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Abstract The microvasculature plays a key role in tissue perfusion and exchange of gases and metabolites. In this study we use human blood vessel organoids (BVOs) as a model of the microvasculature. BVOs fully recapitulate key features of the human microvasculature, including the reliance of mature endothelial cells on glycolytic metabolism, as concluded from metabolic flux assays and mass spectrometry-based metabolomics using stable tracing of 13C-glucose. Pharmacological targeting of PFKFB3, an activator of glycolysis, using two chemical inhibitors results in rapid BVO restructuring, vessel regression with reduced pericyte coverage. PFKFB3 mutant BVOs also display similar structural remodelling. Proteomic analysis of the BVO secretome reveal remodelling of the extracellular matrix and differential expression of paracrine mediators such as CTGF. Treatment with recombinant CTGF recovers microvessel structure. In this work we demonstrate that BVOs rapidly undergo restructuring in response to metabolic changes and identify CTGF as a critical paracrine regulator of microvascular integrity.

Spatial transcriptomics experiments profile genome-wide gene expression at localized spots across a tissue. Here, the authors identify spot swapping, an artifact where RNA expressed at one tissue spot binds probes at another, and they propose SpotClean to adjust for it.

Summary: Ion and analyte changes in the tumor microenvironment (TME) alter the metabolic activity of cancer cells, promote tumor cell growth, and impair anti-tumor immunity. Consequently, accurate determination and visualization of extracellular changes of analytes in real time is desired. In this study, we genetically combined FRET-based biosensors with nanobodies (Nbs) to specifically visualize and monitor extracellular changes in K+, pH, and glucose on cell surfaces. We demonstrated that these Nb-fused biosensors quantitatively visualized K+ alterations on cancer and non-cancer cell lines and primary neurons. By implementing a HER2-specific Nb, we generated functional K+ and pH sensors, which specifically stained HER2-positive breast cancer cells. Based on the successful development of several Nb-fused biosensor combinations, we anticipate that this approach can be readily extended to other biosensors and will open new opportunities for the study of extracellular analytes in advanced experimental settings.

[This corrects the article DOI: 10.1371/journal.pone.0244423.].

An unhealthy diet during childhood directly impacts the risk of developing noncommunicable diseases (NCDs) later on in life. However, well-documented information on this issue is lacking. We investigated the dietary quality of young Indonesian children and assessed the relationship to serum adiponectin levels as an early marker of NCDs. Eighty-five (44 girls and 41 boys) Indonesian preschool-age children in East Jakarta were included in this study. Dietary intake data were gathered by collecting repeated 24-hour recalls for one weekday and one day during the weekend, which were then further converted into participants' Healthy Eating Index (HEI) 2015 scores. Meanwhile, an enzyme-linked immunosorbent assay was performed to determine the serum adiponectin level. A multiple regression analysis was performed to assess the association between the HEI 2015 score and serum adiponectin, adjusting for potential confounders. The mean HEI 2015 score was 33.2 ± 8.3 points, which was far below the recommended score of ≥ 80 points, while the mean serum adiponectin was 10.3 ± 4.1 μg/mL. Multiple linear regression testing showed that a one-point increase in the HEI 2015 score was significantly associated with an increase in the serum adiponectin level by 0.115 μg/mL after adjusting for exclusive breastfeeding history (β = 0.115; 95% CI = 0.010-0.221; p = 0.032). In conclusion, better adherence of young children to a healthy diet has a positive association with their adiponectin level. This result suggests that strengthening children's dietary quality from an early age by involving all parties in the children's environment (e.g., parents, teachers at school, policymakers) may help to reduce the risk of NCDs later on in childhood and during adult life.

BackgroundPropensity score techniques can reduce confounding and bias in observational studies. Such analyses are able to measure and balance pre-determined covariates between treated and untreated groups, leading to results that can approximate those generated by randomized prospective studies when such trials are not feasible. The most commonly used propensity score -based analytic technique is propensity score matching (PSM). Although PSM popularity has continued to increase in medical literature, improper methodology or methodological reporting may lead to biased interpretation of treatment effects or limited scientific reproducibility and generalizability. In this study, we aim to characterize and assess the quality of PSM methodology reporting in high-impact otolaryngologic literature.MethodsPubMed and Embase based systematic review of the top 20 journals in otolaryngology, as measured by impact factor from the Journal Citations Reports from 2012 to 2018, for articles using PSM analysis throughout their publication history. Eligible articles were reviewed and assessed for quality and reporting of PSM methodology.ResultsOur search yielded 101 studies, of which 92 were eligible for final analysis and review. The proportion of studies utilizing PSM increased significantly over time (p < 0.001). Nearly all studies (96.7%, n = 89) specified the covariates used to calculate propensity scores. Covariate balance was illustrated in 67.4% (n = 62) of studies, most frequently through p-values. A minority (17.4%, n = 16) of studies were found to be fully reproducible according to previously established criteria.ConclusionsWhile PSM analysis is becoming increasingly prevalent in otolaryngologic literature, the quality of PSM methodology reporting can be improved. We provide potential recommendations for authors regarding optimal reporting for analyses using PSM.

Clinical oncology is rapidly adopting next-generation sequencing technology for nucleotide variant and indel detection. Here the authors present a three-platform approach (whole-genome, whole-exome, and whole-transcriptome) in pediatric patients for the detection of diverse types of germline and somatic variants.

Cerebrovascular changes and astrogliosis occur in Alzheimer’s disease (AD). Using an in vivo phage display technique, the authors identified a peptide that upon systematic administration, can home to brain endothelial cells and astrocytes in mouse models of AD at the early stages of the disease.

BackgroundIntracranial arteriovenous malformation (AVM) is a common cause of primary intracerebral hemorrhage in young adults. Lesions typically are sporadic and contain somatic mutations in KRAS or BRAF. The purpose of this study was to identify somatic mutations in a cohort of participants with brain AVM and to determine if any genotype-phenotype associations exist.MethodsHuman brain AVM specimens (n = 16) were collected during a clinically-indicated procedure and subjected to multiplex targeted sequencing using molecular inversion probe (MIP-seq) for mutations in KRAS, BRAF, HRAS, NRAS, and MAP2K1. Endothelial cells (ECs) were separated from non-ECs by immune-affinity purification. Droplet digital PCR (ddPCR) was used to confirm mutations and to screen for mutations that may have been missed by MIP-seq. Patient and AVM characteristics were recorded.ResultsWe detected somatic mutations in 10 of 16 specimens (63%). Eight had KRAS mutations [G12D (n = 5), G12V (n = 3)] and two had BRAF mutations [V600E (n = 1), Q636X (n = 1)]. We found no difference in age, sex, presenting symptom, AVM location, or AVM size between patients with a confirmed mutation and those without. Nor did we observe differences in these features between patients with KRAS or BRAF mutations. However, two patients with BRAF mutations presented at an older age than other study participants.ConclusionsSomatic mutations in KRAS and, less commonly in BRAF, are found in many but not all intracranial AVM samples. Currently, there are no obvious genotype-phenotype correlations that can be used to predict whether a somatic mutation will be detected and, if so, which gene will be mutated.

Accurate treatment of traumatic brain injuries, a leading cause of neurological disability and death in young people, is hampered by poor accumulation of drugs in the brain. Here, the authors describe a tetrapeptide that can efficiently target brain injuries and deliver therapeutic or diagnostic payload.

The effect of a multi-faceted handoff strategy in a high volume internal medicine inpatient setting on process and patient outcomes has not been clearly established. We set out to determine if a multi-faceted handoff intervention consisting of education, standardized handoff procedures, including fixed time and location for face-to-face handoff would result in improved rates of handoff compared with usual practice. We also evaluated resident satisfaction, health resource utilization and clinical outcomes.This was a cluster randomized controlled trial in a large academic tertiary care center with 18 inpatient internal medicine ward teams from January-April 2013. We randomized nine inpatient teams to an intervention where they received an education session standardizing who and how to handoff patients, with practice and feedback from facilitators. The control group of 9 teams continued usual non-standardized handoffs. The primary process outcome was the rate of patients handed over per 1000 patient nights. Other process outcomes included perceptions of inadequate handoff by overnight physicians, resource utilization overnight and hospital length of stay. Clinical outcomes included medical errors, frequency of patients requiring higher level of care overnight, and in-hospital mortality.The intervention group demonstrated a significant increase in the rate of patients handed over to the overnight physician (62.90/1000 person-nights vs. 46.86/1000 person-nights, p = 0.002). There was no significant difference in other process outcomes except resource utilization was increased in the intervention group (26.35/1000 person-days vs. 17.57/1000 person-days, p-value = 0.01). There was no significant difference between groups in medical errors (4.8% vs. 4.1%), need for higher level of care or in hospital mortality. Limitations include a dependence of accurate record keeping by the overnight physician, the possibility of cross-contamination in the handoff process, analysis at the cluster level and an overall low number of clinical events.Implementation of a multi-faceted resident handoff intervention did not result in a significant improvement in patient safety although did improve number of patients handed off. Novel methods to improve handoff need to be explored.Registered at ClinicalTrials.gov: NCT01796756.

The original version of the Supplementary Information associated with this Article inadvertently omitted Supplementary Table 1. The HTML has now been updated to include a corrected version of the Supplementary Information.

The reductively activated nitroaromatic class of antimicrobials, which include nitroimidazole and the more metabolically labile nitrofuran antitubercular agents, have demonstrated some potential for development as therapeutics against dormant TB bacilli. In previous studies, the pharmacokinetic properties of nitrofuranyl isoxazolines were improved by incorporation of the outer ring elements of the antitubercular nitroimidazole OPC-67683. This successfully increased stability of the resulting pentacyclic nitrofuran lead compound Lee1106 (referred to herein as 9a). In the current study, we report the synthesis and antimicrobial properties of 9a and panel of 9a analogs, which were developed to increase oral bioavailability. These hybrid nitrofurans remained potent inhibitors of Mycobacterium tuberculosis with favorable selectivity indices (>150) and a narrow spectrum of activity. In vivo, the pentacyclic nitrofuran compounds showed long half-lives and high volumes of distribution. Based on pharmacokinetic testing and lack of toxicity in vivo, 9a remained the series lead. 9a exerted a lengthy post antibiotic effect and was highly active against nonreplicating M. tuberculosis grown under hypoxia. 9a showed a low potential for cross resistance to current antitubercular agents, and a mechanism of activation distinct from pre-clinical tuberculosis candidates PA-824 and OPC-67683. Together these studies show that 9a is a nanomolar inhibitor of actively growing as well as nonreplicating M. tuberculosis.

Frequent and indiscriminate use of existing battery of antibiotics has led to the development of multi drug resistant (MDR) strains of pathogens. As decreasing the concentration of the antibiotic required to treat Salmonellosis might help in combating the development of resistant strains, the present study was designed to assess the synergistic effects, if any, of nisin, in combination with conventional anti-Salmonella antibiotics against Salmonella enterica serovar Typhimurium. Minimum inhibitory concentrations (MICs) of the selected antimicrobial agents were determined by micro and macro broth dilution assays. In-vitro synergy between the agents was evaluated by radial diffusion assay, fractional inhibitory concentration (FIC) index (checkerboard test) and time-kill assay. Scanning electron microscopy (SEM) was also performed to substantiate the effect of the combinations. In-vivo synergistic efficacy of the combinations selected on the basis of in-vitro results was also evaluated in the murine model, in terms of reduction in the number of Salmonellae in liver, spleen and intestine. Nisin-ampicillin and nisin-EDTA combinations were observed to have additive effects, whereas the combinations of nisin-ceftriaxone and nisin-cefotaxime were found to be highly synergistic against serovar Typhimurium as evident by checkerboard test and time-kill assay. SEM results revealed marked changes on the outer membrane of the bacterial cells treated with various combinations. In-vivo synergy was evident from the larger log unit decreases in all the target organs of mice treated with the combinations than in those treated with drugs alone. This study thus highlights that nisin has the potential to act in conjunction with conventional antibiotics at much lower MICs. These observations seem to be significant, as reducing the therapeutic concentrations of antibiotics may be a valuable strategy for avoiding/reducing the development of emerging antibiotic resistance. Value added potential of nisin in the efficacy of conventional antibiotics may thus be exploited not only against Salmonella but against other Gram-negative infections as well.

Although blockade of androgen receptor (AR) signaling represents the main treatment for advanced prostate cancer (PrCa), many patients progress to a lethal phenotype of "Castration-Resistant" prostate cancer (CR-PrCa). With the hypothesis that early PrCa may harbor a population of androgen-unresponsive cancer cells as precursors to CR-recurrent disease, we undertook the propagation of androgen-independent cells from PrCa-prostatectomy samples of early, localized (Stage-I) cases. A collection of 120 surgical specimens from prostatectomy cases was established, among which 54 were adenocarcinomas. Hormone-free cell culture conditions were developed allowing routine propagation of cells expressing prostate basal cell markers and stem/progenitor cell markers, and which proliferated as spheres/spheroids in suspension cultures. Colonies of androgen-independent epithelial cells grew out from 30/43 (70%) of the adenocarcinoma cases studied in detail. Fluorescence microscopy and flow cytometry showed that CR-PrCa cells were positive for CD44, CD133, CK5/14, c-kit, integrin α2β1, SSEA4, E-Cadherin and Aldehyde Dehydrogenase (ALDH). All 30 CR-PrCa cell cultures were also TERT-positive, but negative for TMPRSS2-ERG. Additionally, a subset of 22 of these CR-PrCa cell cultures was examined by orthotopic xenografting in intact and castrated SCID mice, generating histologically typical locally-invasive human PrCa or undifferentiated cancers, respectively, in 6-8 weeks. Cultured PrCa cells and orthotopically-induced in vivo cancers lacked PSA expression. We report here the propagation of Cancer Initiating Cells (CIC) directly from Stage I human PrCa tissue without selection or genetic manipulation. The propagation of stem/progenitor-like CR-PrCa cells derived from early human prostate carcinomas suggests the existence of a subpopulation of cells resistant to androgen-deprivation therapy and which may drive the subsequent emergence of disseminated CR-PrCa.

Active targeting of a drug carrier to a specific target site is crucial to provide a safe and efficient delivery of therapeutics and imaging contrast agents. E-selectin expression is induced on the endothelial cell surface of vessels in response to inflammatory stimuli but is absent in the normal vessels. Thus, E-selectin is an attractive molecular target, and high affinity ligands for E-selectin could be powerful tools for the delivery of therapeutics and/or imaging agents to inflamed vessels. In this study, we identified a thiophosphate modified aptamer (thioaptamer, TA) against E-selectin (ESTA-1) by employing a two-step selection strategy: a recombinant protein-based TA binding selection from a combinatorial library followed by a cell-based TA binding selection using E-selectin expressing human microvascular endothelial cells. ESTA-1 selectively bound to E-selectin with nanomolar binding affinity (K(D) = 47 nM) while exhibiting minimal cross reactivity to P- and L-selectin. Furthermore, ESTA-1 binding to E-selectin on the endothelial cells markedly antagonized the adhesion (over 75% inhibition) of sLe(x) positive HL-60 cells at nanomolar concentration. ESTA-1 also bound specifically to the inflamed tumor-associated vasculature of human carcinomas derived from breast, ovarian, and skin but not to normal organs, and this binding was highly associated with the E-selectin expression level. Similarly, intravenously injected ESTA-1 demonstrated distinct binding to the tumor vasculature in a breast cancer xenograft model. Together, our data substantiates the discovery of a thioaptamer (ESTA-1) that binds to E-selectin with high affinity and specificity, thereby highlighting the potential application of ESTA-1 for E-selectin targeted delivery.

Abstract The prevalence of obesity is rapidly increasing, contributing to 678 million obese adults and rapidly increasing in lower-income countries. This study assessed the magnitude of central obesity and associated factors among public service office employees in Adama Town in the Oromia Regional State in Ethiopia. An institutional-based cross-sectional study was conducted from January 1 to February 26, 2020, among 590 public service employees. The data were collected by using interviewer-administered questionnaires and anthropometric measurements. The data were coded, entered, cleaned, and entered into Epi Info version 7, and subsequently exported to SPSS version 26 for statistical analysis. Binary logistic regression was used to check the associations between the explanatory and outcome variables. The adjusted odds ratio at a 95% confidence interval was used to estimate the strength of associations. A P value

Abstract G Protein-Coupled Receptors (GPCRs) are integral membrane proteins that have gained considerable attention as drug targets, particularly in cancer treatment. In this study, we explored the capacity of bioactive compounds derived from Gnetum gnemon (GG) for the development of of pharmaceuticals targeting GPCRs within the context of cancer therapy. Integrated approach combined network pharmacology and molecular docking to identify and validate the underlying pharmacological mechanisms. We retrieved targets for GG-derived compounds and GPCRs-related cancer from databases. Subsequently, we established a protein-protein interaction (PPI) network by mapping the shared targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were employed to predict the mechanism of action of these targets. Molecular docking was conducted to validate our findings. We identified a total of 265 targets associated with GG-derived bioactive compounds for the treatment of GPCRs-related cancer. Functional enrichment analysis revealed the promising therapeutic effects of these targets on GPCRs-related cancer pathways. The PPI network analysis identified hub targets, including MAPK3, SRC, EGFR, STAT3, ESR1, MTOR, CCND1, and PPARG, which demonstrate as treatment targets for GPCRs-related cancer using GG-derived compounds. Additionally, molecular docking experiments demonstrated the strong binding affinity of gnetin A, gnetin C, (-)-viniferin, and resveratrol dimer, thus inhibiting MAPK3, SRC, EGFR, and MTOR. Survival analysis established the clinical prognostic relevance of identified hub genes in cancer. This study presents a novel approach for comprehending the therapeutic mechanisms of GG-derived active compounds and thereby paving the way for their prospective clinical applications in the field of cancer treatment.

Abstract Development of new organic synthetic methods fascinating the researchers which facilitating the increasing demands of the modern society, environmental friendly with high efficiency and low cost. The introduction of chromophores in an organic molecules facilitating intersystem crossing (ISC) to harvest both singlet and triplet excitons is also currently demanding field. We report a facile synthesis of symmetrical azines from carbonyl compounds and hydrazine hydrate with carboxylic acid esters as catalyst in methanol. This reaction presents a condensation of primary amino groups in hydrazine hydrate and carbonyl compounds took place simultaneously in a very short refluxing time. The prepared azines 1–10 were structurally analysed by various analytical techniques such as LC-MS1, H NMR13, C NMR, UV-Vis, FTIR and single crystal X-ray diffraction. Photoluminescence properties of prepared azines were recorded in CCl4 at 1 × 10−3 M and excitation range from 329 to 362 nm. The photoluminescence analysis results revealed that compounds 1–10 (except 8) were showed delayed fluorescence and 8 was showed fluorescence property. The photophysical properties of compounds 1–10 such as electron density and band gap energies was calculated by density function theory. This results revealed that the intra-molecular charge transfer occurs within the azines. The azine function in the azines enabling intersystem crossing hence, it is showing phosphorescence.

Abstract Okra (Abelmoschus esculentus L. Moench) is a vital vegetable crop known for its nutritional and economic significance, especially in tropical and subtropical regions. Studying heterosis and combining ability in okra is crucial for enhancing its yield, quality, and resistance to pests and diseases. Heterosis can lead to superior offspring with enhanced traits while understanding combining ability helps in identifying the best parent combinations for breeding programs. Okra is an often cross-pollinated crop; therefore, exploiting heterosis is advantageous. The study was conducted from 2021 to 2022 at the Experimental Farm and Quality Analysis Laboratory, Department of Vegetable Science, College of Horticulture, Dr Yashwant Singh Parmar University of Horticulture and Forestry, Nauni, Solan, Himachal Pradesh, India to evaluate the heterosis and combining ability in okra to facilitate the development of high-yielding, resilient cultivars. The experimental material consisted of an F1 population of 30 crosses obtained from 10 parental lines crossed with three testers in a Line × Tester mating design, plus a standard check (Punjab-8). Estimates of heterosis (heterobeltiosis and standard heterosis) of the cross combinations UHFO-6 × Pusa Bhindi-5, UHFO-6 × Arka Anamika and UHFO-9 × Arka Anamika were high for inter-nodal distance, number of pods per plant, average pod weight, pod yield per plant, harvest duration, hundred seed weight, mucilage content, etc. Higher estimates of general combining ability (GCA) effects for pod yield per plant were observed in the parental lines UHFO-6 (123.47) and UHFO-9 (7.49). Among the cross combinations, UHFO-10 × Hisar Unnat (38.81), UHFO-2 × Pusa Bhindi-5 (38.29), UHFO-2 × Arka Anamika (17.42), and UHFO-5 × Arka Anamika (15.06) demonstrated higher estimates of specific combining ability (SCA) effects for pod yield per plant. The cross UHFO-2 × Hisar Unnat (160.00) exhibited the highest heterobeltiosis for mucilage content, while UHFO-10 × Arka Anamika (562.03) showed the highest standard heterosis for total polyphenol content. These cross combinations could produce okra with enhanced nutritional and medicinal properties. The highest GCA and SCA effects for pod yield per plant were observed in UHFO-6 (123.47) and UHFO-10 × Hisar Unnat (38.81), respectively. Identifying these parental lines and cross combinations based on their combining ability can result in the development of okra hybrids with substantially higher yields. In future, after multi-location trials, these parents and crosses can be released to replace existing okra cultivars (hybrids/varieties). Higher yielding and better quality okra cultivars can enhance the profitability for farmers, contribute to food security, and meet market demands more efficiently.

Abstract The current study aimed at population genetic characterization of B. vogeli based on the cytochrome b (cyt b) gene sequences (≥ 685 bp) available in the GenBank. Phylogenetic trees placed all the sequences of B. vogeli in a single large monophyletic clade; however, it was further divided into two subclades (Bv1 and Bv2). Out of seven nucleotide variations observed between Bv1 and Bv2 subclades, four were synonymous (G92A, C170T, T488C and A659G), and three were non-synonymous (G324A, C438A and G465A) resulting in amino acid substitutions at three places (V108I, L146I and V155I). Within different B. vogeli populations, the nucleotide and haplotype diversities were low. The median-joining haplotype network revealed only two haplotypes (Hap_1 and Hap_2). A geographical sub-structuring was noticed in the B. vogeli populations, with moderate genetic differentiation (FST = 0.05000; P

Abstract This retrospective study analyzed prognostic factors for neurological improvement and ambulation in 194 adult patients (≥ 15 years) with traumatic cervical spinal cord injuries treated at the neurological SCI unit (SCIU) at the Karolinska University Hospital Stockholm, Sweden, between 2010 and 2020. The primary outcome was American spinal injury association impairment scale (AIS) improvement, with secondary focus on ambulation restoration. Results showed 41% experienced AIS improvement, with 51% regaining ambulation over a median follow-up of 3.7 years. Significant AIS improvement (p

Abstract Collisions of the transcription and replication machineries on the same DNA strand can pose a significant threat to genomic stability. These collisions occur in part due to the formation of RNA-DNA hybrids termed R-loops, in which a newly transcribed RNA molecule hybridizes with the DNA template strand. This study investigated the role of RAD52, a known DNA repair factor, in preventing collisions by directing R-loop formation and resolution. We show that RAD52 deficiency increases R-loop accumulation, exacerbating collisions and resulting in elevated DNA damage. Furthermore, RAD52’s ability to interact with the transcription machinery, coupled with its capacity to facilitate R-loop dissolution, highlights its role in preventing collisions. Lastly, we provide evidence of an increased mutational burden from double-strand breaks at conserved R-loop sites in human tumor samples, which is increased in tumors with low RAD52 expression. In summary, this study underscores the importance of RAD52 in orchestrating the balance between replication and transcription processes to prevent collisions and maintain genome stability.

Abstract Progress in understanding the impact of mesoscale variability, including gravity waves (GWs), on atmospheric circulation is often limited by the availability of global fine-resolution observations and simulated data. This study presents momentum fluxes due to atmospheric GWs extracted from four months of an experimental “nature run", integrated at a 1 km resolution (XNR1K) using the Integrated Forecast System (IFS) model. Helmholtz decomposition is used to compute zonal and meridional flux of vertical momentum from ~1.5 petabytes of data; quantities often emulated by climate model parameterization of GWs. The fluxes are validated using ERA5 reanalysis, both during the first week after initialization and over the boreal winter period from November 2018 to February 2019. The agreement between reanalysis and IFS demonstrates its capability to generate reliable flux distributions and capture mesoscale dynamic variability in the atmosphere. The dataset could be valuable in advancing our understanding of GW-planetary wave interactions, GW evolution around atmospheric extremes, and as high-quality training data for machine learning (ML) simulation of GWs.

Abstract This paper presents a comprehensive study of 3D point cloud Federated Few-Shot Learning (3DFFL), focusing on addressing challenges such as limited data availability and privacy concerns in point cloud classification for applications such as autonomous vehicles. We introduce a novel approach that integrates Federated Learning with Few-Shot Learning techniques, with a special emphasis on optimizing network architectures for 3D point cloud data. Our method capitalizes on the strengths of PointNet++ for feature extraction and ProtoNet for classification, all within a federated learning framework to ensure data privacy and collaborative learning. Significantly, the approach is augmented with the use of attention and SoftMax layers, enhancing the feature extraction and classification processes. Extensive experiments on the ModelNet40, ShapeNet, and ScanOnjectNN datasets validate our method’s accuracy and adaptability in handling 3D point cloud classification, especially in privacy-sensitive and collaborative scenarios. This study not only demonstrates the potential of integrating attention mechanisms and SoftMax layers in 3DFFL but also lays a robust foundation for future advancements in this evolving field, particularly in technologies dependent on 3D data processing.

Abstract The geometric features and operational parameters of rotary blades on rotary tillers significantly impact their performance characteristics. The sweepback angle is a geometric feature of the 'L'-shaped rotary blade that has remained unexplored in previous studies. This study aimed to analyze the effect of geometrical and operational parameters on the performance dynamics of the 'L'-shaped rotary blade. The investigation was conducted using the discrete element method (DEM) and further validated through experiments conducted in a soil bin. The simulation experiment was conducted by dividing the particle bed into horizontal particle zones. The effect of the geometrical (sweepback angle) and operational parameters (forward speed, rotational speed, and depth) on the power requirement, disturbance intensity, and mixing index was studied. The novel method was adopted to determine the mixing capability of rotary blades in terms of sub-domain mixing index (SMI) and overall mixing index (OMI). The results revealed that the power requirements for a sweepback angle of 18° were 26.39% and 16.50% lower than those for sweepback angles of 6° and 12°, respectively. The sweepback angle tends to have the least effect on the overall mixing index compared to operational parameters. The average particle velocity decreased by 22.19% and 29.60% with sweepback angles of 12° and 18°, respectively, compared to the sweepback angle of 6°. The relative error during the experiment varied between 1.29% and 13.51%. It was concluded that the sweepback angle was found to be a feasible option for reducing the power requirement with good mixing indices.

Abstract Quantum spin liquids (QSLs) have become a key area of research in magnetism due to their remarkable properties, such as long-range entanglement, fractional excitations, and topologically protected phenomena. Recently, the search for QSLs has expanded into the three-dimensional world, despite the suppression of quantum fluctuations due to high dimensionality. A new candidate material, K2Ni2(SO4)3, belongs to the langbeinite family and consists of two interconnected trillium lattices. Although magnetically ordered, it exhibits a highly dynamical and correlated state. In this work, we combine inelastic neutron scattering measurements with density functional theory (DFT), pseudo-fermion functional renormalization group (PFFRG), and classical Monte Carlo (cMC) calculations to study the magnetic properties of K2Ni2(SO4)3, revealing a high level of agreement between experiment and theory. We further reveal the origin of the dynamical state in K2Ni2(SO4)3 to be centred around a magnetic network composed of tetrahedra on a trillium lattice.

Abstract Time courses of neural responses underlie real-time sensory processing and perception. How these temporal dynamics change may be fundamental to how sensory systems adapt to different perceptual demands. By simultaneously recording from hundreds of neurons in mouse primary visual cortex, we examined neural population responses to visual stimuli at sub-second timescales, during different behavioural states. We discovered that during active behavioural states characterised by locomotion, single-neurons shift from transient to sustained response modes, facilitating rapid emergence of visual stimulus tuning. Differences in single-neuron response dynamics were associated with changes in temporal dynamics of neural correlations, including faster stabilisation of stimulus-evoked changes in the structure of correlations during locomotion. Using Factor Analysis, we examined temporal dynamics of latent population responses and discovered that trajectories of population activity make more direct transitions between baseline and stimulus-encoding neural states during locomotion. This could be partly explained by dampening of oscillatory dynamics present during stationary behavioural states. Functionally, changes in temporal response dynamics collectively enabled faster, more stable and more efficient encoding of new visual information during locomotion. These findings reveal a principle of how sensory systems adapt to perceptual demands, where flexible neural population dynamics govern the speed and stability of sensory encoding.

Abstract Birdshot chorioretinopathy is an inflammatory eye condition strongly associated with MHC-I allele HLA-A29. The striking association with MHC-I suggests involvement of T cells, whereas natural killer (NK) cell involvement remains largely unstudied. Here we show that HLA-A29-positive birdshot chorioretinopathy patients have a skewed NK cell pool containing expanded CD16 positive NK cells which produce more proinflammatory cytokines. These NK cells contain populations that express CD8A which is involved in MHC-I recognition on target cells, display gene signatures indicative of high cytotoxic activity (GZMB, PRF1 and ISG15), and signaling through NK cell receptor CD244 (SH2D1B). Long-term monitoring of a cohort of birdshot chorioretinopathy patients with active disease identifies a population of CD8bright CD244bright NK cells, which rapidly declines to normal levels upon clinical remission following successful treatment. Collectively, these studies implicate CD8bright CD244bright NK cells in birdshot chorioretinopathy.

Abstract In many Indian regions, paddy wheat is the main crop rotation and facing the problem of straw incorporation for seed bed preparation in short period. The handling of straw in combine harvested paddy fields is a significant issue in the paddy wheat rotation. In order to solve this issue, efforts were carried out to cut paddy straw into small pieces by the newly proposed counter-rotating blades, followed by the simultaneous incorporation of a rotary tiller into the soil. Therefore, a tractor operated chopping cum tilling mixing machine was developed. In the study, three different blades (straw management system (SMS) Serrated, cutter bar and SMS plain) were tested in the terms of torque and required to chop the straw. SMS serrated blade was best suitable for the chopping mechanism as it required minimum cutting torque for the straw bunches. The developed chopping cum tilling mixing machine was tested at three different levels of forward speed (1.77, 2.3, and 3 km h−1), moisture content at three levels (35 ± 3.4, 24 ± 2.2 and 17 ± 2.6%) with fix rotary tiller rotational speed of 810 rev min−1. Optimum operating condition of the machine was obtained at a forward speed of 1.9 km h−1 and a moisture of 24%. At these optimized values, the mixing index (96%), mean weight diameter (7.9 mm), bulk density (1230 g cc−1) and fuel consumption (3 l h−1) were 96%, 7.9 mm, 1230 g cc−1 and 3.0 l h−1 respectively. The developed machine performs three operations i.e., chopping, tilling, and mixing in single pass for effective in-situ straw management.

Abstract Proper utilization of agricultural land is a big challenge as they often laid over as waste lands. Farming is a significant occupation in any country and improving it further by promoting more farming opportunities will take the country towards making a huge leap forward. The issue in achieving this would be the lack of knowledge of cultivable land for food crops. The objective of this work is to utilize modern computer vision technology to identify and map cultivable land for agricultural needs. With increasing population and demand for food, improving the farming sector is crucial. However, the challenge lies in the lack of suitable land for food crops cultivation. To tackle this issue, we propose to use sophisticated image processing techniques on satellite images of the land to determine the regions that are capable of growing food crops. The solution architecture includes enhancement of satellite imagery using sophisticated pan sharpening techniques, notably the Brovey transformation, aiming to transform dull satellite images into sharper versions, thereby improving the overall quality and interpretability of the visual data. Making use of the weather data on the location observed and taking into factors like the soil moisture, weather, humidity, wind, sunlight times and so on, this data is fed into a generative pre-trained transformer model which makes use of it and gives a set of crops that are suitable to be grown on this piece of land under the said conditions. The results obtained by the proposed fusion approach is compared with the dataset provided by the government for different states in India and the performance was measured. We achieved an accuracy of 80% considering the crop suggested by our model and the predominant crop of the region. Also, the classification report detailing the performance of the proposed model is presented.

Abstract The primary cause behind the degradation of reinforced concrete (RC) structures is the propagation of corrosion in the steel-RC structures. Nowadays, numerous retrofitting techniques are available in the construction sector. Fiber-reinforced polymer (FRP) is one of the efficient rehabilitation measures that can be implemented on corroded structures to enhance structural capacities. However, the estimation of axial strength of FRP-strengthened columns affected by corrosion has been a challenging and tedious task in the laboratory as well as on the site. Considering such shortcomings, the prediction of axial capacity can be done using various analytical methods and artificial intelligence (AI) techniques. In this study, a comprehensive dataset of circular columns was extracted from the literature to predict the axial strength of FRP-wrapped and unstrengthened RC corroded columns. The laboratory results from the assembled dataset were compared to corresponding values estimated using relevant design codes provided by American Concrete Institute (ACI 440.2R-17 and ACI 318-19), and Bureau of Indian Standard (IS 456:2000). Five machine learning models were employed on columns to predict the axial load carrying capacity of FRP-strengthened and un-strengthened RC corroded columns. The results discovered that the extreme gradient boosting (XGBoost) model achieves superior accuracy with the least errors and could be used by the scientific community and FRP applicators to forecast the axial performance of corroded columns strengthened with and without FRP. The findings from the design codes revealed that prediction errors were available in high margins. Furthermore, feature importance analysis was conducted using the Shapley Additive exPlanation algorithm to know the contribution and influence of each input parameter on axial capacity. The feature analysis found that unconfined compressive strength of concrete plays an important role in deciding the axial capacity of columns. Moreover, to enhance the precision of axial capacity computation and improving the overall efficacy in engineering practice, a web-based user-friendly interface was developed for FRP applicators and engineers to simplify the process.

Abstract Health risks due to preventable infections such as human papillomavirus (HPV) are exacerbated by persistent vaccine hesitancy. Due to limited sample sizes and the time needed to roll out, traditional methodologies like surveys and interviews offer restricted insights into quickly evolving vaccine concerns. Social media platforms can serve as fertile ground for monitoring vaccine-related conversations and detecting emerging concerns in a scalable and dynamic manner. Using state-of-the-art large language models, we propose a minimally supervised end-to-end approach to identify concerns against HPV vaccination from social media posts. We detect and characterize the concerns against HPV vaccination pre- and post-2020 to understand the evolution of HPV vaccine discourse. Upon analyzing 653 k HPV-related post-2020 tweets, adverse effects, personal anecdotes, and vaccine mandates emerged as the dominant themes. Compared to pre-2020, there is a shift towards personal anecdotes of vaccine injury with a growing call for parental consent and transparency. The proposed approach provides an end-to-end system, i.e. given a collection of tweets, a list of prevalent concerns is returned, providing critical insights for crafting targeted interventions, debunking messages, and informing public health campaigns.

Abstract Diabetes mellitus (DM) is a prominent global health challenge, characterized by a rising prevalence and substantial morbidity and mortality, especially evident in developing nations. Although DM can be managed with self-care practices despite its complexity and chronic nature, the persistence of poor self-care exacerbates the disease burden. There is a dearth of evidence on the level of poor self-care practices and contributing factors among patients with DM in the study area. Thus, this study assessed the proportion of poor self-care practices and contributing factors among adults with type 2 DM in Adama, Ethiopia. An institution-based cross-sectional study was conducted among 404 patients. Self-care practice was assessed by the summary of diabetes self-care activities questionnaires. Binary logistic regression was used to identify factors associated with poor self-care practices. An adjusted odds ratio with a 95% confidence interval was used to assess the strength of associations. The statistical significance was declared for a p-value

Abstract Human space exploration poses inherent risks to astronauts’ health, leading to molecular changes that can significantly impact their well-being. These alterations encompass genomic instability, mitochondrial dysfunction, increased inflammation, homeostatic dysregulation, and various epigenomic changes. Remarkably, these changes bear similarities to those observed during the aging process on Earth. However, our understanding of the connection between these molecular shifts and disease development in space remains limited. Frailty syndrome, a clinical syndrome associated with biological aging, has not been comprehensively investigated during spaceflight. To bridge this knowledge gap, we leveraged murine data obtained from NASA’s GeneLab, along with astronaut data gathered from the JAXA and Inspiration4 missions. Our objective was to assess the presence of biological markers and pathways related to frailty, aging, and sarcopenia within the spaceflight context. Through our analysis, we identified notable changes in gene expression patterns that may be indicative of the development of a frailty-like condition during space missions. These findings suggest that the parallels between spaceflight and the aging process may extend to encompass frailty as well. Consequently, further investigations exploring the utility of a frailty index in monitoring astronaut health appear to be warranted.

Abstract Mounting ambitions and capabilities for public and private, non-government sector crewed space exploration bring with them an increasingly diverse set of space travelers, raising new and nontrivial ethical, legal, and medical policy and practice concerns which are still relatively underexplored. In this piece, we lay out several pressing issues related to ethical considerations for selecting space travelers and conducting human subject research on them, especially in the context of non-governmental and commercial/private space operations.

Waste cooking oil has the potential to be a raw material for biodiesel. The use of heterogeneous catalysts and ultrasonicator will optimize the transesterification and environmentally friendly. Transesterification study of waste cooking oil with SrO-KF nano catalyst has been carried out. This researchs were: refinement of waste cooking oil, synthesis of SrO-KF nano-catalyst, and the transesterification. The catalyst applied ratio of 1:1, 1:2, and 1:3 of SrO:KF with concentrations of 2%, 3% and 4% by weight of oil respectively. The results of heterogeneous catalyst using XRD and SEM showed that SrF2, SrO and KF compounds had been formed. The optimum transesterification conditions were obtained on SrO-KF catalyst (1:2), concentration of 4% (w/w) with a yield of 84.4% (w/w). The methyl ester of waste cooking oil has density of 884 kg/m3, acid number of 0.48 mg/g, and viscosity of 4.2 cSt. Methyl esters of waste cooking oil were composed of 25.14% methyl palmitate and 33.65% methyl elaidate, 11.27% methyl linoleate, 10.14% methyl lauric and a mixture of methyl esters from waste cooking oil has the potential to be used as biodiesel.

Abstract High temperature stress influences plant growth, seed yield, and fatty acid contents by causing oxidative damage. This study investigated the potential of thiourea (TU) to mitigate oxidative stress and restoring seed oil content and quality in canola. The study thoroughly examined three main factors: (i) growth conditions—control and high temperature stress (35 °C); (ii) TU supplementation (1000 mg/L)—including variations like having no TU, water application at the seedling stage, TU application at seedling stage (BBCH Scale-39), water spray at anthesis stage, and TU application at anthesis stage (BBCH Scale-60); (iii) and two canola genotypes, 45S42 and Hiola-401, were studied separately. High temperature stress reduced growth and tissue water content, as plant height and relative water contents were decreased by 26 and 36% in 45S42 and 27 and 42% Hiola-401, respectively, resulting in a substantial decrease in seed yield per plant by 36 and 38% in 45S42 and Hiola-401. Seed oil content and quality parameters were also negatively affected by high temperature stress as seed oil content was reduced by 32 and 35% in 45S42 and Hiola-401. High-temperature stress increased the plant stress indicators like malondialdehyde, H2O2 content, and electrolyte leakage; these indicators were increased in both canola genotypes as compared to control. Interestingly, TU supplementation restored plant performance, enhancing height, relative water content, foliar chlorophyll (SPAD value), and seed yield per plant by 21, 15, 30, and 28% in 45S42; 19, 13, 26, and 21% in Hiola-401, respectively, under high temperature stress as compared to control. In addition, seed quality, seed oil content, linoleic acid, and linolenic acid were improved by 16, 14, and 22% in 45S42, and 16, 11, and 23% in Hiola-401, as compared to control. The most significant improvements in canola seed yield per plant were observed when TU was applied at the anthesis stage. Additionally, the research highlighted that canola genotype 45S42 responded better to TU applications and exhibited greater resilience against high temperature stress compared to genotype Hiola-401. This interesting study revealed that TU supplementation, particularly at the anthesis stage, improved high temperature stress tolerance, seed oil content, and fatty acid profile in two canola genotypes.

Abstract Liquefaction is a devastating consequence of earthquakes that occurs in loose, saturated soil deposits, resulting in catastrophic ground failure. Accurate prediction of such geotechnical parameter is crucial for mitigating hazards, assessing risks, and advancing geotechnical engineering. This study introduces a novel predictive model that combines Extreme Learning Machine (ELM) with Dingo Optimization Algorithm (DOA) to estimate strain energy-based liquefaction resistance. The hybrid model (ELM-DOA) is compared with the classical ELM, Adaptive Neuro-Fuzzy Inference System with Fuzzy C-Means (ANFIS-FCM model), and Sub-clustering (ANFIS-Sub model). Also, two data pre-processing scenarios are employed, namely traditional linear and non-linear normalization. The results demonstrate that non-linear normalization significantly enhances the prediction performance of all models by approximately 25% compared to linear normalization. Furthermore, the ELM-DOA model achieves the most accurate predictions, exhibiting the lowest root mean square error (484.286 J/m3), mean absolute percentage error (24.900%), mean absolute error (404.416 J/m3), and the highest correlation of determination (0.935). Additionally, a Graphical User Interface (GUI) has been developed, specifically tailored for the ELM-DOA model, to assist engineers and researchers in maximizing the utilization of this predictive model. The GUI provides a user-friendly platform for easy input of data and accessing the model's predictions, enhancing its practical applicability. Overall, the results strongly support the proposed hybrid model with GUI serving as an effective tool for assessing soil liquefaction resistance in geotechnical engineering, aiding in predicting and mitigating liquefaction hazards.

Abstract Cardiac fibrosis contributes to the development of heart failure, and is the response of cardiac fibroblasts (CFs) to pressure or volume overload. Limiting factors in CFs research are the poor availability of human cells and the tendency of CFs to transdifferentiate into myofibroblasts when cultured in vitro. The possibility to generate CFs from induced pluripotent stem cells (iPSC), providing a nearly unlimited cell source, opens new possibilities. However, the behaviour of iPSC-CFs under mechanical stimulation has not been studied yet. Our study aimed to assess the behaviour of iPSC-CFs under mechanical stretch and pro-fibrotic conditions. First, we confirm that iPSC-CFs are comparable to primary CFs at gene, protein and functional level. Furthermore, iPSC-derived CFs adopt a pro-fibrotic response to transforming growth factor beta (TGF-β). In addition, mechanical stretch inhibits TGF-β-induced fibroblast activation in iPSC-CFs. Thus, the responsiveness to cytokines and mechanical stimulation of iPSC-CFs demonstrates they possess key characteristics of primary CFs and may be useful for disease modelling.

Abstract Chickpea is a highly nutritious protein-rich source and one of the major crops to alleviate global malnutrition, but poor seed quality affects its productivity. Seed quality is essential for better crop establishment and higher yields, particularly in the uncertain climate change. The present study investigated the impact of botanical priming versus hydropriming and bavistin seed treatment on chickpea seeds. A detailed physiological (germination percentage, root and shoot length, vigour index) and biochemical (amylase, protease, dehydrogenase, phytase, and lipid peroxidation) analysis was carried out in order to assess the effect of priming treatments. Turmeric-primed seeds showed better germination rate (94.5%), seedling length, enzyme activity, and lower malondialdehyde (MDA) content. Sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis revealed the expression of minor polypeptides of albumin and globulin in the primed seeds. Moreover, field experiments indicated increased crop growth, vigour, days to 50% flowering, yield and its attributing traits in turmeric-primed seeds. Botanical priming can increase chickpea yield by up to 16% over the control group. This low-cost and eco-friendly technique enhances seed and crop performance, making it a powerful tool for augmenting chickpea growth. Therefore, chickpea growers must adopt botanical priming techniques to enhance the quality of seed and crop performance. Moreover, this approach is environmentally sustainable and can help conserve natural resources in the long term. Therefore, this new approach must be widely adopted across the agricultural industry to ensure sustainable and profitable farming practices.

Abstract Amivantamab is the first dual-specificity antibody targeting EGFR and MET, which is approved for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations. Cardiovascular toxicities related to amivantamab have not been reported in the CHRYSALIS study. However, the occurrence of cardiovascular events in the real world is unknown. To comprehensively investigate the clinical characteristics, onset times, and outcomes of cardiovascular toxicities associated with amivantamab. The Food and Drug Administration Adverse Event Reporting System (FAERS) database from 1st quarter of 2019 to the 2nd quarter of 2023 was retrospectively queried to extract reports of cardiovascular adverse events (AEs) associated with amivantamab. To perform disproportionality analysis, the reporting odds ratios (RORs) and information components (ICs) were calculated with statistical shrinkage trans-formation formulas and a lower limit of the 95% confidence interval (CI) for ROR (ROR025) > 1 or IC (IC025) > 0 with at least 3 reports was considered statistically significant. A total of 20,270,918 eligible records were identified, among which 98 records were related to cardiovascular events associated with amivantamab. 4 categories of cardiovascular events exhibited positive signals: venous thrombotic diseases, abnormal blood pressure, arrhythmia, and pericardial effusion. Venous thrombotic diseases and abnormal blood pressure were the two most common signals. The median time to onset (TTO) for cardiovascular AEs was 33 days. The cumulative incidence within 90 days was 100% for cardiac failure, 75% for stroke, 63.16% for arrhythmia, 50% for sudden death, and 44.18% for venous thrombotic diseases. Death accounted for 16.3% of all cardiovascular AEs associated with amivantamab. The mortality rates for Major Adverse Cardiovascular Events (MACE) were up to 60%. This pharmacovigilance study systematically explored the cardiovascular adverse events of amivantamab and provided new safety signals based on past safety information. Early and intensified monitoring is crucial, and attention should be directed towards high-risk signals.

Abstract Grid computing emerged as a powerful computing domain for running large-scale parallel applications. Scheduling computationally intensive parallel applications such as scientific, commercial etc., computational grids is a NP-complete problem. Many researchers have proposed several task scheduling algorithms on grids based on formulating and solving it as an optimization problem with different objective functions such as makespan, cost, energy etc. Further to address the requirements/demands/needs of the users (lesser cost, lower latency etc.) and grid service providers (high utilization and high profitability), a task scheduler needs to be designed based on solving a multi-objective optimization problem due to several trade-offs among the objective functions. In this direction, we propose an efficient multi-objective task scheduling framework to schedule computationally intensive tasks on heterogeneous grid networks. This framework minimizes turnaround time, communication, and execution costs while maximizing grid utilization. We evaluated the performance of our proposed algorithm through experiments conducted on standard, random, and scientific task graphs using the GridSim simulator.

Abstract Medicinal plants can be potential sources of therapeutic agents. Traditional healers use a medicinal plant from Ethiopia, Bersama abyssinica Fresen, to treat various diseases. This study aimed to investigate the phytochemical components and antioxidant and antimicrobial activities of B. abyssinica seed extracts (BASE). Gas chromatography coupled to mass spectroscopy (GC–MS) analysis was used to determine the phytochemical compositions of BASE. The antioxidant activities were assessed by using 2, 2-diphenyl-1-picrylhydrazyl (DPPH) assay, thiobarbituric acid-reactive species (TBARS) assay, ferric chloride reducing assay and hydroxyl scavenging capacity assay. Antimicrobial activity was investigated using the agar well diffusion method. Phytochemical screening showed the presence of saponins, glycosides, tannins, steroids, phenols, flavonoids, terpenoids, and alkaloids. GC–MS analysis revealed the presence of 30 volatile compounds; α-pinene (23.85%), eucalyptol (20.74%), β-pinene (5.75%), d-limonene (4.05%), and o-cymene (5.02%). DPPH-induced free radical scavenging (IC50 = 8.78), TBARS (IC50 = 0.55 µg/mL), and hydroxyl radicals’ scavenging capacities assays (IC50 = 329.23) demonstrated high antioxidant effects of BASE. Reducing power was determined based on Fe3+–Fe2+ transformation in the presence of extract. BASE was found to show promising antibacterial activity against S. aureus, E. coli, and P. aeruginosa (zone of inhibition 15.7 ± 2.5 mm, 16.0 ± 0.0 mm, and 16.7 ± 1.5 mm, respectively), but excellent antifungal activities against C. albican and M. furfur (zone of inhibition 22.0 ± 2.0 mm and 22.0 ± 4.0 mm, respectively). The seeds of B. abyssinica grown in Ethiopia possess high antioxidant potential, promising antibacterial and superior antifungal activity. Therefore, seeds of B. abyssinica provide a potential source for drug discovery.

Abstract Autism spectrum disorder (ASD) is a complicated, lifelong neurodevelopmental disorder affecting verbal and non-verbal communication and social interactions. ASD signs and symptoms appear early in development before the age of 3 years. It is unlikely for a person to acquire autism after a period of normal development. However, we encountered an 8-year-old child who developed ASD later in life although his developmental milestones were normal at the beginning of life. Sequencing the complete coding part of the genome identified a hemizygous nonsense mutation (NM_001367857.2):c.1803C>G; (p.Tyr601Ter) in the gene (SATL1) encoding spermidine/spermine N1-acetyl transferase like 1. Screening an ASD cohort of 28 isolated patients for the SATL1 gene identified another patient with the same variant. Although SATL1 mutations have not been associated with any human diseases, our data suggests that a mutation in SATL1 is the underlying cause of ASD in our cases. In mammals, mutations in spermine synthase (SMS), an enzyme needed for the synthesis of spermidine polyamine, have been reported in a syndromic form of the X-linked mental retardation. Moreover, SATL1 gene expression studies showed a relatively higher expression of SATL1 transcripts in ASD related parts of the brain including the cerebellum, amygdala and frontal cortex. Additionally, spermidine has been characterized in the context of learning and memory and supplementations with spermidine increase neuroprotective effects and decrease age-induced memory impairment. Furthermore, spermidine biosynthesis is required for spontaneous axonal regeneration and prevents α-synuclein neurotoxicity in invertebrate models. Thus, we report, for the first time, that a mutation in the SATL1 gene could be a contributing factor in the development of autistic symptoms in our patients.

Abstract The potential of solid waste as an energy source is clear, owing to its wide availability and renewable properties, which provide a critical answer for energy security. This can be especially effective in reducing the environmental impact of fossil fuels. Countries that rely heavily on coal should examine alternatives such as electricity from solid waste to provide a constant energy supply while also contributing to atmospheric restoration. In this regards, Low Emissions Analysis Platform (LEAP) is used for simulation the entire energy system in Pakistan and forecasted its capital cost and future CO2 emissions in relation to the use of renewable and fossil fuel resources under the different growth rates of solid waste projects like 20%, 30% and 40% for the study period 2023–2053. The results revealed that, 1402.97 TWh units of energy are generated to meet the total energy demand of 1193.93 TWh until 2053. The share of solid waste based electricity in total energy mix is increasing from a mere 0.81% in 2023 to around 9.44% by 2053 under the 20% growth rate, which then increase to 39.67% by 2053 under the 30% growth rate and further increases to 78.33% by 2053 under the 40% growth rate. It is suggested that 40% growth rate for solid waste based electricity projects is suitable for Pakistan until 2053 because under this condition, renewable sources contributes 95.2% and fossil fuels contributed 4.47% in the total energy mix of Pakistan. Hence, CO2 emissions are reduced from 148.26 million metric tons to 35.46 million metric tons until 2053 but capital cost is increased from 13.23 b$ in 2023 to 363.11 b$ by 2053.

Summary: Environmental enteric dysfunction (EED) is a subclinical enteropathy challenging to diagnose due to an overlap of tissue features with other inflammatory enteropathies. EED subjects (n = 52) from Pakistan, controls (n = 25), and a validation EED cohort (n = 30) from Zambia were used to develop a machine-learning-based image analysis classification model. We extracted histologic feature representations from the Pakistan EED model and correlated them to transcriptomics and clinical biomarkers. In-silico metabolic network modeling was used to characterize alterations in metabolic flux between EED and controls and validated using untargeted lipidomics. Genes encoding beta-ureidopropionase, CYP4F3, and epoxide hydrolase 1 correlated to numerous tissue feature representations. Fatty acid and glycerophospholipid metabolism-related reactions showed altered flux. Increased phosphatidylcholine, lysophosphatidylcholine (LPC), and ether-linked LPCs, and decreased ester-linked LPCs were observed in the duodenal lipidome of Pakistan EED subjects, while plasma levels of glycine-conjugated bile acids were significantly increased. Together, these findings elucidate a multi-omic signature of EED.