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Competing Interests: The authors declare that they have no conflict of interest.

Objective: To evaluate the efficacy and safety of subcutaneous (SC) abatacept and standard of care (SOC) for the treatment of idiopathic inflammatory myopathy (IIM) over 52 weeks., Methods: In this randomised, double-blind, placebo-controlled phase III trial, patients with treatment-refractory IIM received SC abatacept (125 mg weekly) + SOC (abatacept group) or placebo + SOC (placebo group) (NCT02971683). A 24-week double-blind period was followed by an open-label period to assess outcomes from continued therapy with abatacept and initiation with abatacept (placebo-to-abatacept switch group) from 24 to 52 weeks. The primary endpoint was International Myositis Assessment and Clinical Studies definition of improvement (IMACS DOI) at week 24. Secondary efficacy and safety endpoints were assessed., Results: Overall, 148 (double-blind) and 133 (open-label) patients were treated. Baseline demographics were well-balanced between treatment groups and disease subtypes. At 24 weeks, improvement per IMACS DOI was 56.0% for the abatacept group and 42.5% for the placebo group (p=0.083); at 52 weeks, improvement was 69.8% (continued abatacept) and 69.0% (placebo-to-abatacept switch). IMACS DOI rate at 24 weeks was greater in the non-dermatomyositis (DM) group (abatacept: 57.1%; placebo: 32.3%; p=0.040) than the DM group (abatacept: 55.0%; placebo: 50.0%; p=0.679). The observed safety profile was similar in both groups., Conclusion: The proportion of patients who met improvement criteria after 24 weeks was similar between abatacept and placebo groups. However, analysis by IIM subtype suggested there may be sustained benefit of SC abatacept for patients with non-DM subtypes., (This article is protected by copyright. All rights reserved.)

Objectives: To explore the association between the extent of CT abnormalities by quantitative imaging analysis (QIA) and clinical/physiological disease parameters in patients with antisynthetase syndrome associated interstitial lung disease (ARS-ILD)., Methods: We analysed 20 patients with antisynthetase antibodies and active ILD enrolled in the Abatacept in Myositis-Associated Interstitial Lung Disease study. High-resolution chest CT was obtained at weeks 0, 24 and 48 and QIA scored the extent of ground glass (quantitative score for ground glass), fibrosis (quantitative score for lung fibrosis, QLF) and total ILD (quantitative ILD, QILD). Mixed-effects models estimated longitudinal QIA scores over time. Associations between QIA scores with clinical/physiological parameters were analysed longitudinally using repeated-measures mixed-effects models., Results: Patients were median age 57 years, 55% males and 85% white. Higher (worse) baseline QIA scores correlated with lower baseline forced vital capacity (FVC) and diffusing capacity adjusted for haemoglobin (DLCO). Longitudinal QIA trajectories trended towards improving scores during the trial, and patients on O 2 at baseline had worsening QIA trajectories which were different from patients who were not on O 2 . Longitudinal QIA scores demonstrated strong associations with both FVC and DLCO over time. Higher QILD scores over time were also associated with worse dyspnoea scores, pulmonary visual analogue scale, physician and patient global disease activity, health status in 6/8 domains of the Short Form-36 and higher oxygen requirements. Patients with significant radiographic improvement at 48 weeks had higher baseline QLF, QILD and worse DLCO., Conclusions: Longitudinal QIA scores associate with lung physiology, patient perception of respiratory status, overall disease activity and quality of life over time in ARS-ILD. QIA may allow reproducible monitoring of disease progression and response to therapy over time., Trial Registration Number: NCT03215927., Competing Interests: Competing interests: GK and JG are on the UCLA patent for the quantitative imaging analysis. RA has received research grants from Boehringer Ingelheim, Bristol Myers Squibb, EMD Serono, Janssen, Mallinckrodt, Pfizer and Q32, and serves as a consultant for Actigraph, Alexion, ANI Pharmaceuticals, Argenx, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Cabaletta Bio, Capella Bioscience, Corbus, CSL Behring, EMD Serono, Galapagos, Horizon Therapeutics, I-Cell, Janssen, Kezar, Kyverna, Merck, Novartis, Nuvig Therapeutics, Octapharma, Pfizer, Regeneron, Roivant, Sanofi, Teva, Artsome, Capstanx and Manta. CC-S has received research grants from Priovant, CSL Behring, Janssen, Octapharma, Pfizer, AbbVie and Bristol Myers Squibb, and serves as a consultant for Boehringer Ingelheim, Recludix, Octapharma, Pfizer, AbbVie and Bristol Myers Squibb. PFD is editor of UpToDate and a member of the FDA Advisory Committee. TJD has received support from Bayer and has been part of a clinical trial funded by Genentech, all unrelated to this study. GMH receives grant support from the NIH including R01 HL111024, R01 HL135142 and R01130974. He has performed consulting work for Boehringer Ingelheim and the Gerson Lehrman Group., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Lineage plasticity and histologic transformation from prostate adenocarcinoma to neuroendocrine prostate cancer (NEPC) occurs in up to 15-20% of patients with castration-resistant prostate cancer (CRPC) as mechanism of treatment resistance and is associated with aggressive disease and poor prognosis. NEPC tumors typically display small cell carcinoma morphology with loss of androgen receptor (AR) expression and gain of neuroendocrine (NE) lineage markers. However, there is a spectrum of phenotypes that are observed during the lineage plasticity process, and the clinical significance of mixed histologies or those that co-express AR and NE markers or lack all markers is not well defined. Translational research studies investigating NEPC have used variable definitions making clinical trial design challenging. Here we discuss the diagnostic workup of metastatic biopsies to help guide the reproducible classification of phenotypic CRPC subtypes. We recommend classifying CRPC tumors based on histomorphology (adenocarcinoma, small cell carcinoma, poorly differentiated carcinoma, other morphologic variant, or mixed morphology) and immunohistochemical markers with a priority for AR, NKX3.1, INSM1, synaptophysin and cell proliferation based on Ki-67 positivity, with additional markers to be considered based on the clinical context. Ultimately, a unified workup of metastatic CRPC biopsies can improve clinical trial design and eventually practice.

Diabetes poses a significant global health challenge, driving the search for effective management strategies. In the past years, α-amylase inhibitors have emerged as promising candidates for regulating blood sugar levels. In this concern, we have synthesized a series of novel 3-methyl-2-aroylthiazolo[3',2':2,3][1,2,4]triazino[5,6- b ]indole derivatives via the regioselective reaction of 2,5-dihydro-3 H -[1,2,4]triazino[5,6- b ]indole-3-thione and 1,3-diketones in the presence of NBS under solvent-free conditions. Subsequently, the inhibitory potential of the newly synthesized 3-methyl-2-aroylthiazolo[3',2':2,3][1,2,4]triazino[5,6- b ]indole derivatives was assessed against the α-amylase enzyme to probe their antidiabetic properties. In vitro studies revealed moderate to excellent α-amylase inhibitory activity, with IC 50 values ranging from 16.14 ± 0.41 to 27.69 ± 0.58 μg ml -1 . Furthermore, SAR analysis showed that compounds containing halogen groups exhibited superior inhibition potential, surpassing the standard drug Acarbose (IC 50 = 18.64 ± 0.42 μg ml -1 ), particularly derivatives substituted with 4-fluoro and 2,4-dichloro groups, with IC 50 values of 16.14 ± 0.41 μg ml -1 and 17.21 ± 0.15 μg ml -1 , respectively. Additionally, molecular docking unveiled the binding modes of ligands with the active site of A. oryzae α-amylase. Encouragingly, the theoretical analyses closely mirrored the experimental findings, further underlining the promise of these synthetic molecules as potent α-amylase inhibitors.

The Immunization and Vaccines-related Implementation Research Advisory Committee (IVIR-AC) is the primary advisory body of the World Health Organization conducting independent reviews of immunization-related implementation research, with a primary focus on transmission and economic modeling analyses that estimate the value and impact of vaccines. From 10 to 13th September 2024, IVIR-AC convened virtually for its second of two semi-annual meetings to provide feedback and recommendations across six sessions including: pneumococcal vaccination strategies that rely on indirect protection; vaccine impact modeling for chikungunya; The Lancet Commission on strengthening the use of epidemiological modeling of emerging and pandemic infectious diseases; methods for immunization coverage estimation; setting immunization research priorities in the South-East Asian Region; and modeling evidence related to typhoid conjugate vaccine schedules. This report summarizes the sessions, proceedings, and recommendations from that meeting., Competing Interests: Declaration of competing interest P. L. is supported financially by the Bill & Melinda Gates Foundation. S. S. was supported by the World Health Organization for this work. A. N. S. was financially supported by the World Health Organization for this work, and is additionally supported by the Bill & Melinda Gates Foundation, Gavi, the Vaccine Alliance, and the National Institutes of Health. M. K. is supported by the Bill & Melinda Gates Foundation. A. B. H. was supported by the Australian National Health and Medical Research Council for this work, is additionally supported by PATH, the World Health Organization, and Gavi, the Vaccine Alliance, and has received consulting fees from the Australian NSW Ministry of Health, WHO Europe and Asian Development Bank. A. P. is supported by Gavi, the Vaccine Alliance, Imperial College London, the Bill & Melinda Gates Foundation, and the World Health Organization. A. N. S. and A. B. H. report travel related support from the World Health Organization to attend previous IVIR-AC meetings. All other authors have no declarations., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The present study reports some fascinating results of Hantzsch's [3 + 2] cyclic condensation of α-bromo-1,3-diketones, a tri-electrophilic synthon generated in situ by bromination of 1,3-diketones using the mild brominating reagent NBS with trinucleophilic N -substituted thioureas. Interestingly, out of a total of 20 combinations, 10 resulted in the exclusive formation of the desired 2-( N -arylamino)-5-acyl-4-methylthiazoles regioselectively, seven led to the formation of unexpected 2-( N -acylimino)-3- N -aryl-4-methylthiazoles through an interesting C-N acyl migration, and three furnished a mixture consisting of both products. The regioselectivity pattern of the two products may be attributed to a greater electrophilicity of the carbonyl carbon of the acetyl group than that of the acyl group towards both nitrogens of thiourea. The structures of the thiazole derivatives were unambiguously assigned using 1 H-NMR, 13 C-NMR, and rigorous heteronuclear 2D-NMR [( 1 H- 13 C) HMQC and ( 1 H- 13 C) HMBC] spectroscopic techniques. The outcomes of the spectroscopic experiments were further concurred through X-ray crystallographic studies, and a plausible mechanism for acyl migration was proposed for the formation of the unexpected rearranged product., Competing Interests: The authors declare no competing interest., (This journal is © The Royal Society of Chemistry.)

Purpose: Evidence surrounding swallowing impairment in sporadic inclusion body myositis (IBM) is based on nonstandardized and nonvalidated assessment methods. We investigated (a) IBM's impact on swallowing function and oral intake status using well-tested assessment frameworks; (b) changes in swallowing over time; and (c) age, sex, and swallowing impairment severity's influence on oral intake status., Method: We conducted a secondary analysis of Modified Barium Swallow Impairment Profile (MBSImP) and Functional Oral Intake Scale (FOIS) data from 13 patients with IBM (seven females; M age = 60.2 [±13.6] years) and 13 age- and sex-matched healthy controls. We compared MBSImP Overall Impression (OI), Oral Total (OT), Pharyngeal Total (PT), and FOIS scores between groups. Specific to the IBM cohort, we analyzed repeated OT and PT scores and calculated whether age, sex, and OT and PT scores predicted FOIS scores., Results: The IBM cohort demonstrated poorer OI scores across six swallowing components than healthy controls (each p < .05). Unlike OT scores ( p = .84), PT ( p = .033) and FOIS ( p < .001) scores were worse in the IBM cohort. Repeated OI scores revealed changes in three swallowing components (each p < .05), but repeated OT ( p = .16) and PT ( p = .30) scores did not significantly change. Age, sex, and OT and PT scores did not influence FOIS scores (each p > .05)., Conclusions: Pharyngeal impairments were most prominent in the IBM cohort, and their oral intake status was adversely affected. Our preliminary data showcase the application of robust assessment methods to investigate swallowing function in IBM, enhancing standardization and comparability across studies., Supplemental Material: https://doi.org/10.23641/asha.27165450.

Background: Dravet syndrome is an infantile-onset developmental and epileptic encephalopathy with limited data on the frequency of SCN1A in Indian children. The study aimed to identify and characterize the burden of SCN1A pathogenic variants associated with the Dravet syndrome phenotype through genetic testing in the North Indian population., Method: In this prospective, cross-sectional study from March 2015 to February 2019, we enrolled 52 children with Dravet syndrome phenotype who underwent genetic testing for SCN1A gene pathogenicity. We assessed variant effect using multiple algorithms, and genetic test results were reported based on recommendations from the American College of Medical Genetics and Genomics guidelines. Additionally, we performed multiplex-ligation dependent probe amplification (MLPA) to detect copy number variations of the SCN1A gene in children without identified genetic pathogenicity (n = 22) and analysed the results using Coffalyser.net., Results: Of the 52 probands studied, pathogenic variants in the SCN1A gene were identified in 30 children. Among these variants, 11 truncating variants (3 frame-shift variants, 3 intronic variants in splice site regions, and 5 nonsense variants) in 12 unrelated probands, and 17 missense variants in 18 unrelated probands were found. The genetic yield of SCN1A pathogenicity in our cohort (n = 52) was 58 %. Additionally, two of the identified variants were novel. Furthermore, MLPA analysis of the SCN1A gene in 22 children without pathogenic variants yielded no results., Conclusion: This work represents a genetic analysis of a Dravet syndrome cohort, revealing a 58 % burden of SCN1A variants in children with the Dravet syndrome phenotype from the North Indian population., 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.)

Anti-synthetase syndrome constitutes a dynamically evolving subset of Idiopathic Inflammatory Myopathy, however, the nomenclature and abbreviations for this syndrome are plagued by heterogeneity, leading to lack of consistency in literature. The objective of this study is to evaluate existing diversity in disease names and abbreviations, with a future goal to develop consensus on the nomenclature. A scoping review format was used for analysis. A comprehensive PUBMED search was conducted from January 1, 1984 (the initial description of anti-synthetase autoantibodies) to November 30, 2023, encompassing all pertinent articles published within this timeframe. Search terms included, ((antisynthetase syndrome) OR (anti synthetase syndrome)) OR (anti-synthetase syndrome)). The articles were screened for presence of terminology and abbreviations used. The search yielded 936 items with the specified terms. After excluding 303 irrelevant articles and 58 non-English publications, the remaining n = 575 articles underwent detailed review of the abstract and full article. Out of n = 575, 54.7% (n = 314) used 'antisynthetase syndrome' and 43.4% (n = 249) preferred 'anti-synthetase syndrome' with few novel names also. Among these, 394 articles used abbreviations while 181 did not. Most utilized term was ASS; in 64.7% (n = 255), followed AS in 11.9% (n = 47), ASSD in 9.9% (n = 39) and ASyS in 7.6% (n = 30). A discordance in nomenclature is evident, with about half using antisynthetase syndrome and other half using anti-synthetase syndrome. Moreover, significant heterogeneity exists in abbreviation use aswell. There is a pressing need to bridge this disparity and establish a uniform identifier for the disease with an objective to develop greater coherence in future research, educational initiatives, and interdisciplinary collaboration., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We present an interesting and rare case of Capillaria hepatica infection in a 2-year-old boy, who presented with fever, rash, hepatomegaly and peripheral eosinophilia. FNAC of hepatic lesion showed parasitic eggs and PCR from the aspirate confirmed the diagnosis. We describe the cytomorphological features and provide educational multiple-choice questions related to the topic., (© 2024 John Wiley & Sons Ltd.)

The present study describes an eco-friendly NBS-assisted regioselective synthesis of new 5-acylfunctionalized 5-acylfunctionalized 2-(1H-pyrazol-1-yl)thiazoles by condensation of 3,5-dimethyl-1H-pyrazole-1-carbothioamide with unsymmetrical 1,3-diketones under solvent-free conditions. The structural elucidation of the newly synthesized compounds was accomplished using various spectroscopic techniques viz. FTIR, NMR and mass spectrometry. All the newly synthesized compounds were examined for their in vitro antimicrobial potential against both pathogenic gram positive and gram negative bacterial and fungal species as well as anthelmintic activity against Pheretima posthuma earthworms. The results of antimicrobial activity revealed that all tested compounds 3 a-j showed excellent antimicrobial potential particularly against S. aureus. It was also observed that compounds 3 e and 3 i (MIC=62.5 μg/mL) showed greater potency against E. coli, whereas compounds 3 a and 3 h (MIC=50 μg/mL and 62.5 μg/mL) demonstrated better activity against P. aeruginosa and compound 3 i (MIC=62.5 μg/mL) exhibited superior activity against S. pyogenus when compared to standard drug Ampicillin (MIC=100μg/mL). Compound 3 e and 3 j revealed remarkable antifungal and anthelmintic activities. To find out binding interactions of target compounds with target proteins and pharmacokinetic parameters of the compounds, in silico investigations involving molecular docking studies and ADMET predictions were also performed., (© 2024 The Authors. ChemistryOpen published by Wiley-VCH GmbH.)

We have functionally characterized the high-affinity phosphate transporter (PiPT) from the root endophyte fungus Piriformospora indica. PiPT belongs to the major facilitator superfamily (MFS). PiPT protein was purified by affinity chromatography (Ni-NTA) and Size Exclusion Chromatography (SEC). The functionality of solubilized PiPT was determined in detergent-solubilized state by fluorescence quenching and in proteoliposomes. In the fluorescence quenching assay, PiPT exhibited a saturation concentration of approximately 2 μM, at a pH of 4.5. Proteoliposomes of size 121.6 nm radius, showed transportation of radioactive phosphate. V max was measured to be 232.2 ± 11 pmol/min/mg protein. We have found K m to be 45.8 ± 6.2 μM suggesting high affinity towards phosphate., Competing Interests: Declaration of competing interest The authors declare that there are no competing interests associated with the manuscript., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: Non-operative management (NOM) has been validated for blunt liver and splenic injuries. Literature on continuous intra-abdominal pressure (IAP) monitoring as a part of NOM remains to be equivocal. The study aimed to find any correlation between clinical parameters and IAP, and their effect on the NOM of patients with blunt liver and splenic injury., Method: A prospective cross-sectional study conducted at a level I trauma center from October 2018 to January 2020 including 174 patients who underwent NOM following blunt liver and splenic injuries. Hemodynamically unstable patients or those on ventilators were excluded, as well as patients who suffered significant head, spinal cord, and/or bladder injuries. The study predominantly included males (83.9%) with a mean age of 32.5 years. IAP was monitored continuously and the relation of IAP with various parameters, interventions, and outcomes were measured. Data were summarized as frequency (percentage) or mean ± SD or median (Q 1 , Q 3 ) as indicated. χ 2 or Fisher's exact test was used for categorical variables, while for continuous variables parametric (independent t-test) or nonparametric tests (Wilcoxon rank sum test) were used as appropriate. Clinical and laboratory correlates of IAP < 12 with p < 0.200 in the univariable logistic regression analysis were included in the multivariable analysis. A p < 0.05 was used to indicate statistical significance., Results: Intra-abdominal hypertension (IAH) was seen in 19.0% of the study population. IAH was strongly associated with a high injury severity score (p < 0.001), and other physiological parameters like respiratory rate (p < 0.001), change in abdominal girth (AG) (p < 0.001), and serum creatinine (p < 0.001). IAH along with the number of solid organs involved, respiratory rate, change in AG, and serum creatinine was associated with the intervention, either operative or non-operative (p = 0.001, p = 0.002, p < 0.001, p < 0.001, p = 0.013, respectively). On multivariable analysis, IAP (p = 0.006) and the mean change of AG (p = 0.004) were significantly associated with the need for intervention., Conclusion: As a part of NOM, IAP should be monitored as a continuous vital. However, the decision for any intervention, either operative or non-operative cannot be guided by IAP values alone., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Chinese Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: The Myositis Interstitial Lung Disease Nintedanib Trial (MINT) is a hybrid trial, which is enrolling patients both at local sites and remotely via a decentralised site. The trial will investigate the efficacy and safety of nintedanib in patients with progressive myositis-associated interstitial lung disease (MA-ILD)., Methods/design: MINT is an exploratory, prospective randomised placebo-controlled trial. Eligible patients will have myositis and evidence of fibrosing ILD on high-resolution computed tomography (HRCT), be taking standard of care medications for myositis, and meet criteria for ILD progression within the prior 24 months based on decline in FVC, worsened fibrosis on HRCT, and/or worsened dyspnoea. Patients will be randomised 1:1 to receive nintedanib 150 mg twice daily or placebo for 12 weeks then open-label nintedanib for 12 weeks. Patients will be enrolled at local sites and a decentralised site. Most study visits will be completed remotely using telemedicine or digital health technologies. The primary endpoint is the change in Living with Pulmonary Fibrosis (L-PF) questionnaire dyspnoea domain score at week 12. Other endpoints include changes in other L-PF questionnaire domains, lung function, imaging, and physical activity, and assessment of adverse events. Data collected using remote versus clinic enrolment, and using home versus clinic spirometry, will be compared., Discussion: MINT is an innovative, hybrid trial that will evaluate the effects of nintedanib on symptoms, quality of life, and ILD progression in patients with progressive MA-ILD and provide valuable information on the utility of decentralised recruitment and remote data collection in clinical trials., Trial Registration: Clinicaltrials.gov NCT05799755 (date of registration: 05/04/2023)., (© 2024. The Author(s).)

Background: Parkinson disease (PD) is a progressive neurodegenerative disorder characterized by motor dysfunctions and nonmotor symptoms. Current treatments do not alter disease progression, highlighting the need for alternative therapies. Music, dance, and mindfulness meditation have shown the potential to improve symptoms and quality of life in patients with PD., Objective: This study aims to evaluate the effectiveness of dance or music and meditation on PD progression, cognitive functions, mood, behavior, and caregiver burden., Methods: This study is a single-blinded, longitudinal, parallel, randomized controlled trial. The participants consist of 30 patients with mild to moderate PD residing in Mumbai, India, who can physically participate in the activities. The exclusion criteria include advanced PD, severe balance issues, age >80 years, and other movement disorders. Participants in the intervention group will engage in dance or music sessions and guided meditation thrice weekly for 6 months. The control group will continue their usual activities and medication. The primary outcome is the progression of PD symptoms, measured using the Unified Parkinson's Disease Rating Scale I-III, and quality of life, measured using the Parkinson's Disease Questionnaire-39. The secondary outcomes include cognitive functions (Mini-Mental State Examination), mood (Beck Depression Inventory and Parkinson Anxiety Scale), mobility (timed up and go and Berg Balance Test), behavioral disorders (Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease Rating Scale), and caregiver burden (Zarit Burden Interview and Parkinson's Disease Questionnaire-Carer)., Results: Data collection was completed in February 2024, with 28 participants finishing the study (intervention group: n=15, 54% and control group: n=13, 46%). Data analysis is underway, with results expected to be published in December 2024., Conclusions: This study aims to provide significant insights into the effectiveness of dance or music and meditation in improving the quality of life and slowing the progression of PD. The findings are anticipated to support using these nonpharmaceutical therapies as complementary approaches to managing PD., Trial Registration: CTRI/2023/03/051064; https://tinyurl.com/2xdus53j., International Registered Report Identifier (irrid): DERR1-10.2196/59018., (©Bhagyashree Mehrotra, Neha Rai, Rajani MR, Aparna Budhakar, Ritika Aggarwal, Raj Vinodkumar Agarbattiwala, Mona Thomas, Sampada Patole, Paresh Doshi. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 29.10.2024.)

Objective: Anti-synthetase syndrome (ASSD) is a rare systemic autoimmune rheumatic disease (SARD) with significant heterogeneity and no shared classification criteria. We aimed to identify clinical and serological features associated with ASSD that may be suitable for inclusion in the data-driven classification criteria for ASSD., Methods: We utilized a large, international, multi-center "Classification Criteria for Anti-synthetase Syndrome" (CLASS) project database, which includes both ASSD patients and controls with mimicking conditions, namely SARDs and/or interstitial lung disease (ILD). The local diagnoses of ASSD and controls were confirmed by project team members. We employed univariable logistic regression and multivariable Ridge regression to evaluate clinical and serological features associated with an ASSD diagnosis in a randomly selected subset of the cohort., Results: Our analysis included 948 ASSD cases and 1077 controls. Joint, muscle, lung, skin, and cardiac involvement were more prevalent in ASSD than in controls. Specific variables associated with ASSD included arthritis, diffuse myalgia, muscle weakness, muscle enzyme elevation, ILD, mechanic's hands, secondary pulmonary hypertension due to ILD, Raynaud phenomenon, and unexplained fever. In terms of serological variables, Jo-1 and non-Jo-1 anti-synthetase autoantibodies, antinuclear antibodies with cytoplasmic pattern, and anti-Ro52 autoantibodies were associated with ASSD. In contrast, isolated arthralgia, dysphagia, electromyography/MRI/muscle biopsy findings suggestive of myopathy, inflammatory rashes, myocarditis, and pulmonary arterial hypertension did not differentiate between ASSD and controls or were inversely associated with ASSD., Conclusion: We identified key clinical and serological variables associated with ASSD, which will help clinicians and offer insights into the development of data-driven classification criteria for ASSD., (This article is protected by copyright. All rights reserved.)

Introduction Diabetes mellitus is characterized by chronic hyperglycemia due to insulin deficiency, leading to complications in vital organs. Among these, dyslipidemia is common, presenting as low high-density lipoprotein cholesterol (HDL-c), high triglycerides (TG), Apolipoprotein-B (Apo-B), and small dense low-density lipoprotein (sdLDL) predominance, collectively known as diabetic dyslipidemia. To assess the atherogenic risk in individuals with type 2 diabetes, the atherogenic index of plasma (AIP) and atherogenic coefficient (AC) provide valuable insights beyond routine lipid tests. AIP, calculated as log (serum TG/serum HDL-c), correlates positively with the occurrence and severity of diabetic microvascular complications. The AC ((total cholesterol (TC)-HDL-c)/HDL-c) serves as an atherogenicity marker. Waist circumference (WC), reflecting central adiposity and body mass index (BMI), are directly related to both AIP and AC, making them useful non-invasive tools to monitor atherogenicity and predict cardiovascular disease (CVD) risk independently of each other in subjects with type 2 diabetes mellitus. Material and methods This was an observational cross-sectional study conducted in the Department of Medicine of a tertiary care hospital. It included 100 type 2 diabetes mellitus patients more than 18 years of age, including both males and females. Observation and results In our study, there were 42 (42%) males and 58 (58%) females. The mean WC of males and females were 105.40 and 100.98 cm, respectively. The mean for BMI, glycated hemoglobin (HbA1c), and urine albumin-to-creatinine ratio (UACR) was 28.83 kg/m 2 , 8.58%, and 100.62 mg/g, respectively. There was positive Pearson's correlation between AIP and WC of males and females (r = 0.324 and 0.269), AC and WC of males and females (r = 0.139 and 0.097), BMI and AIP (r = 0.350), BMI and AC (r = 0.214), HbA1c and AIP (r = 0.207), HbA1c and AC (r = 0.216), UACR and AIP (r = 0.218), and UACR and AC (r = 0.237). Conclusion This study concludes that there is a positive correlation between anthropometric measures, such as WC and BMI, and plasma atherogenicity indexes, including the AIP and AC. This finding suggests that clinicians can effectively use these non-invasive measurements (BMI and WC) to estimate the presence of dyslipidemia and atherogenicity in patients with type 2 diabetes mellitus during routine outpatient care. Early identification of these risk factors allows for timely lifestyle interventions such as dietary modifications and increased physical activity, which could potentially reduce the risk of future cardiovascular diseases., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Institutional Ethics Committee, Lady Hardinge Medical College and Associated Hospitals issued approval LHMC/IEC/2022/PG Thesis/44. The abovementioned thesis research protocol is "Approved" for conduct by Dr. Jayant Kumar Sahani as a PG Thesis work under your guidance under the jurisdiction of Lady Hardinge Medical College and Associated Hospitals, New Delhi. The study should be conducted in accordance with the provisions of New Drugs and Clinical Trial Rules 2019, Good Clinical Practices, and the ICMR Guidelines for Biomedical Research on Human Participants (2017). You are required to inform Member Secretary, IEC, LHMC, about any serious adverse events or death of study participants within 24 hours of the incident. 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, Sahani et al.)

Background: Community pharmacies in England offer convenient and safe disposal of unwanted medicines, including antimicrobials, and better uptake of this service could limit environmental antimicrobial resistance. However, there is limited information on the extent and nature of antibiotic returns to community pharmacies. The impact of an antibiotic amnesty campaign promoting antibiotic disposal through community pharmacies was evaluated with the intention of collecting detailed information on the antibiotics returned., Methods: An antibiotic amnesty campaign was delivered by community pharmacies in the Midlands (England) with an audit of returned antibiotics conducted in 19 community pharmacies in Leicestershire. Detailed information on antibiotics returned for disposal was gathered during the month-long amnesty campaign and again 3 months later in the same pharmacies., Results: Antibiotics accounted for 3.12%-3.35% of all returned medicines. The amnesty campaign led to a significant increase in defined daily doses of returned antibiotics compared to the post-amnesty period ( P  = 0.0165), but there was no difference in the overall number of returned medicines. Penicillins were the most commonly returned antibiotics in both periods (29.3% and 42.5% of packs, respectively), while solid oral dose formulations predominated. A total of 36.6% of antibiotics returned during the amnesty period were expired, increasing to 53.4% in the post-amnesty period. Amnesty conversations had a significant impact on the number of antibiotic returns but campaign posters did not., Conclusions: Antibiotic conversations can increase the amount of antibiotics returned to community pharmacies for safe disposal, and passive campaign materials had limited impact. More research is needed to identify the most effective interventions to increase returns., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Several pyrazole-thiazole hybrids featuring two potentially bioactive pharmacophores with or without linker have been synthesized using the molecular hybridization approach as target structures by medicinal chemists to modulate multiple drug targets simultaneously. The presented review aims to provide an overview of the diversified and wide array of pharmacological activities of these hybrids bestowing anticancer, antifungal, antibacterial, analgesic, anti-inflammatory, antioxidant, antitubercular, antiviral, antiparasitic, and miscellaneous activities. The structure-activity relationships and potential mechanism of action are also reviewed to shed light on the development of more effective and biotargeted candidates. This review focuses on the latest research advances in the biological profile of pyrazole-thiazole hybrids reported from 2015 to the present, providing medicinal researchers with a comprehensive platform to rationally design and develop more promising pyrazole-thiazole hybrids., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

Oral tongue squamous cell carcinoma (OTSCC) is the most aggressive subsite among oral cancers. The poor survival rate has been primarily attributed to high loco-regional recurrence. Two recent developments viz. incorporation depth of invasion (DOI) in American Joint Committee on Cancer (AJCC) TNM 8th edition and elective neck dissection in clinically negative neck have potential to improve survival. We in our study have tried to look at overall survival and factors affecting patients of only OTSCC. 144 patients of OTSCC operated upfront between July 2017 and December 2023 were included in our study. Selective neck dissection was done in all patients with clinically negative neck. T staging was done using both AJCC TNM 7th and 8th edition. Primary objective of the study was to determine the overall survival and factors affecting it. The secondary objectives were to determine the disease-free survival and to look at the effect of forementioned new developments in patients in OTSCC. Mean overall survival and disease-free survival in our study cohort was 48.8 months and 48.3 months respectively in follow up period ranging from 2 months to 75 months. DOI > 10 millimetres and involved margins were factors significantly associated with survival on multivariate analysis. Lymph node metastasis was detected in 32(35.2%) patients out of 91 patients with clinically negative neck and 31(21.6%) of patients were upstaged from T1/T2 in AJCC TNM 7th to T3/T4 according to AJCC TNM 8th edition. The 5-years overall survival of our patients was about 54% with nearly half of our patients presenting in stage III and stage IV. There is need to create awareness in general population as the impact of the new changes will only be seen if patients present at an early stage., Competing Interests: Conflict of InterestThe authors have no conflict of interest to declare., (© Association of Otolaryngologists of India 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Dermatomyositis (DM) is a rare and severely debilitating autoimmune disease that can affect children and adults; however, there is little understanding of the patient-reported experience and uncertainty around validated clinical outcomes assessments (COAs) that could measure changes in the condition during clinical trials of new treatments., Objectives: The aim of this study was to understand the patient experience of DM, with a focus on its cutaneous manifestations, to describe the patient experience and determine the suitability of existing COA measures., Methods: Adult (≥ 18 years) patients (N = 28) with severe active cutaneous manifestations of DM were interviewed. In the 90-min interviews, open-ended questions and probes were used to elicit descriptions of key clinical manifestations and patients' experiences of DM, including the symptoms and impacts on their daily lives and wellbeing., Results: Patients reported 13 different skin manifestations of DM. The most common were rash (n = 28, 100%), itch (n = 28, 100%), dry skin (n = 23, 82%), and swelling of the skin (n = 17, 61%). The head and face, followed by hands, were perceived as the most bothersome body areas affected by skin manifestations, because they are exposed and visible to themselves and other people. All patients (n = 28, 100%) reported at least one impact of DM, which varied greatly between patients, but included emotional, psychological, cognitive, and physical impacts, and those affecting daily life, such as work and sleep. Over half of the patients (n = 19, 67%) reported that their daily activities were impacted by DM., Conclusions: The qualitative interviews with patients revealed that the presentation of DM manifestations is highly variable but affects patients' emotional wellbeing, physical activities, and daily life significantly., (© 2024. The Author(s).)

Introduction: Recruitment for idiopathic inflammatory myopathies (IIM) research is a challenge due to the rarity of the disease and the scarcity of specialized myositis centers. Online recruitment may be a feasible alternative to reach rare disease patients. We evaluated various online recruitment methods in a large longitudinal IIM cohort., Methods: The "Myositis Patient Centered Tele-Research" (My Pacer) is a prospective 6-month observational study of IIM, recruited online and through traditional clinic visits. We utilized diverse recruitment methods, such as physician referrals, social media, websites, direct emails, and partnerships with patient-support organizations. Participants self-enrolled and completed pre-screening, e-consenting, and release of medical information via the study-specific app or website. We compared the effectiveness of various recruitment and enrollment methods and the characteristics of the population recruited., Results: A total of 841 participants completed the pre-screening; 408 completed e-consent and registration. From those, 353 (86.5%) were remotely recruited. Email (201; 49.26%) and social media (77; 18.87%) were important recruitment tools. Patient-support organizations were responsible for disseminating the study to 312 (75.46%) participants. The study app was used by 232 (65.72%) individuals for enrollment, with app users being slightly younger than website users (p = 0.001). Participants were mostly female 317 (77.76%), mean age of 54.84 years, White 328 (80.42%), Black 49 (12%), Asian 13 (3.26%), and non-Hispanic 378 (92.65%). Our study reached all U.S. regions and 45 (90%) U.S. states., Conclusions: Social media and partnerships with patient-support organizations lead to a high rate of recruitment, with a wide reach, and a reasonably diverse population., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Objective: Anti-histidyl-transfer RNA synthetase (Jo-1) antibodies are associated with myositis as well as different extramuscular organ complications comprising the anti-synthetase syndrome. This study aimed to clarify the relationship between anti-Jo-1 epitope recognition patterns and specific clinical features of this syndrome., Methods: B cell epitope mapping was performed via enzyme-linked immunosorbent assay in 180 patients who were anti-Jo-1 antibody-positive using overlapping peptides/protein fragments spanning the amino-terminal 151 amino acids of Jo-1 as substrate antigens. Statistical associations with clinical features were assessed through rank-sum, correlation, and cluster analyses., Results: The level of reactivity against subfragments spanning amino acids 1-151 of Jo-1 paralleled that of full-length Jo-1, confirming the immunodominance of this amino-terminal region. The corresponding frequencies of reactivity to peptides 1 (amino acids [aa] 1-21), 3 (aa 27-47), 4 (aa 40-60), 10 (aa 118-138), and 11 (aa 131-151) were 6.1%, 42.5%, 6.8%, 6.7%, and 20.3%. While anti-full-length Jo-1 antibodies were significantly associated with Raynaud phenomenon, anti-fragment A2 (aa 1-60) and A3 (aa 1-90) antibodies were associated with proximal muscle weakness, Raynaud phenomenon, arthritis, and sicca syndrome. Anti-fragment A4 (aa 1-120) and A5 (aa 1-151) antibodies were also associated with sicca syndrome. Peptide 1 (aa 1-21) antibodies were associated with Raynaud phenomenon and dysphagia. Whereas anti-peptide 3 (aa 27-47) antibodies were also linked to Raynaud phenomenon, anti-peptide 9 (aa 105-125) antibodies were associated with mechanic's hands., Conclusion: Autoantibodies targeting different amino-terminal subfragments and/or peptides of Jo-1 were associated with specific clinical features of the anti-synthetase syndrome, demonstrating the biomarker potential of B cell epitope profiling in this disorder., (© 2024 The Author(s). ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Introduction Anti-diabetic drugs used for the treatment of type 2 diabetes mellitus (T2DM) have a unique effect on the body weight and fat distribution of a patient. This study aimed to find out the change in percentage body fat and body composition with the addition of sulfonylureas or dipeptidyl peptidase 4 (DPP-4) inhibitors to metformin monotherapy. Methods An observational 12-week follow-up study was conducted with a sample size of 52 patients. All patients enrolled in the study were evaluated for baseline percentage body fat and body composition parameters including total body weight, total body water, and skeletal muscle mass using the ACCUNIQ BC300, added on to either sulfonylureas or DPP-4 inhibitors over a stable dose of metformin; repeat assessment performed at 4 weeks and 12 weeks, and change in values was noted. Results Of the 52 patients, 28 patients were on sulfonylureas and 24 were on DPP-4 inhibitors. In the sulfonylurea group, there was an increase in percentage body fat from 31.97 ± 8.77% at baseline to 32.65 ± 8.94% at 12 weeks (p = 0.041), while in the DPP-4 inhibitor group, there was a decrease in percentage body fat from 31.87 ± 7.41% at baseline to 31.24 ± 8.5% at 12 weeks (p = 0.102). In the sulfonylurea group, there was a decrease in body weight from 67.25 ± 14.79 kilograms (kg) at baseline to 66.97 ± 14.62 kg at 12 weeks (p = 0.429). In the DPP-4 inhibitor group, there was a decrease in body weight from 66.56 ± 10.82 kg at baseline to 65.76 ± 12.56 kg at 12 weeks (p = 0.079). In the sulfonylurea group, total body water decreased from 32.54 ± 6.65 L at baseline to 32.06 ± 6.51 L at 12 weeks (p = 0.084), while in the DPP-4 inhibitor group, the total body water decreased from 32.46 ± 5.39 L at baseline to 32.18 ± 5.48 L at 12 weeks (p = 0.741). Skeletal muscle mass decreased from 24.78 ± 5.12 kg to 24.4 ± 5.04 kg (p = 0.041) in the sulfonylurea group and from 24.74 ± 4.2 kg to 24.53 ± 4.25 kg (p = 0.666) in the DPP-4 inhibitor group. Conclusion Our study shows that sulfonylureas are associated with an increase in percentage body fat, while there were no significant changes associated with DPP-4 inhibitors when given in addition to metformin. There are no significant changes in body weight associated with sulfonylureas or DPP-4 inhibitors in addition to metformin. Also, sulfonylureas are associated with a decrease in skeletal muscle mass after 12 weeks., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Ethics Committee issued approval LHMC/IEC/2022/PG Thesis/45. Dr. Ramesh Aggarwal Department of General Medicine Lady Hardinge Medical College & Associated Hospitals New Delhi Sub: IEC approval in respect of the thesis research protocol of Dr. Vishesh Goel, PG student, entitled "Change in percentage body fat at 4 weeks and 12 weeks of addition of Sulfonylureas or DPP-4 inhibitors in type 2 diabetes mellitus patients on metformin.". A meeting of the LHMC, Institutional Ethics Committee (IEC) was held under the chairmanship of Dr Rakesh Kumar on 15/09/2022 in the Swarnjyanti Auditorium, First Floor, MEU Hall, Lady Hardinge Medical College and Associated Hospital, New Delhi. Following members attended the meeting. 1. Dr Rakesh Kumar External Member Chairperson 2. Dr Harish K. Pemde Internal Member Member Secretary and Clinician 3. Mr Rajeev R Singh External Member Social Scientist 4. Dr Monika Bahl External Member Medical Scientist 5. Dr Anup Mohta Internal Member Clinician 6. Dr LH Ghotekar Internal Member Clinician 7. Dr Anita Nangia Internal Member Basic Medical Scientist 8. Dr Manish K. Goel Internal Member Public Health Expert 9. Dr Prerna Kukreti Internal Member Basic Medical Scientist 10. Dr Umesh D Suranagi Internal Member Basic Medical Scientist The above mentioned thesis research protocol is "Approved" for conduct by Dr. Vishesh Goel, as a PG Thesis work under your guidance under the jurisdiction of Lady Hardinge Medical College, and Associated Hospitals, New Delhi. The study should be conducted in accordance with the provisions of New Drugs and Clinical Trial Rules 2019, Good Clinical Practices, and the ICMR Guidelines for Biomedical Research on Human Participants (2017). You are required to inform Member Secretary, IEC, LHMC about any serious adverse events or death of study participants within 24 hours of the incident. Dr. Harish K. Pemde Member Secretary Institutional Ethics Committee, Lady Hardinge Medical College & Associated Hospitals, New Delhi. 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, Goel et al.)

Introduction: Mung beans contain various antinutritional components. Processing and cooking methods can reduce these antinutritional factors and increase the availability and digestibility of nutrients. Resistant starch is also known as dietary fiber, which helps to reduce the cholesterol and glucose level in blood. It is formed during cooking and storage of food at low temperature., Objectives: This study aimed to assess the effects of cooking and storage temperature on the formation of resistant starch in processed mung bean, as well as its effect on blood glucose levels and lipid profile in humans and rats., Methods: The common cooking methods namely boiling, steaming after germination, roasting, and pressure cooking were chosen. The cooked samples were stored at different temperatures including freshly prepared within 1 h (T1), stored for 24 h at room temperature (20-22°C) (T2), kept at 4°C for 24 h (T3), and reheated after storing at 4°C for 24 h (T4)., Results: The study revealed that germinated-steamed mung beans had significantly higher levels of resistant starch (27.63 ± 0.76), and lower level of glycemic index (26.28 ± 3.08) and amylose (40.91 ± 0.06) when stored at 4°C for 24 h (T3) followed by (T2), (T4), and (T1) as compared to other cooking methods (boiling, pressure cooking, and roasting). The germinated-steamed mung beans (T1) resulted in 96% decline in blood glucose parameters of rats (36 Wistar albino rats aged 2 to 3 months were selected) than the control group as observed in 28 days diet intervention (100 mg/kg resistant starch orally)., Conclusion: There is a need to make people aware about the selection of appropriate cooking (steamed after germination) and storage methods (T3) to increase the RS content and to lower the glycemic index of food at domestic level., 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 Chauhan, Kaur, Aggarwal, Kaur and Bains.)

Molecular interactions between proteins and their ligands are important for drug design. A pharmacophore consists of favorable molecular interactions in a protein binding site and can be utilized for virtual screening. Pharmacophores are easiest to identify from co-crystal structures of a bound protein-ligand complex. In this work, however, we develop a deep learning method that can identify pharmacophores in the absence of a ligand. Specifically, we train a CNN model to identify potential favorable interactions in the the binding site, and develop a deep geometric Q-learning algorithm that attempts to select an optimal subset of these interaction points to form a pharmacophore. With this algorithm, we show better prospective virtual screening performance, in terms of F1 scores, on the DUD-E dataset than random selection of ligand identified features from co-crystal structures. We also conduct experiments on the LIT-PCBA dataset and show that it provides efficient solutions for identifying active molecules. Finally, we test our method by screening the COVID moonshot dataset and show that it would be effective in identifying prospective lead molecules even in the absence of fragment screening experiments. Alongside, we provide a Google Colab notebook for ease of use of the developed method., Competing Interests: Additional Declarations: No competing interests reported.

Metastatic castration-resistant prostate cancer (mCRPC) is a lethal disease that resists therapy targeting androgen signaling, the primary driver of prostate cancer. mCRPC resists androgen receptor (AR) inhibitors by amplifying AR signaling or by evolving into therapy-resistant subtypes that do not depend on AR. Elucidation of the epigenetic underpinnings of these subtypes could provide important insights into the drivers of therapy resistance. In this study, we produced chromatin accessibility maps linked to the binding of lineage-specific transcription factors (TF) by performing assay for transposase-accessible chromatin sequencing on 70 mCRPC tissue biopsies integrated with transcriptome and whole-genome sequencing. mCRPC had a distinct global chromatin accessibility profile linked to AR function. Analysis of TF occupancy across accessible chromatin revealed 203 TFs associated with mCRPC subtypes. Notably, ZNF263 was identified as a putative prostate cancer TF with a significant impact on gene activity in the double-negative subtype (AR- neuroendocrine-), potentially activating MYC targets. Overall, this analysis of chromatin accessibility in mCRPC provides valuable insights into epigenetic changes that occur during progression to mCRPC. Significance: Integration of a large cohort of transcriptome, whole-genome, and ATAC sequencing characterizes the chromatin accessibility changes in advanced prostate cancer and identifies therapy-resistant prostate cancer subtype-specific transcription factors that modulate oncogenic programs., (©2024 American Association for Cancer Research.)

The World Health Organization's Immunization and Vaccines-related Implementation Research Advisory Committee (IVIR-AC) serves to independently review and evaluate vaccine-related research to maximize the potential impact of vaccination programs. From 28 June - 1 July 2024, IVIR-AC was convened for an ad hoc meeting to discuss new evidence on criteria for rubella vaccine introduction and the risk of congenital rubella syndrome. This report summarizes background information on rubella virus transmission and the burden of congenital rubella syndrome, meeting structure and presentations, proceedings, and recommendations., Competing Interests: Declaration of competing interest P. L. was supported by the Bill & Melinda Gates Foundation for this work. S. S. was supported by the World Health Organization for this work. A. N. S. was financially supported by the World Health Organization for this work, and is additionally supported by the Bill & Melinda Gates Foundation, Gavi, the Vaccine Alliance, and the National Institutes of Health. K. F. is employed by the Bill & Melinda Gates Foundation. M. F. is supported by the National Science Foundation, the Bill & Melinda Gates Foundation, Gavi, the Vaccine Alliance, Centers for Disease Control and Prevention, and Imperial College London. E. V. was supported for this work by Gavi, the Vaccine Alliance via the Vaccine Impact Modeling Consortium (VIMC), which is jointly funded by Gavi, the Vaccine Alliance and the Bill & Melinda Gates Foundation. C. J. E. M. has previously received travel funds to visit the Max Plank Institute of Evolutionary Anthropology. A. K. W. was supported for this work by Gavi, the Vaccine Alliance, is additionally supported by the Bill & Melinda Gates Foundation, and has previously received travel funds from Gavi, the Vaccine Alliance. M. K. was supported for this work by the Bill & Melinda Gates Foundation. A. P. is supported by Gavi, the Vaccine Alliance, Imperial College London, the Bill & Melinda Gates Foundation, and the World Health Organization. A. B. H. was supported by the Australian National Health and Medical Research Council for this work, is additionally supported by the Australian NSW Ministry of Health, PATH, the World Health Organization, and Gavi, the Vaccine Alliance, and has received consulting fees from the Australian NSW Ministry of Health, WHO Europe and Asian Development Bank. A. N. S. and M. F. report travel related support from the World Health Organization to attend previous IVIR-AC meetings. All other authors have no declarations., (Copyright © 2024. Published by Elsevier Ltd.)

Introduction: Kawasaki disease [KD] is a systemic disorder characterized by acute febrile illness due to widespread medium-vessel vasculitis, mainly affecting children. Despite the ongoing advanced research into the disease pathophysiology and molecular mechanisms, the exact etiopathogenesis of KD is still an enigma. Recently, single-cell RNA sequencing [scRNA-seq], has been utilized to elucidate the pathophysiology of KD at a resolution higher than that of previous methods., Area Covered: In the present article, we re-emphasize the pivotal role of this high-resolution technique, scRNA-seq, in the characterization of immune cell transcriptomic profile and signaling/response pathways in KD and explore the diagnostic, prognostic, and therapeutic potential of this new technique in KD. Using combinations of the search phrases 'KD, scRNA-seq, CAA, childhood vasculitis' a literature search was carried out on Scopus, Google Scholar, and PubMed until the beginning of 2024., Expert Opinion: scRNA-seq presents a transformative tool for dissecting KD at the cellular level. By revealing rare cell populations, gene expression alterations, and disease-specific pathways, scRNA-seq aids in understanding the intricacies of KD pathogenesis. This review will provide new insights into pathogenesis of KD and the field of applications of scRNA-seq in personalized therapeutics for KD in the future.

Cancer, defined by uncontrolled cell growth, poses a significant global health challenge, necessitating the development of new anticancer drugs crucial to address drug resistance, side effects, and the need for combination therapies. The study presents the design, synthesis, and anticancer screening of a series of novel functionalized arylidene-hydrazinyl-thiazoles against various human cancer cell lines. The environmentally benign synthetic protocol involves the visible-light prompted, NBS-mediated domino reaction of thiosemicarbazide, heteroaryl aldehydes, and unsymmetrical 1,3-diketones. The regioselective organic transformation delivered the single regioisomeric product, characterized unambiguously through detailed 2D NMR spectral studies. In vitro cytotoxic studies revealed that the synthesized derivatives exhibited excellent cytotoxic potential against BxPC-3, MOLT-4, and MCF-7 cancer cell lines. Notably, compounds 4m , 4n , and 4r showed significant cytotoxicity, reducing cell survival to 23.85-26.45% for BxPC-3, 30.08-33.30% for MOLT-4, and 44.40-47.63% for MCF-7 at a concentration of 10 μM. These compounds profoundly induced apoptosis, evidenced by increased caspase-3/7 activity, loss of mitochondrial membrane potential, and modulation of Bcl2 and Bax gene expression. Additionally, these compounds caused robust cell cycle arrest at the G 2 /M phase by inhibiting tubulin polymerization, indicating their multifaceted impact on cancer cells., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Objective: The 6-min walk test (6MWT) is a simple test widely used to assess sub-maximal exercise capacity in chronic respiratory diseases. We explored the relationship of 6-min walk distance (6MWD) with measurements of physiological, clinical, radiographic measures in patients with myositis-associated interstitial lung disease (MA-ILD)., Method: We analyzed data from the Abatacept in Myositis Associated Interstitial lung disease (Attack My-ILD) study, a 48-week multicentre randomized trial of patients with anti-synthetase antibodies and active MA-ILD. 6MWD, forced vital capacity (FVC), diffusing capacity (DLCO), high resolution CT, and various physician/patient reported outcome measures were obtained during the trial. Spearman's correlations and repeated-measures analysis with linear mixed-effects models were used to estimate the associations between 6MWD and various physiologic, clinical and radiographic parameters both cross-sectionally and longitudinally., Results: Twenty participants with a median age of 57, 55% male and 85% white were analyzed. Baseline 6MWD did not associate with baseline PFTs. Repeated-measures analysis showed 6MWD over time associated with FVC over time, but not with DLCO. 6MWD over time also correlated with UCSD dyspnea score, Borg scores, as well as global disease activity and muscle strength over time. Emotional role functioning, vitality, general health and physical functioning scores by short form 36 also correlated with 6MWD over time., Conclusions: : Exploratory work in a small cohort of MA-ILD demonstrated 6MWD over time associated with parallel changes in FVC and patient reported outcomes of dyspnea, but not with DLCO. Larger studies are needed to validate the reliability, responsiveness and utility of the 6MWT in MA-ILD., Clinical Trial Registration: ClinicalTrials.gov, NCT03215927., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Healthy state is priority in today's world which can be achieved using effective medicines. But due to overuse and misuse of antibiotics, a menace of resistance has increased in pathogenic microbes. World Health Organization (WHO) has announced ESKAPE pathogens ( Enterococcus faecium , Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) as the top priority pathogens as these have developed resistance against certain antibiotics. To combat such a global issue, it is utmost important to identify novel therapeutic strategies/agents as an alternate to such antibiotics. To name certain antibiotic adjuvants including: inhibitors of beta-lactamase, efflux pumps and permeabilizers for outer membrane can potentially solve the antibiotic resistance problems. In this regard, inhibitors of lytic domain of lytic transglycosylases provide a novel way to not only act as an alternate to antibiotics but also capable of restoring the efficiency of previously resistant antibiotics. Further, use of bacteriophages is another promising strategy to deal with antibiotic resistant pathogens. Taking in consideration the alternatives of antibiotics, a green synthesis nanoparticle-based therapy exemplifies a good option to combat microbial resistance. As horizontal gene transfer (HGT) in bacteria facilitates the evolution of new resistance strains, therefore identifying the mechanism of resistance and development of inhibitors against it can be a novel approach to combat such problems. In our perspective, host-directed therapy (HDT) represents another promising strategy in combating antimicrobial resistance (AMR). This approach involves targeting specific factors within host cells that pathogens rely on for their survival, either through replication or persistence. As many new drugs are under clinical trials it is advisable that more clinical data and antimicrobial stewardship programs should be conducted to fully assess the clinical efficacy and safety of new therapeutic agents.

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.

Notwithstanding the wealth of literature on COVID-19, studies focusing on young adults with autoimmune diseases (AD) are lacking. To determine early (within 7 days) and late (after 7 days) anti-SARS-CoV-2 vaccine-related adverse events (AEs), post-vaccine disease flares, COVID-19 severity and breakthrough infections (B-INFs) in young people with rheumatic diseases (RMDs) and non-rheumatic autoimmune diseases (nr-ADs) compared to healthy controls (HC). Data were captured through the international COVID-19 vaccination in autoimmune diseases (COVAD) 1 and 2 questionnaires. Of 20,685 complete responses, we identified 6010 from patients aged 18-35 years (1692 RMD, 400 nrADs, 3918 HC) who received up to 4 vaccine doses. BNT162b2 was the most frequently administered vaccine and prior to vaccination, 7% of people with nrAD were taking immunosuppressants (IS) versus 80% in RMDs. Early mild AEs were more frequent in RMDs (93%) and nr-ADs (92%) compared to HC (85%). The frequency of late mild AEs was < 20% in all groups. Severe AEs were rare. SARS-CoV-2 infection rates were similar across all groups, however, RMD patients reported a single episode of infection more frequently than nrADs and HC, while nrADs reported multiple infections more frequently than RMD. Self-reported disease flares were reported by 10% or RMD and 7% of nrAD patients. Our study reinforces the safety of anti-SARS-CoV-2 vaccine also in young people with ADs, but it also highlights that among young individuals the number and clinical picture of SARS-CoV-2 infections is affected more by the type of AD rather than by coexisting IS therapy., (© 2024. The Author(s).)

Competing Interests: Disclosures RA reports receiving grants from the Bristol Myers Squibb Pfizer alliance, serving as a consultant for Lexicon Pharmaceuticals and an unpaid research collaboration with Novartis, all outside the submitted work. BLC reports personal fees from Alnylam, personal fees from Cardior, Cardurion, Corvia, Cytokinetics, CVRx, Intellia, and Rocket, outside the submitted work. ASD has received honoraria for consulting or speaking from Abbott, AstraZeneca, Alnylam, Avidity Biopharma, Axon Therapeutics, Bayer, Biofourmis, Boston Scientific, GlaxoSmithKline, Medpace, Medtronic, Merck, New Amsterdam Pharma, Novartis, Parexel, Regeneron, River2Renal, Roche, scPharmaceuticals, Verily, Veristat, and Zydus and has received institutional research grant support from Abbott, Alnylam, AstraZeneca, Bayer, Novartis, and Pfizer. PSJ reports receiving speaker fees from Novartis and AstraZeneca, Alkem metabolomics, Sun Pharmaceuticals and ProAdWise Communications and his employer, University of Glasgow has been paid for his time working on clinical trials by Novartis, AstraZeneca, Bayer and NovoNordisk, and grants from Analog Devices Inc, Boehringer Ingelheim, and Roche Diagnostics outside the submitted work, Director GCTP Ltd. CSPL is supported by a Clinician Scientist Award from the National Medical Research Council of Singapore; has received research support from Novo Nordisk and Roche Diagnostics, has served as consultant to or on the advisory board/steering committee/ executive committee for Alleviant Medical, Allysta Pharma, AnaCardio AB, Applied Therapeutics, AstraZeneca, Bayer, Biopeutics, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, CardioRenal, CPC Clinical Research, Eli Lilly, Impulse Dynamics, Intellia Therapeutics, Ionis Pharmaceutical, Janssen Research & Development, Medscape/WebMD Global, Merck, Novartis, Novo Nordisk, Prosciento, Quidel Corporation, Radcliffe Group, Recardio, ReCor Medical, Roche Diagnostics, Sanofi, Siemens Healthcare Diagnostics and Us2.ai, and serves as cofounder and nonexecutive director of Us2.ai. BP has served as a consultant for Bayer, AstraZeneca, Bristol Meyers Squibb, Boehringer Ingelheim, Lexicon, Anacardia, and G3 Pharmaceuticvals and has served as a consultant and received stock options or stocks from Sea Star Medical, Vifor, Scpharmaceuticals, SQinnovations, KBP Biosciences, Sarfez, Cereno Scientific, Prointel, and Brainstorm Medical; holds a U.S. patent (9931412-site specific delivery of Eplerenone to the myocardium) and has a U.S. patent pending (63/045,783 Histone Modulating agents for the prevention and treatment of organ damage). MS reports personal fees from Novartis, Bayer, Vifor, Abbott, AstraZeneca, Merck, Boehringer Ingelheim, Novo Nordisk, MSD, and Cardurion outside the submitted work. SJS reports personal fees from Bayer during the conduct of the study. The employer of AAV received consultancy fees and/or research support from Adrenomed, Anacardio, AstraZeneca, Bayer AG, BMS, Boehringer Ingelheim, Corteria, EliLilly, Merck, Moderna, Novartis, Novo Nordisk, Roche diagnostics, SalubrisBio. FZ reports steering committee fees during the conduct of the study, personal fees from Boehringer, BMS, CVRx, Cardior, Cereno, Cellprothera, Merck, Owkin, Roche, and Northsea outside the submitted work and stock options at G3Pharmaceutical and equities at Cereno, Cardiorenal, Eshmoun Clinical and is a researchr and founder of CVCT. JL-F is a full-time employee of Bayer and reports personal fees from Bayer outside the submitted work. PV reports that he is a full-time employee of Bayer Pharmaceuticals. JJVM reports payments to his employer, Glasgow University, from Bayer, time spent as coprincipal investigator of the FINEARTS trial with finerenone; other fees from AstraZeneca, Amgen, Cardurion, Cytokinetics, Glaxo Smith Kline, KBP Biosciences, Novartis, and personal fees from George Clinical PTY, Abbott, Alkem Metabolics, AstraZeneca, Blue Ocean Scientific Solutions, Boehringer Ingelheim, Canadian Medical and Surgical Knowledge, Emcure Pharmaceuticals, Eris Lifesciences, European Academy of CME, Hikma Pharmaceuticals, Imagica Health, Intas Pharmaceuticals, J.B. Chemicals & Pharmaceuticals, Lupin Pharmaceuticals, Medscape/Heart.Org., ProAdWise Communications, Radcliffe Cardiology, Sun Pharmaceuticals, The Corpus, Translation Research Group, Translational Medicine Academy, Global Clinical Trial Partners , Alnylam Pharmaceuticals, Bayer, BMS, Ionis Pharmaceuticals, Novartis, Regeneron Pharmaceuticals, and River 2 Renal outside the submitted work. SDS has received research grants from Alexion, Alnylam, AstraZeneca, Bellerophon, Bayer, BMS, Boston Scientific, Cytokinetics, Edgewise, Eidos, Gossamer, GSK, Ionis, Eli Lilly, MyoKardia, NIH/NHLBI, Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, Theracos, US2.AI and has consulted for Abbott, Action, Akros, Alexion, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer-Ingelheim, BMS, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GSK, Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Janssen, Cardiac Dimensions, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, Akros, and Valo. MV has received research grant support, served on advisory boards or had speaker engagements with American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, BMS, Boehringer Ingelheim, Chiesi, Cytokinetics, Lexicon Pharmaceuticals, Merck, Novartis, Novo Nordisk, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health and participates in clinical trial committees for studies sponsored by AstraZeneca, Galmed, Novartis, Bayer AG, Occlutech, and Impulse Dynamics. JWO has nothing to disclose.

Purpose: To create a simple model using standard BI-RADS® descriptors from pre-treatment B-mode ultrasound (US) combined with clinicopathological tumor features, and to assess the potential of the model to predict the presence of residual tumor after neoadjuvant chemotherapy (NAC) in breast cancer (BC) patients., Method: 245 female BC patients receiving NAC between January 2017 and December 2019 were included in this retrospective study. Two breast imaging fellows independently evaluated representative B-mode tumor images from baseline US. Additional clinicopathological tumor features were retrieved. The dataset was split into 170 training and 83 validation cases. Logistic regression was used in the training set to identify independent predictors of residual disease post NAC and to create a model, whose performance was evaluated by ROC curve analysis in the validation set. The reference standard was postoperative histology to determine the absence (pathological complete response, pCR) or presence (non-pCR) of residual invasive tumor in the breast or axillary lymph nodes., Results: 100 patients (40.8%) achieved pCR. Logistic regression demonstrated that tumor size, microlobulated margin, spiculated margin, the presence of calcifications, the presence of edema, HER2-positive molecular subtype, and triple-negative molecular subtype were independent predictors of residual disease. A model using these parameters demonstrated an area under the ROC curve of 0.873 in the training and 0.720 in the validation set for the prediction of residual tumor post NAC., Conclusions: A simple model combining standard BI-RADS® descriptors from pre-treatment B-mode breast US with clinicopathological tumor features predicts the presence of residual disease after NAC., 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 B.V. All rights reserved.)

Objective: To investigate psychological correlates in women referred with suspected ovarian cancer via the fast-track pathway, explore how anxiety and distress levels change at 12 months post-testing, and report cancer conversion rates by age and referral pathway., Design: Single-arm prospective cohort study., Setting: Multicentre. Secondary care including outpatient clinics and emergency admissions., Population: A cohort of 2596 newly presenting symptomatic women with a raised CA125 level, abnormal imaging or both., Methods: Women completed anxiety and distress questionnaires at recruitment and at 12 months for those who had not undergone surgery or a biopsy within 3 months of recruitment., Main Outcome Measures: Anxiety and distress levels measured using a six-item short form of the State-Trait Anxiety Inventory (STAI-6) and the Impact of Event Scale - Revised (IES-r) questionnaire. Ovarian cancer (OC) conversion rates by age, menopausal status and referral pathway., Results: Overall, 1355/2596 (52.1%) and 1781/2596 (68.6%) experienced moderate-to-severe distress and anxiety, respectively, at recruitment. Younger age and emergency presentations had higher distress levels. The clinical category for anxiety and distress remained unchanged/worsened in 76% of respondents at 12 months, despite a non-cancer diagnosis. The OC rates by age were 1.6% (95% CI 0.5%-5.9%) for age <40 years and 10.9% (95% CI 8.7%-13.6%) for age ≥40 years. In women referred through fast-track pathways, 3.3% (95% CI 1.9%-5.7%) of pre- and 18.5% (95% CI 16.1%-21.0%) of postmenopausal women were diagnosed with OC., Conclusions: Women undergoing diagnostic testing display severe anxiety and distress. Younger women are especially vulnerable and should be targeted for support. Women under the age of 40 years have low conversion rates and we advocate reducing testing in this group to reduce the harms of testing., (© 2024 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Objectives: Idiopathic Inflammatory Myopathies (IIM) are rare and characterized by heterogeneous manifestations and clinical trajectories. Utilizing tele-research methods has the potential to improve participant recruitment and advance the understanding of the disease. We aimed to evaluate disease characteristics in IIM patients throughout the U.S. and compare these parameters between patients recruited remotely through mobile application or website vs those recruited locally in myositis clinics., Methods: "Myositis Patient Centered Tele-Research" (My PACER) is a multicentre prospective observational study of U.S. IIM subjects, competitively recruited through traditional in-person clinic visits (Center-Based Cohort [CBC]), and remotely using mobile application or website and social media (Tele-Research Cohort [TRC]). Data collection comprised baseline demographic and clinical variables, encompassing symptoms, organ involvement, diagnostic tests results and medication use., Results: The study included 120 IIM patients, 82 in the TRC and 38 in the CBC. The average age was 55 ± 13.4, 75% females and 81% Caucasians. Both cohorts exhibited similar demographic characteristics. Overall, 41% dermatomyositis, 27% polymyositis, 23% anti-synthetase syndrome, and 9% necrotizing myositis patients were enrolled, with comparable subtypes prevalence among cohorts (p= 0.85). The groups demonstrated similarities in multiple clinical factors, including muscle enzymes, diagnostic delay, employment status, various patient and physician-reported outcomes, functional tests, and the frequency of abnormal findings in chest CT, pulmonary function tests, and electromyography. TRC patients received biologics and csDMARDs more frequently (p< 0.001 and p= 0.013, respectively)., Conclusion: Tele-research recruitment yielded a patient cohort resembling traditionally recruited patients demographically and clinically, indicating its effectiveness for robust and diverse patient recruitment in clinical studies., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: Anti-melanoma differentiation-associated gene 5 antibody-positive (MDA5+) dermatomyositis patients exhibit clinical features that vary by geographical and ethnic/genetic distribution. We therefore investigated whether B cell epitope profiles and corresponding clinical features distinguished two independent cohorts of MDA5+ dermatomyositis., Methods: We used ELISA-based methods to determine the relationship between antibody recognition of overlapping 155 amino acid MDA5 subfragments and clinical features of 17 MDA5+ dermatomyositis patients from Japan. Associations between clinical features and standardized anti-MDA5 subfragment antibody titers were assessed via Brunner Munzel testing and compared with clinical/serological profiles of an independent North American cohort. ROC analyses and Kaplan-Meier curves were used to further assess the relationship between anti-MDA5 fragment antibody levels and specific clinical features/outcomes., Results: Clinical characterization of a Japanese cohort of 17 MDA5+ dermatomyositis patients revealed a high prevalence of arthritis (47%) and interstitial lung disease (ILD) (100%). Serological profiling demonstrated predominant antibody recognition of MDA5 fragments A (aa 1-155), B (aa 130-284), and E (aa 517-671) in a pattern that was distinct from North American MDA5+ patients (n = 24) whose sera preferentially recognized fragment H (aa 905-1026). Statistical analysis revealed a striking association between anti-fragment A antibody levels and rapidly progressive ILD (RP-ILD) among Japanese patients (p< 0.01). ROC and Kaplan Meier curves also demonstrated a strong relationship between anti-fragment A antibody levels, RP-ILD, and pulmonary death in combined cohort analyses., Conclusions: Japanese and North American MDA5+ dermatomyositis patients manifest markedly different B cell epitope profiles that are associated with higher prevalence of RP-ILD and worse clinical outcome among Japanese patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)