The frequency and function of nucleoprotein-specific CD8+ T cells are critical for heterosubtypic immunity against influenza virus infection.

Cytotoxic T lymphocytes (CTLs) mediate host defense against viral and intracellular bacterial infections and tumors. However, the magnitude of CTL response and their function needed to confer heterosubtypic immunity against influenza virus infection are unknown. We addressed the role of CD8+ T cells in the absence of any cross-reactive antibody responses to influenza viral proteins using an adenoviral vector expressing a 9mer amino acid sequence recognized by CD8+ T cells. Our results indicate that both CD8+ T cell frequency and function are crucial for heterosubtypic immunity. Low morbidity, lower viral lung titers, low to minimal lung pathology, and better survival upon heterosubtypic virus challenge correlated with the increased frequency of NP-specific CTLs. NP-CD8+ T cells induced by differential infection doses displayed distinct RNA transcriptome profiles and functional properties. CD8+ T cells induced by a high dose of influenza virus secreted significantly higher levels of IFN-γ and exhibited higher levels of cytotoxic function. The mice that received NP-CD8+ T cells from the high-dose virus recipients through adoptive transfer had lower viral titers following viral challenge than those induced by the low dose of virus, suggesting differential cellular programming by antigen dose. Enhanced NP-CD8+ T-cell functions induced by a higher dose of influenza virus strongly correlated with the increased expression of cellular and metabolic genes, indicating a shift to a more glycolytic metabolic phenotype. These findings have implications for developing effective T cell vaccines against infectious diseases and cancer. IMPORTANCE: Cytotoxic T lymphocytes (CTLs) are an important component of the adaptive immune system that clears virus-infected cells or tumor cells. Hence, developing next-generation vaccines that induce or recall CTL responses against cancer and infectious diseases is crucial. However, it is not clear if the frequency, function, or both are essential in conferring protection, as in the case of influenza. In this study, we demonstrate that both CTL frequency and function are crucial for providing heterosubtypic immunity to influenza by utilizing an Ad-viral vector expressing a CD8 epitope only to rule out the role of antibodies, single-cell RNA-seq analysis, as well as adoptive transfer experiments. Our findings have implications for developing T cell vaccines against infectious diseases and cancer.

Improved outcomes of ABO-incompatible living donor liver transplant with biologically related donors.

Liver transplantation is considered to be the only curative treatment for decompensated liver disease. Shortage of liver allografts is a major impediment to the widespread application of this procedure. ABO-incompatible (ABO-I) grafts have been used successfully, thereby increasing the living donor liver transplantation (LDLT) donor pool. However, ABO-I liver transplantation is associated with complications like acute liver rejection, hepatic artery thrombosis, and higher biliary stricture rates, leading to transplant failure, retransplantations, or sepsis-related complications. Various desensitization strategies have been adopted to improve outcomes. Biologically related donor-recipient pairs have the theoretical advantage of favorable HLA (human leukocyte antigen) match. We have analyzed the outcomes of ABO-I LDLT and compared the results of HLA-matched (biologically related) and HLA-unmatched (biologically unrelated) donor-recipient pairs. Retrospective data of 90 cases of ABO-I liver transplant recipients: HLA-matched (n = 35) and HLA-unmatched (n = 55) for comparison of preoperative and postoperative data. Peak bilirubin levels in HLA-unmatched recipients were higher. Platelet count was lower than HLA-matched recipients (7.3 vs. 8.9 mg/dL). No significant difference in days-to-normal bilirubin, peak International Normalised Ratio, hospital stay, and discharge-day from transplant between both groups. Postoperatively, HLA-unmatched recipients required more pulse-steroids therapy than HLA-matched: 21/55 (38.2%) versus 11/35 (31.4%). Biliary complications and interventions were more prevalent in the HLA-unmatched group (12/55, 21.8%) than in the HLA-matched group (4/35, 11.4%). Renal complications requiring postoperative hemodialysis were more prevalent in the HLA-unmatched group than the HLA-matched group (9/55 [16.4%] vs. 3/35 [8.6%]). The incidence of vascular complications was similar. ABO-I LDLT is an effective and safe method for increasing the donor pool in the absence of an ABO-compatible liver donor. Long-term outcomes of recipients with biologically related donors are marginally better than biologically unrelated ABO-I LDLT recipients. However, the incidence of antibody-mediated graft rejection and biliary complications is higher in biologically unrelated ABO-I liver recipients.

Management of complicated Bouveret's syndrome.

Bouveret's syndrome is an uncommon cause of gastric outlet obstruction caused by the impaction of large gallstones in the duodenal lumen. The gallstones pass into the duodenal lumen through a cholecystogastric or a cholecystoduodenal fistula. Endoscopic retrieval with or without lithotripsy is the first line of management, often with variable success. We present a case of a woman in her 70s who presented with signs of gastric outlet obstruction and was diagnosed with Bouveret's syndrome with a 5 cm diameter gallstone in the third part of her duodenum. Following several unsuccessful attempts of endoscopic extraction, she underwent successful jejunal enterotomy with fragmentation and extraction of the calculus using an Allis tissue holding forceps. Postoperative recovery was uneventful.

Secure and privacy-preserving automated machine learning operations into end-to-end integrated IoT-edge-artificial intelligence-blockchain monitoring system for diabetes mellitus prediction.

Diabetes Mellitus, one of the leading causes of death worldwide, has no cure to date and can lead to severe health complications, such as retinopathy, limb amputation, cardiovascular diseases, and neuronal disease, if left untreated. Consequently, it becomes crucial to be able to monitor and predict the incidence of diabetes. Machine learning approaches have been proposed and evaluated in the literature for diabetes prediction. This paper proposes an IoT-edge-Artificial Intelligence (AI)-blockchain system for diabetes prediction based on risk factors. The proposed system is underpinned by blockchain to obtain a cohesive view of the risk factors data from patients across different hospitals and ensure security and privacy of the user's data. We provide a comparative analysis of different medical sensors, devices, and methods to measure and collect the risk factors values in the system. Numerical experiments and comparative analysis were carried out within our proposed system, using the most accurate random forest (RF) model, and the two most used state-of-the-art machine learning approaches, Logistic Regression (LR) and Support Vector Machine (SVM), using three real-life diabetes datasets. The results show that the proposed system predicts diabetes using RF with 4.57% more accuracy on average in comparison with the other models LR and SVM, with 2.87 times more execution time. Data balancing without feature selection does not show significant improvement. When using feature selection, the performance is improved by 1.14% for PIMA Indian and 0.02% for Sylhet datasets, while it is reduced by 0.89% for MIMIC III.

Hypothyroidism in acute coronary syndrome - A prospective Indian study.

BACKGROUND: Evidence suggests that hypothyroidism may be associated with an increased risk of acute coronary syndrome (ACS). The data regarding the influence of hypothyroidism on cardiovascular disease in the Asian population is conflicting. Therefore, we undertook this study to assess the overall prevalence of hypothyroidism in Acute Coronary Syndrome (ACS) patients and determine if there is a relationship between hypothyroidism, both sub-clinical and overt and other significant risk factors of ACS in an Indian population. METHODS: We studied 487 hospitalized patients between March 2018 and February 2021 with a diagnosis of ACS to determine the prevalence of hypothyroidism, both clinical and sub-clinical and their relationship with other known coronary risk factors. Thyroid function Tests - free T3, free T4 and TSH were collected from all the patients within 24 h of their admission to the coronary care unit (CCU) of 2 major hospitals in New Delhi and Imphal (Manipur). RESULTS: Subclinical hypothyroidism was prevalent in 44 (9 %), followed by overt hypothyroidism in 25 (5.2 %). Subclinical hypothyroidism was more common in females, whereas overt hypothyroidism was more common in males. ST Elevation Myocardial Infarction (STEMI) (52 %), followed by Non-ST-Elevation Myocardial Infarction (NSTEMI) (25 %), was the commonest diagnosis at presentation. Patients with overt hypothyroidism showed a higher proportion of increased triglyceride levels. Patients with hypothyroidism had no differences in the prevalence of concomitant diabetes hypertension and other coronary risk factors. CONCLUSIONS: Patients with ACS without known thyroid disorders should be screened for hypothyroidism since it is found frequently. There might be a case to treat their thyroid dysfunction appropriately.

Pure biochemicals and nanomaterials as next generation biostimulants for sustainable agriculture under abiotic stress - recent advances and future scope.

Sustainable agriculture faces major challenges under abiotic stress conditions owing to extensive application of chemical fertilizers which pollute water, soil and atmosphere. Biostimulants (BSs), comprising of naturally derived complex mixtures of uncharacterized biomolecules, pure biochemicals and nanomaterials, enhance nutrient use efficiency (NUE) and trigger crop's natural defense mechanisms. While it is difficult to specify the metabolic effects of uncharacterized natural mixtures (seaweed extract, protein hydrolyzates, etc.), exogenous application of pure biochemicals and nanomaterials offers an edge as BSs since their physiological roles and mechanisms of action are decipherable. Foliar application or seed treatment of some amino acids, polyamines and biopolymers (chitosan, lipochitin oligosaccharides and thuricin 17) enable plants to overcome drought and salinity stress via activation of mechanisms for reactive oxygen species (ROS) scavenging, osmolyte regulation and chlorophyll accumulation. Interaction of nitric oxide (NO) with some vitamins and melatonin exhibits potential significance as BSs for mitigating stress by ROS scavenging and maintenance of intracellular ionic balance and membrane integrity. Near future is likely to see wide applications of nanoparticles (NPs) and nanomaterials (NMs) as BSs in view of their biphasic mode of action (bio-physical activation of membrane receptors followed by gradual release of BS into the plant cells).

High-Performance Paper-Based Thermoelectric Generator from Cu2SnS3 Nanocubes and Bulk-Traced Bismuth.

Flexible paper-based thermoelectric generators (PTEGs) have drawn significant interest in recent years due to their various advantages such as flexibility, adaptability, environment friendliness, low cost, and easy fabrication process. However, the reported PTEG's output performance still lags behind the performance of other flexible devices as it is not so easy to obtain a compact film on a paper-based substrate with desirable power output with the standard thermoelectric (TE) materials that have been previously utilized. In this direction, Cu2SnS3 (CTS), an earth-abundant, ternary sulfide, can be a good choice p-type semiconductor, when paired with a suitable n-type TE material. In this article, CTS nanocubes are synthesized via a simple hot injection method and a thick film device on emery paper was prepared and optimized. Furthermore, a flexible, 20-pair PTEG is fabricated with p-type CTS legs and traced and pressed n-type bismuth legs assembled using Kapton tape that produced a significantly high output power of 2.18 µW (output power density ∼0.85 nW cm-2 K-1) for a temperature gradient of ΔT = 80 K. The TE properties are also supported by finite element simulation. The bending test conducted for the PTEG suggests device stability for up to 800 cycles with <0.05% change in the internal resistance. A proof-of-concept field-based demonstration for energy harvesting from waste heat of a motorbike exhaust is shown recovering an output power of ∼42 nW for ΔT = 20 K, corroborating the experimental and theoretical results.

Validation of a metabolite-GWAS network for Populus trichocarpa family 1 UDP-glycosyltransferases.

Metabolite genome-wide association studies (mGWASs) are increasingly used to discover the genetic basis of target phenotypes in plants such as Populus trichocarpa, a biofuel feedstock and model woody plant species. Despite their growing importance in plant genetics and metabolomics, few mGWASs are experimentally validated. Here, we present a functional genomics workflow for validating mGWAS-predicted enzyme-substrate relationships. We focus on uridine diphosphate-glycosyltransferases (UGTs), a large family of enzymes that catalyze sugar transfer to a variety of plant secondary metabolites involved in defense, signaling, and lignification. Glycosylation influences physiological roles, localization within cells and tissues, and metabolic fates of these metabolites. UGTs have substantially expanded in P. trichocarpa, presenting a challenge for large-scale characterization. Using a high-throughput assay, we produced substrate acceptance profiles for 40 previously uncharacterized candidate enzymes. Assays confirmed 10 of 13 leaf mGWAS associations, and a focused metabolite screen demonstrated varying levels of substrate specificity among UGTs. A substrate binding model case study of UGT-23 rationalized observed enzyme activities and mGWAS associations, including glycosylation of trichocarpinene to produce trichocarpin, a major higher-order salicylate in P. trichocarpa. We identified UGTs putatively involved in lignan, flavonoid, salicylate, and phytohormone metabolism, with potential implications for cell wall biosynthesis, nitrogen uptake, and biotic and abiotic stress response that determine sustainable biomass crop production. Our results provide new support for in silico analyses and evidence-based guidance for in vivo functional characterization.

Achiral phosphonium induced remarkable circular polarized luminescence in a chiral cadmium(II) halide perovskite material.

Circular polarized luminescence (CPL) sensitive two-dimensional organic inorganic halide perovskites have versatile applications in optical displays, encrypted transmission and quantum communications. Here, a new chiral hybrid [MePh3P]2CdCl4 (PCC) single crystal (SC) is synthesized using an achiral phosphonium cation by a solvent evaporation process at room temperature (rt). SC x-ray study reveals a non-centrosymmetric point group 23, with 21-screw optical axes providing a chiral Sohncke space group. Hirshfeld surface analysis suggests long-range H-bonding and ionic interactions (~ 3-9 kJ mol-1) and short-range Van der Waals and dispersion interactions (∼0.4-4 kJ mol-1). Both the PCC thin films and SCs exhibit prominent circular dichroism (CD) and remarkably superior CPL activity at rt (|gCD| ≈ 5 × 10-3 and |glum| ≈ 4.3 × 10-2).

The Effects of Botulinum Toxin and Casting in Spastic Children With Cerebral Palsy: A Systematic Review and Meta-Analysis.

Cerebral palsy (CP) is a neurological disorder that affects muscle tone, movement, and motor skills in children. One of the most common symptoms of cerebral palsy is spasticity, which is characterised by involuntary muscle contractions and stiffness. Both botulinum toxin and casting have been used as standalone treatments for spasticity in cerebral palsy, but which is better is still unclear. The aim of the present meta-analysis was to compare the effects on spasticity of serial casting and/or botulinum toxin type A (BoNT-A) in conjunction with or as independent therapies. Studies up to February 2022 were identified in four separate databases. The inclusion criteria were randomised controlled trials (RCTs) that compared different therapies (Botulinum toxin A, or BoNT-A, and casting) and assessed spasticity improvement in children with spastic cerebral palsy who were younger than 18 years old and were published in English. With a 95% confidence interval (CI), the standardised mean difference (SMD) was utilised to calculate treatment effects. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 checklist was followed to undertake the current study. The search for relevant literature in four databases generated 147 results. After the abstract and full-text screening, five publications with a total of 190 cerebral palsy patients were included in this systematic review and meta-analysis. In patients with cerebral palsy, both methods - botulinum toxin and casting- apply globally; our systematic review tries to find out the most effective treatment between the two but does not show any significant difference in these methods. As we know, botulinum toxin is expensive, and the casting method is time-consuming and poorly accepted by patients. There is a need for an excellent study to examine the impact of casting and botulinum toxin type A.