturing complications in Crohn's disease [CD] but is limited in determining the degrees of fibrosis and inflammation within a stricture. We developed and validated a radiomics-based machine-learning model for separately characterizing the degree of histopathological inflammation and fibrosis in CD strictures and compared it to centrally read visual radiologist scoring of MRE., Methods: This single-centre, cross-sectional study included 51 CD patients [n = 34 for discovery; n = 17 for validation] with terminal ileal strictures confirmed on diagnostic MRE within 15 weeks of resection. Histopathological specimens were scored for inflammation and fibrosis and spatially linked with corresponding pre-surgical MRE sequences. Annotated stricture regions on MRE were scored visually by radiologists as well as underwent 3D radiomics-based machine learning analysis; both were evaluated against histopathology., Results: Two distinct sets of radiomic features capturing textural heterogeneity within strictures were linked with each of severe inflammation or severe fibrosis across both the discovery (area under the curve [AUC = 0.69, 0.83] and validation [AUC = 0.67, 0.78] cohorts. Radiologist visual scoring had an AUC = 0.67 for identifying severe inflammation and AUC = 0.35 for severe fibrosis. Use of combined radiomics and radiologist scoring robustly augmented identification of severe inflammation [AUC = 0.79] and modestly improved assessment of severe fibrosis [AUC = 0.79 for severe fibrosis] over individual approaches., Conclusions: Radiomic features of CD strictures on MRE can accurately identify severe histopathological inflammation and severe histopathological fibrosis, as well as augment performance of the radiologist visual scoring in stricture characterization., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Bacteria have two trophic lifestyles in aquatic ecosystems, i.e., free-living (FL) and particle-attached (PA), with different but essential ecological roles. However, relevant knowledge is still dearth in the upstream source region of the Himalayan Rivers. Thus, we emphasized a comparative study on community composition, co-occurrence, and geographic distribution of the FL and PA bacteria and the effect of environmental factors in the source region of the Ganges and Brahmaputra Rivers. PA bacteria relative to FL harbored a significantly higher local diversity, richness, and evenness. A significantly higher abundance of Betaproteobacteria, Verrucomicrobiota, and Planctomycetota in PA trophic lifestyle and Gammaproteobacteria and Actinomycetota in FL tropic lifestyle and indicator OTUs belonging to related taxa were observed. The spatial variation of the FL and PA bacterial communities was most significantly impacted by dispersal limitation as a discrete factor. Among the environmental parameters, the total nitrogen (TN) was found to be a significant (P < 0.001) driver of the variation in PA communities. Meanwhile, particulate organic carbon (POC) and TN considerably explained the variation of FL communities. A significant correlation (P < 0.001) of TN with dominant bacterial taxa (Pseudomonadota, Actinomycetota, and Verrucomicrobiota) and FL and PA indicator OTUs associated with these taxa further confirmed nitrogen as the limiting nutrient in the source region of the Ganges and Brahmaputra Rivers. The co-occurrence network topological characteristics showed that the PA network was more stable than the FL network, which was more complicated and unstable. Thus, it can be speculated that FL communities relative to PA are more vulnerable to shifting upon disturbances., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Polyglutamine (PolyQ) diseases including Huntington's disease are devastating neurodegenerative disorders characterized by progressive neuronal loss and motor dysfunction. PolyQ pathology involves multiple cellular events and phytochemicals with multi-target mechanisms hold promise to treat these diseases with least side effects. One such promising phytochemical is Eugenol, which possesses antioxidant and anti-inflammatory properties, potentially targeting disrupted cellular pathways in PolyQ diseases. The present study investigated the effects of Eugenol on neurodegeneration and motor dysfunction in transgenic Drosophila models of PolyQ diseases. In this study, the robust pseudopupil assay was performed to analyze adult photoreceptor neuron degeneration, a marker of widespread degenerative events. Furthermore, the well-established crawling and climbing assays were conducted to evaluate progressive motor dysfunction in the PolyQ larvae and flies. This study found that Eugenol administration at disease onset or after progression reduced PolyQ disease phenotypes, particularly, neurodegeneration and motor dysfunction in a dose-dependent manner and with no side effects. Thus, this study suggests that Eugenol could be a viable candidate for developing treatments for PolyQ diseases, offering a multi-target approach with the potential for minimal or no side effects compared to conventional therapies., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Aim: To identify incidence, type of drug abuse study clinical and angiographic profile in very young population presenting with acute coronary syndrome (ACS)., Materials and Methods: All consecutive patients less than 30 years with ACS included and segregated into Group 1 and 2 (with and without drug abuse respectively) RESULT: n = 153; n = 17 in group 1 of whom 35.29 % consumed opium, 17.64 % energy drinks, 17.64 % whey protein supplements, 17.64 % inhaled marijuana, 5.88 % heroin and spasmoproxyvon and 23.52 % multi-substance abusers. STEMI, Single vessel disease and urban domicile were predominant. Rising trends of drug abuse were identified in prospective (28.20 %) versus retrospective (5.30 %) timeframe (p = 0.011)., Conclusion: Rising trends of drug abuse, a potentially modifiable risk factor of ACS in the young are alarming. Strict regulations are needed to curb this menace., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr Shibba Chhabra reports was provided by Dayanand Medical College and Hospital. NONE., (Copyright © 2024 Cardiological Society of India. Published by Elsevier, a division of RELX India, Pvt. Ltd. All rights reserved.)

Nuclear receptors are multidomain transcription factors whose full-length quaternary architecture is poorly described and understood. Most nuclear receptors bind DNA as heterodimers or homodimers, which could encompass a variety of arrangements of the individual domains. Only a handful of experimental structures currently exist describing these architectures. Given that domain interactions and protein-DNA interactions within transcriptional complexes are tightly linked to function, understanding the arrangement of nuclear receptor domains on DNA is of utmost importance. Here, we employ modeling and molecular dynamics (MD) simulations to describe the structure of the full-length farnesoid X receptor (FXR) and retinoid X receptor alpha (RXR) heterodimer bound to DNA. Combining over 100 microseconds of atomistic MD simulations with enhanced sampling simulations, we characterize the dynamic behavior of eight FXR-RXR-DNA complexes, showing that these complexes support a range of quaternary architectures. Our simulations reveal critical roles for the hinge in the DNA-bound dimer in facilitating interdomain allostery, mediating DNA binding and driving the dynamic flexibility of the complex. These roles have been hard to appreciate previously due to experimental limitations in studying the flexible hinge. These studies provide a much-needed framework that will enable the field to obtain a complete understanding of nuclear receptor quaternary architectures.

Background: Emerging clinical and epidemiological data indicates that human immunodeficiency virus (HIV) is associated with an increased risk of stroke and aggravated brain damage. We aimed to develop a reproducible murine model of photothrombotic-stroke with HIV infection that mimics the clinical situation., Method: To evaluate the impact of HIV infection on stroke, male C57BL/6 mice were infected with EcoHIV (p24 2-4 × 10 6 /mouse; i.v.) or mock control. Four weeks post-infection, a stroke was induced by the photothrombotic method (pt-MCAO). After 72 h, a catwalk test was performed for gait impairments, and mice were euthanized for stroke outcomes., Results: EcoHIV-infection exhibited a larger infarction, brain edema, higher IgG extravasation, hemorrhagic transformation, and gait impairments following pt-MCAO vs mock control. EcoHIV-infected mice showed higher levels of IFN-y and lower levels of IL-6, indicating immune activation without affecting IL-1β and MCP-1 in plasma and brain compared to mock pt-MCAO, suggesting unaltered inflammation. EcoHIV-infection showed increased oxidative stress markers (nitrotyrosine, and 4-hydroxynonenal) and thioredoxin interacting protein expression. Further, EcoHIV-infection significantly activated the microglia and astrocyte cells., Conclusions: This animal model would be reliable and clinically relevant to future studies investigating pathophysiological mechanisms and developing new therapeutic approaches in stroke patients with HIV conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Dental treatment is challenging for children experiencing pain and anxiety. Effective administration of local anesthesia (LA) is crucial for most pediatric dentistry treatments. Eye Movement Desensitization and Reprocessing (EMDR) therapy has emerged primarily to manage post-traumatic stress disorder (PTSD) and a wide variety of anxiety- and pain-related conditions. However, the use of this therapy to manage pain in pediatric dentistry has not yet been reported. This study aimed to assess the trends in pain in pediatric dental patients with and without EMDR therapy during LA and extraction. The need for analgesic consumption within 24 h post extraction and the overall dental experience were also evaluated., Methods: Sixty children aged 8-12 years participated in a randomized controlled clinical trial with the goal of extracting the primary mandibular first or second molar on the right or left side and were stratified into: group I: EMDR therapy; group II: Tender Love and Care. Pain was measured at three different time intervals. An unpaired t-test was performed for intergroup comparison of continuous data, and the repeated measures ANOVA was applied for intergroup comparison between the groups., Results: Pain was significantly lower in group I (pain after topical LA gel application, P = 0.229; pain after LA administration, P = 0.036; pain after extraction, P < 0.001). The need for analgesic consumption was lower in this group (P = 0.072), and the overall dental experience was rated better (P < 0.0001)., Conclusion: Research has shown that EMDR therapy effectively reduces pain in children, making it a recommended practice for pediatric dentists trained in this technique., Competing Interests: CONFLICT OF INTEREST: The authors declare no conflicts of interest., (Copyright © 2024 Journal of Dental Anesthesia and Pain Medicine.)

A pandemic of acute respiratory infection, which was specified as coronavirus disease 2019, was instigated by a different strain of the virulent coronavirus SARS-CoV-2 that first appeared in late 2019. Since viral infections spread fast and there is presently no effective treatment, the use of plants with a long history of use in treating these infections has been explored regularly. The pandemic of coronavirus disease 2019 (COVID-19) has brought to light the dearth of medications with approval to treat acute viral illnesses. Because of this, the illness had a high fatality rate. The mortality rate was initially quite high and varied according to the patient's geographic location. For instance, among Chinese patients, the rate was 3·6%, whereas 1·5% of COVID-19-related deaths were documented outside of China. As of 2020, India has a 1.4% case fatality rate (CFR) of COVID-19 mortality, compared to 2.8% in Brazil and 1.8% in the USA. Many studies are being conducted to create pharmaceutical compounds specifically targeting important SARS-CoV-2 proteins. Several drug discovery initiatives are being undertaken to find powerful inhibitors by combining biochemical assay and computer-aided drug design techniques. Although plant-derived compounds have not had much success in the dominion of antivirals, plants are, however, believed to be a limitless supply of medications for a variety of diseases and clinical conditions. The scientific foundation required for developing novel natural source medications is provided by the chemical characterization and analysis of plant components. Most viral infections treated by ethnobotanical applications and historical literature on ayurveda, and traditional medicine are generally attributed to phytochemicals, which are compounds derived from medicinal plants. In this review, we have described the application of vascular plant-derived chemicals, such as tannins, polyphenols, alkaloids, and flavonoids, as antivirals, especially for managing COVID-19. This article discusses novel bioactive compounds and their molecular structures that target the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as prospective candidates for anti-coronavirus disease drugs. Moreover, to confirm the effectiveness of the phytochemicals that have demonstrated antiviral activity, clinical trials would need to be conducted in addition to the preclinical research that has already been done. To ensure spectacular findings, more applications of the compound would need to be studied to fully understand the effects of those phytochemicals whose clinical usefulness has already been established., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Thermochemical treatment is rapidly emerging as an alternative method for the management of stabilised sewage sludges (biosolids) to effectively reduce waste volume, degrade contaminants, and generate valuable products, particularly biochar and hydrochar. Biosolids-derived char has a relatively high concentration of heavy metals compared with agricultural chars but is still applied to land due to its beneficial properties and ability to retain metals. However, non-agricultural applications can provide additional economic and environmental benefits, promote sustainability and support a circular economy. This review identifies extensive non-agricultural opportunity for biosolids biochar, including adsorption, catalysis, energy storage systems, biological process enhancement, and as additives for rubber compounding and construction. Biosolids chars have received limited attention vs agricultural char, and we draw on both areas of literature, as well as evaluating differences between agricultural and biosolids chars. A key opportunity for biosolids biochar in comparison with other materials and agricultural chars is its sustainable and low-cost nature, relatively high metals content, improving catalyst properties, and ability to modify in various stages to tune it to specific applications. The specific opportunities for hydrochar have only received limited attention. Research needs to include better understanding of the benefits and limitations for specific applications, as well as adjacent drivers, including society, regulation, and market and economics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To evaluate the potency and efficacy of a library of dopamine receptor D2 (D2R) antagonists in the mitigation of fibrotic activation in retinal pigment epithelial (RPE) cells. Methods: ARPE-19 cells were cultured and treated with methotrexate or 27 district D2R antagonists using a fibronectin deposition assay. The most potent compounds were then further assessed in assays measuring cellular proliferation, cellular migration, and profibrotic gene expression. Results: The previously established antifibrotic D2R antagonist loxapine exerted a robust and dose-dependent inhibition of fibronectin deposition, whereas methotrexate exerted minimal inhibition. The most potent D2R antagonist identified, fluphenazine, effectively blocked in vitro models of fibrosis at 300-1,000 nM concentrations. Conclusions: Here we found multiple FDA-approved D2R antagonists that potently block RPE cell fibrogenesis. These findings further support the potential of D2R antagonism as a potential therapeutic for retinal fibrotic disease.

Wastewater is a geospatially- and temporally-linked microbial fingerprint of a given population, making it a potentially valuable tool for tracking public health across locales and time. Here, we integrate targeted and bulk RNA sequencing (N = 2238 samples) to track the viral, bacterial, and functional content over geospatially distinct areas within Miami Dade County, USA, from 2020-2022. We used targeted amplicon sequencing to track diverse SARS-CoV-2 variants across space and time, and we found a tight correspondence with positive PCR tests from University students and Miami-Dade hospital patients. Additionally, in bulk metatranscriptomic data, we demonstrate that the bacterial content of different wastewater sampling locations serving small population sizes can be used to detect putative, host-derived microorganisms that themselves have known associations with human health and diet. We also detect multiple enteric pathogens (e.g., Norovirus) and characterize viral diversity across sites. Moreover, we observed an enrichment of antimicrobial resistance genes (ARGs) in hospital wastewater; antibiotic-specific ARGs correlated to total prescriptions of those same antibiotics (e.g Ampicillin, Gentamicin). Overall, this effort lays the groundwork for systematic characterization of wastewater that can potentially influence public health decision-making., (© 2024. The Author(s).)

Nuclear receptors are ligand-induced transcription factors that bind directly to target genes and regulate their expression. Ligand binding initiates conformational changes that propagate to other domains, allosterically regulating their activity. The nature of this interdomain communication in nuclear receptors is poorly understood, largely owing to the difficulty of experimentally characterizing full-length structures. We have applied computational modeling approaches to describe and study the structure of the full-length farnesoid X receptor (FXR), approximated by the DNA binding domain (DBD) and ligand binding domain (LBD) connected by the flexible hinge region. Using extended molecular dynamics simulations (>10 microseconds) and enhanced sampling simulations, we provide evidence that ligands selectively induce domain rearrangement, leading to interdomain contact. We use protein-protein interaction assays to provide experimental evidence of these interactions, identifying a critical role of the hinge in mediating interdomain contact. Our results illuminate previously unknown aspects of interdomain communication in FXR and provide a framework to enable characterization of other full-length nuclear receptors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Cannabis, also known as marijuana or hemp, has been utilized since ancient times for industrial, religious, recreational, and medical uses. However, regardless of the intended use, there are legal requirements for quantitative testing of cannabinoids across the supply chains. This investigation aimed to evaluate the genetic diversity of 54 Cannabis samples collected from tropical and subtropical regions in India. The research found a high genotypic coefficient of variation (GCV), phenotypic coefficient of variation (PCV), heritability, and genetic advance for total cannabidiol (CBD) content. The genotypic and phenotypic correlation among the morpho-chemical characters revealed strong positive correlations among most characters. Clustering and Principal component analysis identified three accessions in cluster II (CIM-CS-65, CIM-CS-189 & CIM-CS-64) with high CBD content that could be used for breeding and as sources of high CBD content in Cannabis. CIM-CS-64, with its high CBD content with 0.01%THC content, holds potential as a valuable parental line for utilization in hybridization programs and recombinant breeding. Furthermore, in accordance with the NDPC Act of 1985, CIM-CS-64 can be commercialized for medicinal purposes, making it a promising source for the development of medicinal CBD products., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Tobacco use is markedly prevalent among individuals with schizophrenia, presenting significant challenges to their physical health and psychiatric treatment. This comprehensive review evaluates the impact of motivational enhancement therapy (MET) on tobacco cessation in this population. Schizophrenia, a chronic mental disorder characterized by symptoms such as delusions and hallucinations, is frequently accompanied by high rates of smoking, which exacerbates health risks and complicates treatment regimens. MET, a client-centered approach rooted in motivational interviewing, aims to enhance intrinsic motivation for behavior change through empathetic and non-confrontational therapeutic sessions. This review synthesizes evidence from clinical studies on MET's effectiveness in promoting smoking cessation among individuals with schizophrenia. The review highlights the therapy's strengths, including its adaptability and client-focused nature, which are particularly beneficial for addressing the unique challenges faced by this population. It also discusses the broader health benefits of smoking cessation, such as improved physical health and enhanced efficacy of psychiatric medications. Despite promising results, the review identifies limitations and challenges in applying MET, such as potential barriers to implementation and the need for further research. In conclusion, MET offers a valuable intervention for tobacco cessation in individuals with schizophrenia, with the potential to significantly improve health outcomes and quality of life. Future research should focus on optimizing MET strategies and exploring their broader impacts on this vulnerable population., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, . et al.)

Nightmares are distressing dreams that evoke strong negative emotions, such as fear or anxiety, often leading to waking from sleep and subsequent sleep disruption. They are prevalent across various age groups, with significant psychological and physiological health implications. This review explores the nature of nightmares, distinguishing them from other sleep disturbances like night terrors and sleep paralysis. It examines the prevalence of nightmares in children and adults, highlighting their impact on mental health and daily functioning. The review also emphasizes the importance of addressing nightmares through effective treatment strategies. While pharmacological options are available, psychosocial interventions offer promising non-pharmacological solutions. Cognitive behavioral therapy (CBT), imagery rehearsal therapy (IRT), and mindfulness-based therapies are discussed as key approaches for managing nightmares. These strategies focus on altering maladaptive thought patterns and emotional responses, reducing nightmares' frequency and intensity, and improving overall sleep quality. Psychosocial interventions provide a comprehensive approach to treating nightmares by addressing the underlying cognitive and emotional factors, benefitting individuals across different age groups. This review aims to highlight the efficacy of these strategies and their role in enhancing the quality of life for those affected by persistent nightmares., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Sahu et al.)

Post-transcriptional regulation has emerged as a key mechanism for regulating stem cell renewal and differentiation, which is essential for understanding tissue regeneration and homeostasis. Poly(A)-binding proteins are a family of RNA-binding proteins that play a vital role in post-transcriptional regulation by controlling mRNA stability and protein synthesis. The involvement of poly(A) binding proteins in a wide range of cellular functions is increasingly being investigated. In this study, we used the regenerative model planarian organism Schmidtea mediterranea to demonstrate the critical role of poly(A)-binding protein 2 (PABP2) in regulating neoblast maintenance and differentiation. A deficit in PABP2 blocks the transition of neoblasts toward immediate early progenitors, leading to an enhanced pool of non-committed neoblasts and a decreased progenitor population. This is reflected in variations in the transcriptome profile, providing evidence of downregulation in multiple lineages. Thus, an insufficiency of PABP2 resulted in defective formation and organization of tissue, leading to abnormal regeneration. Our study reveals the essential role of PABP2 in regulating genes that mediate stem cell commitment to early progenitors during tissue regeneration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mukundan, Hariharan, Sasidharan, Lakshmanan, Palakodeti and Jamora.)

Background Babies born between 37 weeks +0 days and 38 weeks +6 days by scheduled caesarean delivery before the onset of labour are more prone to developing respiratory complications than babies delivered between 39 weeks +0 days and 40 weeks +0 days. Antenatal corticosteroids have been used in preterm births for lung maturity. The advantages of administering antenatal corticosteroids before a scheduled caesarean delivery in the early term remain a subject of debate. While some studies have reported benefits, including a reduction in respiratory issues, the evidence is still inconclusive. The study's main objective is to compare the efficacy and safety of intramuscular dexamethasone and betamethasone phosphate with standard treatment protocols in early-term infants. Methodology A total of 241 pregnant women scheduled for caesarean delivery were screened for eligibility to participate in the study. Out of these, 192 women met the inclusion criteria and were enrolled in the study after providing written informed consent; they were randomised into three groups, with 64 in each group, and were given either betamethasone phosphate or dexamethasone intramuscularly or were considered under standard management protocol (no administration of corticosteroids). The primary comparison was done to observe the development of respiratory distress syndrome, transient tachypnoea in newborns, and the need for neonatal intensive care unit (NICU) admission. Results Among 192 pregnant females observed, the incidence of development of respiratory distress syndrome did not differ significantly between the betamethasone, dexamethasone, and standard management groups, with rates of 6.25%, 7.81%, and 4.7%, respectively. Additionally, out of the 192 infants, 15 required neonatal intensive care, including 6 (9.4%) from the betamethasone group, 5 (7.8%) from the dexamethasone group, and 4 (6.3%) from the standard management group. All of these infants had a maximum stay of four days in the NICU, did not require mechanical support, and improved with oxygen therapy. Conclusion In our study, in early-term gestation, both the corticosteroid groups showed similar effects to those of the standard management group in reducing neonatal morbidity, with no significant statistical difference. Hence, the choice lies with the treating obstetrician to consider the administration of corticosteroids in early-term caesarean deliveries., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Ethics Committee BLDE (Deemed to be University) issued approval BLDE(DU)/IEC/766/2022-23. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Gupta et al.)

The need for ending plastic waste and creating a circular economy has prompted significant interest in developing a new family of composite materials through recycling and recovery of waste resources (including bio-sourced materials). In this work, a family of natural fiber-reinforced plastic composites has been developed from paint pail waste recycled polypropylene (rPP) and waste wool fibers of different diameter and aspect ratio. Composites were fabricated by melt processing using polypropylene-graft-maleic anhydride as a compatibilizer. The internal morphology, interfacial and thermal characteristics, viscoelastic behavior, water sorption/wettability, and mechanical properties of composites were studied using electron microscopy, high-resolution synchrotron Fourier transform infrared microspectroscopy, thermal analysis, rheology, immersion test, contact angle measurement, tensile test and flexural test. The composite matrix exhibited an internal morphology of coalescent micro-droplets due to the presence of polyethylene and dry paint in the rPP phase. In general, the rheological and mechanical properties of the composites comprising higher-aspect-ratio (lower diameter) fibers exhibited relatively superior performance. About an 18% increase in tensile strength and a 39% increase in flexural strength were measured for composites with an optimal fiber loading of 10 wt.%. Interfacial debonding and fiber pull-out were observed as the main failure mechanism of the composites. The developed composites have potential for applications in automotive, decking, and building industries.

Targeted and efficient gene delivery systems hold tremendous potential for the improvement of cancer therapy by enabling appropriate modification of biological processes. Herein, we report the design and synthesis of a novel cationic di-block copolypeptide, incorporating homoarginine (HAG) and shikimoyl (LSA) functionalities (HDA-b-PHAGm-b-PLSAn), tailored for enhanced gene transfection specifically in cancer cells. The di-block copolypeptide was synthesized via sequential N -carboxyanhydride (NCA) ring-opening polymerization (ROP) techniques and its physicochemical properties were characterized, including molecular weight, dispersity, secondary conformation, size, morphology, and surface charge. In contrast to the cationic poly-L-homoarginine, we observed a significantly reduced cytotoxic effect of this di-block copolypeptide due to the inclusion of the shikimoyl glyco-polypeptide block, which also added selectivity in internalizing particular cells. This di-block copolypeptide was internalized via mannose-receptor-mediated endocytosis, which was investigated by competitive receptor blocking with mannan. We evaluated the transfection efficiency of the copolypeptide in HEK 293T (noncancerous cells), MDA-MB-231 (breast cancer cells), and RAW 264.7 (dendritic cells) and compared it with commonly employed transfection agents (Lipofectamine). Our findings demonstrate that the homoarginine and shikimoyl-functionalized cationic di-block copolypeptide exhibits potent gene transfection capabilities with minimal cytotoxic effects, particularly in cancer cells, while it is ineffective for normal cells, indicative of its potential as a promising platform for cancer cell-specific gene delivery systems. To evaluate this, we delivered an artificially designed miRNA-plasmid against Hsp90 (amiR-Hsp90) which upon successful transfection depleted the Hsp90 (a chaperone protein responsible for tumour growth) level specifically in cancerous cells and enforced apoptosis. This innovative approach offers a new avenue for the development of targeted therapeutics with an improved efficacy and safety profile in cancer treatment.

In this study, we analyze the relationship between polypharmacy and surgical treatment in a population at a single teaching institution. The design of the study is a case-control analysis of hip fractures. The setting is at a single teaching institution located in Galveston, Texas, USA. Over a 5-year period, we conducted a retrospective review of patients within our medical record who underwent surgery for a hip fracture, identified by current procedural terminology codes 27235 and 27236. Our primary variable was a prescription of opioids, benzodiazepines, or both 30 days preoperatively and surgery performed. The main outcome measures were prescription of controlled medications and surgical class. We used descriptive analysis to summarize each variable as mean or frequency for continuous and categorical variables and subsequently assessed the association between demographic variables and drug prescription and surgical class. Of the 378 patients who met our inclusion criteria, 68.0% were females and 32.0% were males. The average age was 77.8 years. Most patients had a displaced hip fracture (61%). Most patients underwent a hip hemiarthroplasty (233, 61.6%) versus either a closed reduction with percutaneous pinning (125, 33.1%) or hip open reduction internal fixation (20, 5.3%). There was no significant difference between polypharmacy and hip fracture surgery; however, reported alcohol use was significant in both groups. In our patient population, opioid and/or benzodiazepine prescriptions were not significantly linked to hip fracture surgery, but documented alcohol use was found to be significant in both groups. We noted a higher prevalence of opioid and benzodiazepine prescriptions than was previously reported. As patients age, we should be cautious about the effects of polypharmacy and alcohol use and their impacts on the elderly., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Environmental pollution, especially from coal-based thermal power plants, poses significant risks to human respiratory health and the environment. This study evaluates the diversity of lichens in the areas. Physiological and bioaccumulation responses of two crustose lichens ( Bacidia incongruens and Rindoina sophodes ) and one foliose lichen ( Pyxine cocoes ) in the vicinity of the Feroz Gandhi Unchahar National Thermal Power Corporation, Raebareli, Uttar Pradesh, India were also assessed. These lichens, exposed to emissions including fly ash, greenhouse gases, metals, and particulate matter were analyzed for metal accumulation and physiological responses. Changes in physiological parameters and metal profiles concerning distance from the coal-based thermal power plant to the outskirts were analyzed for B. incongruens, R. sophodes and P. cocoes by utilizing Inductively Coupled Plasma Mass Spectrometry (ICP-MS). The study identified 18 lichen species from 12 genera and 10 families in the area, with Pyxine sorediata newly recorded in Uttar Pradesh. The dominant species, B. incongruens, P. cocoes, and R. sophodes , preferred substrates like Mangifera indica, Acacia nilotica, and Azadirachta indica bark. Physiological analyses revealed variations in pigment concentrations, with significant differences in chlorophyll a, chlorophyll b, total chlorophyll, carotenoids, and chlorophyll degradation, while protein content remained stable. Metal accumulation studies showed nine metals with distinct patterns, B. incongruens had higher concentrations in the west (52730.61 µg g -1 ) and P. cocoes in the east (23628.32 µg g -1 ). Correlation analyses indicated significant relationships between paired elements, suggesting specific sources of environmental contamination. This research highlights the significance of integrating physiological and environmental factors to understand lichen responses to coal based thermal power plant.

Background: We evaluated the association of achieving endoscopic outcomes at week 12 of induction with improvements in clinical outcomes and quality of life (QoL) at week 52 of maintenance in patients with moderately to severely active Crohn's disease (CD) treated with upadacitinib (UPA)., Methods: This post hoc analysis evaluated data from 2 phase 3 induction trials (NCT03345836 and NCT03345849) and 1 maintenance (NCT03345823) trial. Clinical responders to 12-week induction therapy with UPA who also received 52-week maintenance treatment with UPA were included. Endoscopic response, remission, healing, and ulcer-free endoscopy were assessed at week 12. Meaningful improvements in clinical and QoL outcomes were evaluated at week 52., Results: A significantly greater proportion of patients who achieved an endoscopic response at the end of induction, compared with patients who did not, attained Crohn's Disease Activity Index (CDAI) remission (52.0% vs 34.6%; P ≤ .01), corticosteroid-free CDAI remission (50.0% vs 30.9%), Inflammatory Bowel Disease Questionnaire remission (52.6% vs 30.3%), and meaningful improvements in Functional Assessment of Chronic Illness Therapy-Fatigue response (46.7% vs 25.9%), overall work impairment (47.1% vs 26.5%), and daily activity impairment (53.3% vs 34.1%) (all P < .05) at week 52. Similar findings were observed for patients who achieved endoscopic remission, endoscopic healing, and ulcer-free endoscopy at the end of induction vs those who did not., Conclusions: Early improvement in endoscopic outcomes after UPA induction treatment was associated with long-term meaningful improvements in clinical outcomes and QoL in patients with CD., Clinical Registration Number: U-EXCEED induction trial (NCT03345836), U-EXCEL induction trial (NCT03345849), and U-ENDURE maintenance trial (NCT03345823)., (© 2024 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Information on the effects of changing agricultural management on crop and livestock performance is critical for developing evidence-based policies, investments, and programs. Evidence for Resilient Agriculture (ERA) v1.0.1 presents a dataset that harmonizes and aggregates 112,859 observations from 2,011 agricultural studies taken place in Africa between 1934 and 2018. The dataset includes information on the effect of 364 combinations of management practices and technologies on 87 environmental, social, and economic indicators of outcomes. Observations are geolocated and temporally tagged and thus can be linked to other datasets such as historical weather, soil properties, and road networks. ERA offers a new resource for understanding the impacts of changing farming practices under diverse environmental contexts, providing data to support strategic interventions aimed to enhance productivity, resilience, and sustainability of African agriculture., (© 2024. The Author(s).)

Objective: Dermatomyositis (DM) symptoms negatively affect the quality of life of individuals living with the disease. Disease-specific, patient-reported outcome (PRO) instruments are needed to assess symptoms important to individuals with DM. This study aimed to conceptualize patient DM experience and disease activity definition to refine the development of the Dermatomyositis Disease Symptom Questionnaire (DM-DSQ), a novel PRO instrument capturing patient-reported symptoms., Methods: An observational, qualitative study was conducted with 30 individuals with DM (aged ≥ 18 yrs) in the US. A 1-hour semistructured interview, including concept elicitation and cognitive debriefing, was conducted with each participant. Inductive coding was used to identify concepts; a saturation analysis was conducted to confirm sample size. Concepts from transcripts were used to refine the preliminary conceptual model and DM-DSQ items., Results: Concept elicitation analysis findings included disease symptoms (eg, muscle weakness) and functional impacts (eg, walking). The analysis achieved conceptual saturation; the first 5 interviews uncovered most of the concepts. During cognitive debriefing of the DM-DSQ, participants found the items relevant, comprehensive, and easily understood (except for "skin sensitivity in sunlight"). The revised DM-DSQ content appears preliminarily valid in the patient population surveyed, pending further additions and debriefing based on refinement of the preliminary conceptual disease model and items., Conclusion: The DM-DSQ is being used in a phase II clinical trial and could become a valuable tool for studies evaluating PROs in patients with DM. Preliminary results indicate its content validity; extensive psychometric analysis using clinical trial data will determine its ability to capture symptoms for patients with DM.

Context: Interventions to improve the quality of care for people affected by serious illness commonly fail to reach patients from marginalized and underserved communities, which include those characterized by racialized or indigenous identity, sexual and gender minority status, and rural living. Interventions to improve care through serious illness conversations have demonstrated benefit, but little is known about their implementation in health systems that predominantly serve these patient groups., Objectives: The study aimed to understand factors influencing implementation of a serious illness communication-focused intervention-the Serious Illness Care Program in health systems who primarily provide care to marginalized and underserved communities., Methods: Qualitative interviews (16) and focus groups (3) were conducted with 19 interdisciplinary team members from six geographically diverse U.S. healthcare systems. Using a template analysis approach, investigators coded data inductively and deductively to identify themes., Results: Three themes emerged: patient factors, intervention elements, and health system contextual factors. Participants highlighted mission-driven efforts, creativity, interprofessional practice, and trainees as enablers of success. They identified weaknesses in the intervention's communication tool-the Serious Illness Conversation Guide as barriers to implementation of conversations. Resource constraints, socio-economic vulnerability, and mistrust in the health system were seen as additional barriers., Conclusions: Health systems that provide care to underserved and marginalized communities face unique challenges implementing the Serious Illness Care Program. They also possess assets, some unique to these settings, that support program adoption. Findings suggest that implementation of similar programs in low-resource healthcare settings may help address unmet needs among marginalized populations., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the contribution of ultra-processed foods (UPFs) to overall macronutrient intake and their association with anthropometric measurements, and to explore the perceptions regarding UPF consumption among young adults in Puducherry, India., Methods: This study included 630 participants from three colleges selected using multistage cluster sampling. Following the demonstration of portion estimation, dietary data from previous day were collected using a Google Form-based tool. The participant's anthropometric measures were taken. Food items were classified into NOVA groups and intake analysis was performed using DietSoft software. The participants with low and high consumption were identified and focus group discussions were conducted in each group using criterion sampling., Results: Of all the participants, 178 (28.3%) were overweight or obese. UPF contributed 9.3% of total energy intake and 2.8% protein, 9.9% fat, and 9.9% carbohydrates. The most consumed UPFs were biscuits, wafers (25%), and potato chips(16.2%). No significant association was found between anthropometric measures and UPF consumption. Qualitative findings revealed four major themes, further explained using the socio-ecological framework., Conclusion: UPF consumption in the region was lower than that reported in other global and Indian studies. While our study did not find a significant association between UPF consumption and anthropometric measures, there is a concerning shift from traditional diets to increased UPF reliance, driven by convenience and commercial factors. Addressing this is crucial for healthier choices and combating non-communicable diseases during this pivotal life stage., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The long-term consequences of concussions may include pathological neurodegeneration as seen in Alzheimer's disease (AD) and chronic traumatic encephalopathy (CTE). Tau-PET showed promise as a method to detect tau pathology of CTE, but more studies are needed OBJECTIVE: This study aimed (1) to assess the association of imaging evidence of tau pathology with brain volumes in retired athletes and (2) to examine the relationship between tau-PET and neuropsychological functioning., Methods: Former contact sport athletes were recruited through the Canadian Football League Alumni Association or the Canadian Concussion Centre clinic. Athletes completed MRI, [ 18 F]flortaucipir tau-PET, and a neuropsychological battery. Memory composite was created by averaging the Rey Auditory Verbal Learning Test and Rey Visual Design Learning Test z-scores. Grey matter (GM) volumes were age/intracranial volume corrected using normal control MRIs. Tau-PET % positivity in GM was calculated as the number of positive voxels (≥ 1.3 standardized uptake value ratio (SUVR)/total voxels)., Results: 47 retired contact sport athletes negative for AD (age:51 ± 14; concussions/athlete:15 ± 2) and 54 normal controls (age:50 ± 13) were included. Tau-PET positive voxels had significantly lower GM volumes, compared to tau-PET negative voxels (- 0.37 ± 0.41 vs. - 0.31 ± 0.37, paired p = .006). There was a significant relationship between GM tau-PET % positivity and memory composite score (r =  - .366, p = .02), controlled for age, PET scanner, and PET scan duration. There was no relationship between tau-PET measures and concussion number, or years of sport played., Conclusion: A higher tau-PET signal was associated with reduced GM volumes and lower memory scores. Tau-PET may be useful for identifying those at risk for neurodegeneration., (© 2024. The Author(s).)

A novel Escherichia coli phage designated as EC BD was isolated from cattle dung samples. Transmission electron microscopy demonstrated that the morphology of phage EC BD belongs to the family Myoviridae. The efficiency of plating (EOP) and scanning electron microscopy revealed the strong lytic activity of phage EC BD with a large burst size and a short latent period. Whole genome data analysis suggested that phage EC BD was inclined towards being completely lytic and revealed the absence of toxins, virulence and antibiotic resistance genes. Phylogenomic analysis of phage EC BD receptor binding proteins (RBPs) showed 74-100 % similarity with sixteen Enterobacter phages, representing their broad host range. The phage genome contains 262 ORFs, of which 107 displayed a unique pattern and additionally, the presence of a tRNA gene directed their fast replication and high stability. Comparative genome analysis suggested phage EC BD as a novel member of the genus Duplodnaviria and family Myoviridae. The efficiency of phage EC BD was determined in dairy food matrices (milk, cheese and paneer) artificially contaminated with enterotoxigenic E. coli strains ETEC H10407, ETEC K 12S and ETEC PB 176 with a significant reduction of 4.8, 6.0 and 5.3 log CFU/mL in milk and a substantial 4.9, 5.8 and 4.6 log CFU/mL reduction in cheese samples after 6 days at low storage temperature (4 °C); furthermore, within the similar conditions, paneer samples showed 4, 5.1 and 3.5 log CFU/mL reduction. EC BD phage treatment represents the complete eradication of three ETEC strains in liquid and semisolid dairy food matrices. This study suggested that phage EC BD might have potential as a biocontrol approach against ETEC foodborne infections., Competing Interests: Declaration of competing interest The authors declare no competing interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Clavicular brachial plexus blocks are a popular method to provide analgesia in upper limb surgery. Two common approaches include the infraclavicular (IC) and supraclavicular (SC) blocks. These two techniques have been compared previously; however, it is still being determined from the current literature whether one should be favoured., Methods: A search was performed on the following databases: Ovid Medline, EMBASE and the Web of Science from inception until 30.04.2023. All RCTs comparing SC and IC approaches in upper limb orthopaedic surgery were included. The primary outcome was block success rate., Results: Eighteen RCTs comprising 1389 patients were included. The success rate of IC blocks was higher than SC blocks, odds ratio 0.61 (95% CI 0.41-0.91, p = 0.01). A small number of studies reported on secondary outcomes. A reduced rate of Horner's syndrome was observed in the IC group. Otherwise, no difference was noted between the approaches in terms of procedure time, sensory onset time, patient satisfaction, pain and vascular puncture., Conclusion: IC blocks demonstrate a higher success rate over SC blocks. Across all studies a large variance in outcome reporting and definitions was observed. Future studies should conform to an agreed definition set to facilitate comparison., (© 2024. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Background and objective Cesarean sections (CS) are common and occasionally critical surgical procedures. Nausea, vomiting, and postoperative ileus (POI) frequently occur in patients undergoing cesarean delivery with regional anesthesia. These issues affect patient comfort, slow down wound healing, and prolong hospital stays. Studies have employed various strategies to address these challenges. Chewing gum post-surgery is a cost-effective approach to stimulate intestinal movement, promoting early initiation of oral intake, early mobilization, shorter hospital stays, and reduced overall hospitalization time. In this study, we aimed to investigate the potential benefits of chewing gum in this patient population. Methodology We randomly assigned a total of 314 women scheduled for elective or emergency lower segment CS (LSCS) to either a gum-chewing group (Group A, n=157) or a control group receiving standard postoperative care (Group B, n=157). Participants in the gum-chewing group chewed sugar-free gum for one hour postoperatively in sessions lasting 15 minutes each, continuing until bowel sounds resumed, and were allowed to have oral sips of water. In contrast, the control group's bowel sounds were checked every half hour till they appeared, and women were allowed to have sips of water once the bowel sounds were heard. The primary comparisons between the groups focused on the timing of first bowel sounds, first passage of flatus, and first bowel movement. Secondary endpoints included time to mobilization, removal of the catheter, and subjective sense of well-being. Results The average age of women in both groups was 24 years. There were no statistically significant differences between the study and control groups concerning age, parity, occupation, type of CS, reasons for CS, skin incision, or intraperitoneal adhesions. In Group A, the mean time for bowel sounds to appear was 3.39 hours, compared to 6.91 hours in Group B. For flatus passage, the mean time was 12.74 hours in Group A and 20.51 hours in Group B. Stool passage took an average of 41.59 hours in Group A and 64.03 hours in Group B. Conclusions Chewing gum, a type of simulated eating, is linked to faster restoration of gastrointestinal function following CS. This study elucidates the mechanisms behind the benefits of chewing gum and explores its potential in diverse surgical populations. Ultimately, integrating chewing gum into postoperative care may offer a valuable tool for enhancing patient outcomes and accelerating recovery, provided it is used in conjunction with comprehensive and personalized postoperative care strategies. It is a cost-effective approach that accelerates the recovery of intestinal movement post-surgery, decreasing the length of hospital stay and overall burden on patients., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. BLDE(DU) IRB issued approval BLDE(DU)/IEC/762/2022-23. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, N et al.)

Background: Endoscopic remission has emerged as an important treatment target in Crohn's disease (CD) and has been associated with improvement in long-term outcomes. We examined the relationship between achievement of endoscopic remission and hospitalizations using pooled 52-week Phase III risankizumab and upadacitinib maintenance trials for patients with moderate-to-severely active CD., Methods: Included patients received maintenance therapy after achieving a clinical response following a 12-week induction with risankizumab or upadacitinib. Endoscopic remission defined as a Simple Endoscopic Score for CD no greater than 4 with at least a 2-point reduction versus induction baseline and no subscore greater than 1. All subsequent hospitalization events were recorded until completion of the maintenance trial or discontinuation. Exposure-adjusted negative binomial regression models were estimated to assess the relationship between post-induction endoscopic remission and long-term hospitalization, controlling for demographics, clinical variables, and treatment arm., Results: Post-induction hospitalization rates were lower in patients who achieved endoscopic remission at the end of the induction period. In multivariable models, post-induction endoscopic remission was independently associated with an IRR of 0.45 (95% CI [0.22-0.95], p=0.036) and 0.71 (95% CI [0.44-1.14], p=0.156) for long-term disease-related and all-cause hospitalizations, respectively., Conclusions: Week 12 endoscopic remission is independently associated with reducing 52-week disease-related hospitalizations. However, achieving this stringent endpoint within 12 weeks of therapy may be challenging. Endoscopic response may be a more realistic early endoscopic target in the post-induction timeframe. Additional research is needed to evaluate early achievement of alternative endoscopic endpoints in CD., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Purpose: Autologous serum is widely used for the treatment of severe ocular surface disease with mixed efficacy. Extracellular vesicles (EVs) are small membrane bound structures present in all body fluids, including serum. This study compared the proteomic, metabolomic, and inflammatory cytokine composition of serum-derived EVs (SDEVs) to that of the soluble free protein fraction and the subsequent capacity of SDEVs to induce corneal epithelial cell migration and inflammation., Methods: SDEVs were isolated from human serum using size exclusion chromatography. SDEVs were analyzed using nanoparticle tracking analysis, transmission electron microscopy, and western blotting. The effects of SDEVs on corneal epithelial cell migration were tested using a standard scratch assay. Inflammatory cytokines in SDEVs and the free protein fraction were quantified using a microarray. A mutli-omics approach was further used to define SDEV cargo. The ability of SDEVs to modulate inflammation in corneal epithelial cells was quantified using ELISAs., Results: Western blot and TEM confirmed the presence of SDEVs. Proinflammatory cytokines, along with complement proteins and TGF-β, were decreased in SDEVs compared to serum. Metabolites present in SDEVs were mostly involved in amino acid biosynthesis, the TCA cycle and oxidative phosphorylation. SDEVs exhibited pro-migratory effects similar to serum however, SDEVs did not induce secretion of IL-6 or IL-8., Conclusions: SDEVs exhibit reduced levels of pro-inflammatory cytokines while retaining the beneficial wound healing properties of serum. Unlike serum, SDEVs do not induce inflammation. SDEVs may represent an alternative option for patients with severe ocular surface disease where traditional autologous serum has failed., Competing Interests: Declaration of Competing Interest None of the authors of this manuscript have any conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

The presence of high endothelial venules (HEV) and tertiary lymphoid structures (TLS) in solid tumors is correlated with favorable prognosis and better responses to immune-checkpoint blockade (ICB) in many cancer types. Elucidation of the molecular mechanisms underlying intratumoral HEV and TLS formation and their contribution to anti-tumor responses may facilitate development of improved treatment strategies. Lymphotoxin beta receptor (LTβR) signaling is a critical regulator of lymph node organogenesis and can cooperate with antiangiogenic and ICB treatment to augment tumor-associated HEV formation. Here, we demonstrated that LTβR signaling modulates the tumor microenvironment via multiple mechanisms to promote anti-tumor T cell responses. Systemic activation of the LTβR pathway via agonistic antibody treatment induced tumor-specific HEV formation, upregulated the expression of TLS-related chemokines, and enhanced dendritic cell (DC) and T cell infiltration and activation in syngeneic tumor models. In vitro studies confirmed direct effects of LTβR agonism on DC activation and maturation and associated DC-mediated T cell activation. Single agent LTβR agonist treatment inhibited syngeneic tumor growth in a CD8+ T cell- and HEV-dependent manner, and the LTβR agonist enhanced anti-tumor effects of anti-PD-1 and CAR T cell therapies. An in vivo tumor screen for TLS-inducing cytokines revealed that the combination of LTβR agonism and lymphotoxin alpha (LT⍺) expression promoted robust intratumoral TLS induction and enhanced tumor responses to anti-CTLA-4 treatment. Collectively, this study highlights crucial functions of LTβR signaling in modulating the tumor microenvironment and could inform future HEV/TLS-based strategies for cancer treatments.