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In congenital heart surgery, redo-sternotomies are very common. In most cases, sternal re-entry is achieved without serious complications. However, sometimes elective institution of peripheral cardiopulmonary bypass is needed for safe sternotomy, albeit with a long cardio-pulmonary bypass time. We report our initial experience of three-dimensional reconstruction and virtual dissection of the retrosternal space, using Horos®, an open-source software, which uses the computed tomography (CT) scan dataset from a 64-slice CT pulmonary angiogram. We reconstructed three-dimensional images to help us conceptualize the retrosternal space for safer re-entry, which could be viewed in stereo with depth perception using anaglyph glasses. Once reconstructed, the substernal space could be viewed from multiple angles and this helped us better understand the anatomy for re-entry. The CT scans, though being the age-old imaging modality for assessment of the anatomy, leave room for assessment of the sub-sternal space. Recently, we encountered three patients in whom the sternal re-entry was deemed to be difficult. The CT scan left ambiguity in assessment of the substernal space and all three patients were assessed with 3-dimensional (3D) reconstruction and virtual dissection prior to sternotomy. All three patients underwent a safe redo-sternotomy without institution of cardiopulmonary bypass. Three-dimensional rendering of CT dataset as a novel technique has the potential to help surgeons visualize the retrosternal space in three dimensions and better understand the spatial relation of the heart with the inner table of the sternum., Supplementary Information: The online version contains supplementary material available at 10.1007/s12055-024-01879-3., Competing Interests: Conflict of interestNone., (© Indian Association of Cardiovascular-Thoracic Surgeons 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.)

Introduction: Granule cell dispersion (GCD) is pathognomonic of hippocampal sclerosis seen in the mesial temporal lobe epilepsy (MTLE). Current animal studies indicate deficiency of Reelin is associated with abnormal granule cell migration leading to GCD. The present study aimed to evaluate complete Reelin signalling pathway to assess whether Reelin deficiency is related to MTLE., Materials and Methods: Hippocampal sclerosis was confirmed by H and E stain. To explore the amount and cellular location of the Reelin cascade molecules, the hippocampal tissues from MTLE surgery and controls ( n  = 15 each) were studied using Immuno-histochemistry (IHC). Additionally, confocal imaging was used to validate the IHC findings by co-localization of different proteins. Quantification of IHC images was performed using histo-score and confocal images by Image J software., Results: Immune expression of active Reelin was significantly reduced in patients. Reelin receptors were deranged, apolipoprotein E receptor 2 was increased while very low-density lipoprotein receptor was reduced. Disabled-1, a downstream molecule was significantly reduced in MTLE. Its ultimate target, cofilin was thus disinhibited and expressed more in MTLE. Reelin cleaving protease, matrix metalloprotease-9 (MMP-9) and MMP-9 inhibitor, tissue inhibitor of matrix protease-1, showed reduced expression in extracellular matrix. Semi-quantification of immunohistochemistry was done using Histo (H) score. H score of Reelin in diseased patients was 15 against 125 for control patients. These results were validated by confocal fluorescence microscopy., Conclusions: Reelin signalling cascade was deranged in chronic MTLE. Pharmacological manipulation of Reelin cascade can be done at various levels and it may provide novel treatment options for MTLE.

The precise identification of various toxic gases is important to prevent health and environmental hazards using cost-effective, efficient, metal oxide-based chemiresistive sensing methods. This study explores the sensing properties of a chemiresistive sensor based on a Zn 2 SnO 4 -SnO 2 microcomposite for detecting n -butanol vapours. The microcomposite, enriched with oxygen vacancies, was thoroughly characterized, confirming its structure, crystallinity, morphology and elemental composition. The sensor demonstrated high repeatability across a temperature range of 275-350 °C and concentrations from 100 to 1000 ppm, with the highest response observed at 350 °C. The concentration-dependent response of the sensor towards n -butanol follows a linear relationship within the studied operating temperature range. The response time increases as the concentration of n -butanol increases. Conductance transients were modelled using the Langmuir-Hinshelwood mechanism, showing temperature-dependent oxidation kinetics. At lower temperatures, the rate-determining step involved n -butanol oxidation, while at higher temperatures, simultaneous oxidation and desorption processes dominated. The calculated activation energy for the n -butanol oxidation step was 0.12 eV. Furthermore, principal component analysis (PCA) effectively discriminated n -butanol from other volatile organic compounds (VOCs), emphasizing the sensor's potential for selective n -butanol detection through a combination of kinetic modelling and statistical analysis.

Itaconate, an abundant metabolite produced by macrophages upon interferon-γ stimulation, possesses both antibacterial and immunomodulatory properties. Despite its crucial role in immunity and antimicrobial control, its mechanism of action and dissimilation are poorly understood. Here, we demonstrate that infection of mice with Mycobacterium tuberculosis increases itaconate levels in lung tissues. We also show that exposure to itaconate inhibits M. tuberculosis growth in vitro, in macrophages, and mice. We report that exposure to sodium itaconate (ITA) interferes with the central carbon metabolism of M. tuberculosis . In addition to the inhibition of isocitrate lyase (ICL), we demonstrate that itaconate inhibits aldolase and inosine monophosphate (IMP) dehydrogenase in a concentration-dependent manner. Previous studies have shown that Rv2498c from M. tuberculosis is the bona fide (S)-citramalyl-CoA lyase, but the remaining components of the pathway remain elusive. Here, we report that Rv2503c and Rv3272 possess itaconate:succinyl-CoA transferase activity, and Rv2499c and Rv3389c possess itaconyl-CoA hydratase activity. Relative to the parental and complemented strains, the ΔRv3389c strain of M. tuberculosis was attenuated for growth in itaconate-containing medium, in macrophages, mice, and guinea pigs. The attenuated phenotype of ΔRv3389c strain of M. tuberculosis is associated with a defect in the itaconate dissimilation and propionyl-CoA detoxification pathway. This study thus reveals that multiple metabolic enzymes are targeted by itaconate in M. tuberculosis. Furthermore, we have assigned the two remaining enzymes responsible for the degradation of itaconic acid into pyruvate and acetyl-CoA. Finally, we also demonstrate the importance of enzymes involved in the itaconate dissimilation pathway for M. tuberculosis pathogenesis., Competing Interests: Competing interests statement:The authors declare no competing interest.

Statement of Problem: Clinical studies evaluating the levels of interleukin-1 beta (IL-1β) in tears and conjunctival secretions of patients with ocular defects after using ocular prostheses are lacking. Therefore, a comparative evaluation of IL-1β levels in the defective eye before and after placement of an ocular prosthesis is needed., Purpose: The purpose of this clinical study was to compare the microbiota and IL-1β in tears and conjunctival secretions of patients with an ocular defect after using an ocular prosthesis., Material and Methods: Patients visiting the prosthodontic department for the rehabilitation of an eye defect that could be restored with an ocular prosthesis were screened with predetermined inclusion and exclusion criteria. Twenty participants were enrolled in the study, and written informed consent was obtained. An ocular prosthesis was provided for each participant to manage anophthalmia. Tear samples for the evaluation of microbiota and IL-1β levels were collected from each participant from the healthy and the defective eye before and after using the ocular prosthesis. The culture method was used to identify microbiotas, and the IL-1β was quantified using an enzyme-linked immunosorbent assay sandwich kit. The obtained data of all parameters were tabulated and compared by using a statistical software program (α=.05)., Results: A statistically significant difference was observed on comparing microbiota and the levels of IL-1β, with a significant increase in the levels after the ocular prosthesis was provided (P<.05)., Conclusions: Levels of IL-1 β in the test group increased as compared with the control group. The increase might be attributed to the inflammatory changes as a result of change in microbiota., (Copyright © 2025. Published by Elsevier Inc.)

Background: Neurodevelopmental disability is a common long-term concern following surgery for congenital heart disease (CHD). Little information is available from low-resource environments where the majority of children with CHD are born. Several challenges in the CHD care continuum exist in such environments., Methods: We followed 1346 infants who were operated for CHD using cardiopulmonary bypass from five paediatric cardiac programmes across India. The neurodevelopmental assessment was done using the Developmental Assessment Scale for Indian Infants (DASII) at 6 months after surgery., Results: A total of 1145 (94.8%) infants were alive at 6 months and 127 (11.1%) were lost to follow-up. The mean age of participants at baseline was 5.2 (3.6) months. The mean motor developmental quotient (DMoQ) and mental developmental quotient (DMeQ) of the remaining 1018 infants were 81.8 (69.5, 93.0) and 87.7 (77.1, 95.7), respectively. A total of 262 (25.7%) infants had motor developmental delay and 157 (15.4%) had mental developmental delay. Syndromic association, younger age at surgery, duration of mechanical ventilation and head circumference were significantly associated with DMoQ. The DMeQ was associated with syndromes, duration of hospital and intensive care unit stay and socioeconomic status. The preoperative condition did not impact mental and motor development. Motor clusters with maximum delay included body control and locomotion. Mental clusters with maximum delay included reaching and manipulation, social interaction-imitative behaviour and vocabulary comprehension., Conclusions: Survivors of infant heart surgery experience significant motor and mental neurodevelopmental delay. This delay is associated with similar factors reported by earlier studies. As more high-risk infants undergo cardiac surgery in low-resource settings, a growing population will require significant societal resources for neurodevelopmental assessment as well as neurodevelopmental rehabilitation. These resources include trained personnel for comprehensive developmental assessment of survivors of CHD surgery, as well as infrastructural requirements for dedicated assessment rooms in centres providing surgical care for CHD patients., Competing Interests: Competing interests: None declared, (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Bacterial infections impede wound healing and pose significant challenges in clinical care. There is an immediate need for safe and targeted antivirulence agents to fight bacterial infections effectively. In this regard, bioderived nanovesicles have shown significant promise. This work demonstrated significant antibacterial properties of extracellular nanovesicles derived from plant (mint) leaf juice (MENV). A hydrogel (HG) was developed using oxidized alginate and chitosan and loaded with antibacterial MENVs (MENV-HG). This formulation was investigated for topical HG dressings to treat Gram-positive Micrococcus luteus and Gram-negative Escherichia coli -invasive wounds. The developed HG was injectable, biocompatible (>95% cell was viable), nonhemolytic (<5% hemolytic capacity), self-healing and exhibited strong physical and mechanical interactions with the bacteria cells (MENV-HG-treated bacteria were significantly more elastic compared to the control in both M. luteus (1.01 ± 0.3 MPa, p < 0.005 vs 5.03 ± 2.6) and E. coli (5.81 ± 2.1 MPa vs 10.81 ± 3.8, p < 0.005). MENV-HG was topically applied on wounds with a slow MENV release profile, ensuring effective healing. These in vivo results demonstrated decreased inflammation and expedited healing within 10 days of treatment (wound area closure was 99% with MENV-HG treatment and 87% for control). Taken together, MENV-HGs have the potential for a scalable and sustainable wound dressing strategy that works satisfactorily for bacteria-infected wound healing and to be validated in clinical trials.

The present investigation attempts to evaluate the impact of the dietary inclusion of chia ( Salvia hispanica ) seed oil (CSO) on the indices of haemato-immunology, metabolic enzymes, and expression of immune-responsive cytokine genes in Labeo rohita (rohu) fingerlings. The responses were observed in a 60-day feeding trial, set up with a total of 180 rohu fingerlings (19.74 ± 0.33 g) randomly allocated to four treatment groups with three replicates each. The groups were fed with a basal diet incorporated with 0%, 1.0%, 2.0%, and 3.0% CSO, denoted as control, CSO (1), CSO (2), and CSO (3), respectively. Significant ( p < 0.05) augmentation of hematological indices such as total protein and globulin levels was observed in the group fed a 1.0% CSO-supplemented diet. Serum glucose, cholesterol, triglycerides, and complement reactive protein levels declined, whereas marker anti-oxidative enzymes (SOD, CAT, and GST) and protein metabolic enzymes (ALT and AST) increased ( p < 0.05) in the lowest CSO-supplemented group. A significant upregulation of inflammatory cytokine viz. IL-1β, IFN-γ, TNF-α, and TLR22 alongside downregulation of IL-10 was noted in various tissues. The results support the inclusion of 1.0% CSO as a prospective dietary vegan substitute to fish oil in rohu aquaculture.

The present study investigates the supplemental effects of chia seed oil (CSO) on the growth performance and modulation of intestinal microbiota in Labeo rohita fingerlings. Four diets were formulated with graded levels of CSO: 1.0%, 2.0%, and 3.0% represented as CSO (1), CSO (2), and, CSO (3) groups alongside a control group without CSO. L. rohita fingerlings (n = 180) (mean weight = 19.74 ± 0.33 g) were randomly distributed in triplicates for 60 days to these treatment groups. The results depicted significant improvements (p < 0.05) in weight gain (WG) %, specific growth rate (SGR), feed conversion ratio (FCR), and feed conversion efficiency (FCE) in the group supplemented with the lowest level of CSO. Gut microbial analysis evidenced the ability of CSO at 1.0% to augment the relative abundance of bacterial phyla such as Verrucomicrobiota, Actinobacteria, Bacteroidota, Fusobacteria and Firmicutes, as well as genera Luteolibacter and Cetobacterium, indicating higher alpha diversity compared to the control. Principle coordinate analysis (PCoA) demonstrated a distinct composition of microbial communities in CSO-supplemented groups relative to the control (p < 0.001). Correlation analysis further revealed a significant (p < 0.05) association of specific microbial taxa with growth performance parameters. The predictions of metabolic pathways suggested the involvement of carbohydrate and amino acid metabolic pathways in the CSO (1) group, indicating improved nutrient transport and metabolism. Overall, the findings highlight the beneficial effects of 1.0% CSO supplementation on growth performance and modulation of gut microbiota in L. rohita fingerlings., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Narrow band green emitting phosphors have gained widespread attention due to their application in white light emitting diode (wLED) backlight displays. Commercial backlight displays have a broad band green phosphor which limits their performance. In this work, bright, narrow and thermally stable green emitting MgGa 2 O 4 :Mn 2+ (MGO-Mn) has been synthesized. Time-resolved emission spectroscopy suggested that Mn 2+ ions are distributed at both Mg 2+ and Ga 3+ sites of the MGO spinel, which resulted in a high internal quantum efficiency of 63%. The colour purity of MGO-Mn (76.4%) superseded that of the commercial green phosphor β-SiAlON:Eu 2+ (59.12%). Doping-induced creation of oxygen vacancies endows MGO-Mn with excellent persistent luminescence with a time duration of more than 900 s upon 4 min charging with 270 nm UV light and persistent radioluminescence of more than 6000 s when charged with X-rays for 1 min. Finally, tunable white LEDs (cool and neutral white LEDs) are fabricated by combining the RGB mixture of the green phosphor with commercial red and blue phosphors along with a 280 nm UV LED chip. This work also showcases the importance of different annealing atmospheres in the photoluminescence and persistent luminescence of the MGO-Mn phosphor.

Indian Himalayan Region (IHR) supports a plethora of biodiversity with a unique assemblage of many charismatic and endemic species. We assessed the genetic diversity, demographic history, and habitat suitability of blue sheep (Pseudois nayaur) in the IHR through the analysis of the mitochondrial DNA (mtDNA) control region (CR) and Cytochrome b gene, and 14 ecological predictor variables. We observed high genetic divergence and designated them into two genetic lineage groups, i.e., the Himalayan blue sheep (P. n. nayaur) in the western part, and the Chinese blue sheep (P. n. szechuanensis) in the eastern part. They exhibited poor connectivity due to landscape resistance. The genetic distance value suggested substantial genetic differentiation between them. The habitat selection by blue sheep indicated the disparity between the residence preferences in the western and eastern Himalayas. In both the regions, the habitat suitability was mostly influenced by the minimum temperature of the coldest month. However, in the eastern Himalayas, precipitation seasonality emerged as a significant variable influencing habitat suitability. These findings provided strong support for the presumption that the habitats preferred by blue sheep in the western Himalayas are dryer, compared with the preferred habitats in the eastern region, which were moister. The identification of two separate lineages of P. nayaur in the IHR has significant conservation implications as it underlines the necessity for a unique management approach for each lineage. In order to preserve genetic integrity, conservation efforts must make sure that each population is maintained and monitored separately, as genetic divergence across the lineages that might indicate reproductive isolation. This study has potential conservation implications as it provides insights on the crucial ecological information of a relatively lesser-known ungulates species of Himalaya essential for effective conservation planning., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no financial support received for this study. The authors declare that they have no competing interests in this study. Ethical approval: Before conducting the field survey, the necessary approval was obtained from the concerned authority, namely, the Forest Departments of Uttarakhand, Himachal Pradesh, Ladakh, and Sikkim. We were authorized to conduct research and collect non-invasive biological samples. We used our own images in this study. The sampling location and distribution maps were created in-house using the template of the Survey of India map. Research Involving Human and Animal Participants: We did not use any live animals in this study and utilized only non-invasive samples. Hence, no Institutional Animal Ethics Committee approval was required., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Shortwave infrared (SWIR)-emitting materials have emerged as superior light sources with increasing demand for potential applications in noninvasive analysis, night vision illumination, and medical diagnosis. For developing next-generation SWIR phosphor-converted light-emitting diodes (pc-LEDs), the scarcity of intense blue-light-pumped broadband SWIR luminescent materials and poor thermal stability of current Ni 2+ -activated phosphors are the ongoing challenges. Here, a blue-light-excitable (440 nm) Y 3 Al 2 Ga 3 O 12 :Cr 3+ ,Ni 2+ phosphor with ultrawide SWIR emission centered at ∼1430 nm (FWHM ∼264 nm) is reported. The efficient Cr 3+ → Ni 2+ energy transfer is exploited for a remarkable enhancement of 18-fold in SWIR emission under blue-light excitation. Significantly, the excellent thermal stability (90% at 440 K) of the SWIR band is obtained in the codoped phosphor which is the best among reported SWIR phosphors. Besides, the experimental techniques (XANES and EXAFS) and density functional theory calculations are employed to investigate the local structure and propose [GaO 6 ] octahedrons as favorable occupation sites for Ni 2+ /Cr 3+ ions. A SWIR pc-LED is fabricated using a blue chip as a proof of concept for invisible illumination technology, nondestructive spectroscopic analysis, anticounterfeiting, and imaging applications. This work offers effective insights into energy transfer-assisted SWIR enhancement and presents a thermally robust Cr 3+ -Ni 2+ -codoped phosphor for designing future mini-SWIR pc-LEDs for spectroscopy applications.

Proton pump inhibitors (PPIs) are one of the standards of care of eosinophilic esophagitis (EoE) treatment, though PPI response rates are variable ranging from 23 to 63% in pediatric studies. We sought to determine if expression of select genes in esophageal mucosa can predict PPI responsiveness in EoE. Children with a new diagnosis of EoE (15 or more eosinophils/hpf on esophageal biopsy) were prospectively treated with 8 weeks of PPI therapy before follow-up esophagogastroduodenoscopy (EGD). Children with <15 eosinophils/hpf on follow-up were classified as having PPI-Responsive EoE (PPI-R) and ≥ 15 eosinophils/hpf as PPI-Nonresponsive EoE (PPI-NR). Using the Nanostring nCounter Analysis System, mRNA expression of a custom panel of genes was measured in esophageal biopsies. Immunohistochemical staining of biopsies was performed. Among children with EoE, 32% (8/25) had PPI-R EoE. ATP12A, ATP4A, tryptase-beta 2 (TPSB2), CLC and IL13 had higher expression in PPI-NR EoE compared to PPI-R EoE or controls. Immunohistochemical staining of ATP12A was higher among PPI-R EoE and PPI-NR EoE, compared to non-EoE controls. In this study, PPI-NR EoE had significantly higher baseline gene expression of mast cell, cytokine, proton pump, and eosinophil genes compared to PPI-R EoE. PPIs may be involved in an inflammatory cascade of mast cell activation that stimulates IL-13 release, which upregulates ATP12A and ATP4A that leads to eosinophil recruitment. Histologic PPI failure may occur when increased gene expression of these components is high and cannot be overcome pharmacologically, especially in the case of proton pump genes., (© The Author(s) 2024. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Animal translocations provide striking examples of the human footprint on biodiversity. Combining continental-wide genomic and DNA-barcoding analyses, we reconstructed the historical biogeography of the Asian black-spined toad (Duttaphrynus melanostictus), a toxic commensal amphibian that currently threatens two biodiversity hotspots through biological invasions (Wallacea and Madagascar). The results emphasize a complex diversification shaped by speciation and mitochondrial introgression that comprises two distinct species. One species (true D. melanostictus) is distributed in the Indian subcontinent and is invasive in Wallacea. The other species, whose nomenclature remains unsettled, diverged from D. melanostictus in the Miocene era (~7 Mya) and diversified across Southeast Asia, from where it was introduced to Madagascar. Remarkably, the Indonesian population of D. melanostictus was recently established from India, which suggests historical, possibly human-assisted dispersal across the Bay of Bengal, reflecting the centuries-old connection between these regions., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Isostructural Dy(III) and Er(III) complexes [L 1 2 Ln(H 2 O) 5 ][I] 3  ⋅ L 1 2  ⋅ (CH 2 Cl 2 ) (Ln=Dy (1), Er (3)) and [L 2 2 Ln(H 2 O) 5 ][I] 3  ⋅ L 2 2  ⋅ (CH 2 Cl 2 ) 2 (Ln=Dy (2), Er (4)), with distorted pentagonal bipyramidal geometry (D 5h ) around the central metal were synthesized by utilizing two bulky phosphonamide ligands, adamantyl phosphonamide, (Ad)P(O)(NH i Pr) 2 (L 1 ) and carbazolyl phosphoramide (Cz)P(O)(NH i Pr) 2 (L 2 ). The resultant complexes were investigated for their magnetic properties in order to elucidate the impact of modification of the coordinating P-O bond environment either by increasing steric bulk and/or introduction of a third P-N bond at the central phosphorus atom. Magnetic studies revealed substantial energy barriers (U eff ) of 640 K and 491 K for Dy compounds 1 and 2, respectively, rendering them as some of the best-performing air-stable SIMs amongst the class of SIMs with D 5h symmetry. Compounds 1 and 2 exhibit magnetization blocking (T B ) at 6.5 K and 6 K, respectively, at a sweep rate of 20 Oe/s. Compound 1 benefits from increased lattice intermetallic distances due to bulky adamantyl substituent, but exhibits a significant deviation from linear axial (P)O-Dy-O(P) geometry (173.7(1)°). In addition to the deviation from linearity, the incorporation of a bulky adamantane (or carbazole) ligand in complex 1 (or 2) was found to result in relatively strong Dy…H-C agostic interactions, with distances of 3.698 Å (3.376 Å). These interactions are expected to induce transverse anisotropy. Ab initio CASSCF/RASSI-SO/SINGLE&#95;ANISO calculations offer valuable insights into the dynamics of magnetic relaxation and the impact of axial bulkiness on the anisotropy of D 5h systems. Beyond highlighting the crucial role of crystal field and symmetry in achieving high-temperature SIMs, this study also explores how the secondary coordination sphere can be engineered to create novel SIMs., (© 2025 Wiley-VCH GmbH.)

Introduction: Endoscopy, standard-of-care for monitoring eosinophilic esophagitis (EoE), assesses mucosal inflammation. The Esophageal String Test (EST), a minimally invasive swallowed capsule and immunoassays, quantifies EoE inflammation. We determined whether the EST/EoEScore can monitor disease in patients undergoing treatment., Methods: Thirty-three samples from 14 patients with EoE (7 children, 7 adults) who underwent repeat endoscopies and ESTs were studied. Biopsies were analyzed for peak eosinophil counts; ESTs were analyzed for EoEScores., Results: Eosinophil counts and EoEScores significantly correlated during treatment, distinguishing patients with active EoE from treatment-associated remissions for 93.9% of ESTs performed., Discussion: The EST can be used to longitudinally monitor responses to treatment in EoE., (Copyright © 2024 by The American College of Gastroenterology.)

Speedy decomposition of organic manure and efficient utilization of rice husk waste are two critical challenges for sustainable environment and soil health management. However, understanding the synergistic effects of rice husk biochar (B) and organic manure (OM) on soil properties and crop growth in subtropical conditions remains unclear. A field study was conducted to investigate the impact of sole and combined application of rice husk biochar (0 t ha -1 , 3 t ha -1 ), farmyard manure (FYM), and vermicompost (VC) on soil aggregation, aggregate-associated carbon, water use efficiency (WUE), economic benefits, and yield of radish crop in sandy clay loam organic soil. Biochar application enhanced the macroaggregate stability and aggregate associated C contents. Soil moisture, infiltration rate (IR) and WUE were significantly improved by 9.2%, 20.8% and 13.6%, respectively, with addition of biochar, which might be related to improved aggregate-associated carbon and water retention in the soil. Similarly, improved soil properties, WUE were noticed in the treatment receiving combination of FYM + VC over the control. 16% and 30.9% higher radish yield was observed with biochar and FYM + VC amended treatments compared without B0 and manure OM0, respectively. The integrated use of biochar (3 t ha -1 ) and OM (FYM + VC) resulted in highest economic benefits of net return (₹ 138,325 ha -1 ) and B:C (1:5) ratio and least in control plots. These results indicate that adding biochar in organic management practices considerably improved the soil properties, WUE which resulted in increased organic radish production., 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 Ltd. All rights reserved.)

Dynamin-1 (DNM1) is crucial for synaptic activity, neurotransmission, and associative memory, positioning it as a potential biomarker of cancer-related cognitive impairment (CRCI), a neurological consequence of cancer treatment characterized by memory loss, poor concentration, and impaired executive function. Through a stepwise approach, this study investigated the role of DNM1 in CRCI pathogenesis, incorporating both human data and animal models. The human study recruited newly diagnosed, chemotherapy-naïve adolescent and young adult cancer and non-cancer controls to complete a cognitive instrument (FACT-Cog) and blood draws for up to three time points. Following that, a syngeneic young-adult WT (C57BL/6) female mouse model of breast cancer chemobrain was developed to study DNM1 expression in the hippocampus. Samples from eighty-six participants with 30 adolescent and young adult (AYA) cancer and 56 non-cancer participants were analyzed. DNM1 levels were 32 ​% lower (P ​= ​0.041) among cancer participants compared to non-cancer prior to treatment. After receiving cytotoxic treatment, cognitively impaired cancer patients were found to have 46 ​% lower DNM1 levels than those without impairment (P ​= ​0.049). In murine breast cancer-bearing mice receiving chemotherapy, we found a greater than 40 ​% decline (P ​< ​0.0001) in DNM1 immunoreactivity in the hippocampal CA1 and CA3 subregions concurrent with a deterioration in spatial recognition memory (P ​< ​0.02), compared to control mice without exposure to cancer and chemotherapy. Consistently observed in both human and animal studies, the downregulation of DNM1 is linked with the onset of CRCI. DNM1 might be a biomarker and therapeutic target for CRCI., Competing Interests: Declaration of Competing Interest We do not have any 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 Inc. All rights reserved.)

Competing Interests: All authors declare no conflicts of interest. All authors have read and approved the manuscript.

The phenotypic feature of tetralogy of Fallot is anterocephalad deviation of the muscular outlet septum, or its fibrous remnant, relative to the septoparietal trabeculation, coupled with hypertrophy of septoparietal trabeculations. Although this feature permits recognition of the entity, no two cases are identical. Once diagnosed, treatment is surgical. The results of surgical treatment have improved remarkably over recent decades. The results are now sufficiently excellent, including those in the developing world, that attention is now directed toward avoidance of morbidity, while still seeking, of course to minimize any fatalities due to surgical intervention. It is perhaps surprising that attention thus far has not been directed on the potential significance of phenotypic variation relative to either mortality or morbidity subsequent to surgical correction. The only study we have found specifically addressing this variability focused on the extent of aortic override, and associated malformations, but made no mention of variability in the right ventricular margins of the interventricular communication, nor the substrates for subpulmonary obstruction. In this review, therefore, we assessed the potential significance of known morphological variability to the outcomes of surgical intervention in over 1,000 individuals undergoing correction by the same surgeon in a center of excellence in a developing country. We sought to assess whether the variations were associated with an increased risk of postoperative death, or problems of rhythm. In our hands, double outlet ventriculoarterial connection was associated with increased risk of death, while the presence of a juxta-arterial defect with perimembranous extension was associated with rhythm problems., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Enteroenteric fistula in the pediatric age group is an unusual presentation. It can create a diagnostic dilemma for the physician, particularly in the absence of any previous surgery, prolonged abdominal symptoms, or inflammatory bowel disease. The patient is a 10-year-old girl who presented with mild-grade fever, abdominal distension, scanty stool passage, and foul-smelling vomiting for the past 10 days. Before this, the patient had received treatment for 20 days for her fever and diarrhea from a quack, and her symptoms had improved. There was no history of prolonged fever, chronic diarrhea, weight loss, blood in the stool, trauma, foreign body ingestion, or hospitalization for any medical or surgical condition. After resuscitation, the patient was evaluated with blood tests, serum tests, and other necessary investigations, and surgery was planned. Intraoperative findings included pyoperitoneum with dilated small bowel. The omentum was densely adhered to the distal ileum, causing distal ileal obstruction, with a perforation approximately 1 cm in diameter in the cecum. The appendix appeared normal. Ten centimeters proximal to the ileocecal junction, there was a nondistensible and redundant segment of the distal ileum with a nondissectible gangrenous omentum. This segment was causing complete obstruction of the small bowel contents. Just proximal to this segment, an ileotransverse colon fistula was present. A double-barrel ileostomy was created for the patient, and she was discharged on postoperative day 10. In pediatric intestinal obstruction, common causes include simple band obstruction, Meckel's band obstruction, intestinal adhesions, intussusception, and complicated appendicitis, among others. However, surgeons may encounter the unusual presentation of an enteroenteric fistula as a cause of intestinal obstruction., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Gupta et al.)

Sirtuins are the major players in host immunometabolic regulation. However, the role of sirtuins in the modulation of the immune metabolism pertaining to salmonellosis is largely unknown. Here, our investigation focussed on the role of two important sirtuins, SIRT1 and SIRT3, shedding light on their impact on intracellular Salmonella 's metabolic switch and pathogenesis establishment. Our study indicated the ability of the live Salmonella Typhimurium to differentially regulate the levels of SIRT1 and SIRT3 for maintaining the high glycolytic metabolism and low fatty acid metabolism in Salmonella . Perturbing SIRT1 or SIRT3 through knockdown or inhibition resulted in a remarkable shift in the host metabolism to low fatty acid oxidation and high glycolysis. This switch led to decreased proliferation of Salmonella in the macrophages. Further, Salmonella -induced higher levels of SIRT1 and SIRT3 led to a skewed polarization state of the macrophages from a pro-inflammatory M1 state toward an immunosuppressive M2, making it more conducive for the intracellular life of Salmonella . Alongside, governing immunological functions by modulating p65 NF-κB acetylation, SIRT1, and SIRT3 also skew Salmonella- induced host metabolic switch by regulating the acetylation status of HIF-1α and PDHA1. Interestingly, though knockdown of SIRT1/3 attenuated Salmonella proliferation in macrophages, in in vivo mice model of infection, inhibition or knockdown of SIRT1/3 led to more dissemination and higher organ burden, which can be attributed to enhanced ROS and IL-6 production. Our study hence reports for the first time that Salmonella modulates SIRT1/3 levels to maintain its own metabolism for successful pathogenesis., Competing Interests: DH, RR, AC, SG, DC No competing interests declared, (© 2024, Hajra et al.)

Salmonella enterica serotype Typhimurium (Salmonella) resides and multiplies intracellularly in cholesterol-rich compartments called Salmonella-containing vacuoles (SCVs) with actin-rich tubular extensions known as Salmonella-induced filaments (SIFs). SCV maturation depends on host-derived cholesterol, but the transport mechanism of low-density lipoprotein (LDL)-derived cholesterol to SCVs remains unclear. Here we find that peroxisomes are recruited to SCVs and function as pro-bacterial organelle. The Salmonella effector protein SseI is required for the interaction between peroxisomes and the SCV. SseI contains a variant of the PTS1 peroxisome-targeting sequence, GKM, localizes to the peroxisomes and activates the host Ras GTPase, ADP-ribosylation factor-1 (ARF-1). Activation of ARF-1 leads to the recruitment of phosphatidylinsolitol-5-phosphate-4 kinase and the generation of phosphatidylinsolitol-4-5-bisphosphate on peroxisomes. This enhances the interaction of peroxisomes with lysosomes and allows for the transfer of lysosomal cholesterol to SCVs using peroxisomes as a bridge. Salmonella infection of peroxisome-depleted cells leads to the depletion of cholesterol on the SCVs, resulting in reduced SIF formation and bacterial proliferation. Taken together, our work identified peroxisomes as a target of Salmonella secretory effectors, and as conveyance of host cholesterol to enhance SCV stability, SIF integrity, and intracellular bacterial growth., Competing Interests: Disclosure and competing interests statement. The authors declare no competing interests., (© 2024. The Author(s).)

Polymicrobial wound infections caused by Gram-negative bacteria and associated inflammation are challenging to manage, as many antibiotics do not work against these infections. Utilizing adjuvants to repurpose the existing antibiotics for mitigating microbial infections presents an alternative therapeutic strategy. We designed and developed a niacin-cholic acid-peptide conjugate ( 1 ) to rejuvenate the therapeutic efficacy of macrolide antibiotics against Gram-negative pathogens. We conjugated niacin with anti-inflammatory properties at the carboxyl terminal of the cholic acid and dipeptide (glycine-valine) at the three hydroxyl terminals of cholic acid to obtain the amphiphile 1 . Our findings demonstrated that amphiphile 1 serves as a microbial membrane disruptor that facilitates the entry of erythromycin (ERY) in bacterial cells. The combination of amphiphile 1 and ERY is bactericidal and can effectively eliminate monomicrobial and polymicrobial Gram-negative bacterial biofilms. We further demonstrated the antibacterial effectiveness of combining 1 and ERY against monomicrobial and polymicrobial wound infections. Together, these findings indicate that amphiphile 1 revitalizes the remedial efficacy of ERY against Gram-negative bacteria.

The mutants resistant to ethylene are helpful in deciphering the role of ethylene in plant development. We isolated an ethylene-resistant tomato (Solanum lycopersicum) mutant by screening for acetylene-resistant (atr-1) seedlings. The atr-1 mutant displayed resistance to kinetin, suggesting attenuation of the ethylene sensing response. atr-1 also exhibited resistance to ABA- and glucose-mediated inhibition of seed germination. Unlike the Never-ripe (Nr) mutant seedlings that were hypersensitive to glucose, atr-1 seedlings were resistant to glucose, indicating ethylene sensing in atr-1 is compromised in a manner distinct from Nr. Metabolically, atr-1 seedlings had lower levels of amino acids but higher levels of several phytohormones, including ABA. atr-1 plants grew faster and produced more flowers, leading to a higher fruit set. However, the atr-1 fruits took a longer duration to reach the red-ripe (RR) stage. The ripened atr-1 fruits retained high β-carotene and lycopene levels post-RR stage and had longer on-vine longevity. The metabolome profiles of post-RR stage atr-1 fruits revealed increased levels of sugars. The atr-1 had a P279L mutation in the GAF domain of the ETR4, a key ethylene receptor regulating tomato ripening. The atr-1 exhibits phenotypic traits distinct from the Sletr4-1 (G154S) mutant, thus represents a new ETR4 allele named Sletr4-2. Our study highlights that novel alleles in ethylene receptors may aid in enhancing the nutritional quality of tomato., 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 Masson SAS.)

Background: Ovarian tumors are the most prevalent neoplasms worldwide, affecting women of all ages. According to Globocan's 2022 projections, by 2050, the number of women diagnosed with ovarian cancer worldwide will increase by over 55% to 503,448. The number of women dying from ovarian cancer is projected to increase to 350,956 each year, an increase of almost 70% from 2022., Aims and Objectives: The aim of this study was to analyze the various histopathological spectra of ovarian tumors according to the latest 2020 WHO classification and to assess the age distribution, frequency of incidence, and laterality of different subtypes of ovarian tumors., Materials and Methods: This retrospective study included 190 cases of histopathologically proven ovarian tumors reported by the pathology department from March 2020 to March 2024 at the Rajendra Institute of Medical Sciences, Ranchi, Jharkhand, India., Results: A total of 190 cases were studied, 154 (81.1%) were benign, 8 (4.2%) were borderline, and 28 (14.7%) cases were malignant. Surface epithelial tumors (SETs) were the most common (n = 139, 73.2%), followed by germ cell tumors (GCTs) (n = 38, 20%). Serous cystadenomas (n = 63, 33%) were the most common benign tumors, whereas the most common malignant tumors were serous carcinomas ( n=11, 5.7% ). Most ovarian tumors (n = 45, 23.68%) occurred in the 31-40-year-old age group., Conclusion: The present study showed various histopathological patterns of ovarian tumors. This study indicated a slight increase in the prevalence of malignant ovarian tumors in the middle-aged group and and a relative increase in the percentage of SETs over GCTs in recent years in our tertiary care center in Jharkhand, India. With limited resources in our institute, histopathological examination remains the mainstay for the early diagnosis of these tumors and their timlely and appropriate management. Categories: Pathology., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Family Medicine and Primary Care.)

Locally advanced buccal mucosa cancer is typically treated with surgery and adjuvant postoperative radiation therapy, which includes concurrent Cisplatin 100 mg/m2 on Day 1, plus 5-Fluorouracil 1000 mg/m2 from Day 1 to 4 every three weeks. Ipsilateral face radiotherapy is a de-escalated treatment that spares the opposite side of the face, enhancing post-treatment chewing function. The availability of electron beam radiotherapy for treating recurrences on the opposite side has increased the use of ipsilateral face radiotherapy. This retrospective study aimed to assess treatment outcomes and patterns of disease recurrence in patients with carcinoma of the buccal mucosa treated with different schedules. We retrospectively reviewed records of 54 patients with a pathological diagnosis of buccal mucosa cancers treated between 2018 and 2023. We extracted patients' demographic, disease, and treatment criteria. Indications for postoperative radiotherapy included a close margin of less than 3 mm and lymph node positivity. The primary tumor (face) and neck were considered separately for radiotherapy treatment. One patient who refused surgery, radiotherapy, and chemotherapy but regularly came for follow-up after receiving Ayurvedic treatment died of the disease after 2 years and 1 month. Fifty-three patients received concurrent chemoradiotherapy with Cisplatin 100 mg/m2 on Day 1, plus 5-Fluorouracil 1000 mg/m2 from Day 1 to 4 every three weeks for three cycles. Postoperative patients were treated with radiotherapy fields covering the face (bilateral or ipsilateral wedged fields) and the whole neck field with central shielding for the initial 44 Gy in 22 fractions over 4.5 weeks followed by a boost dose of 16 Gy to the primary tumor and involved neck. For radical radiotherapy, patients received a similar radiation field but the boost dose delivered was 26 Gy in 13 fractions over 2.5 weeks. For ipsilateral radiotherapy fields, the average face anterior field size was 6 W x 8 cm; the thick edge of the wedge laterally; depth 4 cm and lateral 8 W x 8 cm radiation field with a thick edge of the wedge anteriorly; depth 3 cm. The median dose to high-risk clinical target volume was 60 Gy/30 fractions in postoperative cases. Forty-eight patients received radical radiotherapy with a higher dose (66 Gy/33 fractions to 70 Gy/35 fractions); twenty-eight patients received radiotherapy fields of bilateral face and neck with a central spinal shield of 2 cm. Statistical analysis was conducted at the Community Medicine Department using SPSS software version 21.0. The Chi-square test and Fisher Exact test were applied to compare various groups. Fifty-four patients were analyzed. The median follow-up was 9 months. Surgery consisted of Composite Resection (Commando operation) plus Radical Neck dissection in three (5.5%) patients and non-composite resection surgeries (Wide excision of the lesion plus supra-omohyoid dissection) in nine (16.6%) cases, of which six (50%) cases had lymph node involvement but no patient with positive dissection had extracapsular extension. Tumor thickness by histopathology was found to be between 5 and 15 mm. Sixteen (28.1%) patients failed locally and 11 (20.3%) had lymph node recurrences. One patient (1.8%) with mucoepidermoid cancer had bony metastases at D9, L1, and the pelvis after 4 months of treatment. Death occurred in 12 (20.3%; one due to a non-oncologic cause) out of 54 patients during our study. The majority (88%) of patients in our study are male, aged less than 50 (55%). A KPS of 70/>70 was present in 83.3% of patients. The majority of patients in this study are T3 (37%) and T4a (29.6%). Nodal status of patients included 29.6% N0; 27.7% N1, and 35.1% N2. The majority of patients (57.4%) have well-differentiated carcinoma followed by moderately differentiated carcinoma in 38.8% of patients. The difference in death is non-significant when ipsilateral face + neck radiotherapy is compared to bilateral face + neck radiotherapy by Fisher Exact test (statistical value = 0.1246; p  > 0.05, statistically not significant), and in other groups, it could not be compared due to the small number of patients. Our results show the non-inferiority of non-composite resection surgery + bilateral face + neck radiotherapy to non-operative radical radiotherapy (bilateral or ipsilateral face wedged radiotherapy + neck radiotherapy), so the majority of patients can be treated by these modalities of treatment. De-escalation of radiotherapy by the use of ipsilateral face wedged + neck radiotherapy is possible as there is no statistically significant difference in local and nodal relapse when compared to bilateral face + neck radiotherapy, and it results in sparing of the opposite side of the face. Buccal mucosa carcinoma in eastern Uttar Pradesh is a very aggressive disease, with 12 (20.3%; one due to a non-oncologic cause) out of 54 patients dying. Our results are different compared to historical data, possibly due to the use of concurrent Cisplatin + 5-Fluorouracil chemotherapy and the lower number of patients in the composite resection group as the majority of patients were frail and did not consent to composite resection., Competing Interests: Competing InterestsI confirm that all authors of the manuscript 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.)

The methionine-choline-deficient (MCD) diet-induced non-alcoholic steatohepatitis (NASH) in mice is a well-established model. Our study aims to elucidate the factors influencing liver pathology in the MCD mouse model by examining physiological, biochemical, and molecular changes using histology, molecular techniques, and OMICS approaches (lipidomics, metabolomics, and metagenomics). Male C57BL/6J mice were fed a standard chow diet, a methionine-choline-sufficient (MCS) diet, or an MCD diet for 10 weeks. The MCD diet resulted in reduced body weight and fat mass, along with decreased plasma triglyceride, cholesterol, glucose, and insulin levels. However, it notably induced steatosis, inflammation, and alterations in gene expression associated with lipogenesis, inflammation, fibrosis, and the synthesis of apolipoproteins, sphingolipids, ceramides, and carboxylesterases. Lipid analysis revealed significant changes in plasma and tissues: most ceramide non-hydroxy-sphingosine lipids significantly decreased in the liver and plasma but increased in the adipose tissue of MCD diet-fed animals. Oxidized glycerophospholipids mostly increased in the liver but decreased in the adipose tissue of the MCD diet-fed group. The gut microbiome of the MCD diet-fed group showed an increase in Firmicutes and a decrease in Bacteroidetes and Actinobacteria. Metabolomic profiling demonstrated that the MCD diet significantly altered amino acid biosynthesis, metabolism, and nucleic acid metabolism pathways in plasma, liver, fecal, and cecal samples. LC-MS data indicated higher total plasma bile acid intensity and reduced fecal glycohyodeoxycholic acid intensity in the MCD diet group. This study demonstrates that although the MCD diet induces hepatic steatosis, the mechanisms underlying NASH in this model differ from those in human NASH pathology., 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.)

Perioperative opioids are associated with several adverse effects including nausea, vomiting, and long-term addiction. Opioid-free anesthesia may reduce postoperative morbidity, enable daycare surgery, and decrease cancer recurrence. In our study, we aimed to assess the efficacy of opioid-free anesthesia versus opioid-based anesthesia in patients undergoing breast cancer surgery in terms of postoperative opioid use, pain scores, expression of immune cells, and side effects. Hundred patients undergoing breast cancer surgery were randomized into two groups (1:1 ratio). Group O received opioid-based anesthesia and Group N did not receive any opioid intraoperatively. Our primary outcome was total postoperative morphine consumption in 24 h managed with a patient-controlled analgesia (PCA) pump containing morphine in both groups. Secondary outcomes were numerical rating scale (NRS) at rest and movement at immediate postoperative period, 30 min, 1 h, 2 h, 6 h, and 24 h postoperatively was measured. Blood samples were also taken at different time points to measure inflammatory markers. There was no statistical difference in the total 24 h postoperative morphine consumption in between the two groups ( p  = 0.13). The patient satisfaction scores and NRS at rest and on movement at various time points postoperatively were similar ( p  > 0.05). There was a significant difference in neutrophil lymphocyte ratio (NLR) between the two groups in the samples taken at 24 h postoperative period ( p  = 0.03). No complications were reported in any group. While our study did not show opioid-free anesthesia's superiority in postoperative morphine consumption, it established the feasibility and safety of a non-opioid technique for breast cancer surgery. The approach may offer advantages, including potential immunosuppression relief, making it a viable option for patients prone to opioid-related side effects., Competing Interests: Competing InterestsThe authors declare no competing interests., (© The Author(s), under exclusive licence to Indian Association of Surgical Oncology 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.)

Breast cancer is the most common cancer among women, and in some cases, it also affects men. Since early detection allows for proper treatment, automated data classification is essential. Although such classifications provide timely results, the resource requirements for such models, i.e., computation and storage, are high. As a result, these models are not suitable for resource-constrained devices (for example, IOT). In this work, we highlight the U-Net model, and to deploy it to IOT devices, we compress the same model using a genetic algorithm. We assess the proposed method using a publicly accessible, bench-marked dataset. To verify the efficacy of the suggested methodology, we conducted experiments on two more datasets, specifically CamVid and Potato leaf disease. In addition, we used the suggested method to shrink the MiniSegNet and FCN 32 models, which shows that the compressed U-Net approach works for classifying breast cancer. The results of the study indicate a significant decrease in the storage capacity of UNet with 96.12% compression for the breast cancer dataset with 1.97x enhancement in inference time. However, after compression of the model, there is a drop in accuracy of only 1.33%., 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 Ltd. All rights reserved.)

Recently, many studies have revealed the association between environmental stresses and skin disorders. Skin protects the inner body organs as a first line of defence against various environmental detriments. The physical, chemical, biological, and environmental stresses and internal factors, including reactive oxygen species, can lead to skin aging, laxity, wrinkles, dryness, and coarse texture. Therefore, utilizing naturally occurring bioactive phytochemicals has increased in recent years because of advancements in green technology, and new extraction techniques have made their use more compatible, enabling sustainable development. Alga, both macroalgae and microalgae are photosynthetic organisms that are highly exploited in food, feed, pharmaceuticals, nutraceutical, and cosmetic industries. Algae widely synthesize primary and secondary bioactive metabolites such as polysaccharides, vitamins, flavonoids, carotenoids, pigments, phenolic, and mycosporine-like amino acids, etc. Many cosmetic formulations use algal bioactive metabolites or algal cells as a moisturizer, texture-enhancing agents, anti-wrinkle agents, whitening agents, sunscreen, anti-cellulite, thickening agents, and also for hair care. The current review focuses on a better understanding and recent advancements in the application of algal extract and its biomass in a cosmetic formulation. It also briefly describes the current market scenario, challenges, and future prospectus of algae-based cosmetic products., Competing Interests: Conflict of interestThe authors declare no conflict of interest., (© Association of Microbiologists 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: The mechanistic basis of the variable symptomatology seen in eosinophilic esophagitis (EoE) remains poorly understood., Objective: We examined the correlation of a validated, patient-reported outcome metric with a broad spectrum of esophageal transcripts to uncover potential symptom pathogenesis., Methods: We extracted data from 146 adults with EoE through the Consortium of Eosinophilic Gastrointestinal Disease Researchers. Patients were subgrouped by esophageal dilation history. We compared a validated patient-reported outcome metric, the EoE Activity Index (EEsAI), with a set of transcripts expressed in the esophagus of patients with EoE, the EoE Diagnostic Panel (EDP). We used single-cell RNA sequencing data to identify the cellular source of EEsAI-related EDP genes and further analyzed patients with mild and severe symptoms., Results: The EEsAI correlated with the EDP total score, especially in patients without recent esophageal dilation (r = -0.31; P = .003). We identified 14 EDP genes that correlated with EEsAI scores (r ≥ 0.3; P < .05). Of these, 11 were expressed in nonepithelial cells and three in epithelial cells. During histologic remission, only four of 11 nonepithelial genes (36%) versus all three epithelial genes (100%) had decreased expression to less than 50% of that in active EoE. Fibroblasts expressed five of 11 nonepithelial EEsAI-associated EDP genes (45%). A subset of nonepithelial genes (eight of 11; 73%), but not EoE-representative genes (none of four; 0%; CCL26, CAPN14, DSG1, and SPINK7), was upregulated in patients with EoE with the highest versus lowest symptom burden., Conclusion: The correlation of symptoms and nonepithelial esophageal gene expression substantiates that nonepithelial cells (eg, fibroblasts) likely contribute to symptom severity., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Oxidative and nitrosative stress play pivotal roles in normal physiological processes and the pathogenesis of metabolic disorders. Previous studies from our lab demonstrated insulin resistance (IR), and dyslipidemia in iNOS -/- mice, emphasizing the importance of maintaining optimal redox balance. These mice exhibited altered gut microbiota with decreased Lactobacillus. Therefore, we hypothesized that Lactobacillus supplementation could mitigate metabolic disturbances in iNOS -/- mice. To test this hypothesis, iNOS -/- mice and wild-type (WT) mice were divided into four groups: iNOS -/- with or without Lactobacillus supplementation, WT with or without Lactobacillus supplementation and glucose tolerance, insulin resistance, gluconeogenesis, lipids, gene expression related to glucose and lipid metabolism (qPCR), fecal gut microbiota (16S rRNA sequencing), and serum and caecum metabolomics (LC-MS) were monitored. IR and dyslipidemic iNOS -/- mice exhibited reduced microbial diversity, diminished presence of Lactobacillus, and altered serum metabolites, indicating metabolic dysregulation. Lactobacillus supplementation in iNOS -/- mice effectively reversed glucose intolerance, IR, dyslipidemia, and associated metabolic irregularities compared to WT. These improvements correlated with changes in gene expression related to fatty acid synthesis in liver and adipose tissue, lipid oxidation in liver, and lipid efflux in intestinal tissue as compared to untreated iNOS -/- mice. Despite the positive effects on metabolic markers, Lactobacillus supplementation did not reduce body weight or rectify disrupted energy balance, as evidenced by reduced VCO 2 production, heat generation, and metabolic rates in iNOS -/- mice. The results suggest that Lactobacillus supplementation ameliorates metabolic disturbances but did not fully restore disrupted energy balance, highlighting complex interactions between the gut microbiome and metabolism., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Alzheimer's Disease (AD) is a debilitating neurocognitive disorder with an unclear underlying mechanism. Recent studies have implicated gut microbiota dysbiosis with the onset and progression of AD. The connection between gut microbiota and AD can significantly affect the prevention and treatment of AD patients. This systematic review summarizes primary outcomes of human and mouse AD models concerning gut microbiota alterations. A systematic literature search in February through March 2023 was conducted on PubMed, Embase, and Web of Science. We identified 711 as potential manuscripts of which 672 were excluded because of irrelevance to the identified search criteria. Primary outcomes include microbiota compositions of control and AD models in humans and mice. In total, 39 studies were included (19 mouse and 20 human studies), published between 2017 and 2023. We included studies involving well-established mice models of AD (5xFAD, 3xTg-AD, APP/PS1, Tg2576, and APPPS2) which harbor mutations and genes that drive the formation of Aß plaques. All human studies were included on those with AD or mild cognitive impairment. Among alterations in gut microbiota, most studies found a decreased abundance of the phyla Firmicutes and Bifidobacteria, a genus of the phylum Actinomycetota. An increased abundance of the phyla Bacteroidetes and Proteobacteria were identified in animal and human studies. Studies indicated that gut microbiota alter the pathogenesis of AD through its impact on neuroinflammation and permeability of the gastrointestinal tract. The ensuing increase in blood-brain barrier permeability may accelerate Aβ penetrance and formation of neuritic plaques that align with the amyloid hypothesis of AD pathogenesis. Further studies should assess the relationship between gut microbiota and AD progression and therapy preserving beneficial gut microbiota., Competing Interests: Conflict of interest The authors also declare that there is no other conflict of interest regarding the publication of this manuscript., (Published by Elsevier Inc.)

Objective: Fixed dose combination (FDC) dolutegravir (DTG) plus rilpivirine (RPV) is an approved antiretroviral treatment regimen for people with HIV. The steady-state pharmacokinetics (PK) of FDC DTG+RPV in hemodialysis (HD) has not been previously studied., Design: We performed a single-center, prospective evaluation of the steady-state PK of FDC DTG +RPV in 4 adults without HIV either requiring HD and in 4 matched participants with normal renal function., Methods: All participants received FDC DTG(50mg)+RPV(25mg) daily for 10-14 days with food before undergoing an intensive 24-hour PK evaluation (performed between dialysis days for those requiring HD). Plasma drug and metabolite concentrations were measured using a validated UHPLC/MS/MS. Descriptive PK parameters were calculated., Results: The HD and normal renal function participants (each group with 2 men and 2 women) were of similar ages (range, 50-60 years) and body mass index (range, 18.5-34.5 kg/m2). No participant experienced serious or grade 3-4 adverse events; there were no study discontinuations. The AUC0-τ mean (SD) ratios of HD to normal renal function for DTG and RPV were 1.1 (0.4) and 1.1 (0.9), respectively. The mean (SD) Cmin for DTG and RPV in the HD group were 1033 (252) ng/mL and 49 (18) ng/mL, respectively., Conclusions: HD did not lead to clinically appreciable differential exposures to DTG and RPV. Exposures throughout the dosing interval were greater than the reported protein-binding adjusted IC90 efficacy values for DTG (64 ng/mL) and RPV (12 ng/mL) in all participants. These data suggest no dosing modifications are needed for the FDC DTG+RPV regimen in HD., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Global warming causes heat stress (HS) in animals, impacting nutrient absorption and metabolism. Antioxidant nutrients are crucial for combating HS. This study assessed the impact of increased dietary Zn on nutrient utilization, mineral absorption, and expression of Zn homeostasis regulators, superoxide dismutase-1 (SOD1), and heat shock protein-70 (HSP70) genes in rats under HS. Seventy-two four-week-old Wistar rats were assigned to six groups in a 3×2 factorial design, with three dietary Zn levels (14.6, 32.7, and 48.9 ppm) and two environments, thermo-neutral (TN) and HS, for 42 days, including 14 days of HS exposure. Results showed that HS reduced nutrient intake across Zn levels, though ether extract digestibility increased at 32.7 and 48.9 ppm Zn. Intake, excretion, and apparent daily absorption of Ca, P, Zn, Cu, Mn, and Fe were lower in HS than in TN groups. Hepatic metallothionein-1 (MT1) mRNA expression was downregulated in rats fed 14.6 and 32.7 ppm Zn compared to 48.9 ppm Zn under both environmental conditions. Duodenal Zinc transporter-1 (ZnT1) and Zrt- and Irt-like protein-1 (ZIP1) mRNA expression increased with dietary Zn under TN and HS conditions, respectively. Hepatic SOD1 mRNA expression was significantly downregulated in HS groups, while hepatic HSP70 mRNA expression was significantly upregulated at 48.9 ppm Zn under HS. Present study suggests that, under HS conditions in rats, a higher dietary Zn level of 48.9 ppm may be optimal for improving Zn absorption, enhancing ZIP1, MT1, and HSP70 gene expression, and alleviating the negative effects of HS., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests. Ethics approval: The present study was approved by the Institute Animal Ethics Committee under supervision of the Committee for the Control and Supervision of Experiments on Animals (CCSEA, India)., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Remdesivir, an RNA-polymerase prodrug inhibitor approved for treatment of coronavirus disease 2019 (COVID-19), shortens recovery time and improves clinical outcomes. This prespecified analysis compared remdesivir plus standard of care (SOC) with SOC alone in adults hospitalized with COVID-19 requiring oxygen support in the early stage of the pandemic., Methods: Data for 10-day remdesivir treatment plus SOC from the extension phase of an open-label study (NCT04292899) were compared with real-world, retrospective data on SOC alone (EUPAS34303). Both studies included patients aged ≥18 years hospitalized with severe acute respiratory syndrome coronavirus 2 up to 30 May 2020, with oxygen saturation ≤94% on room air or supplemental oxygen (all forms), and with pulmonary infiltrates. Propensity score weighting was used to balance patient demographics and clinical characteristics across treatment groups. The primary endpoint was time to all-cause mortality or end of study (day 28). Time to discharge, with a 10-day landmark to account for duration of remdesivir treatment, was a secondary endpoint., Results: A total of 1974 patients treated with remdesivir plus SOC, and 1426 with SOC alone, were included after weighting. Remdesivir significantly reduced mortality versus SOC (hazard ratio [HR], 0.46; 95% confidence interval, .39-.54). This association was observed at each oxygen support level, with the lowest HR for patients on low-flow oxygen. Remdesivir significantly increased the likelihood of discharge at day 28 versus SOC in the 10-day landmark analysis (HR, 1.64; 95% confidence interval: 1.43-1.87)., Conclusions: Remdesivir plus early-2020 SOC was associated with a 54% lower mortality risk and shorter hospital stays compared with SOC alone in patients hospitalized with COVID-19 requiring oxygen support. Clinical Trials Registration.  ClinicalTrials.gov NCT04292899 and EUPAS34303., Competing Interests: Potential conflicts of interest. D. F. has served on advisory boards for Gilead Sciences, Inc. and Axcella, and as site principal investigator for clinical trials sponsored by Gilead Sciences, Inc., MetroBiotech, LLC, the National Institutes of Health (NIH; DMID COVAIL), and Regeneron. H. F. G. has received honoraria as a member of DMC or advisory boards for Gilead Sciences, Inc., GSK, Janssen, Johnson and Johnson, Merck, Novartis, and ViiV Healthcare. Furthermore, he has received grants outside of this work from the NIH, Swiss HIV Cohort Study, Swiss National Science Foundation, and Yvonne Jacob Foundation; and has received unrestricted research grants from Gilead Sciences, Inc. All grants were paid to his institution. He has also received a travel grant from Gilead Sciences, Inc. for conference attendance. S. K. G. has received independent grant funding from Indiana University, the NIH, and ViiV Healthcare; and has received consulting/advisory fees from Gilead Sciences, Inc. and ViiV Healthcare. D. K. has received consulting fees from E.R. Squibb & Sons, LLC, and holds stock options in HCA Healthcare. B. B. has received grants from AstraZeneca, Gilead Sciences, Inc., and NIH; has received consulting fees, speaker honoraria, and travel support from Gilead Sciences, Inc.; has participated on a Data Safety Monitoring Board (DSMB) or advisory board for Gilead Sciences, Inc. and is a Gilead Sciences, Inc. speaker for their hepatitis C virus antiviral agent. S. O. has received research funding from HRSA Ryan White Funds. J. A. A. has received institutional research support for clinical trials from Emergent BioSolutions, Frontier Technologies, Gilead Sciences, Inc., GSK, Janssen, Merck, Pfizer, Regeneron, and ViiV Healthcare; has received personal fees for advisory boards from GSK/ViiV Healthcare and Merck; and has participated on a DSMB for Kintor Pharmaceutical, all outside the submitted work. I. M., L. E. T., Y. T., C. B., G. W., R. H., C.-Y. W., A. P. C., and A. O. O. are employees of, and stockholders in, Gilead Sciences, Inc. C.-M. W. has received research funding and travel grants from Gilead Sciences, Inc. for this study; has received research grants or contracts; consulting fees, payment, or honoraria for lectures, presentations, or educational events; and travel support from AbbVie, AstraZeneca, BeiGene, BioNTech, Hoffmann-La Roche, Janssen, and Moderna; and has participated on a Data DSMB or advisory board for AbbVie, AstraZeneca, BeiGene, BioNTech, Hoffmann-La Roche, Janssen, and Moderna. R. L. G. has received grants or contracts to his institution from Eli Lilly, Gilead Sciences, Inc., Johnson & Johnson, Pfizer, Regeneron, and Roivant Sciences (Kinevant Sciences); has received consulting fees from AbbVie, Eli Lilly, Gilead Sciences, Inc., GSK, and Roche; has received payment or honoraria for lectures/speaker fees from Gilead Sciences, Inc. and Pfizer (for an unrelated field); has received travel support from Gilead Sciences, Inc.; has participated on advisory boards for AbbVie, AstraZeneca, Eli Lilly, Gilead Sciences, Inc., GSK, Johnson & Johnson, Kinevant Sciences, and Roche/Genentech; is a de minimis stockholder at AbCellera; and received a gift-in-kind to his institution for an unrelated clinical trial (NCT03383419) from Gilead Sciences, Inc. during the conduct of this study. 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.)

Chemotherapy-induced neurodegeneration represents a significant challenge in cancer survivorship, manifesting in cognitive impairments that severely affect patients' quality of life. Emerging neuroregenerative therapies offer promise in mitigating these adverse effects, with miRNA-124 playing a pivotal role due to its critical functions in neural differentiation, neurogenesis, and neuroprotection. This review article delves into the innovative approach of using miRNA-124-loaded extracellular vesicles (EVs) encapsulated within hydrogel matrices as a targeted strategy for combating chemotherapy-induced neurodegeneration. We explore the biological underpinnings of miR-124 in neuroregeneration, detailing its mechanisms of action and therapeutic potential. The article further examines the roles and advantages of EVs as natural delivery systems for miRNAs and the application of hydrogel matrices in creating a sustained release environment conducive to neural tissue regeneration. By integrating these advanced materials and biological agents, we highlight a synergistic therapeutic strategy that leverages the bioactive properties of miR-124, the targeting capabilities of EVs, and the supportive framework of hydrogels. Preclinical studies and potential pathways to clinical translation are discussed, alongside the challenges, ethical considerations, and future directions in the field. This comprehensive review underscores the transformative potential of miR-124-loaded EVs in hydrogel matrices, offering insights into their development as a novel and integrative approach for addressing the complexities of chemotherapy-induced neurodegeneration., 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 Inc. All rights reserved.)

Aortopulmonary window is a rare CHD, which comprises a communication between the ascending aorta and the pulmonary artery. The standard treatment of aortopulmonary window is surgical; however, few cases are amenable to closure via percutaneous intervention. We present a case of aortopulmonary window closure using Lifetech™ Konar-MF occluder device (Lifetech Scientific Co. Ltd., Shenzhen).

Insecticidal potential of seven commonly available alkaloids against melon thrips (Thrips palmi Karny) was investigated through in vivo experiments and the bioactivity was explained via in silico approaches. In vivo screening showed highest mortality of T. plami larvae for reserpine (43%), closely followed by tropinone (41%) after 24 h of incubation. After 48 h, tropinone surpassed reserpine with 83% mortality, indicating its prolonged insecticidal activity. A detailed bioassay of tropinone revealed its LC 50 values as 1187.9 and 686.9 µg mL -1 after 24 and 48 h, respectively. While studying the molecular interactions between the alkaloids and four physiologically important target proteins of T. palmi, tropinone demonstrated the highest ligand efficiency and lowest predicted inhibitory constant, particularly when forming complexes with CathB protein. However, binding energy calculations of the docked complexes showed most favorable binding of reserpine with CathB. To clear the ambiguity, considering both binding energy and ligand efficiency as the evaluation parameters, a molecular dynamics study was carried out, which predicted higher stability of CathB-tropinone complex than CathB-reserpine complex in terms of the total energy of the system. These in silico findings aligned well with the in vivo results, confirming tropinone as a promising candidate for effective thrips management programs., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

DFT-based calculations were undertaken to, first, fully optimize and study the structural and electrical properties of bare BP nanowire (NW) in its hexagonal wurtzite (WZ) phase. The bare BP NW was found to have an indirect bandgap of 1.362 eV. Hence, the optimization of BP/GaN and BP/GaP core/shell nanowires (CSNWs) was performed to check if an indirect-to-direct band transition occurred. Both the CSNWs showed direct bandgaps of 0.225 eV and 1.252 eV, respectively. The Shockley-Queisser limits for the bare BP NW and BP/GaP CSNW were calculated and compared to gauge their respective photovoltaic efficiencies. The bare BP NW and BP/GaP CSNW yielded almost identical SQ efficiencies of 33.80% and 33.55%, respectively. However, as far as the nano- and micro-photovoltaic cell applications are concerned, the BP/GaP CSNW would be preferable, owing to its direct bandgap. Furthermore, the adsorption of some small oxide gases like carbon monoxide (CO), carbon dioxide (CO 2 ), nitrogen dioxide (NO 2 ) and sulfur dioxide (SO 2 ) gases on BP/GaN and BP/GaP CSNWs was studied. On the basis of the charge transfer and work function mechanisms, NO 2 and SO 2 gases showed selectivity to be detected by both the CSNWs. However, the very highly escalated desorption times for these gases would reduce the repeatability of sensors. Conversely, both BP/GaN and BP/GaP CSNWs could find applications in the fabrication of entrapment devices for NO 2 and SO 2 . The current-voltage ( I - V ) curves for the CSNWs before and after adsorption were also plotted and analyzed. The occurrence of negative differential conductance (NDC) can be observed in both the CSNWs. The CO 2 , NO 2 and SO 2 gases show significantly higher values of current than the pristine BP/GaN CSNW for voltages beyond 0.5 V. Thus, these gases are good proponents to be detected by BP/GaN CSNWs with negligible selectivity amongst them. However, CO@BP/GaN is a stand-out case with a characteristically unique NDC region at 0.9 V. In the case of BP/GaP CSNWs, CO and CO 2 gases can be selectively detected, with a unique NDC region for CO at 0.9 V. Thus, the BP/GaP CSNW, in particular, stands out as an extremely versatile material that can be used to fabricate nano-photovoltaic and nano-sensing devices of the next generation.

Main Conclusion: The pearl millet gene PgPM19 inhibits seed dormancy by negatively regulating the ABA biosynthesis and ABA signaling pathways in response to salinity stress in Arabidopsis. Abscisic acid (ABA) plays a pivotal role in orchestrating plant stress responses and development. However, how the ABA signal is transmitted in response to stresses remains primarily uncertain, particularly in monocotyledonous plants. In this study, PgPM19, a gene whose expression is induced by drought, salinity, heat, and ABA in both leaf and root tissues, was isolated from pearl millet. The expression of PgPM19 in yeast cells did not influence their growth when subjected to mannitol, sorbitol, or NaCl stress. However, Arabidopsis plants overexpressing PgPM19 (PgPM19&#95;OE plants) exhibited increased germination rates, greater fresh weights and longer roots under salinity stress during germination, compared to wild-type (WT) plants. Conversely, the pm19L1 (SALK&#95;075435) mutant, featuring a transfer DNA insertion in a closely related PgPM19 homolog (AT1G04560) in Arabidopsis, demonstrated reduced germination rates and smaller fresh weights under salinity-stressed condition than did WT and PgPM19&#95;OE plants. A pivotal ABA biosynthesis gene, NCED3, ABA signaling pathway genes, such as PYL6 and SnRK2.7, alongside downstream ABI genes and stress-responsive genes RAB28 and RD29, were downregulated in PgPM19&#95;OE plants, as evidenced by both transcriptome analysis and quantitative reverse transcription-PCR. These findings raise the possibility that PgPM19 is involved in regulating seed germination by mediating ABA biosynthesis and signaling pathway in response to salinity stress in Arabidopsis. This study contributes to a better understanding of PgPM19 in response to salinity stress and establishes a foundation for unraveling the crosstalk of stress responses and ABA in Arabidopsis and other plant species., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Glucuronoxylan is present mainly in the dicot of the secondary cell walls, often O-acetylated, which stabilizes cell structure by maintaining interaction with cellulose and other cell wall components. Some members of the Golgi localized Trichome Birefringence-Like (TBL) family function as xylan O-acetyl transferase (XOAT). The primary XOAT in the stem of Arabidopsis is ESKIMO1/TBL29, and its disruption results in decreased xylan acetylation, stunted plant growth, and collapsed xylem vessels. To elucidate the effect on metabolic reprogramming and identify the underlying cause of the stunted growth in eskimo1, we performed transcriptomic, targeted, and untargeted metabolome analysis, mainly in the inflorescence stem tissue. RNA sequencing analysis revealed that the genes involved in the biosynthesis, regulation, and transport of aliphatic glucosinolates (GSLs) were upregulated, whereas those responsible for indolic GSL metabolism were unaffected in the eskimo1 inflorescence stem. Consistently, aliphatic GSLs, such as 4-methylsulfinylbutyl (4MSOB), were increased in stem tissues and seeds. This shift in the profile of aliphatic GSLs in eskimo1 was further supported by the quantification of the soluble acetate, decrease in accumulation of GSL precursor, i.e., methionine, and increase in the level of jasmonic acid., (© 2024 Scandinavian Plant Physiology Society.)

Background: Because young children cannot self-report symptoms, there is a need for parent surrogate reports. Although early work suggested parent-child alignment for eosinophil esophagitis (EoE) patient-reported outcomes (PROs), the longitudinal alignment is unclear., Objective: We sought to assess the agreement and longitudinal stability of PROs between children with EoE and their parents., Methods: A total of 292 parent-child respondents completed 723 questionnaires over 5 years in an observational trial in the Consortium of Eosinophilic Gastrointestinal Disease Researchers. The change in and agreement between parent and child Pediatric Eosinophilic Esophagitis Symptom Score version 2 (PEESSv2.0) and Pediatric Quality of Life Eosinophilic Esophagitis Module (PedsQL-EoE) PROs over time were assessed using Pearson correlation and Bland-Altman analyses. Clinical factors influencing PROs and their agreement were evaluated using linear mixed models., Results: The cohort had a median disease duration equaling 3.7 years and was predominantly male (73.6%) and White (85.3%). Child and parent PEESSv2.0 response groups were identified and were stable over time. There was strong correlation between child and parent reports (PEESSv2.0, 0.83;PedsQL-EoE, 0.74), with minimal pairwise differences for symptoms. Longitudinally, parent-reported PedsQL-EoE scores were stable (P ≥ .32), whereas child-reported PedsQL-EoE scores improved (P = .026). A larger difference in parent and child PedsQL-EoE reports was associated with younger age (P < .001), and differences were driven by psychosocial PRO domains., Conclusions: There is strong longitudinal alignment between child and parent reports using EoE PROs. These data provide evidence that parent report is a stable proxy for objective EoE symptoms in their children., Competing Interests: Disclosure statement CEGIR (U54 AI117804) is part of the Rare Disease Clinical Research Network, an initiative of the Office of Rare Diseases Research, National Center for Advancing Translational Sciences (NCATS), and is funded through a collaboration between NIAID, the National Institute of Diabetes and Digestive and Kidney Diseases, and NCATS and funded in part by the Division of Intramural Research, NIAID. CEGIR is also supported by patient advocacy groups including the American Partnership for Eosinophilic Disorders, Campaign Urging Research for Eosinophilic Diseases, and Eosinophilic Family Coalition. As a member of the Rare Disease Clinical Research Network, CEGIR is supported by its Data Management and Coordinating Center (grant no. U2CTR002818). Funding support for the Data Management and Coordinating Center is provided by NCATS and the National Institute of Neurological Disorders and Stroke. G.S.H. is supported by a grant from the National Institutes of Health (NIH) (grant no. K23 DK131341). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Disclosure of potential conflict of interest: M. E. Rothenberg is a consultant for Pulm One, Spoon Guru, ClostraBio, Serpin Pharm, Allakos, Celldex, Nexstone One, Santa Ana Bio, EnZen Therapeutics, Bristol Myers Squibb, AstraZeneca, Pfizer, GlaxoSmithKline, Regeneron/Sanofi, Revolo Biotherapeutics, and Guidepoint and has an equity interest in the first 9 listed; receives royalties from Teva Pharmaceuticals (reslizumab), Mapi Research Trust (PEESSv2.0), and UpToDate; and is an inventor of patents owned by Cincinnati Children’s Hospital. J. M. Spergel is a consultant for ReadySetfood, Regeneron/Sanofi, and ARS Pharma; has grant support from Novartis, Regeneron/Sanofi, Bristol Myers Squibb, Food Allergy Research and Education (FARE), and NIH; receives royalties from UpToDate; and serves on the Data Safety and Monitoring Board for Alladapt and NIAID. M. H. Collins is a consultant for Allakos, Arena/Pfizer, AstraZeneca, Calypso Biotech, EsoCap Biotech, GlaxoSmithKline, Receptos/Celgene/Bristol Myers Squibb, Regeneron Pharmaceuticals, Robarts Clinical Trials, Inc/Alimentiv, Inc, and Shire/Takeda. S. S Aceves is a consultant and an educational speaker for Regeneron/Sanofi; has grant support from the NIH, Campaign Urging Research for Eosinophilic Diseases, Bristol Myers Squibb, and Implicit Biosciences; and is a coinventor of oral viscous budesonide patented by the University of California San Diego and licensed by Takeda. M. Pletneva is a consultant for Allakos. S. K. Gupta is a consultant and/or Data Safety and Monitoring Board member for Adare, Bristol Myers Squibb, QOL, Takeda, Medscape, PVI, ViaSkin, and UpToDate; and receives research support from Allakos, Ellodi, and AstraZeneca. J. B. Wechsler is a consultant for Bristol Myers Squibb, Ellodi, AstraZeneca, Allakos, and Regeneron/Sanofi; and receives research support from Regeneron. N. Gonsalves is a consultant for AstraZeneca, Allakos, Sanofi/Regeneron, AbbVie, Knopp, and Bristol Myers Squibb; is on the speaker bureau for Sanofi/Regeneron; and receives publication royalties from UpToDate. G. W. Falk is a consultant for Allakos, Bristol Myers Squibb/Celgene, Adare/Ellodi, Nexstone, Upstream Bio, and Sanofi/Regeneron; and receives research support from Allakos, Adare/Ellodi, Bristol Myers Squibb/Celgene, and Regeneron/Sanofi. I. Hirano has received research funding from Adare Pharmaceuticals/Ellodi Pharmaceuticals, Allakos, AstraZeneca, Meritage Pharma, Inc, Receptos/Celgene/Bristol Myers Squibb, Regeneron Pharmaceuticals, and Shire/Takeda; and is a consultant for Adare Pharmaceuticals/Ellodi Pharmaceuticals, Allakos, Arena Pharmaceuticals, Aslan Pharmaceuticals, AstraZeneca, Calyx/Parexel, Celldex Therapeutics, Inc, Dermavant, EsoCap Biotech, Gossamer Bio, Eli Lilly, Nexstone, Meritage Pharma, Inc, Phathom Pharmaceuticals, Receptos/Celgene/Bristol Myers Squibb, Sanofi/Regeneron Pharmaceuticals, and Shire/Takeda. M. Chehade has received consultant fees from Regeneron, Adare/Ellodi, AstraZeneca, Sanofi, Bristol Myers Squibb, Recludix Pharma, Allakos, Shire/Takeda, and Phathom; and has received research support from Regeneron, Allakos, Shire/Takeda, AstraZeneca, Adare/Ellodi, and Danone. C. M. Davis has received grant funding from DBV Technologies, Aimmune Therapeutics, Regeneron Pharmaceuticals, and Allergenis. E. S. Dellon is a consultant for Abbott, AbbVie, Adare/Ellodi, Aimmune, Akesobio, Alfasigma, ALK, Allakos, Amgen, Aqilion, Arena/Pfizer, Aslan, AstraZeneca, Avir, Biorasi, Calypso, Celgene/Receptos/Bristol Myers Squibb, Celldex, Eli Lilly, EsoCap, Eupraxia, Ferring, GlaxoSmithKline, Gossamer Bio, Holoclara, Invea, Knightpoint, Landos, LucidDx, Morphic, Nexstone Immunology, Nutricia, Parexel/Calyx, Phathom, Regeneron, Revolo, Robarts/Alimentiv, Salix, Sanofi, Shire/Takeda, Target RWE, and Upstream Bio; has received research funding from Adare/Ellodi, Allakos, Arena/Pfizer, AstraZeneca, GlaxoSmithKline, Meritage, Miraca, Nutricia, Celgene/Receptos/Bristol Myers Squibb, Regeneron, Revolo, and Shire/Takeda; and has received an educational grant from Allakos, Aqilion, Holoclara, and Invea. G. T. Furuta is Chief Medical Officer for EnteroTrack; and receives research funding from Arena/Pfizer. The rest of the authors declare that they have no relevant conflicts of interest., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Background: Atrial fibrillation (AF) ablation carries the risk of silent cerebral event (SCE) and silent cerebral lesion (SCL). Although "silent," these may have long-term clinical implications and are challenging to study as postprocedural magnetic resonance imaging (MRI) is not standard of care., Objective: The neurological assessment subgroup (NAS) of ADVENT compared cerebral effects of pulsed field ablation (PFA) with standard-of-care thermal ablation., Methods: The NAS included consecutive randomized PFA and thermal ablation patients who received postprocedural brain MRI 12-48 hours after ablation. Patients with apparent SCE or SCL findings underwent a modified Rankin scale assessment. MRI images were subsequently reviewed by a blinded brain imaging core laboratory., Results: In total, 77 patients with paroxysmal AF were enrolled at 6 centers; 71 had analyzable scans (34 PFA; 37 thermal ablation). Through individual center review, 6 PFA and 4 thermal scans were identified as SCE/SCL positive, of which 3 PFA and 0 thermal SCE/SCL findings were confirmed by a blinded core laboratory. MRI findings revealed 1 patient with 2- to 4-mm SCEs, 1 patient with a 3-mm SCE, and 1 patient with 2 SCLs (5.5 mm and 11 mm). All modified Rankin scale and National Institutes of Health Stroke Scale scores were 0 before discharge and at 90-day follow-up. There were only 2 neurological safety events (1 transient ischemic attack [PFA] and 1 stroke [thermal ablation]) in the ADVENT study, neither of which was part of the NAS., Conclusion: The ADVENT trial provides the first prospective, randomized data on the cerebral impact of PFA and thermal ablation of AF. Incidence of SCE/SCL after ablation in the NAS was low., Competing Interests: Disclosures C.P., consultant for Boston Scientific. E.P.G., consultant to Farapulse Inc and serves as an unpaid consultant to Boston Scientific Inc; lecture honoraria from Boston Scientific Inc. S.K.G., consultant for Medtronic and Boston Scientific. J.W., consultant for Biosense Webster, Abbott, Boston Scientific, and Thermedical. C.W., equity in inHEART and SoloPace, intellectual property with ensoETM and SoloPace; travel funds from Abbott and AtriCure. A.N., consultant for Abbott, Biosense Webster, and Boston Scientific. J.W.L., consultant to and received equity from Farapulse Inc (now divested) and serves as a consultant to Boston Scientific Inc. M.M., consultant for Boston Scientific. V.Y.R., consultant to and received equity from Farapulse Inc (now divested), and receives grant support from and serves as a consultant to Boston Scientific Inc; and unrelated to this manuscript, V.Y.R. has served as a consultant for and has equity in Ablacon, Acutus Medical, Affera-Medtronic, Anumana, Apama Medical–Boston Scientific, APN Health, Aquaheart, Atacor, Autonomix, Axon Therapies, Backbeat, BioSig, CardiaCare, CardioNXT/AFTx, Circa Scientific, CoRISMA, Corvia Medical, Dinova-Hangzhou DiNovA EP Technology, East End Medical, EPD-Philips, EP Frontiers, Epix Therapeutics–Medtronic, EpiEP, Eximo, Field Medical, Focused Therapeutics, HRT, Intershunt, Javelin, Kardium, Keystone Heart, LuxMed, Medlumics, Middlepeak, Neutrace, Nuvera-Biosense Webster, Oracle Health, Restore Medical, Sirona Medical, SoundCath, Valcare; and unrelated to this work, V.Y.R. has served as a consultant for Abbott, Adagio Medical, AtriAN, Biosense-Webster, BioTel Heart, Biotronik, Cairdac, Cardiofocus, Cardionomic, CoreMap, Fire1, Gore & Associates, Impulse Dynamics, Medtronic, Novartis, Philips, Pulse Biosciences; and unrelated to this work, V.Y.R. has equity in Atraverse, Manual Surgical Sciences, Newpace, Nyra Medical, Surecor, and Vizaramed., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Alzheimer's Disease (AD), a multifaceted neurodegenerative disorder, is increasingly understood through the regulatory lens of microRNAs (miRNAs). This review comprehensively examines the pivotal roles of miRNAs in AD pathogenesis, shedding light on their influence across various pathways. We delve into the biogenesis and mechanisms of miRNAs, emphasizing their significant roles in brain function and regulation. The review then navigates the complex landscape of AD pathogenesis, identifying key genetic, environmental, and molecular factors, with a focus on hallmark pathological features like amyloid-beta accumulation and tau protein hyperphosphorylation. Central to our discussion is the intricate involvement of miRNAs in these processes, highlighting their altered expression patterns in AD and subsequent functional implications, from amyloid-beta metabolism to tau pathology, neuroinflammation, oxidative stress, and synaptic dysfunction. The predictive analysis of miRNA targets using computational methods, complemented by experimental validations, forms a crucial part of our discourse, unraveling the contributions of specific miRNAs to AD. Moreover, we explore the therapeutic potential of miRNAs as biomarkers and in miRNA-based interventions, while addressing the challenges in translating these findings into clinical practice. This review aims to enhance understanding of miRNAs in AD, offering a foundation for future research directions and novel 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 Elsevier B.V. All rights reserved.)

Background: REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) led to new guidelines for statin use among people with HIV (PWH) with low to moderate risk for atherosclerotic cardiovascular disease (ASCVD). Little is known about the natural history of diabetes mellitus (DM) or mechanisms contributing to statin effects on DM among this population., Objective: To determine the contribution of known DM risk factors to excess risk for DM with pitavastatin in REPRIEVE., Design: Phase 3, primary ASCVD prevention trial over a median of 5.6 years of follow-up. (ClinicalTrials.gov: NCT02344290)., Setting: Global, multicenter trial., Participants: 7731 PWH aged 40 to 75 years with low to moderate ASCVD risk (by the pooled cohort equations from the American College of Cardiology and American Heart Association) without DM at study entry., Intervention: Random 1:1 assignment to pitavastatin, 4 mg daily, or placebo., Measurements: New-onset DM was determined at each visit by clinical diagnosis requiring initiation of medication treatment for DM. The incidence of new-onset DM was assessed in relation to predefined demographic and metabolic risk factors, stratified by treatment group. Treatment effects of pitavastatin on progression to new DM in key subgroups were determined., Results: Participants with at least 3 DM risk factors (vs. no risk factors) had increased risk for DM in each treatment group (incidence rate, 3.24 per 100 person-years [PY] vs. 0.34 per 100 PY [pitavastatin] and 2.66 per 100 PY vs. 0.27 per 100 PY [placebo]). The incidence of DM was highest in South Asia. In adjusted analyses, high body mass index, prediabetes, and metabolic syndrome components were strongly associated with new-onset DM (all P  < 0.005)., Limitation: Pitavastatin was the only statin assessed; DM was assessed clinically., Conclusion: Metabolic risk factors, including prediabetes and obesity, contributed to new-onset DM in statin- and placebo-treated participants. A clinically significant effect of pitavastatin on DM was seen primarily among those with multiple risk factors for DM at entry. Strategies targeting key metabolic risk factors, like obesity and prediabetes, may help protect against DM among PWH., Primary Funding Source: National Heart, Lung, and Blood Institute of the National Institutes of Health., Competing Interests: Disclosures: Disclosure forms are available with the article online.

Melanoma is a metastatic, drug-refractory cancer with the ability to evade immunosurveillance. Cancer immune evasion involves interaction between tumor intrinsic properties and the microenvironment. The transcription factor E2F1 is a key driver of tumor evolution and metastasis. To explore E2F1's role in immune regulation in presence of aggressive melanoma cells, we established a coculture system and utilized transcriptome and cytokine arrays combined with bioinformatics and structural modeling. We identified an E2F1-dependent gene regulatory network with IL6 as a central hub. E2F1-induced IL-6 secretion unleashes an autocrine inflammatory feedback loop driving invasiveness and epithelial-to-mesenchymal transition. IL-6-activated STAT3 physically interacts with E2F1 and cooperatively enhances IL-6 expression by binding to an E2F1-STAT3-responsive promoter element. The E2F1-STAT3/IL-6 axis strongly modulates the immune niche and generates a crosstalk with CD4 + cells resulting in transcriptional changes of immunoregulatory genes in melanoma and immune cells that is indicative of an inflammatory and immunosuppressive environment. Clinical data from TCGA demonstrated that elevated E2F1, STAT3, and IL-6 correlate with infiltration of Th2, while simultaneously blocking Th1 in primary and metastatic melanomas. Strikingly, E2F1 depletion reduces the secretion of typical type-2 cytokines thereby launching a Th2-to-Th1 phenotype shift towards an antitumor immune response. The impact of activated E2F1-STAT3/IL-6 axis on melanoma-immune cell communication and its prognostic/therapeutic value was validated by mathematical modeling. This study addresses important molecular aspects of the tumor-associated microenvironment in modulating immune responses, and will contribute significantly to the improvement of future cancer therapies., 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 Spitschak, Dhar, Singh, Casalegno Garduño, Gupta, Vera, Musella, Murr, Stoll and Pützer.)