Two-step continuous flow-driven synthesis of 1,1-cyclopropane aminoketones.

The continuous flow telescoped synthesis of 1,1-cyclopropane aminoketones was achieved by optimizing the photocyclization of 1,2-diketones to 2-hydroxycylobutanones (HCBs) and their reaction with aryl- and alkylamines, tandem condensation C4-C3-ring contraction reaction. With the achieved operational conditions, we were able to obtain a library of cyclopropylamines with good chemical yields, high productivity, and short residence times.

Third-Generation CALPHAD Modeling of Elemental Nb and Zr and Partial Re-Assessment of Their Binary Phase Diagram.

Liquid metals and metallic alloys often exist as metastable phases or can be undercooled below their equilibrium melting point. The Traditional CALPHAD (CALculation of PHAse Diagrams) approach struggles to accurately model these metastable conditions, which are important in rapid quenching techniques like additive manufacturing, and to understand glass formation or oxidation phenomena occurring in the liquid phase during nuclear and high-temperature aerospace applications. On the contrary, the third-generation CALPHAD models have the potential to accurately describe metastable phase diagrams to provide better predictions of molten phase behavior under non-equilibrium conditions.

Nephrotoxicity in locally advanced head and neck cancer: when the end justifies the means to preserve nutritional status during chemoradiation.

Cisplatin is a nephrotoxic agent able to damage renal function both in acute and chronic phases. Radiotherapy concomitant with cisplatin 100 mg/m given once every 3 weeks is the curative standard of care for locally advanced head and neck cancer. A prospective evaluation of a wide range of biochemical and anthropometrical parameters, handgrip strength, risk of malnutrition, visual analogue scale of appetite, and body composition was performed before, during, and after concomitant chemoradiotherapy in 60 consecutive patients affected by locally advanced head and neck cancer.

3D variability analysis reveals a hidden conformational change controlling ammonia transport in human asparagine synthetase.

Advances in X-ray crystallography and cryogenic electron microscopy (cryo-EM) offer the promise of elucidating functionally relevant conformational changes that are not easily studied by other biophysical methods. Here we show that 3D variability analysis (3DVA) of the cryo-EM map for wild-type (WT) human asparagine synthetase (ASNS) identifies a functional role for the Arg-142 side chain and test this hypothesis experimentally by characterizing the R142I variant in which Arg-142 is replaced by isoleucine. Support for Arg-142 playing a role in the intramolecular translocation of ammonia between the active site of the enzyme is provided by the glutamine-dependent synthetase activity of the R142 variant relative to WT ASNS, and MD simulations provide a possible molecular mechanism for these findings.

"Artificial histology" in colonic Neoplasia: A critical approach.

Background: The histological assessment of colorectal precancer and cancer lesions is challenging and primarily impacts the clinical strategies of secondary colon cancer prevention. Artificial intelligence (AI) models may potentially assist in the histological diagnosis of this spectrum of phenotypical changes.

Objectives: To provide a current overview of the evidence on AI-based methods for histologically assessing colonic precancer and cancer lesions.

Infection-Associated Flares in Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is characterised by generalised immune dysfunction, including infection susceptibility. Infection-associated flares (IAFs) are common and might rapidly self-resolve, paralleling infection resolution, but their specific clinical phenotype is poorly understood. Therefore, we screened 2039 consecutive visits and identified 134 flares, defined as a loss of the lupus low disease activity state (LLDAS), from 1089 visits at risk spanning over multiple follow-up years, yielding an average yearly LLDAS deterioration rate of 17%.

Chromatography-Based Metabolomics as a Tool in Bioorganic Research of Honey.

This review presents the latest research on chromatography-based metabolomics for bioorganic research of honey, considering targeted, suspect, and untargeted metabolomics involving metabolite profiling and metabolite fingerprinting. These approaches give an insight into the metabolic diversity of different honey varieties and reveal different classes of organic compounds in the metabolic profiles, among which, key metabolites such as biomarkers and bioactive compounds can be highlighted. Chromatography-based metabolomics strategies have significantly impacted different aspects of bioorganic research, including primary areas such as botanical origins, honey origin traceability, entomological origins, and honey maturity.

A highly conducting tetrathiafulvalene-tetracarboxylate based dysprosium(iii) 2D metal-organic framework with single molecule magnet behaviour.

The synthesis and whole characterization by a multitechnique approach of an unprecedented dysprosium(iii) 2D metal organic framework (MOF), involving the redox-active tetrathiafulvalene (TTF)-based linker TTF-tetracarboxylate (TTF-TC), are herein reported. The single-crystal X-ray structure, formulated as [Dy(TTF-TC)(HO)]·21HO (1), reveals a complex 2D topology, with hexanuclear Dy clusters as secondary building units (SBUs) interconnected by five linkers, stacked almost parallel in each layer and eclipsed along the [111] direction, leading to the formation of 1D channels filled by water molecules. The mixed valence of the TTF units is confirmed by both bond distance analysis, Raman microscopy and diffuse reflectance spectroscopy, and further supported by band structure calculations, which also predict activated conductivity for this material.

IL-17 in serum and cerebrospinal fluid of pediatric patients with acute neuropsychiatric disorders: Implications for PANDAS and PANS.

Background: Acute neuropsychiatric disorders are heterogeneous conditions resulting from interaction between genetic and environmental features. Among these, post infectious forms like Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) are common. Preclinical studies suggest a role of CNS T-helper-17/interleukin-17 (IL-17) inflammatory mediated response in the pathogenesis of these disorders.

Reproducibility and explainability in digital pathology: The need to make black-box artificial intelligence systems more transparent.

Artificial intelligence (AI), and more specifically Machine Learning (ML) and Deep learning (DL), has permeated the digital pathology field in recent years, with many algorithms successfully applied as new advanced tools to analyze pathological tissues. The introduction of high-resolution scanners in histopathology services has represented a real revolution for pathologists, allowing the analysis of digital whole-slide images (WSI) on a screen without a microscope at hand. However, it means a transition from microscope to algorithms in the absence of specific training for most pathologists involved in clinical practice.

Hereditary angioedema due to C1-inhibitor deficiency: current therapeutic approaches.

Purpose Of Review: For decades, treatment options for hereditary angioedema (HAE) were limited by major adverse effects, insufficient efficacy, and difficult routes of administration. However, the growing body of knowledge regarding HAE pathophysiology has led to the development of innovative drugs for self-administered, on-demand therapy and for short- and long-term prophylaxis. This review provides a comprehensive overview of the approved drugs and the development of HAE treatments.

Single Crystal Sn-Based Halide Perovskites.

Sn-based halide perovskites are expected to be the best replacement for toxic lead-based counterparts, owing to their similar ionic radii and the optimal band gap for use in solar cells, as well as their versatile use in light-emitting diodes and photodetection applications. Concerns, however, exist about their stability under ambient conditions, an issue that is exacerbated in polycrystalline films because grain boundaries present large concentrations of defects and act as entrance points for oxygen and water, causing Sn oxidation. A current thriving research area in perovskite materials is the fabrication of perovskite single crystals, promising improved optoelectronic properties due to excellent uniformity, reduced defects, and the absence of grain boundaries.

Association of depressive symptoms with incidence and mortality rates of COVID-19 over 2 years among healthcare workers in 20 countries: multi-country serial cross-sectional study.

Background: Long-term deterioration in the mental health of healthcare workers (HCWs) has been reported during and after the COVID-19 pandemic. Determining the impact of COVID-19 incidence and mortality rates on the mental health of HCWs is essential to prepare for potential new pandemics. This study aimed to investigate the association of COVID-19 incidence and mortality rates with depressive symptoms over 2 years among HCWs in 20 countries during and after the COVID-19 pandemic.

Substrate-dependent regiodivergence in [3 + 2] annulation reactions of 2-(phenacylethylidene)cyclobutanones with thioureas.

The [3 + 2] annulation reaction between a thiourea, an ambident dinucleophile, and a 2-(phenacylethylidene)cyclobutanone, containing a novel pull-pull alkene system, could in principle proceed with several chemo- and regioselectivity profiles. Here we describe a convenient synthesis of the functionalized cyclobutanone substrates and show that they react with thioureas in a manner that is rationalized mechanistically in terms of the steric and electronic effects at play. The [3 + 2] annulation proceeds in mild, additive-free conditions to provide access to previously unknown cyclobutane-fused imidazolidine-2-thione and thiazolidine-2-imine derivatives in good yields.

Tunable SIM properties in a family of 3D anilato-based lanthanide-MOFs.

By reacting a 3,6-ditriazolyl-2,5-dihydroxybenzoquinone (HtrzAn) anilato linker with Ln ions (Ln = Dy, Tb, Ho), two different series of polymorphs, formulated as [Ln(trzAn)(HO)] ·10HO (Dy, 1a; Tb, 2a, Ho, 3a) and [Ln(trzAn)(HO)] ·7HO (Dy, 1b, Tb, 2b, Ho, 3b) have been obtained. In these series the two Dy-coordination networks (1a and 1b) and the Tb-coordination polymer (2b) show a Single Ion Magnet (SIM) behavior. 1-3a MOFs show reversible structural flexibility upon removal of a coordinated water molecule from a distorted hexagonal 2D framework to a distorted 3,6-brickwall rectangular 3D structure in [Ln(trzAn)(HO)] ·2HO (Dy, 1a_des; Tb, 2a_des, Ho, 3a_des) involving shrinkage/expansion of the hexagonal-rectangular networks.

An Unsupervised Learning Tool for Plaque Tissue Characterization in Histopathological Images.

Stroke is the second leading cause of death and a major cause of disability around the world, and the development of atherosclerotic plaques in the carotid arteries is generally considered the leading cause of severe cerebrovascular events. In recent years, new reports have reinforced the role of an accurate histopathological analysis of carotid plaques to perform the stratification of affected patients and proceed to the correct prevention of complications. This work proposes applying an unsupervised learning approach to analyze complex whole-slide images (WSIs) of atherosclerotic carotid plaques to allow a simple and fast examination of their most relevant features.

Salt Crystallization in Limestone: Materials Decay and Chemomechanical Approach.

Salt crystallization is a particularly relevant issue in the conservation of limestones used in Cultural Heritage sites. In this study, various facies of limestones were characterized through porosimetric and mechanical tests. The samples were subjected to experiments to determine their resistance to salt crystallization by verifying the number of cycles at which 50% of them began to lose weight.

C1-4 Alkylation of Aryl Bromides with Light Alkanes enabled by Metallaphotocatalysis in Flow.

@AntonioPulcine1, @KenYamazaki5, @EvelineTiekink, @TrevorAHamlin, @tnoel82, @HimsUva, @VU Science, @NoelGroupUvA.The homologous series of gaseous C1-4 alkanes represents one of the most abundant sources of short alkyl fragments. However, their application in synthetic organic chemistry is exceedingly rare due to the challenging C-H bond cleavage, which typically demands high temperatures and pressures, thereby limiting their utility in the construction of complex organic molecules.

An improved dataset of force fields, electronic and physicochemical descriptors of metabolic substrates.

In silico prediction of xenobiotic metabolism is an important strategy to accelerate the drug discovery process, as candidate compounds often fail in clinical phases due to their poor pharmacokinetic profiles. Here we present Meta, a dataset of quantum-mechanical (QM) optimized metabolic substrates, including force field parameters, electronic and physicochemical properties. Meta comprises 2054 metabolic substrates extracted from the MetaQSAR database.

Neoarchaean oxygen-based nitrogen cycle en route to the Great Oxidation Event.

The nitrogen isotopic composition of sedimentary rocks (δN) can trace redox-dependent biological pathways and early Earth oxygenation. However, there is no substantial change in the sedimentary δN record across the Great Oxidation Event about 2.45 billion years ago (Ga), a prominent redox change.