Search

Abstract: The European LeukemiaNet (ELN) acute myeloid leukemia (AML) genetic risk classification systems are based on response to intensive chemotherapy; their ability to discriminate outcomes in older patients treated with venetoclax-azacitidine may be suboptimal. This pooled analysis of the phase 3 VIALE-A trial (NCT02993523) and phase 1b study (NCT02203773) examined prognostic stratification according to the 2017 and 2022 ELN risk classifications and derived new molecular signatures differentiating venetoclax-azacitidine-treated patients based on overall survival (OS). Overall, 279 patients treated with venetoclax-azacitidine and 113 patients treated with placebo-azacitidine were analyzed. The ELN 2017 or 2022 prognostic criteria classified most patients as adverse-risk AML (60.2% and 72.8% for venetoclax-azacitidine and 65.5% and 75.2% for placebo-azacitidine, respectively). Although outcomes with venetoclax-azacitidine improved across all ELN risk groups compared with placebo-azacitidine, ELN classification systems poorly discriminated venetoclax-azacitidine outcomes. By applying a bioinformatic algorithm, new molecular signatures were derived differentiating OS outcomes with venetoclax-azacitidine. The mutational status of TP53, FLT3 internal tandem duplication (FLT3-ITD), NRAS, and KRAS categorized patients into higher-, intermediate-, and lower-benefit groups (52%, 25%, and 23% of patients, respectively), each associated with a distinct median OS (26.5 months [95% confidence interval (CI), 20.2-32.7]; 12.1 months [95% CI, 7.3-15.2]; and 5.5 months [95% CI, 2.8-7.6], respectively). ELN prognostic classifiers did not provide clinically meaningful risk stratification of OS outcomes in patients treated with venetoclax-azacitidine. TP53, FLT3-ITD, NRAS, and KRAS mutation status allows the classification of these patients into 3 risk groups with distinct differences in median OS. These trials were registered at www.clinicaltrials.gov as #NCT02993523 and #NCT02203773., (© 2024 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Analyzing root exudates during drought poses a serious challenge; sampling root exudates in soil is destructive to roots and leads to biased molecular analysis, along with microbial decomposition and exudate sorption to soil components. Hydroponic approaches are useful to overcome these problems but lack the utility to induce drought. Nondestructive sampling techniques are thus needed to analyze root exudates from the same plants over time in combination with highly controlled variable water/nutrient stress. The proposed aeroponic approach demonstrated that cotton could be grown to maturity in the aeroponic system, then a progressive drought treatment applied while simultaneously collecting root exudates from the same plants over time. Treatments of varying irrigation rates consisted of well-watered cotton (control) that was compared to cotton given progressive water stress (drought) and subsequent drought recovery for two weeks. Plants were entering flowering as drought treatment was applied. Nondestructive morphological measurements of plant productivity were made. Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) was employed to analyze the molecular profile of exudates, whereas gas chromatography-mass spectroscopy (GC-MS) was used to quantify abscisic acid (ABA). Plant development was highly responsive to reduced irrigation intervals with decreased canopy height, number of green leaves, biomass, and water content. As revealed by FT-ICR MS, the complexity and connectivity of unique biochemical transformation networks in response to drought was greatest at 9 days after treatment, where severe visual symptoms were observed. Overall, the aeroponic approach is a promising technology to simulate drought while sampling root exudates nondestructively, advancing root system research and plant-stress response mechanisms., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Spin-helical Dirac Fermions at a doped topological insulator's boundaries can support Majorana quasiparticles when coupled with s -wave superconductors, but in n -doped systems, the requisite induced Cooper pairing in topological states is often buried at heterointerfaces or complicated by degenerate coupling with bulk conduction carriers. Rarely probed are p -doped topological structures with nondegenerate Dirac and bulk valence bands at the Fermi level, which may foster long-range superconductivity without sacrificing Majorana physics. Using ultrahigh-resolution photoemission, we report proximity pairing with a large decay length in p -doped topological Sb 2 Te 3 on superconducting Nb. Despite no momentum-space degeneracy, the topological and bulk states of Sb 2 Te 3 /Nb exhibit the same isotropic superconducting gaps at low temperatures. Our results unify principles for realizing accessible pairing in Dirac Fermions relevant to topological superconductivity.

Objectives: Oral squamous cell carcinoma poses a substantial global health challenge marked by rising mortality rate. Recently, immunotherapy has shown promising results in cancer management by enhancing immune response. Thus, identifying additional immune-related markers is critical for advancing immunotherapy treatments., Methods: Data-independent acquisition mass spectrometry approach was used to explore differentially expressed immune-related proteins in oral cancer tissues compared to adjacent non-cancerous tissues. Functional significance was identified through Gene Ontology, pathway, and network analysis. Gene expression of identified proteins was validated using transcriptomic data., Results: DIA analysis identified 29,459 precursors corresponding to 3429 proteins. Among these, 1060 proteins were differentially expressed, with 166 being immune-related. Differentially regulated proteins were involved in innate immune response, mitochondrial ATP synthesis, and neutrophil degranulation. Pathway analysis of immune-related proteins showed perturbation in anti-tumor immunity-related pathways such as interferon signaling, TCR signaling, PD-1 signaling and antigen processing and presentation. Significance of these pathways was further reinforced by the strong interactions identified in the protein-protein interaction network analysis. Additionally, gene expression analysis showed similar mRNA expression patterns for key proteins involved in altered pathways, including ISG15, IFIT1/3, HLA-A/C and OAS2/3., Conclusions: Further validation of these proteins could establish them as potential targets for personalized therapy.

Objectives: Balloon dilation eustachian tuboplasty (BDET) has gained popularity as a treatment modality for chronic eustachian tube dysfunction (ETD) in both adults and children. Although its safety and efficacy in the adult population have been well described, very few large-sample studies assessing its safety profile have been performed in the pediatric population. This study serves as a follow-up to a previously published analysis assessing the safety of BDET in the pediatric population., Methods: Retrospective chart review of 71 pediatric patients (139 ears) aged 11 ± 7 years who underwent BDET from 2019 to 2023. Medical records were reviewed from the extended postoperative period. A standardized grading scale that assesses severity of surgical complications was used., Results: A total of five minor complications (7%) were noted. These included transient postoperative tinnitus, hyperacusis, otalgia, nausea, and epistaxis. There were no major complications requiring repeat intervention or need for imaging or hospital admission. In all cases, these symptoms had resolved in the postoperative time frame, with majority of them demonstrating complete resolution before the first postoperative visit.When combining these findings with the previously published paper by the same institution, the overall complication rate is 6.1% with 114 total patients. All complications between both papers are considered minor with no long-term effects., Conclusions: In this retrospective analysis, BDET is shown to be a relatively safe procedure when performed in the pediatric population. Upon review of the literature, this is the largest safety analysis of exclusively pediatric patients who underwent BDET., Level of Evidence: 4., (Copyright © 2024, Otology & Neurotology, Inc.)

Purpose: Gene fusions are critical oncogenic mutations that drive cancer development and serve as diagnostic and prognostic biomarkers. Despite the increasing cancer burden in India, large-scale analyses of molecular landscapes, particularly gene fusions, have been relatively scarce., Materials and Methods: This retrospective study used RNA-exome data from 1,392 Indian patients with cancer across 15 major cancer types to explore gene fusions. The study used a comprehensive framework that integrated open-source and proprietary tools to detect gene fusions from formalin-fixed paraffin-embedded tumor samples. The process involved RNA extraction, RNA-exome library preparation, and analysis using tools such as FastQC, DRAGEN RNA Pipeline, STAR-Fusion, and FusionInspector. We validated and filtered potential false-positive fusion calls using AGFusion and FusionAnnotator to annotate fusion breakpoints and their functional impact through various in silico tools., Results: The study found a notable prevalence of FGFR fusions across cancer types, especially FGFR3, with FGFR3::TACC3 as the most recurrent. Kinase fusions were prevalent in the cohort accounting for 37% of incidence in the patients. We also identified 91 novel potential driver fusions, including those involving FGFR2 , MET , ESR1 , and PDGFRA., Conclusion: This study underscores the critical role of gene fusions as biomarkers in cancer, extending beyond fusion-driven malignancies to encompass all cancer types. Gene fusions serve as both diagnostic markers and tumor-agnostic therapeutic targets within the current cancer treatment paradigm. Our insights into the prevalence of oncogenic drivers and novel targets expand the understanding of gene fusions, shedding new light on their mechanisms and clinical implications.

Although the overall prognosis for patients with non-small cell lung cancer (NSCLC) has improved over the past several decades, there are still survival differences that are not accurately defined by clinicopathological factors. Thus, there is an unmet clinical need to develop novel approaches to enhance prognostic accuracy for these patients. Keratin 17 (K17) is a negative prognostic biomarker in a wide range of cancer types, including pancreatic ductal adenocarcinoma, head and neck squamous cell carcinoma, and pulmonary adenocarcinoma (LUAD), but has yet to be investigated as a prognostic biomarker in primary lung squamous cell carcinoma (LSCC). Based on TCGA RNA-seq data, alpha-2-macroglobulin like 1 (A2ML1), a protease inhibitor, is highly correlated with K17 in other solid tumors, including pancreatic ductal adenocarcinoma and is also a prognostic biomarker for LSCC, although the prognostic accuracy of A2ML1 for LUAD has not been tested. Thus, we hypothesized that A2ML1 expression correlates with K17 expression and that K17/A2ML1 co-testing could provide complementary prognostic data for NSCLC. The aims of this study were to explore K17 and A2ML1 as dual prognostic biomarkers, using publicly available gene expression databases [The Cancer Genome Atlas (TCGA)] LSCC (n=266), LUAD (n=271)] and multiplexed immunohistochemistry (mIHC) on representative sections of LSCC (n=104) and LUAD (n=107) from two major academic medical centers. Our results suggest that using either mRNA or mIHC-based methods, combined K17 and A2ML1 testing provides information, independent of other clinicopathologic variables, that could impact treatment decisions for patients with NSCLC., Competing Interests: Declaration of Competing Interest K.R.S and L.F.E.-H. are consultants to KDx Diagnostics Inc. All other authors report no competing interests with the current study., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Objectives: Balloon dilation eustachian tuboplasty (BDET) has been proven to be a safe treatment option for children with eustachian tube dysfunction (ETD). This study aims to analyze the long-term outcomes of children who underwent concurrent BDET and tympanostomy tube (TT) placement. We hypothesize that patients who underwent simultaneous therapy have experienced a low overall rate of middle ear pathology and have consistent hearing quality at subsequent office visits., Methods: Retrospective chart review of 19 pediatric patients (36 ears) who previously underwent concurrent BDET and TT placement. Patient charts within the extended postoperative period were reviewed. Specific data points included need for reoperation, rates of middle ear pathology, audiological outcomes, and number of previous TT placements., Results: Pediatric patients who underwent concurrent BDET and TT placement had long-term success in 34/36 ears (94.4%). All postoperative tympanograms and audiograms (100%) were normal when performed within 12 months after the procedure. Notably, 34/36 ears (94.4%) had history of tube placement in the past. Patients had an average of three sets of tympanostomy tubes prior to undergoing concurrent BDET and TT., Conclusion: Concurrent BDET and TT placement may be an effective treatment option for pediatric patients with persistent eustachian tube dysfunction. Specifically, BDET may be a useful adjunct tool in pediatric patients with refractory ETD despite having multiple sets of tympanostomy tubes. This study aims to strengthen the argument of performing multimodal therapy in pediatric patients with recurrent middle ear disease., Level of Evidence: 4 Laryngoscope, 134:4799-4802, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

This study reports on the development and pilot testing of an emotional support provision training intervention for interpersonal support providers to those with chronic illnesses. Using findings from a needs assessment in combination with existing theory and research, we created a training framework consisting of verbal person-centered message design, empathic listening, and communicated perspective-taking. Then, we recruited 282 individuals to participate in a pre-training questionnaire, the online training module, a post-training questionnaire, and a two-week post-training questionnaire. Outcome variables included emotional support knowledge, efficacy, and intentions, as well as general support efficacy, response efficacy, and quality. Repeated measures MANCOVA revealed significant increases from T1 to T2 for all variables of interest. These increases were sustained at T3 for emotional support knowledge and efficacy, and support provision response efficacy. Participants rated the training favorably and provided helpful suggestions for improvement. This study answers the call for more theoretically-grounded support interventions that not only assess theory in real-world settings, but also help people better their supportive communication skills.

Atmospheric aerosols have a serious impact on altering the radiation balance of the vulnerable Himalayan atmosphere. Organic aerosol (OA), one of the least resolved aerosol fractions in the Himalayas, constrain our competence to assess their climate impacts on the region. Here we investigate water-soluble OA molecules in PM 10 samples collected from March to May 2019 at Lachung (27.4°N and 88.4°E), a high-altitude location (2700 m a.s.l.) in the eastern Himalaya, to elucidate their origin and formation process. The dominance of oxalic acid (C 2 ) reveals that water-soluble OA in the eastern Himalaya are atmospherically processed. Backward air mass trajectories and mass concentration ratios of organic tracers as well as relationships with inorganic species (K + , SO 4 2- , NH 4 + ) suggest an anthropogenic origin of water-soluble OA with significant atmospheric processing during long-range transport to the eastern Himalayan region. We used the thermodynamic prediction of aerosol liquid water (ALW) to examine the formation mechanism of secondary OA (SOA) such as oxalic acid. Correlations of ALW with SO 4 2- and water-soluble organic matter show that ALW is sensitive to both anthropogenic sulfate and water-soluble organic compounds in Himalayan aerosols. A strong positive relationship of C 2 acid with predicted ALW provides evidence of extensive SOA formation from precursors via aqueous phase photochemical processes. This inference is supported by positive correlations of C 2 acid relative abundance with diagnostic mass concentration ratios of C 2 acid to precursor molecules. Our findings underscore the importance of anthropogenic sources and ALW in SOA formation through aqueous phase processes in the eastern Himalaya., 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.)

Objective: Diabetic neuropathy is associated with mitochondrial dysfunction and neuroinflammation. Chronic hyperglycemia triggers inflammatory responses and oxidative stress, causing peripheral neuropathy, whereas mitochondrial dysfunction caused by increased ROS generation and reduced bioenergetics maintains the inflammatory cycle. The purpose of this study is to evaluate the pharmacological efficacy of Bay 11-7082 (B11) against diabetic neuropathy in rats., Methods: B11 was administered at doses of 1 and 3 mg/kg to STZ-induced diabetic animals (55 mg/kg, i.p). Behavioral and functional assessments were conducted to assess neuropathy. Molecular protein expressions were evaluated for B11's efficacy against STZ-induced diabetic neuropathic rats and in SHSY5Y cells exposed to 175 mM of d-glucose., Results: Diabetic rats exhibited deficits in nerve functions, altered nociceptive parameters, and increased expression of NLRP3, ASC, Caspase-1, and NF-κB. Additionally, diabetic animals showed reduced levels of PGC1α/Nrf2/HO-1, with an overexpression of PARP1. Compromised mitochondrial function was evident through increased mitochondrial dynamic marker DRP1 and elevated levels of inflammatory cytokines TNF-α, IL-1β, IL-18, and IL-6. However, B11 administration significantly ameliorated these changes, suggesting that B11's NLRP3 inhibition may be attributed to the activation of the mitochondrial biogenesis pathway via PGC1α/Nrf2/HO-1, along with improved mitochondrial health. In high glucose exposed SHSY5Y cells, B11 treatment attenuated neuroinflammation by inhibiting NLRP3 activation and reducing mitochondrial damage., Conclusion: B11, showed a protective effect against diabetic neuropathy by inhibiting oxidative stress, NLRP3 activation, and improving mitochondrial health in experimental diabetic neuropathy. This study provides new mechanistic insights into the neuroprotective role of Bay 11-7082 against diabetic neuropathy., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest. Data availability Data will be made available on request., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: To characterize the inflammatory cytokine profiles in children with TB in the presence and absence of SARS-CoV2 seropositivity., Methods: This study evaluated cytokine responses in two groups of children with TB: CoV2+ (TB and SARS-CoV2 seropositive) and CoV2- (TB and SARS-CoV2 seronegative). Each group had 30 children, and cytokine levels were measured at baseline, months 3 and 6., Results: At baseline, CoV2+ children exhibited significantly elevated levels of cytokines, including IFN-γ, IL-2, TNFα, IL-1α, and IL-6, and reduced levels of IL-1β and IL-18, compared to CoV2- children. No significant differences in cytokine levels between the groups were observed at months 3 and 6. Additionally, a general decline in cytokine levels was noted over the course of treatment in both groups. A positive correlation was found between most cytokines and SARS-CoV2 IgG spike protein levels at baseline and at month 3 in the CoV2+ group., Conclusions: This study is one of the first studies to characterize the systemic inflammatory responses in SARS-CoV2 seropositive and seronegative children with TB from a TB endemic country. The findings enhance our understanding of the immunopathogenesis of TB and SARS-CoV2 seropositivity in children and may inform future therapeutic strategies., 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 Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: By 2023, COVID-19 had caused 6.8 million deaths in the United States. COVID-19 presents more severely in leukemia compared to solid tumors (OR 1.6, p<0.05). However, data on Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) are limited. We investigated the mortality in AML and MDS patients with COVID-19., Methods: Data from the 2020-2021 National Inpatient Sample was used to conduct a cross-sectional analysis. We identified AML and MDS patients with COVID-19 hospitalizations through ICD-10 codes. Analysis was done by propensity matching and multivariate regression with a p-value of ≤0.05., Results: Of 28,028 AML admissions, 336 (1.2%) were admitted for COVID-19. AML-COVID-19 cohort had a lower hospitalization risk (aOR 0.3, p=0.000) and higher mortality (21.7% vs 8.7%; aOR 1.6, p=0.023) than AML patients admitted for other causes. AML patients post-HSCT (Hematopoietic Stem Cell Transplantation) had a higher risk of COVID-19 (20.2% vs 9.8%; aOR 2.6, p=0.000) and increased mortality (19.1% vs 6.7%; aOR 4.1, p=0.000) compared to other causes. Similarly, of 28,148 MDS patients, 769 (2.7%) were admitted for COVID-19. The MDS-COVID-19 cohort had a lower hospitalization risk (aOR 0.59, p=0.000) and higher mortality (19.6% vs 6.6%; aOR 2.2, p=0.000) compared to other causes. In MDS, HSCT did not alter the risk of COVID-19 hospitalizations (3% vs 3.9%; aOR 0.9, p=0.662), but these patients had higher mortality (17.4% vs 5.1%; aOR 4.0, p=0.032)., Conclusion: COVID-19 hospitalization was low in AML and MDS but carried a high mortality risk. Post-HSCT, the mortality is high, warranting research into understanding the underlying factors., 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 Sivasubramanian, Joshi, Ravkumar, Madhumithaa Jagannathan, Babu, Sripathi, Javvaji, Jain, Kumar Shanmugam, Swami Kannan, Tirupathi and Dalal.)

We assessed the oxidative potential (OP) of PM 2.5 ( n = 230) using dithiothreitol (DTT) assay to identify the major emission sources in Bhubaneswar (20.20°N, 85.80°E), one of the non-attainment cities under the National Clean Air Program, situated on the eastern coast of India. Continuous day and night PM 2.5 samples were collected during periods influenced by marine airmass (MAM; April-May 2019) as well as continental airmass (CAM; October 2019-December 2019). Volume normalized DTT (DDTv) activities were approximately two times higher during CAM compared to MAM periods. In contrast, mass normalized DTT activity (DDTm) showed insignificant variations between CAM and MAM periods. This might be due to particulate organic matter, which accounted for more than one-fifth of the PM 2.5 mass loading and remained surprisingly invariant during the study periods. Positive matrix factorization (PMF) identified secondary aerosols (MAM: 26% and CAM: 33%) as dominant contributors to PM 2.5 mass in both periods. OP, is, however, dominated by vehicular emissions (21%) as identified through multiple linear regression. Conditional Bivariate Probability Function (CBPF) analysis indicated that local sources were the primary drivers for the catalytic activity of PM 2.5 in the study region. Additionally, stagnant meteorological conditions, combined with the chemical aging of species during regional transport of pollutants, likely enhanced redox activity of PM 2.5 during the CAM period. The study highlights that increasing traffic congestion is primarily responsible for adverse health outcomes in the region. Therefore, it is important to regulate mobility and vehicular movement to mitigate the hazardous impact of PM 2.5 in Bhubaneswar.

In this prospective cohort of 2006 individuals with drug-susceptible tuberculosis in India, 18% had unfavorable treatment outcomes (4.7% treatment failure, 2.5% recurrent infection, 4.1% death, 6.8% loss to follow-up) over a median 12-month follow-up period. Age, male sex, low education, nutritional status, and alcohol use were predictors of unfavorable outcomes., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. 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.)

Chest X-rays (CXRs) are crucial for diagnosing and managing lung conditions. While CXR is a common and cost-effective diagnostic tool, interpreting the high volume of CXRs is challenging due to workforce limitations. Artificial intelligence (AI) offers promise in enhancing efficiency and accuracy. However, real-world applicability and generalizability across diverse patient cohorts remain areas of concerns. In our study, the LUNIT INSIGHT CXR Triage software was evaluated in a diverse patient cohort. Forty-three radiologists, blinded to AI results, assessed CXRs categorized into normal, non-urgent, and urgent using a 3-tier classification system. Performance metrics and turnaround times were analyzed. The AI system demonstrated sensitivity of 89% for normal CXRs, specificity of 93%, PPV of 83%, and NPV of 95%, with an F1 score of 0.86 and an AUC of 0.91. For non-urgent CXRs, sensitivity and specificity were 93% and 91%, with PPV and NPV at 94% and 89%, respectively, and an F1 score of 0.94 and an AUC of 0.92. In the urgent category, sensitivity was 82%, specificity 99%, PPV 90%, and NPV 98%. Subgroup analysis revealed consistently high accuracy across various age groups (Young, Adult, Senior), genders, and ethnicities (Chinese, Malay, Indian, Others), with sensitivity, specificity, and AUC consistently above 84%. The AI system also significantly reduced turnaround times across all subgroups, indicating its robust performance and generalizability in diverse healthcare settings., 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.)

Preconception and prenatal genetic counseling is a well-established means of risk assessment in many parts of the world, and in recent years, an emerging concept in India. Likelihood of an offspring having autosomal recessive disorder increases based on the degree of consanguinity. Hence, genetic testing of the couple for the identification of carrier status for disease-causing variants is crucial. The purpose of this study is to understand the frequency of genetic abnormalities in consanguineous marriages by using a comprehensive genetic testing algorithm where in karyotyping, FISH, exome sequencing and microarray are used sequentially to determine the genetic etiology based on the clinical presentation and to evaluate the need and benefits of preconceptional and prenatal genetic counseling. This retrospective study includes 66 couples having consanguinity referred for genetic counseling and testing. Of the 66 couples, 58 underwent comprehensive genetic testing which included Karyotyping, Fluorescence in Situ Hybridization (FISH), Microarray and Exome sequencing based on their clinical presentation. The analyses revealed a genetic abnormality in approximately 31% and chromosomal polymorphic variations & variants of uncertain significance in 17% of the couples. Counseling in these couples helped in identifying the carrier status and enabled them to take an informed decision in subsequent pregnancies. These findings reiterate the acute need for preconception and prenatal genetic counseling services in India., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The seed serves as the primary source for establishing microbial populations in plants across subsequent generations, influencing plant growth and overall health. Cropping conditions, especially farming practices, can influence the composition and functionality of the seed microbiome. Very little is known about the differences in seed microbiome between organic and conventional production systems. In this study, we characterized the endophytic microbial populations in seeds of rice grown under organic and conventional management practices through culture-dependent and -independent analyses. The V4 region of 16S rRNA was used for bacterial taxa identification, and the ITS1 region was used for the identification of fungal taxa. Our results revealed significantly higher Shannon and Simpson indices for bacterial diversity in the conventional farming system, whereas the fungal diversity was higher for observed, Shannon, and Simpson indices in the organic farming system. The cultivable endophytic bacteria were isolated and identified using the full-length 16S rRNA gene. There was no difference in culturable endophytic bacterial isolates in rice seeds grown under both conventional and organic farming systems. Among 33 unique isolates tested in vitro , three bacteria- Bacillus sp. ST24, Burkholderia sp. OR5, and Pantoea sp. ST25-showed antagonistic activities against Marasmius graminum, Rhizoctonia solani AG4, and R. solani AG11, the fungal pathogens causing seedling blight in rice., Importance: In this paper, we studied the differences in the endophytic microbial composition of rice seeds grown in conventional and organic farming systems. Our results demonstrate a greater bacterial diversity in conventional farming, while organic farming showcases a higher fungal diversity. Additionally, our research reveals the ability of seed bacterial endophytes to inhibit the growth of three fungal pathogens responsible for causing seedling blight in rice. This study provides valuable insights into the potential use of beneficial seed microbial endophytes for developing a novel microbiome-based strategy in the management of rice diseases. Such an approach has the potential to enhance overall plant health and improve crop productivity., Competing Interests: The authors declare no conflict of interest.

Introduction: Cortical thinning is well-documented in individuals with amyotrophic lateral sclerosis (ALS), yet its association with speech deterioration remains understudied. This study characterizes anatomical changes in the brain within the context of speech impairment patterns in individuals with ALS, providing insight into the disease's multiregional spread and biology., Methods: To evaluate patterns of cortical thickness in speakers with ALS with and without functional speech changes compared to healthy controls (HCs) using whole-brain and region of interest (ROI) analyses. Forty individuals with ALS and 22 HCs underwent a T1-weighted 3-Tesla magnetic resonance imaging (MRI). Individuals with ALS were divided into two groups based on the preserved speech [ps-ALS] ( n = 18) or deteriorated speech [ds-ALS] ( n = 22) as measured by the ALSFRSF-R speech subscore (=4 or <4 points, respectively). Sixteen a priori-defined and automatically segmented cortical and subcortical brain ROIs were selected based on their previously documented roles in speech production. Two cortical thickness analyses were performed: (1) group-level whole-brain surface-based analyses and (2) group-level ROI analyses. A case study of 6 ALS individuals examined the cortical thickness, and their speech was characterized using quantitative and qualitative measures., Results: Based on the group-level whole-brain surface-based analyses, the ds-ALS group demonstrated significant cortical thinning compared to HCs in the left primary motor and somatosensory cortices and the right inferior parietal lobe with its adjacent lateral occipital cortical regions. The ps-ALS group demonstrated no significant cortical thinning compared to HCs. Based on the group-level ROI analyses, the ds-ALS group demonstrated significant cortical thinning compared to HCs in bilateral middle motor cortices, right posterior dorsal premotor cortex, and left anterior cingulate cortex. The case study analysis revealed that ALS speakers with speech features characteristic of spastic dysarthria exhibited cortical thinning, while those with speech features characteristic of flaccid dysarthria did not., Discussion: Individuals with ALS have anatomical changes involving multiregional neocortical areas beyond the primary motor cortex that may manifest as subjective (i.e., clinical judgment) and objective (i.e., speaking rate) changes in speech production. Further longitudinal work in ALS is needed to better understand the link between MRI cortical thickness changes and bulbar dysfunction., 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 Zaninotto, Makary, Rowe, Eshghi, Tseng, Chan, Zürcher, Hooker, Lewis, Keegan, Gifford, Green and Babu.)

The Oomycetes fungus Phytophthora spp. which causes Abnormal leaf fall (ALF) disease poses a significant threat as one of the most devastating diseases affecting rubber trees in India. A total of 30 Phytophthora isolates were obtained from ALF-affected samples collected during the Southwest monsoon season of Kerala. The colony morphology of Phytophthora isolates revealed eight different types of growth patterns, with stellate, stellate striated, and petaloid patterns growing rapidly, whereas chrysanthemum pattern grew slowly. Sporangia were papillate to non-papillate in various shapes, and sporangiophores exhibited simple, simple sympodial, or irregularly branching patterns. Highly virulent isolates exhibited petaloid morphology and rapid growth rates. Regardless of their virulence, all isolates showed susceptibility to the fungicide metalaxyl. Under in vitro conditions, the highly virulent isolate (R17) from rubber caused severe infections in chili, brinjal, and tomato with brown water-soaked lesions. Sequence analysis and multi-locus phylogeny of Internal transcribed spacer (ITS), cCytochrome c oxidase 1 (COX 1), Heat shock protein 90 (HSP 90), and Ribosomal protein L10 (RPL 10) confirmed the pathogen as Phytophthora meadii. A comprehensive understanding of both morphological and molecular traits of P. meadii is crucial for precise identification and future genetic variability studies., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 British Mycological Society. Published by Elsevier Ltd. All rights reserved.)

The title hydrated mol-ecular salt, C 19 H 15 N 4 + ·Cl - ·2.5H 2 O, has two tri-phenyl-tetra-zolium cations, two chloride anions and five water mol-ecules in the asymmetric unit. The cations differ in the conformations of the phenyl rings with respect to the heterocyclic core, most notably for the C-bonded phenyl ring, for which the N-C-C-C torsion angles differ by 36.4 (3)°. This is likely a result of one cation accepting an O-H⋯N hydrogen bond from a water mol-ecule [O⋯N = 3.1605 (15) Å], while the other cation accepts no hydrogen bonds. In the extended structure, the water mol-ecules are involved in centrosymmetric (H 2 O) 2 Cl 2 rings as well as (H 2 O) 4 chains. An unusual O-H⋯π inter-action and weak C-H⋯O and C-H⋯Cl hydrogen bonds are also observed., (© Uppu et al. 2024.)

Objective: This study sought to understand the current experiences and subsequent needs of digital maternal health application users based on an interdisciplinary analysis of features currently available in the digital marketplace (including mobile applications and mobile-friendly websites)., Methods: Following secondary analysis of previously collected interview and focus group data, we used qualitative thematic analysis to observe recurring themes within current maternal health applications and prospective augmentation of related technology for future development., Results: Study findings suggested tailored features would best serve the target population, and eleven unique themes comprising additions and improvements to maternal health applications emerged. These included seven major areas: improved mental health support, need for forums and support groups, lack of lactation and breastfeeding support, lack of quality food and nutrition access and product finders, minimal financial literacy information, tailored culturally competent information, and need for localized information and resources. Findings also suggested four main improvements for digital offerings in the current maternal health space: increased emphasis on resources available for postpartum care, importance of minimizing the number of hubs used, need for making information more digestible by ensuring it is written, edited, and provided at appropriate reading levels by more coordinated interaction of words and graphics, and ensuring the trust and credibility of such applications., Conclusions: Maternal health applications are improving; however, more features can be added in a localized manner. Additional improvements could be made to current offerings, maximizing the utility of applications, especially in hard-to-reach areas such as maternity care deserts. With the advent of artificial intelligence, developers are poised with the ability to make platforms more focused and tailored for their users., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Objective: While ambulatory capacity is a readily assessable clinical indicator of functional status, its association with outcomes after endovascular aneurysm repair (EVAR) remains underexplored. This study aimed to investigate the association between pre-operative ambulatory status and outcomes following elective EVAR., Methods: A retrospective review of the multi-institutional Vascular Quality Initiative database was conducted for all patients who underwent elective infrarenal EVAR from 2009 - 2022. Patients were categorised into independent ambulation and impaired ambulation groups. A propensity score matched analysis was performed to produce two well matched cohorts in a 1:1 ratio without replacement. The primary outcome was 30 day death. Secondary outcomes included one year survival and in hospital major complications., Results: Among 11 474 patients, 10 539 (91.8%) were independently ambulatory pre-operatively. Propensity score matching resulted in 885 matched pairs. The impaired ambulation group, although older (mean 77.6 vs. 76.3 years; p = .001), showed comparable baseline characteristics. Post-operatively, the impaired ambulation group had higher cumulative in hospital complications and death as well as 30 day death. Even after adjustment for age, impaired pre-operative ambulation was associated with increased in hospital and 30 day death (hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.26 - 3.95; p = .006). Multivariable analysis demonstrated increasing cumulative risk of 30 day death in the setting of impaired pre-operative ambulatory status with age > 75 years requiring post-operative red blood cell transfusion > 2 units (HR 5.75, 95% CI 2.09 - 15.88; p < .001). Beyond 30 days, impaired pre-operative ambulation was not associated with increased one year death (HR 1.09, 95% CI 0.81 - 1.48; p = .570)., Conclusion: Among patients who underwent elective infrarenal EVAR in this matched analysis, impaired pre-operative ambulatory capacity was associated with an increased risk of in hospital and 30 day death, further compounded by advanced age and post-operative transfusion. As such, a threshold higher than the traditional size criteria should be considered in shared decision making when determining options for the management of abdominal aortic aneurysm in this high risk cohort., (Copyright © 2024 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Reactive oxygen species production, inflammation, an elevated serum profile, mitochondrial dysfunction, and up-regulation of proapoptotic mediators are the main mechanisms underlying chemotherapy-related hepatotoxicity, which results in hepatocyte disorders such as hepatitis, steatohepatitis, and fibrosis. The article aims to examine a prospective herbal remedy and its bioactive ingredients in terms of its antioxidant, anti-inflammatory, and anti-apoptotic capabilities, which offer superior protection against liver damage during chemotherapy administration. Plants including Silybum marianun, Nelumbo nucifera, Phyllanthus amarus, Plumbago zeylanica, Glycyrrhiza glabra, Citrus limon, and Nigella sativa may have hepatoprotective properties, according to the author. Last but not least, this will give aspiring scientists new knowledge for natural-based development in mitigating liver damage caused by chemotherapy medications., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Antimicrobial peptides are an important component of host defense against Mycobacterium tuberculosis. However, the ability of BCG to induce AMPs as part of its mechanism of action has not been investigated in detail., Methods: We investigated the impact of Bacillus Calmette-Guerin (BCG) vaccination on circulating plasma levels and TB-antigen stimulated plasma levels of AMPs in a healthy elderly population. We assessed the association of AMPs, including Human Beta Defensin 2 (HBD-2), Human Neutrophil Peptide 1-3 (HNP1-3), Granulysin, and Cathelicidin (LL37), in circulating plasma and TB-antigen stimulated plasma (using IGRA supernatants) at baseline (pre-vaccination) and at Month 1 and Month 6 post vaccination., Results: Post BCG vaccination, both circulating plasma levels and TB-antigen stimulated plasma levels of AMPs significantly increased at Month 1 and Month 6 compared to pre-vaccination levels in the elderly population. However, the association of AMP levels with latent TB (LTB) status did not exhibit statistical significance., Conclusion: Our findings indicate that BCG vaccination is linked to heightened circulating levels of AMPs in the elderly population, which are also TB-antigen-specific. This suggests a potential mechanism underlying the immune effects of BCG in enhancing host defense against TB.

Arctic regions are extremely sensitive to global warming. Aerosols are one of the most important short-lived climate-forcing agents affecting the Arctic climate. The present study examines the summertime chemical characteristics and potential sources of various organic and inorganic aerosols at a Norwegian Arctic site, Ny-Ålesund (79°N). The results show that organic matter (OM) accounts for 60 % of the total PM 10 mass, followed by sulfate (SO 4 2- ). Water-soluble organic carbon (WSOC) contributes 62 % of OC. Photochemical processes involving diverse anthropogenic and biogenic precursor compounds are identified as the major sources of WSOC, while water-insoluble organic carbon (WIOC) aerosols are predominantly linked to primary marine emissions. Despite being a remote pristine site, the aerosols show a sign of chemical aging, evidenced by a significant chloride depletion, which was about 82 % on average during the study period. Nitrogen-containing aerosols are likely stemming from migratory seabird colonies and local dust sources around the sampling site. While biogenic, crustal, and sea salt-derived SO 4 2- account for 37%, 8%, and 5% respectively, the remaining 50% is attributed to anthropogenic SO 4 2- . Through chemical tracers, Pearson correlation coefficient matrix, and Hierarchical Cluster Analysis (HCA), the present study identifies soil biota (terrestrial biogenic) and marine emissions, along with their photochemical oxidation processes, as potential sources of Arctic aerosols during summer, while biomass burning and combustion-related sources have a minor contribution. The chemical closure of hygroscopicity highlights that while organics predominantly control aerosol hygroscopicity in the Arctic summer, specific inorganic components like (NH 4 ) 2 SO 4 can significantly increase it on certain days, affecting aerosol-cloud interactions and climate processes over the Arctic during summer. The present study highlights the high abundance of organics and their vital role in the Arctic climate during summer when natural aerosols are conquered., 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 research work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Apilimod dimesylate is a first-in-class phosphoinositide kinase, FYVE-type zinc finger-containing (PIKfyve) inhibitor with a favourable clinical safety profile and has demonstrated activity in preclinical C9orf72 and TDP-43 amyotrophic lateral sclerosis (ALS) models. In this ALS clinical trial, the safety, tolerability, CNS penetrance and modulation of pharmacodynamic target engagement biomarkers were evaluated. This phase 2a, randomized, double-blind, placebo-controlled, biomarker-end-point clinical trial was conducted in four US centres (ClinicalTrials.gov NCT05163886). Participants with C9orf72 repeat expansions were randomly assigned (2:1) to receive twice-daily oral treatment with 125 mg apilimod dimesylate capsules or matching placebo for 12 weeks, followed by a 12-week open-label extension. Safety was measured as the occurrence of treatment-emergent or serious adverse events attributable to the study drug and tolerability at trial completion or treatment over 12 weeks. Changes from baseline in plasma and CSF and concentrations of apilimod dimesylate and its active metabolites and of pharmacodynamic biomarkers of PIKfyve inhibition [soluble glycoprotein nonmetastatic melanoma protein B (sGPNMB) upregulation] and disease-specific CNS target engagement [poly(GP)] were measured. Between 16 December 2021 and 7 July 2022, 15 eligible participants were enrolled. There were no drug-related serious adverse events reported in the trial. Fourteen (93%) participants completed the double-blind period with 99% dose compliance [n = 9 (90%) apilimod dimesylate; n = 5 (100%) placebo]. At Week 12, apilimod dimesylate was measurable in CSF at 1.63 ng/ml [standard deviation (SD): 0.937]. At Week 12, apilimod dimesylate increased plasma sGPNMB by >2.5-fold (P < 0.001), indicating PIKfyve inhibition, and lowered CSF poly(GP) protein levels by 73% (P < 0.001), indicating CNS tissue-level proof of mechanism. Apilimod dimesylate met prespecified key safety and biomarker end-points in this phase 2a trial and demonstrated CNS penetrance and pharmacodynamic target engagement. Apilimod dimesylate was observed to result in the greatest reduction in CSF poly(GP) levels observed to date in C9orf72 clinical trials., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. 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.)

Objectives: To determine the role of keratin 17 (K17) as a predictive biomarker for response to chemotherapy by defining thresholds of K17 expression based on immunohistochemical tests that could be used to optimize therapeutic intervention for patients with pancreatic ductal adenocarcinoma (PDAC)., Methods: We profiled K17 expression, a hallmark of the basal molecular subtype of PDAC, by immunohistochemistry in 2 cohorts of formalin-fixed, paraffin-embedded PDACs (n = 305). We determined a K17 threshold of expression to optimize prognostic stratification according to the lowest Akaike information criterion and explored the potential relationship between K17 and chemoresistance by multivariate predictive analyses., Results: Patients with advanced-stage, low K17 PDACs treated using 5-fluorouracil (5-FU)-based chemotherapeutic regimens had 3-fold longer survival than corresponding cases treated with gemcitabine-based chemotherapy. By contrast, PDACs with high K17 did not respond to either regimen. The predictive value of K17 was independent of tumor mutation status and other clinicopathologic variables., Conclusions: The detection of K17 in 10% or greater of PDAC cells identified patients with shortest survival. Among patients with low K17 PDACs, 5-FU-based treatment was more likely than gemcitabine-based therapies to extend survival., (© American Society for Clinical Pathology, 2024.)

Proton-exchange-membrane fuel cells (PEMFCs) offer a long-term, carbon-emission free solution to the energy needs of the transportation sector. However, high cost continues to limit PEMFC commercialization. Replacing expensive platinum group metal (PGM) catalysts with PGM-free catalysts could reduce cost, but the low active site density of PGM-free catalysts necessitates the use of thick electrodes that suffer from substantial mass transport losses. In these thick PGM-free electrodes, effective water management and oxygen transport are crucial to achieve high performance. In this work, we investigate the role of anode and cathode gas diffusion layer (GDL) configurations in controlling water management. Asymmetric GDL configurations, in which the anode GDL exhibits higher permeability than the cathode GDL, showed higher performance compared to conventional symmetric configurations. Computational modeling showed that the improved performance is mainly due to improved water management, resulting in lower liquid water saturation and faster oxygen transport in the cathode., Competing Interests: 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., (© 2024 The Authors.)

Background: Metformin (MET), by boosting immunity, has been suggested as a host-adjunctive therapy to anti-tuberculosis treatment (ATT)., Methods: We evaluated whether adding MET to the standard ATT can alter the host chemokine response. We investigated the influence of metformin on the plasma levels of a wide panel of chemokines in a group of active tuberculosis patients before treatment, at 2nd month of ATT and at 6-months of ATT as part of our clinical study to examine the effect of metformin on ATT., Results: Our results demonstrated that addition of metformin resulted in diminished CC (CCL1 and CCL3) and CXC (CXCL-2 and CXCL-10) chemokines in MET arm as compared to non-MET arm at the 2nd month and 6th month of ATT. In addition to this, MET arm showed significantly diminished chemokines in individuals with high bacterial burden and cavitary disease., Conclusion: Our current data suggest that metformin alters chemokines responses that could potentially curb excessive inflammation during ATT., 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.)

Background: Hexanucleotide repeat expansion of C9orf72 is a common genetic cause of amyotrophic lateral sclerosis (ALS). No C9orf72-targeted treatments are available. BIIB078 is an investigational antisense oligonucleotide targeting C9orf72 sense RNA. We aimed to assess the safety, tolerability, and pharmacokinetics of BIIB078 in participants with C9orf72-associated ALS., Methods: This phase 1, randomised controlled trial was done at 22 sites in six countries (Canada, Ireland, Netherlands, Switzerland, UK, and USA). Adults with ALS and a pathogenic repeat expansion in C9orf72 were randomly assigned within six cohorts, via Interactive Response Technology in a 3:1 ratio per cohort, to receive BIIB078 (5 mg, 10 mg, 20 mg, 35 mg, 60 mg, or 90 mg in cohorts 1-6, respectively) or placebo, via an intrathecal bolus injection. The treatment period consisted of three loading doses of study treatment, administered approximately once every 2 weeks, followed by monthly maintenance doses during a treatment period of about 3 months for cohorts 1-3 and about 6 months for cohorts 4-6. Patients and investigators were masked to treatment assignment. The primary endpoint was the incidence of adverse events and serious adverse events. This trial was registered with ClinicalTrials.gov (NCT03626012) and is completed., Findings: Between Sept 10, 2018, and Nov 17, 2021, 124 patients were screened for inclusion in the study. 18 patients were excluded and 106 participants were enrolled and randomly assigned to receive 5 mg (n=6), 10 mg (n=9), 20 mg (n=9), 35 mg (n=19), 60 mg (n=18), or 90 mg (n=18) of BIIB078, or placebo (n=27). 58 (55%) of 106 patients were female. All patients received at least one dose of study treatment and were included in all analyses. All participants had at least one adverse event; most adverse events were mild or moderate in severity and did not lead to treatment discontinuation. The most common adverse events in BIIB078-treated participants were falls, procedural pain, headache, and post lumbar puncture syndrome. 14 (18%) of 79 patients who received any dose of BIIB078 reported serious adverse events, compared with nine (33%) of 27 patients who received placebo. Five participants who received BIIB078 and three participants who received placebo had fatal adverse events: respiratory failure in a participant who received 10 mg BIIB078, ALS worsening in two participants who received 35 mg BIIB078, traumatic intracerebral haemorrhage in one participant who received 35 mg BIIB078, pulmonary embolism in one participant who received 60 mg BIIB078, and respiratory failure in three participants who received placebo. All deaths were assessed as not related to the study treatment by the reporting investigator., Interpretation: On the basis of these phase 1 study results, including secondary and exploratory findings showing no reduction in neurofilament levels and no benefit on clinical outcomes relative to the placebo cohort, BIIB078 clinical development has been discontinued. However, these results will be informative in furthering our understanding of the complex pathobiology of C9orf72-associated ALS., Funding: Biogen., Competing Interests: Declaration of interests LHvdB: advisory board for Amylyx, Biogen, Cytokinetics, Denali, QurAlis, Corcept, Novartis, Ferrer, and Sanofi. JDR: advisory board for Expansion Therapeutics and Sanofi and receives support from AbbVie Foundation, ALS Association, ALS Finding a Cure Foundation, American Airlines, Answer ALS Foundation, Aviators Against ALS, Bruce Edwards Foundation, Calico, Caterpillar Foundation, Chan Zuckerberg Initiative, Fishman Family Foundation, F Prime, Glaxo Smith Kline, Microsoft, M Armstrong, Muscular Dystrophy Association, National Football League, National Institutes of Health, Stay, Strong Vs ALS, Team Gleason, The Judith and Jean Pape Adams Charitable Foundation, Travelers Insurance, and the US Department of Defense. PJS: advisory board member for Aclipse Therapeutics, Benevolent AI, Biogen, Bristol Meyers Squibb, Darby Rimmer Foundation, Lilly, Novartis, Quell Therapeutics, QurAlis, Samsara Therapeutics, and Pangea Botanica; receives research support from US Department of Defense, EU Horizon 2020, EU Innovative Medicines Initiative, Fight MND, LifeArc, the Medical Research Council, MND Association, My Name'5 Doddie Foundation, NIHR, Pfizer, Quell Therapeutics, SwanBio, and Wolfson Foundation; and has received support for clinical trials participation from Alexion, Biogen, the EU Horizon programme, and UK NIHR. SB: received research funding from National Institutes of Health, American Academy of Neurology, American Association for Electrodiagnostic and Neuromuscular Medicine (AANEM), Muscular Dystrophy Association, OrphAI Therapeutics, Biogen, Ionis, Medicinova, Novartis, Orion, Voyager Therapeutics, and Denali Therapeutics; honoraria for patient and clinician educational activities related to ALS from AANEM Foundation, McCourt Foundation, and Medscape; institutional consulting or advisory board fees from OrphAI Therapeutics and Biogen; and platform trial coordination centre activities from HEALEY ALS. MB: consultant to Alector, Annexon, Arrowhead, Biogen, Denali, Eli Lilly, Novartis, Roche, Sanofi, UniQure, and Woolsey; clinical trial site investigator for Biogen and Orphazyme; and intellectual property licensed to Biogen and Orphazyme. RCB: advisory board for MT Pharma, has a consulting role with Biogen, has Equity in Neuroquestions LLC, and receives a recurring annual gift from a patient's family for research on neuralgic amyotrophy. AG: ad hoc consultant for genetic testing for Biogen; consultant on ALS trial design for Alexion, AL-S Pharma, Calico, Cytokinetics, and Sanofi; and CMO at QurAlis. JDG: institution was contracted by Biogen as a trial site and was paid for those services; received grants from Muscular Dystrophy Association and National Institutes of Health The Amyotrophic Lateral Sclerosis Association and received commercial sponsorships for clinical trials from Amylyx, Biogen, Cytokinetics, and Neuralstem. OH: funding from Science Foundation Ireland (grants SFI 16/RC/3948 and 20/SP/8953); received consulting fees from Accelsior, Biogen, Cytokinetics, Denali, Novartis, Orion, and Wave Pharmaceuticals; and is Editor-in-Chief of the journal Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. VL: institution was contracted by Biogen as a trial site and was paid for those services; and Chair of independent data monitoring committee at Vico Therapeutics and member of independent data monitoring committees at QurAlis and Cyclo Therapeutics. TM: consultant to Amylyx, Biogen, Cytokinetics, and QurAlis. BO: serves as a consultant for Columbia University/Tsumura, MediciNova, Biogen, UniQure, Amylyx, and Mitsubishi and has research grants from Columbia University/Tsumura, Biogen, MediciNova, Cytokinetics, Mitsubishi, Calico, Novartis, Sanofi, Ashvattha, and TARGET ALS. GLP: medical advisory roles for Amylyx, Avanir, Biogen, Catalyst, Cytokinetics, MT Pharma, Otsuka, and the US Department of Defense. JR: serves on advisory boards to Libra, Golgi, and Transposon and consultant to Verge, Iris, and Zydus. MW: consultant to Allmiral, Biogen, Mitsubishi Tanabe Pharma, Neuraxpharm, and Novartis. LZ: received honorarium for being on a Biogen advisory board. PJ-n and FR: paid employees of Ionis Pharmaceuticals. LL, DG, MM, JI, SS, SG, and SF: employees of and may hold stock in Biogen. TAF, ALG, and SE: employees of Biogen at the time the study was conducted. CES: declares no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

It is estimated that there are 65 million people globally - 19 million U.S. adults alone - who have long COVID, or persistent symptoms and conditions that continue or develop after an initial SARS-CoV-2 infection. Amidst their suffering and the ambiguity surrounding their health, people with long COVID engage processes of reintegrating from disruptions brought upon by their COVID-19 infection and its fallout, as well as the pandemic writ large. This process is communicative resilience (Buzzanell, 2010, 2017, 2019), and the purpose of this study is to document the experiences of people with long COVID as they sensemake, adapt, and transform their lives through communication. We employed longitudinal interviewing during the middle stages of the pandemic (Summer 2021 to Summer 2022), talking to 19 people with long COVID over the course of one year (five interviews each; 89 total interviews). Grounded in the six processes of communicative resilience, findings center the temporal and dialectic nature of resilience, with throughlines of grief, patience, and hope set against a tumultuous sociopolitical backdrop. Findings of this study have implications for how resilience is studied across time; how people learn to live with chronic illnesses; and how to support people living with long COVID and those who provide them care.

Ethnopharmacological Relevance: Tecoma stans (L.) Juss.ex Kunth (Bignoniaceae) is mainly found in tropical and subtropical regions of Africa and Asia. The leaves, flowers, roots, and bark are used to treat various aliments includes, skin infections, kidney problems, intestinal disorders, jaundice, toothaches, joint pain and repair cracked bones, antidotes for snake, scorpion, and rat bites., Aim of the Study: The objective of the study is to assess the anti-arthritic properties of T. stans leaf using Complete Freund's adjuvant (CFA)-induced rat., Materials and Method: The ethanol extract of T. stans leaf (ETSL) was subjected toGas Chromatography-Mass Spectrometry (GC-MS) and Liquid Chromatography-Mass Spectrometry (LC-MS) analysis for the identification of potential bioactive. The anti-arthritic activity was carried out by administering CFA (0.1 ml) into the sub-plantar surface of the right hind paw. The experimental animals were treated with indomethacin (10 mg/kg) and ETSL (250, 500 mg/kg) once a day orally for fourteen days. The arthritic parameters and hematological and biochemical parameters were evaluated using standard kit reagents. The levels of pro-inflammatory cytokines and inflammatory mediators were measured in blood serum. Antioxidant parameters were assessed in homogenized liver and joint tissues. Radiological and histopathological analysis of joint was performed. A computational molecular docking investigation of the phytoconstituents was conducted against COX-2, IL-1β, IL-6, and TNF-α receptors., Results: The ETSL at 500 mg/kg demonstrated significant (p < 0.01) restoration of arthritic parameters, hematological and biochemical indices and oxidative stress in CFA-induced rats which was further supported by radiological histological examination. In addition, there was significant (p < 0.05) reduction observed in pro-inflammatory cytokines, inflammatory mediators and up-regulation of anti-inflammatory cytokines in the treated group. Verbascoside was found to exhibit better biding affinities -10.4, -7.4, -7 and -6.2 kcal/mol against COX-2, IL-1β, TNF-α, and IL-6 respectively, confirmed through in silico study., Conclusions: The observed outcome suggests that ETSL at a dosage of 500 mg/kg demonstrated notable anti-arthritic effects by suppressing pro-inflammatory cytokines and oxidative stress biomarkers. This effect could potentially be attributed to the presence of bioactive verbascoside identified in the LC-MS analysis., 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.)

Competing Interests: Conflicts of interest: None.

Amyotrophic lateral sclerosis (ALS) is a relentless, fatal neurodegenerative disease. The progressive loss of voluntary muscle function, diagnostic delays, lack of effective treatments, and challenges accessing multidisciplinary care and resources have tremendous impact on quality of life. The congressionally directed ALS committee of the National Academies of Science, Engineering, and Medicine, in their 2024 report "Living with ALS," recommends critical actions for specific United States stakeholders to make ALS a livable disease over the next decade. This review summarizes the context and recommendations of the report. Advocacy efforts are critical to make these recommendations a reality for the ALS community. ANN NEUROL 2024;96:1035-1039., (© 2024 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Recent progress in therapeutics for amyotrophic lateral sclerosis (ALS) has spurred development and imbued the field of ALS with hope for more breakthroughs, yet substantial scientific gaps persist. This unmet need remains a stark reminder that innovative paradigms are needed to invigorate ALS research. To move toward more informative, targeted, and personalized drug development, the National Institutes of Health (NIH) established a national ALS clinical research consortium called Access for ALL in ALS (ALL ALS). This new consortium is a multi-institutional effort that aims to organize the ALS clinical research landscape in the United States. ALL ALS is operating in partnership with several stakeholders to operationalize the recommendations of the Accelerating Access to Critical Therapies for ALS Act (ACT for ALS) Public Private Partnership. ALL ALS will provide a large-scale, centralized, and readily accessible infrastructure for the collection and storage of a wide range of data from people living with ALS (symptomatic cohort) or who may be at risk of developing ALS (asymptomatic ALS gene carriers). Importantly, ALL ALS is designed to encourage community engagement, equity, and inclusion. The consortium is prioritizing the enrollment of geographically, ethnoculturally, and socioeconomically diverse participants. Collected data include longitudinal clinical data and biofluids, genomic, and digital biomarkers that will be harmonized and linked to the central Accelerating Medicines Partnership for ALS (AMP ALS) portal for sharing with the research community. The aim of ALL ALS is to deliver a comprehensive, inclusive, open-science dataset to help researchers answer important scientific questions of clinical relevance in ALS., (© 2024 The Author(s). Muscle & Nerve published by Wiley Periodicals LLC.)

Gastric cancer (GC) is a global health concern. To facilitate improved management of GCs, protein biomarkers have been identified through mass spectrometry-based proteomics platforms. In order to exhibit clinical utility of such data, we congregated over 6800 differentially regulated proteins in GCs from proteomics studies and recorded the mass spectrometry platforms, association of the protein with infectious agents, protein identifiers, sample size and clinical characters of samples used with details on validation. Development of targeted proteomics methods is the cornerstone for pursuing these markers into clinical utility. Therefore, we developed Protein Biomarker Matrix for Gastric Cancer (PBMGC), a simple catalogue of robustness of each protein. This analysis yielded the identification of robust tissue, serum, and urine diagnostic and prognostic protein biomarker panels which can be further tested for their clinical utility. We also ascertained proteotypic tryptic peptides of 5631 proteins suitable for developing multiple reaction monitoring (MRM) assays. Extensive characterization of these peptides was carried out to record peptide ions, mass/charge and enhanced specific peptide features. With the vision of catering to proteomics researchers, the data generated through this analysis has been catalogued at Gastric Cancer Proteomics DataBase (GCPDB) (https://ciods.in/gcpdb/). Users can browse and download the data and improve GCPDB by submitting recently published data. SIGNIFICANCE: Mass spectrometry-based proteomics platforms have accumulated substantial data on proteins differentially regulated in gastric cancer (GC) clinical samples. The utility of such data in clinical applications is limited by search for suitable biomarker panels for assessment of GCs. We assembled over 6800 differentially regulated proteins in GCs from proteomics studies and recorded the corresponding details including mass spectrometry platforms, status on the association of the protein with infectious agents, protein identifiers from different databases, sample size and clinical characters of samples used in test and control conditions along with details on their validation. Towards the vision of utilizing these markers in clinical assays, Protein Biomarker Matrix for Gastric Cancer (PBMGC) was developed and clinically relevant multi-protein panels were identified. We also demonstrated identification and characterization of tryptic proteotypic tryptic peptides of 5631 proteins biomarkers of GCs which are suitable for development of MRM assays in a SCIEX QTRAP instrument. Aimed to caterproteomics researchers, the data generated through this analysis has been catalogued at Gastric Cancer Proteomics DataBase (GCPDB) (https://ciods.in/gcpdb/). The users can browse and download details on different markers and improve GCPDB by submitting recently published data. Such an analysis could lay a cornerstone for building more such resources or conduct such analysis in different clinical conditions to uptake and develop targeted proteomics as the method of choice for clinical applications., Competing Interests: Declaration of competing interest The authors have no financial or proprietary interests in any of the material discussed in this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Tuberculosis (TB) remains a significant health concern in India, and its complexity is exacerbated by the rising occurrence of non-communicable diseases such as diabetes mellitus (DM). Recognizing that DM is a risk factor for active TB, the emerging comorbidity of TB and PDM (TB-PDM) presents a particular challenge. Our study focused on the impact of PDM on cytokine and chemokine profiles in patients with pulmonary tuberculosis TB) who also have PDM., Materials and Methods: We measured and compared the cytokine (GM-CSF, IFN-γ, IL-1α/IL-1F1, IL-1β/IL-1F2, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, IL-13, IL-17/IL-17A, IL-18/IL-1F4, TNF-α) and chemokine (CCL1, CCL2, CCL3, CCL4, CCL11, CXCL1, CXCL2, CXCL9, CXCL10, and CXCL11) levels in plasma samples of TB-PDM, only TB or only PDM using multiplex assay., Results: We observed that PDM was linked to higher mycobacterial loads in TB. Patients with coexisting TB and PDM showed elevated levels of various cytokines (including IFNγ, TNFα, IL-2, IL-17, IL-1α, IL-1β, IL-6, IL-12, IL-18, and GM-CSF) and chemokines (such as CCL1, CCL2, CCL3, CCL4, CCL11, CXCL1, CXCL9, CXCL10, and CXCL11). Additionally, cytokines such as IL-18 and GM-CSF, along with the chemokine CCL11, were closely linked to levels of glycated hemoglobin (HbA1c), hinting at an interaction between glycemic control and immune response in TB patients with PDM., Conclusion: Our results highlight the complex interplay between metabolic disturbances, immune responses, and TB pathology in the context of PDM, particularly highlighting the impact of changes in HbA1c levels. This emphasizes the need for specialized approaches to manage and treat TB-PDM comorbidity., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Rajamanickam, Kothandaraman, Kumar, Viswanathan, Shanmugam, Hissar, Nott, Kornfeld and Babu.)

Applying organic manure to crops positively impacts the soil microbial community which is negatively impacted when chemical fertilizers are used. Organic manures also add new microbes to the soil in addition to influencing the growth of native ones. Metagenomic analysis of different organic manures, soil, and pot culture experiments conducted under various fertilizer conditions constitute the primary methodologies employed in this study. We compared the effect of two organic manure combinations and an inorganic fertilizer combination on microbial community of rhizosphere soil and leaves of sunflower plants. Metagenomic sequencing data analysis revealed that the diversity of bacteria and fungi is higher in organic manure than in chemical fertilizers. Each organic manure combination selectively increased population of some specific microbes and supported new microbes. Application of chemical fertilizer hurts many plant beneficial fungi and bacteria. In summary, our study points out the superiority of organic manure combinations in enhancing microbial diversity and supporting beneficial microbes. These findings enhance the profound influence of fertilizer types on sunflower microbial communities, shedding light on the intricate dynamics within the rhizosphere and leaf microbiome. Bacterial genera such as Bacillus, Serratia, Sphingomonas, Pseudomonas, Methylobacterium, Acinetobacter, Stenotrophomonas, and fungal genera such as Wallemia, Aspergillus, Cladosporium, and Penicillium constitute the key microbes of sunflower plants., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Agriculture sector is major sufferer of climate change both at a global level as well as at India level. Cereals account for about 92 % of India's total food grain output and climate change has a significant influence on the production of cereals. This study aimed to evaluate the long-term and short-term effects of climatic and non-climatic variables, specifically temperature, precipitation, cereal area, total cropped area, fertilizer consumption, and pesticide consumption, on cereal production in India. The study included annual time series data that covered the period from 1960 to 2018, covering a period of 58 years. Various econometric techniques were employed to examine these relationships. The validity of a long-term and short-term relationship among the relevant variables included in the study was validated by employing the Autoregressive Distributed Lag (ARDL) technique and the Johansen cointegration test. The ARDL model's estimation outcomes reveals that input factors such as cereal area became a key factor in rising cereal production, as evidenced by its positive coefficient. Similarly, fertilizer consumption and precipitation had positive effects on production in the long run whereas total cropped area and minimum temperature has little influence over the results of production both in short run as well as long run. Furthermore, the long-term findings were also supported using econometric tools like Canonical Cointegrating Regression (CCR) and Fully Modified Least Squares (FMOLS). These methods confirmed that variations in cereal production in India were significantly influenced by both climatic factors and agricultural inputs and factors. The study emphasizes the urgency for policymakers to prioritize proactive measures aimed at reducing the adverse impacts of climate change on cereal production in India. This necessitates a comprehensive strategy integrating sustainable practices, technological innovations, and robust policy frameworks to ensure resilient agricultural sectors and sustainable food production., Competing Interests: The authors declare that they have no competing interests., (© 2024 The Authors.)

Dismissal of women's health concerns is a discursive phenomenon with social and material consequences. A burgeoning literature documents how women experience dismissal through various forms of disenfranchising talk. Yet, women are not only subjected to disenfranchising talk; they are called to respond to it. Meaning, analyses of dis enfranchisement should also examine efforts toward en franchisement. One process by which scholars can study communicative (dis)enfranchisement is through people's scalar activity, or how they contextualize experiences at different levels of social reality. Studies of scale demonstrate that the language people use to narrate their personal experiences has meaning for how they position themselves in relation to other social actors, as well as how they make statements about what matters, how much, and to whom. Drawing on 36 interviews with women whose health issues have been dismissed, we apply scale as a theoretical lens and methodological tool to study how women use language in particular, meaningful, and patterned ways in narratives about health dismissal. Our findings suggest that women's narrative discourse is enfranchising in so much as women critique, resist, and transform the contexts of their dismissal. We document how they and others scale "realness" and "normality" across narrated and narrating events. We also note how women scale up from their own experiences to women's experiences writ large, asserting truth claims about issues borne of the broader U.S. healthcare system. Findings have implications for how critical health communication researchers study how women's health issues are constructed in talk.

Catalyst development for upgrading bio-based chemicals towards primary amines has increasingly attracted owing to their applications in the pharmaceutical and polymer industries. The surface acidic sites in metal oxide-based catalysts play a key role in the reductive amination of aldehydes/ketones involving H 2 and NH 3 ; however, the crucial role of the type of surface acidic species and their strength remains unclear. Herein, this study exhibits the catalytic reductive amination of furfural (FUR) to furfurylamine (FUA) with Ru supported on tetragonal (Ru/T-ZrO 2 ) and monoclinic (Ru/M-ZrO 2 ) ZrO 2 . Ru/T-ZrO 2 exhibited an 11.8-fold higher rate of reductive amination than Ru/M-ZrO 2 , giving a quantitative yield of FUA (99 %) at 80 °C in 2.5 h and is recyclable up to four runs. Catalyst surface investigation using spectroscopic techniques, like X-ray photoelectron, electron paramagnetic resonance, and Raman, confirm higher oxygen vacancy sites (1.6 times) on the surface of Ru/T-ZrO 2 compared to Ru/M-ZrO 2 . Moreover, in-situ NH 3 -diffuse reflectance infrared Fourier transform spectroscopy studies display that Ru/T-ZrO 2 has more moderate Bronsted acidic sites (surface H-bonded hydroxyl groups) than Ru/M-ZrO 2 . Further, the controlled experiments and poisoning studies with KSCN and 2,6-lutidine suggest the crucial role of O v sites (Lewis acidic sites) and surface hydroxyl groups (Bronsted acidic sites) for selective FUA formation., (© 2024 Wiley-VCH GmbH.)

The global prevalence of type 2 diabetes mellitus (T2D) is increasing rapidly, with an anticipated 600 million cases by 2035. While infectious diseases such as helminth infections have decreased due to improved sanitation and health care, recent research suggests a link between helminth infections and T2D, with helminths such as Schistosoma , Nippostrongylus , Strongyloides , and Heligmosomoides potentially mitigating or slowing down T2D progression in human and animal models. Helminth infections enhance host immunity by promoting interactions between innate and adaptive immune systems. In T2D, type 1 immune responses are suppressed and type 2 responses are augmented, expanding regulatory T cells and innate immune cells, particularly type 2 immune cells and macrophages. This article reviews recent research shedding light on the favorable effects of helminth infections on T2D. The potential defense mechanisms identified include heightened insulin sensitivity and reduced inflammation. The synthesis of findings from studies investigating parasitic helminths and their derivatives underscores promising avenues for defense against T2D.

Introduction: Fungal prosthetic joint infections (PJIs) are very rare in immunocompetent patients. PJI can present either early, delayed, or as late chronic infections. Diagnosis of fungal PJI presenting late is challenging due to the difficulty in isolation as well as the clinical presentation very similar to an aseptic loosening. There are no clear guidelines regarding the management of these patients., Case Report: We present five cases of Candida parapsilosis PJI presenting as late chronic infections. All five patients were culture-negative preoperatively, immunocompetent, and with good soft-tissue condition. There were three infected knee prostheses and two infected hip hemiarthroplasty. All of them were treated with extensive debridement, meticulous sampling, and extended culture. We treated all of them with long-term antifungals without any disease reactivation or recurrence till the last follow-up., Conclusion: Fungal infection should be suspected in immunocompetent patients presenting early with features of aseptic loosening but without typical signs of periprosthetic infection. Revision with long-term suppressive therapy can give good results in these patients., Competing Interests: Conflict of Interest: Nil, (Copyright: © Indian Orthopaedic Research Group.)