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AbstractAn eco-friendlylactobacillussp. (microbe) assisted synthesis of titanium nanoparticles is reported. The synthesis is performed at room temperature. X-ray and transmission electron microscopy analyses are performed to ascertain the formation of Ti nanoparticles. Individual nanoparticles as well as a number of aggregates almost spherical in shape having a size of 40–60 nm are found.

The study of using deep learning for detection of various thoracic diseases has been an active and challenging research area. Chest X-rays are currently the most common and globally used radiology practices for detecting thoracic diseases. Patients suffering from thoracic diseases need to take Chest X-Rays which are read by radiologists and a report is generated by them. However, today with the increase in the number of thoracic patients, a quick method to classify the disease and generate the report has become necessary. Also, patient history has to be considered for diagnosis. This paper offers a comparative study on the various deep learning techniques that can process chest x-rays and are capable of detecting the different thoracic diseases. Also, a technique has been proposed to classify 14 diseases namely Atelectasis, Cardiomegaly, Consolidation, Edema, Effusion, Emphysema, Fibrosis, Hernia, Infiltration, Mass, Nodule, Pneumonia, Pneumothorax, Pleural thickening based on the given X-rays using Residual Neural Network.

ABCs are expansile osteolytic lesions typically containing blood-filled spaces separated by fibrous septae. Standard treatment includes surgical resection or curettage and packing; however, for some spinal lesions, the standard approach is not optimal. One therapeutic strategy is to treat spinal ABC with an agent that targets a pathway that is dysregulated in a disease with similar pathophysiology. Denosumab, a human monoclonal antibody to RANKL is effective in the treatment of GCT's. Spinal ABCs are a therapeutic challenge and local recurrence is a concern. We report a case of aggressive recurrent ABC of dorsal spine in a 14-year old female with progressive neurologic deficit who underwent surgical excision and decompression with a recurrence in a short period for which a decompression and fixation was done. She had a recurrence after an asymptomatic period of 6 months and neurologic worsening. Having ruled out use of embolization and radiotherapy, a remission was achieved by treatment with Denosumab using the regimen for GCTs for a duration of 6 months. Follow-up MRI and CT scans at 24 months following inception of Denosumab depicted complete resolution and no recurrence. We conclude that Denosumab can result in symptomatic and radiological improvement in the recurrent locally aggressive ABC and may be useful in selected cases. Long-term results are mandatory to confirm the efficacy of Denosumab and to evaluate local recurrence after stopping Denosumab.

Introduction: Precise targeted excision of the C5–C6 osteoid osteoma with placement of reference array on clavicle with minimal disturbance of anatomy and motion. Methods: A 20-year-old male presented with an osteoid osteoma in the superior end plate of the C6 vertebra abutting the spinal canal causing intractable pain. The authors curetted the nidus using a 3D C-arm-based intraoperative scan integrated with an optical navigation system through a minimal access anterior cervical exposure. The patient reference array was affixed to the left clavicle using a threaded pin. Results: The postoperative CT-scan revealed complete excision. Follow-up MRI and CT after 12 months revealed C5–C6 intervertebral disc to be intact without evidence of any tumor recurrence. VAS for neck pain improved from 8/10 to 2/10 immediately postoperatively and 0/10 at 1 year follow-up with no limitation of cervical movement. A motion segment was preserved with this technique. Conclusions: Navigation allowed safe curettage of the nidus with minimal disturbance to the anatomy and motion. The site of attachment of patient reference array on clavicle can be recommended as stable, meeting all the criteria for optimal accuracy and stability.

We conducted a radiological safety and quality assurance (QA) audit of 118 medical X-ray diagnostic machines installed in 45 major hospitals in India. The main objective of the audit was to verify compliance with the regulatory requirements stipulated by the national regulatory body. The audit mainly covered accuracy check of accelerating potential (kVp), linearity of tube current (mA station) and timer, congruence of radiation and optical field, and total filtration; in addition, we also reviewed medical X-ray diagnostic installations with reference to room layout of X-ray machines and conduct of radiological protection survey. A QA kit consisting of a kVp Test-O-Meter (ToM) (Model RAD/FLU-9001), dose Test-O-Meter (ToM) (Model 6001), ionization chamber-based radiation survey meter model Gun Monitor and other standard accessories were used for the required measurements. The important areas where there was noncompliance with the national safety code were: inaccuracy of kVp calibration (23%), lack of congruence of radiation and optical field (23%), nonlinearity of mA station (16%) and timer (9%), improper collimator/diaphragm (19.6%), faulty adjustor knob for alignment of field size (4%), nonavailability of warning light (red light) at the entrance of the X-ray room (29%), and use of mobile protective barriers without lead glass viewing window (14%). The present study on the radiological safety status of diagnostic X-ray installations may be a reasonably good representation of the situation in the country as a whole. The study contributes significantly to the improvement of radiological safety by the way of the steps already taken and by providing a vital feed back to the national regulatory body.

Forecasting can be utilized to predict future trends in physiological demands, which can be beneficial for developing effective interventions. This study implemented forecasting models to predict fatigue level progression when performing exoskeleton (EXO)-assisted tasks. Specifically, perceived and muscle activity data were utilized from nine recruited participants who performed 45° trunk flexion tasks intermittently with and without assistance until they reached medium-high exertion in the low-back region. Two forecasting algorithms, Autoregressive Integrated Moving Average (ARIMA) and Facebook Prophet, were implemented using perceived fatigue levels alone, and with external features of low-back muscle activity. Findings showed that univariate models without external features performed better with the Prophet model having the lowest mean (SD) of root mean squared error (RMSE) across participants of 0.62 (0.24) and 0.67 (0.29) with and without EXO-assisted tasks, respectively. Temporal effects of BSIE on delaying fatigue progression were then evaluated by forecasting back fatigue up to 20 trials. The slope of fatigue progression for 20 trials without assistance was ~48-52% higher vs. with assistance. Median benefits of 54% and 43% were observed for ARIMA (with external features) and Prophet algorithms, respectively. This study demonstrates some potential applications for forecasting models for workforce health monitoring, intervention assessment, and injury prevention.

Nanoengineered metal@zeolite materials have recently emerged as a promising class of catalysts for several industrially relevant reactions. These materials, which consist of small transition metal nanoclusters confined within three-dimensional zeolite pores, are interesting because they show higher stability and better sintering resistance under reaction conditions. While several such hybrid catalysts have been reported experimentally, key questions such as the impact of the zeolite frameworks on the properties of the metal clusters are not well understood. To address such knowledge gaps, in this study, we report a robust and transferable machine learning-based potential (MLP) that is capable of describing the structure, stability, and dynamics of zeolite-confined gold nanoclusters. Specifically, we show that the resulting MLP maintains ab initio accuracy across a range of temperatures (300-1000 K) and can be used to investigate time scales (>10 ns), length scales (ca. 10,000 atoms), and phenomena (e.g., ensemble-averaged stability and diffusivity) that are typically inaccessible using density functional theory (DFT). Taken together, this study represents an important step in enabling the rational theory-guided design of metal@zeolite catalysts.

The reduction of CO 2 is known to promote increased alkene yields from alkane dehydrogenations when the reactions are cocatalyzed. The mechanism of this promotion is not understood in the context of catalyst active-site environments because CO 2 is amphoteric, and even general aspects of the chemistry, including the significance of competing side reactions, differ significantly across catalysts. Atomically dispersed chromium cations stabilized in highly siliceous MFI zeolite are shown here to enable the study of the role of parallel CO 2 reduction during ethylene-selective ethane dehydrogenation. Based on infrared spectroscopy and X-ray absorption spectroscopy data interpreted through calculations using density functional theory (DFT), the synthesized catalyst contains atomically dispersed Cr cations stabilized by silanol nests in micropores. Reactor studies show that cofeeding CO 2 increases stable ethylene-selective ethane dehydrogenation rates over a wide range of partial pressures. Operando X-ray absorption near-edge structure (XANES) and extended X-ray absorption fine-structure (EXAFS) spectra indicate that during reaction at 650 °C the Cr cations maintain a nominal 2+ charge and a total Cr-O coordination number of approximately 2. However, CO 2 reduction induces a change, correlated with the CO 2 partial pressure, in the population of two distinct Cr-O scattering paths. This indicates that the promotional effect of parallel CO 2 reduction can be attributed to a subtle change in Cr-O bond lengths in the local coordination environment of the active site. These insights are made possible by simultaneously fitting multiple EXAFS spectra recorded in different reaction conditions; this novel procedure is expected to be generally applicable for interpreting operando catalysis EXAFS data.

Supported noble metal catalysts, ubiquitous in chemical technology, often undergo dynamic transformations between reduced and oxidized states-which influence the metal nuclearities, oxidation states, and catalytic properties. In this investigation, we report the results of in situ X-ray absorption spectroscopy, scanning transmission electron microscopy, and other physical characterization techniques, bolstered by density functional theory, to elucidate the structural transformations of a set of MgO-supported palladium catalysts under oxidative treatment conditions. As the calcination temperature increased, the as-synthesized supported metallic palladium nanoparticles underwent oxidation to form palladium oxides (at approximately 400 °C), which, at approximately 500 °C, were oxidatively fragmented to form mixtures of atomically dispersed palladium cations. The data indicate two distinct types of atomically dispersed species: palladium cations located at MgO steps and those embedded in the first subsurface layer of MgO. The former exhibit significantly higher (>500 times) catalytic activity for ethylene hydrogenation than the latter. The results pave the way for designing highly active and stable supported palladium hydrogenation catalysts with optimized metal utilization., Competing Interests: The authors declare no conflict of interests., (This journal is © The Royal Society of Chemistry.)

Isolated platinum(II) ions anchored at acid sites in the pores of zeolite HZSM-5, initially introduced by aqueous ion exchange, were reduced to form platinum nanoparticles that are stably dispersed with a narrow size distribution (1.3 ± 0.4 nm in average diameter). The nanoparticles were confined in reservoirs within the porous zeolite particles, as shown by electron beam tomography and the shape-selective catalysis of alkene hydrogenation. When the nanoparticles were oxidatively fragmented in dry air at elevated temperature, platinum returned to its initial in-pore atomically dispersed state with a charge of +2, as shown previously by X-ray absorption spectroscopy. The results determine the conditions under which platinum is retained within the pores of HZSM-5 particles during redox cycles that are characteristic of the reductive conditions of catalyst operation and the oxidative conditions of catalyst regeneration., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

This work aims to address the challenge of developing interpretable ML-based models when access to large-scale computational resources is limited. Using CoMoFeNiCu high-entropy alloy catalysts as an example, we present a cost-effective workflow that synergistically combines descriptor-based approaches, machine learning-based force fields, and low-cost density functional theory (DFT) calculations to predict high-quality adsorption energies for H, N, and NH x ( x = 1, 2, and 3) adsorbates. This is achieved using three specific modifications to typical DFT workflows including: (1) using a sequential optimization protocol, (2) developing a new geometry-based descriptor, and (3) repurposing the already-available low-cost DFT optimization trajectories to develop a ML-FF. Taken together, this study illustrates how cost-effective DFT calculations and appropriately designed descriptors can be used to develop cheap but useful models for predicting high-quality adsorption energies at significantly lower computational costs. We anticipate that this resource-efficient philosophy may be broadly relevant to the larger surface catalysis community.

Machine learning (ML), when used synergistically with atomistic simulations, has recently emerged as a powerful tool for accelerated catalyst discovery. However, the application of these techniques has been limited by the lack of interpretable and transferable ML models. In this work, we propose a curriculum-based training (CBT) philosophy to systematically develop reactive machine learning potentials (rMLPs) for high-throughput screening of zeolite catalysts. Our CBT approach combines several different types of calculations to gradually teach the ML model about the relevant regions of the reactive potential energy surface. The resulting rMLPs are accurate, transferable, and interpretable. We further demonstrate the effectiveness of this approach by exhaustively screening thousands of [CuOCu] 2+ sites across hundreds of Cu-zeolites for the industrially relevant methane activation reaction. Specifically, this large-scale analysis of the entire International Zeolite Association (IZA) database identifies a set of previously unexplored zeolites (i.e., MEI, ATN, EWO, and CAS) that show the highest ensemble-averaged rates for [CuOCu] 2+ -catalyzed methane activation. We believe that this CBT philosophy can be generally applied to other zeolite-catalyzed reactions and, subsequently, to other types of heterogeneous catalysts. Thus, this represents an important step toward overcoming the long-standing barriers within the computational heterogeneous catalysis community., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background Glomerular filtration rate (GFR) estimation is pivotal in the evaluation of kidney donors. There are various methods available for assessing GFR, but there has been a lack of consensus on the measurement of GFR and the frequency of renal evaluation after kidney donation. Our study aims to analyze the measured GFR (m-GFR) before and three months after kidney donation and note the compensatory abilities of the remnant kidney in live related kidney donors. Methods This prospective observational study was conducted at the Department of Nephrology, Dr. D. Y. Patil Medical College, Hospital & Research Centre, Pune, from April 2021 to December 2022. The study included 30 donors from both genders aged between 23 and 73 years. The measured GFR was calculated using a technetium-99m diethylene triamine pentaacetic acid (Tc-99m DTPA) scan. We analyzed donor characteristics and various parameters that included demography, anthropometry, blood pressure, and serum creatinine and measured GFR (m-GFR) using a Tc-99m DTPA scan, which was compared before and three months after donor nephrectomy. Results Of the 30 donors, 25 (83.3%) were females and five (16.7%) were males. The mean age of donors was 49.23 ± 12.29 years. The mean body mass index (BMI) was noted to be 24.73 ± 5.58 kg/m 2 , whereas the mean body surface area (BSA) was 1.59 ± 0.12 m 2 . In terms of the measured GFR by DTPA scan, pre-donation and post-donation, the average GFR for our population was 103.83 ± 10.07 mL/minute/1.73 m 2 and   60.47±6.57 mL/minute/1.73 m 2 , respectively. The mean measured GFR of remnant kidney increased by 9.21 ± 4.39 mL/minute/1.73 m 2 in 28 donors, while two donors had a fall in the mean measured GFR by 6.8 ± 1.69 mL/minute/1.73 m 2 . Conclusions To safeguard donor health, accurate measurement of GFR at various timelines after kidney donation should be considered as there are various limitations associated with the use of serum creatinine-based GFR estimating equations for solitary kidneys. However, long-term studies are required to analyze the changes in GFR after nephrectomy and determine the adequacy of compensatory changes in the remnant kidney post-kidney donation., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Chavan et al.)

Background Diabetic nephropathy is one of the important causes of end-stage kidney disease (ESKD). Of the various cytokines playing a role in the pathogenesis of diabetic nephropathy, transforming growth factor beta-1 (TGF-β1) is an important one. Its major role is to mediate extracellular matrix deposition. Increased renal expression of TGF-β1 is found in diabetic nephropathy and its urinary excretion can serve as a useful marker of outcomes. Material and methods A prospective observational study was conducted, which included 10 cases of diabetic nephropathy in group A with age ≥ 18 years and a urinary protein creatinine ratio (UPCR) value of > 0.5 mg/mg and 10 healthy controls in group B. Patients with active urinary tract infection, chronic kidney disease (CKD) stage Vd patients on maintenance hemodialysis, and renal transplant recipients were excluded from the study. Urinary TGF-β1 level estimation in a 24-hour urine sample, 24-hour urine protein, and other baseline laboratory investigations were done. Results In diabetic nephropathy cases (group A), the mean value of urinary TGF-β1 levels was 88.33± 12.44 ng/24 hours. In the control group (group B), the mean value of urinary TGF-β1 was 29.03 ± 3.23 ng/24 hours. Urinary TGF-β1 levels were significantly elevated in group A as compared to group B (p<0.001). There was no significant correlation between urinary TGF-β1 levels and estimated glomerular filtration rate (eGFR) (r=0.376, p= 0.285) as well as the urinary TGF-β1 levels and 24-hour urine protein levels (p = 0.334, r = 0.341) in diabetic nephropathy cases. Glycosylated hemoglobin (HbA1c) levels didn't correlate with the urinary TGF-β1 levels (r = -0.265, p = 0.46). Conclusion The urinary TGF-β1 levels were significantly elevated in diabetic nephropathy patients as compared to healthy controls. There was no significant correlation between urinary TGF-β1 levels and proteinuria, eGFR, or HbA1c levels in diabetic nephropathy patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Kulkarni et al.)

Intracellular oxidative stress generation is a root cause of the dysfunctioning of mitochondria that is accountable for neurodegenerative disorders. In nano-CeO 2 , the intrinsic redox cycle (Ce 3+ ⇔ Ce 4+ ) confers them with a distinct oxygen buffering ability. Thus, increasing the Ce 3+ /Ce 4+ ratio by preferentially engineering oxygen vacancies is expected to boost the antioxidant characteristics in CeO 2 nanocrystals (NCs) and hold promise in nanotherapeutics of neurodegenerative disorders. Here, a pristine, economic, and scalable synthesis route with rapid nucleation-growth to yield monodispersed CeO 2 NCs of 4 nm has been employed. The NCs demonstrated sustained colloidal stability (zeta potential ~ -30.3±7.2 mV). The survival rate (~96.1% for 0.1 mg/mL) of healthy L929 cells and cell apoptosis induced on the SH-SY5Y cells (~ 30.2% for 0.1 mg/mL) indicate nano-CeO 2 s' prospects in nanomedicine. The formulated sustainable synthesis strategy for the enrichment of defects in these NCs is anticipated to pave the way for nanocrystal-based-treatments in smart healthcare.Clinical Relevance-This investigation signifies the oxygen vacancy-dependent therapeutic efficacy of CeO 2 NCs by ensuring ~96.1% survival rate of L929 cells while demonstrating cell apoptosis on SH-SY5Y cells (~ 30.2%) to establish newer insights on treatment of neurodegenerative disorders.

Background and Study Aim: The study was designed to detect novel Adverse Events (AEs) of pantoprazole by disproportionality analysis in the FDA (Food and Drug Administration) database of Adverse Event Reporting System (FAERS) using Data Mining Algorithms (DMAs). Pantoprazole, the most commonly over-utilized Over The Counter (OTC) medication, was selected to assess any short-term or long-term AEs. The study aimed to analyze the novel adverse events of pantoprazole using the FAERS database., Materials and Methods: A retrospective case/non-case disproportionality analysis was performed in the FAERS database. This study was based on AEs reported to FAERS from 2006Q1-2021Q3. Openvigil 2.1 was used for data extraction. Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), and Information Component (IC) were applied to measure the disproportionality in reporting. A value of ROR-1.96SE > 1, PRR ≥ 2, and IC-2SD > 0 were considered as the threshold for a positive signal., Results: A total of 1050 reports of dyspepsia, 7248 reports of hypocalcemia and 995 reports of hyponatremia were identified. A potential positive signal for dyspepsia (ROR-1.96SE = 2.231, PRR = 2.359, IC-2SD = 1.13), hypocalcemia (4.961, 5.45, 2.23) and hyponatremia (3.948, 4.179, 1.92) were identified for pantoprazole., Conclusion: Data mining in the FAERS database produced three potential signals associated with pantoprazole. As a result, further clinical surveillance is needed to quantify and validate potential hazards associated with pantoprazole-related adverse events., Competing Interests: Declaration of competinginterests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.)

Machine learning potentials (MLPs) capable of accurately describing complex ab initio potential energy surfaces (PESs) have revolutionized the field of multiscale atomistic modeling. In this work, using an extensive density functional theory (DFT) data set (denoted as Si-ZEO22) consisting of 219 unique zeolite topologies (350,000 unique DFT calculations) found in the International Zeolite Association (IZA) database, we have trained a DeePMD-kit MLP to model the dynamics of silica frameworks. The performance of our model is evaluated by calculating various properties that probe the accuracy of the energy and force predictions. This MLP demonstrates impressive agreement with DFT for predicting zeolite structural properties, energy-volume trends, and phonon density of states. Furthermore, our model achieves reasonable predictions for stress-strain relationships without including DFT stress data during training. These results highlight the ability of MLPs to capture the flexibility of zeolite frameworks and motivate further MLP development for nanoporous materials with near- ab initio accuracy., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Metal organic frameworks (MOFs) that incorporate metal oxide cluster nodes, exemplified by UiO-66, have been widely studied, especially in terms of their deviations from the ideal, defect-free crystalline structures. Although defects such as missing linkers, missing nodes, and the presence of adventitious synthesis-derived node ligands (such as acetates and formates) have been proposed, their exact structures remain unknown. Previously, it was demonstrated that defects are correlated and span multiple unit cells. The highly specialized techniques used in these studies are not easily applicable to other MOFs. Thus, there is a need to develop new experimental and computational approaches to understand the structure and properties of defects in a wider variety of MOFs. Here, we show how low-frequency phonon modes measured by inelastic neutron scattering (INS) spectroscopy can be combined with density functional theory (DFT) simulations to provide unprecedented insights into the defect structure of UiO-66. We are able to identify and assign peaks in the fingerprint region (<100 cm -1 ) which correspond to phonon modes only present in certain defective topologies. Specifically, this analysis suggests that our sample of UiO-66 consists of predominantly defect-free fcu regions with smaller domains corresponding to a defective bcu topology with 4 and 2 acetate ligands bound to the Zr 6 O 8 nodes. Importantly, the INS/DFT approach provides detailed structural insights ( e.g. , relative positions and numbers of acetate ligands) that are not accessible with microscopy-based techniques. The quantitative agreement between DFT simulations and the experimental INS spectrum combined with the relative simplicity of sample preparation, suggests that this methodology may become part of the standard and preferred protocol for the characterization of MOFs, and, in particular, for elucidating the structure defects in these materials.

Catalysts composed of platinum dispersed on zeolite supports are widely applied in industry, and coking and sintering of platinum during operation under reactive conditions require their oxidative regeneration, with the platinum cycling between clusters and cations. The intermediate platinum species have remained only incompletely understood. Here, we report an experimental and theoretical investigation of the structure, bonding, and local environment of cationic platinum species in zeolite ZSM-5, which are key intermediates in this cycling. Upon exposure of platinum clusters to O 2 at 700 °C, oxidative fragmentation occurs, and Pt 2+ ions are stabilized at six-membered rings in the zeolite that contain paired aluminum sites. When exposed to CO under mild conditions, these Pt 2+ ions form highly uniform platinum gem -dicarbonyls, which can be converted in H 2 to Pt δ+ monocarbonyls. This conversion, which weakens the platinum-zeolite bonding, is a first step toward platinum migration and aggregation into clusters. X-ray absorption and infrared spectra provide evidence of the reductive and oxidative transformations in various gas environments. The chemistry is general, as shown by the observation of platinum gem -dicarbonyls in several commercially used zeolites (ZSM-5, Beta, mordenite, and Y).

The versatility of ZnO quantum dots (QDs) exhibiting size-tunable visible photoluminescence has propelled them to the forefront of leading-edge innovations in healthcare. At the nano-bio interface, enhancing the singly-ionized oxygen vacancy defects (V O • ) through holistic, sustainable synthesis protocols driven by the synergistic influence of QDs' nucleation-growth kinetics has implications on their bioactivity, physiochemical, and optical performance. Recently, robust continuous flow platforms have transcended the conventional batch reactors by alleviating the concerns of "hot-spot" formation due to inhomogeneous heat distribution, acute energy consumption, poor quality, and yield. However, complexities exist in translating batch chemistries into flow processes. Here, a unique, rationally designed continuous flow synthesis of luminescent defect-engineered ZnO QDs (E-QDs) via helical-reactor assembly that can adequately synthesize on a large scale is reported. The crux of this lies in the amalgamation of "green chemistry" and flow synthesis, which results in Lamer-mechanism mediated monodispersed E-QDs demonstrating high photoluminescence quantum yield (PLQY) of 89% under an accurately regulated synthesis environment. Process intensification corroborated that the bio-stable E-QDs manifested admirable photostability, broad-spectrum UV-shielding (400-250 nm), colloidal stability, in vitro biocompatibility against L929 and HaCaT cells, and antioxidant activity. These attributes were better compared to the commercial ZnO nanoparticles (ZnO C -NPs) used for skin UV protection. Delving deeper, the main drivers for the high density of intrinsic V O • formation (I v /I o ∼42.5) were revealed to be the reactor's hydrodynamic performance and the improvised heating rate (2.5°C/sec). Hence, these E-QDs have potential as a new, safe, and economical multifunctional active ingredient for skin UV protection and antioxidants for treating ROS-mediated disorders. STATEMENT OF SIGNIFICANCE: UV filters exhibiting questionable UV-attenuation efficacy and phototoxicity are significant impediments to the healthcare industry emphasizing skin cancer prevention. Although least explored, V O • -governed aberrant photoactive, biological, and surface-reactive qualities of engineered ZnO QDs (E-QDs) have created ample room to investigate these hallmarks for skin UV protection. However, the bottlenecks in stereotypical ZnO QDs production confined by inefficient process control are annihilated by continuous flow strategies. Herein, the high-throughput continuous flow helical reactor assembly was designed and fabricated to successfully showcase optimized transport properties, reproducibility, yield, and quality E-QDs. Anticipating a skyrocketing demand for E-QDs as bioactive-sunscreen components, the comprehensive investigation has demonstrated unprecedented biofunctionality and ROS-scavenging behaviour, even upon UVR exposure, contrary to the traditional nanoparticulate ZnO UV filters., Competing Interests: Declaration of Competing Interest The authors have no potential conflicts of interest to declare., (Copyright © 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Atomically dispersed metals on metal oxide supports are a rapidly growing class of catalysts. Developing an understanding of where and how the metals are bonded to the supports is challenging because support surfaces are heterogeneous, and most reports lack a detailed consideration of these points. Herein, we report two atomically dispersed CO oxidation catalysts having markedly different metal-support interactions: platinum in the first layer of crystalline MgO powder and platinum in the second layer of this support. Structural models have been determined on the basis of data and computations, including those determined by extended X-ray absorption fine structure and X-ray absorption near edge structure spectroscopies, infrared spectroscopy of adsorbed CO, and scanning transmission electron microscopy. The data demonstrate the transformation of surface to subsurface platinum as the temperature of sample calcination increased. Catalyst performance data demonstrate the lower activity but greater stability of the subsurface platinum than of the surface platinum.

Atomically dispersed supported metal catalysts offer new properties and the benefits of maximized metal accessibility and utilization. The characterization of these materials, however, remains challenging. Using atomically dispersed platinum supported on crystalline MgO (chosen for its well-defined bonding sites) as a prototypical example, we demonstrate how systematic density functional theory calculations for assessing all the potentially stable platinum sites, combined with automated analysis of extended X-ray absorption fine structure (EXAFS) spectra, leads to unbiased identification of isolated, surface-enveloped platinum cations as the catalytic species for CO oxidation. The catalyst has been characterized by atomic-resolution imaging and EXAFS and high-energy resolution fluorescence detection X-ray absorption near edge spectroscopy. The proposed platinum sites are in agreement with experiment. This theory-guided workflow leads to rigorously determined structural models and provides a more detailed picture of the structure of the catalytically active site than what is currently possible with conventional EXAFS analyses. As this approach is efficient and agnostic to the metal, support, and catalytic reaction, we posit that it will be of broad interest to the materials characterization and catalysis communities.

Objectives: There exists a wide gap in the availability of mechanical ventilator devices and their acute need in the context of the COVID-19 pandemic. An initial triaging method that accurately identifies the need for mechanical ventilation in hospitalised patients with COVID-19 is needed. We aimed to investigate if a potentially deteriorating clinical course in hospitalised patients with COVID-19 can be detected using all X-ray images taken during hospitalisation., Methods: We exploited the well-established DenseNet121 deep learning architecture for this purpose on 663 X-ray images acquired from 528 hospitalised patients with COVID-19. Two Pulmonary and Critical Care experts blindly and independently evaluated the same X-ray images for the purpose of validation., Results: We found that our deep learning model predicted the need for mechanical ventilation with a high accuracy, sensitivity and specificity (90.06%, 86.34% and 84.38%, respectively). This prediction was done approximately 3 days ahead of the actual intubation event. Our model also outperformed two Pulmonary and Critical Care experts who evaluated the same X-ray images and provided an incremental accuracy of 7.24%-13.25%., Conclusions: Our deep learning model accurately predicted the need for mechanical ventilation early during hospitalisation of patients with COVID-19. Until effective preventive or treatment measures become widely available for patients with COVID-19, prognostic stratification as provided by our model is likely to be highly valuable., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels having many functions including inflammation control, as part of the cholinergic anti-inflammatory pathway. Genome wide association studies implicated RIC3, a chaperone of nAChRs, in multiple sclerosis (MS), a neuroinflammatory disease. To understand the involvement of RIC3 in inflammatory diseases we examined its expression, regulation, and function in activated immune cells. Our results show that immune activation leads to dynamic changes in RIC3 expression, in a mouse model of MS and in human lymphocytes and macrophages. We also show similarities in the expression dynamics of RIC3 and CHRNA7, encoding for the α7 nAChR subunit. Homomeric α7 nAChRs were shown to mediate the anti-inflammatory effects of cholinergic agonists. Thus, similarity in expression dynamics between RIC3 and CHRNA7 is suggestive of functional concordance. Indeed, siRNA mediated silencing of RIC3 in a mouse macrophage cell line eliminates the anti-inflammatory effects of cholinergic agonists. Furthermore, we show increased average expression of RIC3 and CHRNA7 in lymphocytes from MS patients, and a strong correlation between expression levels of these two genes in MS patients but not in healthy donors. Together, our results are consistent with a role for RIC3 and for the mechanisms regulating its expression in inflammatory processes and in neuroinflammatory diseases., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Homomeric α 7 nicotinic acetylcholine receptors (nAChR) have an intrinsically low probability of opening that can be overcome by α 7-selective positive allosteric modulators (PAMs), which bind at a site involving the second transmembrane domain (TM2). Mutation of a methionine that is unique to α 7 at the 15' position of TM2 to leucine, the residue in most other nAChR subunits, largely eliminates the activity of such PAMs. We tested the effect of the reverse mutation (L15'M) in heteromeric nAChR receptors containing α 4 and β 2, which are the nAChR subunits that are most abundant in the brain. Receptors containing these mutations were found to be strongly potentiated by the α 7 PAM 3 a ,4,5,9 b -tetrahydro-4-(1-naphthalenyl)-3 H -cyclopentan[ c ]quinoline-8-sulfonamide (TQS) but insensitive to the alternative PAM 1-(5-chloro-2,4-dimethoxyphenyl)-3-(5-methylisoxazol-3-yl)-urea. The presence of the mutation in the β 2 subunit was necessary and sufficient for TQS sensitivity. The primary effect of the mutation in the α 4 subunit was to reduce responses to acetylcholine applied alone. Sensitivity to TQS required only a single mutant β subunit, regardless of the position of the mutant β subunit within the pentameric complex. Similar results were obtained when β 2L15'M was coexpressed with α 2 or α 3 and when the L15'M mutation was placed in β 4 and coexpressed with α 2, α 3, or α 4. Functional receptors were not observed when β 1L15'M subunits were coexpressed with other muscle nAChR subunits. The unique structure-activity relationship of PAMs and the α 4 β 2L15'M receptor compared with α 7 and the availability of high-resolution α 4 β 2 structures may provide new insights into the fundamental mechanisms of nAChR allosteric potentiation. SIGNIFICANCE STATEMENT: Heteromeric neuronal nAChRs have a relatively high initial probability of channel activation compared to receptors that are homomers of α7 subunits but are insensitive to PAMs, which greatly increase the open probability of α7 receptors. These features of heteromeric nAChR can be reversed by mutation of a single residue present in all neuronal heteromeric nAChR subunits to the sequence found in α7. Specifically, the mutation of the TM2 15' leucine to methionine in α subunits reduces heteromeric receptor channel activation, while the same mutation in neuronal β subunits allows heteromeric receptors to respond to select α 7 PAMs. The results indicate a key role for this residue in the functional differences in the two main classes of neuronal nAChRs., (Copyright © 2019 by The American Society for Pharmacology and Experimental Therapeutics.)

Ideal multifunctional ultraviolet radiation (UVR) absorbents with excellent photostability, high molar absorptivity, broadband UVR screening, and desired skin sensorial properties remain a significant challenge for the sunscreen industry. The potential of the nanocomplex (NCx) formed by microwave synthesis of ZnO quantum dots (QDs) in the presence of Avobenzone (Av) for achieving these goals is reported. The NCx exhibits unique synergy between ZnO QD and Av components, which enhances the photostability and molar absorptivity, extends UVA filtering range, and provides a visible emission that matches the typical human in vivo skin emission color. Density functional theory (DFT) and time-dependent DFT calculations of ZnO-Av hybrid structures and comparison of their spectroscopic features with experiments suggest that ZnO QDs catalyze the formation of highly photostable surface enolate species via aldol condensation reaction. The combination of experiments and computations used in this study can advance the science and technology of photoprotection., Competing Interests: The authors declare no conflict of interest., (© 2018 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background and Purpose: GAT107 ((3aR,4S,9bS)-4-(4-bromo-phenyl)-3a,4,5,9b-tetrahydro-3H-cyclopenta-[c]quinoline-8-sulfonamide) is a positive allosteric modulator (PAM) and agonist of α7 nicotinic acetylcholine receptors (nAChRs)that can cause a prolonged period of primed potentiation of acetylcholine responses after drug washout. NS6740 is a silent agonist of α7 nAChRs that has little or no efficacy for activating the ion channel but induces stable desensitization states, some of which can be converted into channel-active states by PAMs. Although GAT107 and NS6740 appear to stably induce different non-conducting states, both agents are effective treatment for inflammation and inflammatory pain models. We sought to better understand how both of these drugs that have opposite effects on channel activation could regulate signal transduction., Experimental Approach: Voltage-clamp experiments were conducted with α7 nAChRs expressed in Xenopus oocytes., Key Results: Long-lived sensitivity to a PAM or to an agonist was produced by NS6740 or GAT107 respectively. With sequential applications, these two drugs induced varying levels of persistent activation, which is a unique condition for a receptor that is known for rapid desensitization. The non-conducting states induced by NS6740 or GAT107 differ in their sensitivity to an α7 nAChR-selective antagonist and in how effectively they promote current., Conclusions & Implications: Our data suggest that the persistent currents represent a dynamic interconversion between different stable desensitized states and the PAM-inducible conducting states. However, the similarity of NS6740 and GAT107 effects on inflammation and pain suggests that the different stable non-conducting states have common activity on signal transduction., Linked Articles: This article is part of a themed section on Nicotinic Acetylcholine Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.11/issuetoc., (© 2017 The British Pharmacological Society.)

Recently, α7 nicotinic acetylcholine receptors (nAChRs), primarily activated by binding of orthosteric agonists, represent a target for anti-inflammatory and analgesic drug development. These receptors may also be modulated by positive allosteric modulators (PAMs), ago-allosteric ligands (ago-PAMs), and α7-silent agonists. Activation of α7 nAChRs has been reported to increase the brain levels of endogenous ligands for nuclear peroxisome proliferator-activated receptors type-α (PPAR-α), palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), in a Ca 2+ -dependent manner. Here, we investigated potential crosstalk between α7 nAChR and PPAR-α, using the formalin test, a mouse model of tonic pain. Using pharmacological and genetic approaches, we found that PNU282987, a full α7 agonist, attenuated formalin-induced nociceptive behavior in α7-dependent manner. Interestingly, the selective PPAR-α antagonist GW6471 blocked the antinociceptive effects of PNU282987, but did not alter the antinociceptive responses evoked by the α7 nAChR PAM PNU120596, ago-PAM GAT107, and silent agonist NS6740. Moreover, GW6471 administered systemically or spinally, but not via the intraplantar surface of the formalin-injected paw blocked PNU282987-induced antinociception. Conversely, exogenous administration of the naturally occurring PPAR-α agonist PEA potentiated the antinociceptive effects of PNU282987. In contrast, the cannabinoid CB 1 antagonist rimonabant and the CB 2 antagonist SR144528 failed to reverse the antinociceptive effects of PNU282987. These findings suggest that PPAR-α plays a key role in a putative antinociceptive α7 nicotinic signaling pathway., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The purpose of this study was to estimate eye lens dose during brain scans in 16-, 64-, 128- and 256-slice multidetector computed tomography (CT) scanners in helical acquisition mode and to test the feasibility of using radiochromic film as eye lens dosemeter during CT scanning. Eye lens dose measurements were performed using Gafchromic XR-QA2 film on a polystyrene head phantom designed with outer dimensions equivalent to the head size of a reference Indian man. The response accuracy of XR-QA2 film was validated by using thermoluminescence dosemeters. The eye lens dose measured using XR-QA2 film on head phantom for plain brain scanning in helical mode ranged from 43.8 to 45.8 mGy. The XR-QA2 film measured dose values were in agreement with TLD measured dose values within a maximum variation of 8.9%. The good correlation between the two data sets confirms the viability of using XR-QA2 film for eye lens dosimetry., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Introduction: Post-mastectomy breast reconstruction has become an increasingly important component of breast cancer treatment. Unfortunately, some patients experience severe postoperative pain, placing them at risk for increased clinical morbidity and the development of disabling chronic pain. In an attempt to identify at-risk patients, we prospectively evaluated patient characteristics and medical/surgical variables associated with more severe acute post-reconstruction pain., Methods: Women (N = 2207; one-week 82.8% response rate) undergoing breast reconstruction were assessed for pain experience, anxiety, depression, and sociodemographic characteristics prior to surgery. Pain assessments were made preoperatively and postoperative at 1-week using validated survey instruments including the McGill Pain Questionnaire-Short Form (MPQ-SF), Numerical Pain Rating Scale (NPRS), and BREAST-Q Chest and Upper Body scale. Depressive symptoms and anxiety severity were assessed by the Patient Health Questionnaire and Generalized Anxiety Disorders Scale, respectively. Mixed-effects regression modeling was used to examine the relationships between patient characteristics and medical/surgical factors and 1-week postoperative pain., Results: Younger age, bilateral reconstruction, and severity of preoperative pain, anxiety and depression were all associated with more severe acute postoperative pain on all the pain measures and BREAST-Q. Comparison of surgical procedure type indicated less severe postoperative pain for PTRAM, DIEP and SIEA reconstructive surgery compared to tissue expander/implant reconstruction., Conclusions: This study identified patients at risk for greater acute postoperative pain following breast reconstruction. These findings will allow plastic surgeons to better tailor postoperative care to improve patient comfort, reduce clinical morbidity, and further enhance patient satisfaction with their surgical outcome., Competing Interests: Conflict of Interest Statement The authors declare no conflict of interest and none of the authors received royalties or remuneration from their participation in this study.

We report a facile, microwave-accelerated, one-pot tandem synthesis of unsymmetrical ureas via a Curtius rearrangement. In this method, one-pot microwave irradiation of commercially available (hetero)aromatic acids and amines in the presence of diphenylphosphoryl azide enabled extremely rapid (1-5 min) construction of an array of unsymmetrical ureas in good to excellent yields. We demonstrate the utility of our method in the efficient, gram-scale synthesis of key biologically active compounds targeting the cannabinoid 1 and α7 nicotinic acetylcholine receptors.

Also expressed in various peripheral tissues, the type-1 cannabinoid receptor (CB1R) is the predominant G protein-coupled receptor (GPCR) in brain, where it is responsible for retrograde control of neurotransmitter release. Cellular signaling mediated by CB1R is involved in numerous physiological processes, and pharmacological CB1R modulation is considered a tenable therapeutic approach for diseases ranging from substance-use disorders and glaucoma to metabolic syndrome. Despite the design and synthesis of a variety of bioactive small molecules targeted to the CB1R orthosteric ligand-binding site, the potential of CB1R as a therapeutic GPCR has been largely unrealized due to adverse events associated with typical orthosteric CB1R agonists and antagonists/inverse agonists. Modulation of CB1R-mediated signal transmission by targeting alternative allosteric ligand-binding site(s) on the receptor has garnered interest as a potentially safer and more effective therapeutic modality. This chapter highlights the design and synthesis of novel, pharmacologically active CB1R allosteric modulators and emphasizes how their molecular properties and the positive and negative allosteric control they exert can lead to improved CB1R-targeted pharmacotherapeutics, as well as designer covalent probes that can be used to map CB1R allosteric binding domains and inform structure-based drug design., (© 2017 Elsevier Inc. All rights reserved.)