Haploidentical Transplant in Radiosensitive Severe Combined Immunodeficiency Disease.

Severe combined immunodeficiency (SCID) is an inborn error of immunity invariably resulting in mortality in infancy until managed by hematopoietic stem cell transplant (HSCT). We present an unusual case of SCID with a rare mutation involving the non-homologous end-joining 1 (NHEJ1) gene, where a haploidentical HSCT was carried out with modified conditioning and graft versus host prophylaxis regimen using proteasome inhibitor bortezomib with a successful outcome.

Estimation of Physiologic Pressures: Invasive and Non-Invasive Techniques, AI Models, and Future Perspectives.

The measurement of physiologic pressure helps diagnose and prevent associated health complications. From typical conventional methods to more complicated modalities, such as the estimation of intracranial pressures, numerous invasive and noninvasive tools that provide us with insight into daily physiology and aid in understanding pathology are within our grasp. Currently, our standards for estimating vital pressures, including continuous BP measurements, pulmonary capillary wedge pressures, and hepatic portal gradients, involve the use of invasive modalities. As an emerging field in medical technology, artificial intelligence (AI) has been incorporated into analyzing and predicting patterns of physiologic pressures. AI has been used to construct models that have clinical applicability both in hospital settings and at-home settings for ease of use for patients. Studies applying AI to each of these compartmental pressures were searched and shortlisted for thorough assessment and review. There are several AI-based innovations in noninvasive blood pressure estimation based on imaging, auscultation, oscillometry and wearable technology employing biosignals. The purpose of this review is to provide an in-depth assessment of the involved physiologies, prevailing methodologies and emerging technologies incorporating AI in clinical practice for each type of compartmental pressure measurement. We also bring to the forefront AI-based noninvasive estimation techniques for physiologic pressure based on microwave systems that have promising potential for clinical practice.

Enroute sustainability: metal free C-H bond functionalisation.

The term "C-H functionalisation" incorporates C-H activation followed by its transformation. In a single line, this can be defined as the conversion of carbon-hydrogen bonds into carbon-carbon or carbon-heteroatom bonds. The catalytic functionalisation of C-H bonds using transition metals has emerged as an atom-economical technique to engender new bonds without activated precursors which can be considered as a major drawback while attempting large-scale synthesis. Replacing the transition-metal-catalysed approach with a metal-free strategy significantly offers an alternative route that is not only inexpensive but also environmentally benign to functionalize C-H bonds. Recently metal free synthetic approaches have been flourishing to functionalize C-H bonds, motivated by the search for greener, cost-effective, and non-toxic catalysts. In this review, we will highlight the comprehensive and up-to-date discussion on recent examples of ground-breaking research on green and sustainable metal-free C-H bond functionalisation.

Machine Learning-Based Classification of Abnormal Liver Tissues Using Relative Permittivity.

The search for non-invasive, fast, and low-cost diagnostic tools has gained significant traction among many researchers worldwide. Dielectric properties calculated from microwave signals offer unique insights into biological tissue. Material properties, such as relative permittivity (εr) and conductivity (σ), can vary significantly between healthy and unhealthy tissue types at a given frequency. Understanding this difference in properties is key for identifying the disease state. The frequency-dependent nature of the dielectric measurements results in large datasets, which can be postprocessed using artificial intelligence (AI) methods. In this work, the dielectric properties of liver tissues in three mouse models of liver disease are characterized using dielectric spectroscopy. The measurements are grouped into four categories based on the diets or disease state of the mice, i.e., healthy mice, mice with non-alcoholic steatohepatitis (NASH) induced by choline-deficient high-fat diet, mice with NASH induced by western diet, and mice with liver fibrosis. Multi-class classification machine learning (ML) models are then explored to differentiate the liver tissue groups based on dielectric measurements. The results show that the support vector machine (SVM) model was able to differentiate the tissue groups with an accuracy up to 90%. This technology pipeline, thus, shows great potential for developing the next generation non-invasive diagnostic tools.

Non-local triple quantum dot thermometer based on Coulomb-coupled systems.

Recent proposals towards non-local thermoelectric voltage-based thermometry, in the conventional dual quantum dot set-up, demand an asymmetric step-like system-to-reservoir coupling around the ground states for optimal operation (Physica E, 114, 113635, 2019). In addition to such demand for unrealistic coupling, the sensitivity in such a strategy also depends on the average measurement terminal temperature, which may result in erroneous temperature assessment. In this paper, we propose non-local current based thermometry in the dual dot set-up as a practical alternative and demonstrate that in the regime of high bias, the sensitivity remains robust against fluctuations of the measurement terminal temperature. Proceeding further, we propose a non-local triple quantum dot thermometer, that provides an enhanced sensitivity while bypassing the demand for unrealistic step-like system-to-reservoir coupling and being robust against fabrication induced variability in Coulomb coupling. In addition, we show that the heat extracted from (to) the target reservoir, in the triple dot design, can also be suppressed drastically by appropriate fabrication strategy, to prevent thermometry induced drift in reservoir temperature. The proposed triple dot setup thus offers a multitude of benefits and could potentially pave the path towards the practical realization and deployment of high-performance non-local "sub-Kelvin range" thermometers.

Photo-Excited Nickel-Catalyzed Silyl-Radical-Mediated Direct Activation of Carbamoyl Chlorides To Access (Hetero)aryl Carbamides.

Amide bonds connect the amino acids in proteins and exist as a prevalent structural motif in biomolecules. Herein, we have exploited the concept of cross-electrophile coupling by merging the photo-redox and transition-metal catalysis to construct carbamides from superabundant (hetero)aryl halides along with commercially feasible carbamoyl chlorides. The success of this method relies on the prior formation of NiII -aryl halide intermediates, which involves in a photoexcited Ni-halide homolysis event by energy transfer from aryl bromide and single-electron transfer from aryl chloride to assist generation of the vital carbamoyl radical. The breadth of application of this technique is demonstrated both in inter- as well as intramolecular routes for the synthesis of a plethora of (hetero)aryl carbamides with diverse functionalities, and biologically important benzolactams.

Stereochemistry of the Benzylidene γ-Butyrolactone Dictates the Reductive Heck Cyclization Mode in the Asymmetric Synthesis of Aryltetralin Lignans: A Detailed Experimental and Theoretical Study.

The reductive Heck cyclization of nonracemic benzylidene γ-butyrolactone is studied toward the asymmetric synthesis of aryltetralin lignans, where the stereochemistry of the benzylidene lactone is found to control the mode of cyclization. The Z-isomer undergoes mostly 6-endo-cyclization and provides the desired (-)-isopodophyllotoxin along with a minor amount of 5-exo-cyclized product, but the E-isomer goes through exclusively 5-exo-cyclization, leading to the undesired dihydroindenolactone compound instead of (-)-podophyllotoxin. The experimental results are well-supported by the DFT studies.

Feedback Inhibition in Chemical Catalysis Leads the Dynamic Kinetic to Kinetic Resolution in C3-Indolylation of Spiro-epoxyoxindoles.

The first feedback inhibition, similar to enzyme catalysis, in the Co(III)salen-catalyzed asymmetric ring-opening reaction of N-free spiro-epoxyoxyindole has been discovered, which leads dynamic kinetic to kinetic resolution. This is the first report of the enantioselective construction of all carbon quaternary center from any epoxide employing metal-salen catalyst until date. This protocol provides an easy access of 3-(3- indolyl)oxindole methanols, a privileged building block for the synthesis of a large variety of 3,3'-bisindole alkaloids.

Controlling the regioselectivity of the ring opening of spiro-epoxyoxindoles for efficient synthesis of C(3)-N(1')-bisindoles and C(3)-N(1')-diindolylmethane.

An efficient strategy for the construction of both C(3)-N(1') bisindoles and C(3)-N(1') diindolylmethane has been explored via proper tuning of the nucleophilicity of indoline/indole to spiro-epoxyoxindole. Lewis acid-catalyzed highly regio- as well as chemoselective coupling at the C-3 centre of spiro-epoxyoxindoles with indolines furnishes C(3)-N(1') bisindoles whereas base mediated and Lewis acid-catalyzed regioselective coupling at the less hindered site of spiro-epoyoxindoles with indoles via the SN2 mechanism provides C(3)-N(1') diindolylmethane.

Reagent-Controlled Reversal of Regioselectivity in Nucleophilic Fluorination of Spiro-epoxyoxindole: Synthesis of 3-Fluoro-3-hydroxymethyloxindole and 3-Aryl-3-fluoromethyloxindole.

A convenient and metal/catalyst-free approach for the reversal of regioselectivity in nucleophilic fluorination of a wide range of spiro-epoxyoxindoles has been reported simply by altering the nucleophilic fluoride reagents. Py·(HF) x-mediated fluorination at the tertiary sp3-C center of spiro-epoxyoxindole furnishes 3-fluoro-3-hydroxymethyloxindoles, whereas TBAF-mediated fluoride addition at the primary sp3-C center renders 3-fluoromethyl-3-hydroxyoxindoles, which have been utilized for the synthesis of 3-aryl-3-fluoromethyloxindole.

Domino Corey-Chaykovsky Reaction for One-Pot Access to Spirocyclopropyl Oxindoles.

The development of the sequential Corey-Chaykovsky reactions of isatins, spiroepoxy-, or spiroaziridine oxindoles with sulfur ylide has led to the discovery of a unique reaction mode that allows easy and direct one-pot access to a range of spirocyclopropyl oxindoles.

Reversal of Selectivity in C3-Allylation and Formal [3 + 2]-Cycloaddition of Spiro-epoxyoxindole: Unified Synthesis of Spiro-furanooxindole, (±)-N-Methylcoerulescine, (±)-Physovenine, and 3a-Allylhexahydropyrrolo[2,3-b]indole.

An effective Lewis acid catalyzed regioselective C3-allylation and a formal [3 + 2]-annulation reaction of spiro-epoxyoxindoles have been developed and can be accessed simply by changing the reaction conditions. This method has been successfully employed for the synthesis of spiro(pyrrolidinyloxindole), 3a-allylhexahydropyrrolo[2,3-b]indole, and furanoindoline.