Cu Based Dilute Alloys for Tuning the C2+ Selectivity of Electrochemical CO2 Reduction.

Electrochemical CO2 reduction is a promising technology for replacing fossil fuel feedstocks in the chemical industry but further improvements in catalyst selectivity need to be made. So far, only copper-based catalysts have shown efficient conversion of CO2 into the desired multi-carbon (C2+) products. This work explores Cu-based dilute alloys to systematically tune the energy landscape of CO2 electrolysis toward C2+ products. Selection of the dilute alloy components is guided by grand canonical density functional theory simulations using the calculated binding energies of the reaction intermediates CO*, CHO*, and OCCO* dimer as descriptors for the selectivity toward C2+ products. A physical vapor deposition catalyst testing platform is employed to isolate the effect of alloy composition on the C2+/C1 product branching ratio without interference from catalyst morphology or catalyst integration. Six dilute alloy catalysts are prepared and tested with respect to their C2+/C1 product ratio using different electrolyzer environments including selected tests in a 100-cm2 electrolyzer. Consistent with theory, CuAl, CuB, CuGa and especially CuSc show increased selectivity toward C2+ products by making CO dimerization energetically more favorable on the dominant Cu facets, demonstrating the power of using the dilute alloy approach to tune the selectivity of CO2 electrolysis.

A gain-of-function variant in SREBF1 causes generalized skin hyperpigmentation with congenital cataracts.

BACKGROUND: Lipid metabolism plays essential roles in skin barrier formation and the regulation of skin inflammation. Moreover, lipid homeostasis regulates skin melanogenesis, although the underlying mechanism remains largely unknown. Sterol regulatory element binding protein 1 (SREBP-1) is a key transcription factor essential for cellular lipid metabolism. Loss-of-function variants in SREBF1 are responsible for autosomal-dominant ichthyosis follicularis, alopecia, and photophobia syndrome, emphasizing the significance of lipid homeostasis in skin keratinization. OBJECTIVES: To identify the genetic basis of a new entity featuring diffuse skin hyperpigmentation with congenital cataracts, and to unravel the underlying mechanism for the pathogenesis of the SREBF1 variant. METHODS: Whole-exome sequencing was performed to identify the underlying genetic variants. Quantitative PCR, western blot, and immunofluorescent staining were employed to assess the expression and the subcellular localization of the SREBF1 variant. The transcriptional activity of the mutant SREBP-1 was determined by luciferase reporter assay. A transgenic zebrafish model was constructed. RESULTS: Two patients of different ethnicities presented with generalized skin hyperpigmentation with skin xerosis, congenital cataracts, and extracutaneous symptoms. We identified a de novo nonsense variant c.1289C>A (p.Ser430*) in the SREBF1 gene in both patients. The variant encoded a truncated protein which showed preferential nucleus localization, in contrast to wild-type SREBP-1 which is mainly localized in cytoplasm in sterol-sufficient conditions. Luciferase reporter assay revealed that the Ser430* mutant exhibited an enhanced transcriptional activity. The primary cultured melanocytes from the patient showed increased melanin synthesis compared to those from normal controls. The Ser430* transgenic zebrafish model exhibited more black spots, along with upregulated expression of melanogenic genes at 35 days post-fertilization. CONCLUSIONS: We demonstrated that a gain-of-function variant in SREBF1 caused a previously undescribed disorder characterized by generalized skin hyperpigmentation and congenital cataracts. Our study reveals the involvement of SREBP-1 in melanogenesis and lens development and paves the way for developing novel therapeutic targets for skin dyspigmentation or cataracts.

Advancements in Pancreatic Cancer Detection: Integrating Biomarkers, Imaging Technologies, and Machine Learning for Early Diagnosis.

Artificial intelligence (AI) has come to play a pivotal role in revolutionizing medical practices, particularly in the field of pancreatic cancer detection and management. As a leading cause of cancer-related deaths, pancreatic cancer warrants innovative approaches due to its typically advanced stage at diagnosis and dismal survival rates. Present detection methods, constrained by limitations in accuracy and efficiency, underscore the necessity for novel solutions. AI-driven methodologies present promising avenues for enhancing early detection and prognosis forecasting. Through the analysis of imaging data, biomarker profiles, and clinical information, AI algorithms excel in discerning subtle abnormalities indicative of pancreatic cancer with remarkable precision. Moreover, machine learning (ML) algorithms facilitate the amalgamation of diverse data sources to optimize patient care. However, despite its huge potential, the implementation of AI in pancreatic cancer detection faces various challenges. Issues such as the scarcity of comprehensive datasets, biases in algorithm development, and concerns regarding data privacy and security necessitate thorough scrutiny. While AI offers immense promise in transforming pancreatic cancer detection and management, ongoing research and collaborative efforts are indispensable in overcoming technical hurdles and ethical dilemmas. This review delves into the evolution of AI, its application in pancreatic cancer detection, and the challenges and ethical considerations inherent in its integration.

Application of Otoform to Study Variations of Sinus Tympani: A Novel Technique.

The sinus tympani is a deep pocket of varying dimensions situated in the retrotympanum. It lies medial to the facial nerve thereby making surgical access difficult. It is this area which is frequently involved in chronic otitis media attico-antral type. Removal of disease from sinus tympani is cumbersome and expedites Cholesteatoma Recidivism. In India, very limited studies have been conducted describing the variations of Sinus tympani. Hence, this study is dedicated to estimating it's variations in volume. This is a one-year Observational Cross-sectional study conducted between January 2020 to December 2020 in Temporal Bone Dissection Lab of Department of Otorhinolaryngology and Head and Neck Surgery, J. N. Medical College, KAHER, Belgaum. 40 Human temporal bone (both left and right) have been dissected. The middle ear cavity was filled carefully with a moulding material i.e. Otoform. Once set, a 3-dimensional model of the middle ear cavity was made, which was removed carefully without causing any damage. The volume of the middle ear cavity was calculated. The other contents and parameters were measured using a measuring probe. Forty bones were dissected. The volume of the sinus tympani was measured to be 8.77 cubic mm with a range of 6.5 cubic mm to. 10.9 cubic mm hence showing that sinus tympani show a larger variability in terms of size, shape and volume. The ponticulus was Complete in 65% of the cases (26 bones) and incomplete in 35% of the cases (14 bones). The ponticulus and subiculum were found to be complete in a well pneumatized mastoid bone. The volume of the middle ear cavity was measured to be 1.17 cubic cm. The sinus tympani volume was calculated in this study employing a novel technique called the Otoform mould in cadaveric temporal bones, enabling for accurate measurement. The study concluded that sinus tympani showed a wide range in volume thus owing that it is the structure which has highest variability in terms of size and shape in the middle ear.

Theoretical Investigation of the Adsorbate and Potential-Induced Stability of Cu Facets During Electrochemical CO2 and CO Reduction.

The activity and product selectivity of electrocatalysts for reactions like the carbon dioxide reduction reaction (CO2RR) are intimately dependent on the catalyst's structure and composition. While engineering catalytic surfaces can improve performance, discovering the key sets of rational design principles remains challenging due to limitations in modeling catalyst stability under operating conditions. Herein, we perform first-principles density functional calculations adopting implicit solvation methods with potential control to study the influence of adsorbates and applied potential on the stability of different facets of model Cu electrocatalysts. Using coverage dependencies extracted from microkinetic models, we describe an approach for calculating potential and adsorbate-dependent contributions to surface energies under reaction conditions, where Wulff constructions are used to understand the morphological evolution of Cu electrocatalysts under CO2RR conditions. We identify that CO*, a key reaction intermediate, exhibits higher kinetically and thermodynamically accessible coverages on (100) relative to (111) facets, which can translate into an increased relative stabilization of the (100) facet during CO2RR. Our results support the known tendency for increased (111) faceting of Cu nanoparticles under more reducing conditions and that the relative increase in (100) faceting observed under CO2RR conditions is likely attributed to differences in CO* coverage between these facets.

Pediatric consultative dermatology: A survey of the Society for Pediatric Dermatology workforce reveals shortcomings in existing practice models of pediatric dermatology consult services in the United States.

The rate of pediatric hospitalization for cutaneous pathology has been increasing in recent years, often requiring the expertise of consulting pediatric dermatologists; however, the infrastructure of inpatient pediatric dermatology consultative services remains poorly characterized. We sought to assess the structure, consult volume, physician compensation, and utilization of teledermatology in pediatric dermatology inpatient services to better understand the current care model. Our survey of 118 pediatric dermatologists revealed that 89% of respondents see between 1 and 10 new consults per week, 39% perform all inpatient consults including evening and weekends without assistance from other providers, 71% do not have protected time during the week to provide inpatient consultations, and only 10% receive financial compensation via stipend. By highlighting both the high demand for pediatric consultative dermatology as well as the significant burden placed on these providers by existing practice models, we hope to encourage a reappraisal of the current infrastructure of pediatric inpatient dermatology to increase structural and financial support for this vital service.

Poliosis, hair pigment dilution, and premature graying of the hair: A diagnostic approach in pediatric patients and review of the literature.

Poliosis is defined as the absence of melanin in hair, and hair graying typically occurs with hair melanin reduction. Poliosis can occur at any age but presents in childhood in certain genetic and acquired conditions, with many families seeking evaluation from a pediatric dermatologist. Poliosis presents as white hair typically restricted to a certain location of the scalp. Children may also present with a reduction of expected hair pigmentation, referred to as pigment dilution, or the development of hair graying. This review aims to provide a streamlined diagnostic approach for pediatric dermatologists when presented with these hair findings. Poliosis should be recognized as a potential diagnostic feature or initial sign in many syndromes and thus can guide clinicians in diagnosing and managing conditions earlier in a patient's care. Since many of the genetic and acquired conditions that present with poliosis or hair pigment dilution have extracutaneous manifestations, early diagnosis is vital in establishing multidisciplinary care.

Comparing Efficiency Epley and Semont Manoeuvre with Videonystagmography.

Videonystagmography (VNG) is useful and reliable in diagnosing vertigo. Benign Paroxysmal Positional Vertigo (BPPV) is the most common peripheral vestibular disorder in adults, and posterior canal is the commonest canalinvolved. The treatment of choice for posterior canal BPPV is repositioning manoeuvres. Epley and Semontmanoeuvres are the two most commonly used treatment manoeuvres for the management of posterior canalBPPV. In this study, we use VNG to compare the two. Epley Repositioning Manoeuvre was found to be moreeffective than Semont Liberatory Manoeuvre. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-03901-3.

Hyperglycemic conditions induce rapid cell dysfunction-promoting transcriptional alterations in human aortic endothelial cells.

Hyperglycemia is a major risk factor in the development of diabetic complications and promotes vascular complications through dysregulation of endothelial cell function. Various mechanisms have been proposed for endothelial cell dysregulation but the early transcriptomic alterations of endothelial cells under hyperglycemic conditions are not well documented. Here we use deep time-series RNA-seq profiling of human aortic endothelial cells (HAECs) following exposure to normal (NG) and high glucose (HG) conditions over a time course from baseline to 24 h to identify the early and transient transcriptomic changes, alteration of molecular networks, and their temporal dynamics. The analysis revealed that the most significant pathway activation/inhibition events take place in the 1- to 4-h transition and identified distinct clusters of genes that underlie a cascade of coordinated transcriptional events unique to HG conditions. Temporal co-expression and causal network analysis implicate the activation of type 2 diabetes (T2D) and growth factor signalling pathways including STAT3 and NF-κB. These results document HAEC transcriptional changes induced by hyperglycemic conditions and provide basic insight into the rapid molecular alterations that promote endothelial cell dysfunction.

Rilonacept and Anakinra in Recurrent Pericarditis: A Systematic Review and Meta-Analysis.

Interleukin 1 (IL-1) has been indicated as a mediator of recurrent pericarditis. Rilonacept, a soluble IL-1 receptor chimeric fusion protein neutralizing interleukin 1 alpha (IL-1α) and interleukin 1 beta (IL-1ß), has demonstrated promising results in a phase II study in recurrent or refractory pericarditis. Anakinra is a recombinant inhibitor of the IL-1 receptor with a demonstrated reduction in the incidence of recurrent pericarditis. Definite pharmacological management of pericarditis is key to preventing recurrences, mostly treatment options for recurrent pericarditis refractory to conventional drugs. Here we critically discuss the existing therapy options for recurrent pericarditis, with a focus on new pharmacological approaches: rilonacept and anakinra. A systematic search was conducted across online databases such as PubMed, Cochrane, Google Scholar, ScienceDirect, CINAHL, Scopus, and Embase to obtain clinical trials that assess the effectiveness of anti-interleukin 1 therapy such as anakinra and rilonacept in the management of recurrent pericarditis. Our study concluded that anti-interleukin 1 therapy significantly improved both the quality of life and the clinical outcomes of the study population. These outcomes were most prominent with the use of rilonacept and anakinra in the trial treatment. Rilonacept and anakinra are valuable options in case of recurrent pericarditis refractory to conventional drugs.

Clinical Effectiveness of Telemedicine-Based Pediatric Genetics Care.

BACKGROUND AND OBJECTIVES: Telemedicine may increase access to medical genetics care. However, in the pediatric setting, how telemedicine may affect the diagnostic rate is unknown, partially because of the perceived importance of the dysmorphology physical examination. We studied the clinical effectiveness of telemedicine for patients with suspected or confirmed genetic conditions. METHODS: We conducted a retrospective cohort study of outpatient encounters before and after the widespread implementation of telemedicine (N = 5854). Visit types, diagnoses, patient demographic characteristics, and laboratory data were acquired from the electronic health record. Patient satisfaction was assessed through survey responses. New molecular diagnosis was the primary end point. RESULTS: Patients seen by telemedicine were more likely to report non-Hispanic White ancestry, prefer to speak English, live in zip codes with higher median incomes, and have commercial insurance (all P < .01). Genetic testing was recommended for more patients evaluated by telemedicine than in person (79.5% vs 70.9%; P < .001). Patients seen in person were more likely to have a sample collected, resulting in similar test completion rates (telemedicine, 51.2%; in person, 55.1%; P = .09). There was no significant difference in molecular diagnosis rate between visit modalities (telemedicine, 13.8%; in person, 12.4%; P = .40). CONCLUSIONS: Telemedicine and traditional in-person evaluation resulted in similar molecular diagnosis rates. However, improved methodologies for remote sample collection may be required. This study reveals the feasibility of telemedicine in a large academic medical genetics practice and is applicable to other pediatric specialties with perceived importance of physical examination.

Challenges and Updates in the Diagnosis and Treatment of Infective Endocarditis.

Infective endocarditis is a life-threatening disease of the endocardium of the heart and cardiac valves, caused by several infectious agents, ranging from Streptococci to rickettsia. It has continued to be a serious cause of cardiac infection, with a rise in the incidence globally over the last 5 years. Despite diagnostic and therapeutic advances, its prognosis remains poor, and a surge in morbidity and hospital mortality highlights the significance of the swift diagnosis of this disease. Given its complexity, patients with infective endocarditis need rapid response and prompt diagnosis from a multidisciplinary team with a timely diagnostic protocol and treatment in the critical phase. Still, there is a lack of evidence regarding the timing of surgery or the role of antibiotic prophylaxis in the management. In this review, we detail the epidemiological transition, challenges in the diagnosis, and the newer avenues in the medical and surgical management of infective endocarditis.

The Risk of Cardiovascular Disease Among Immigrants in Canada.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. The global surge in migration to high-income countries, especially Canada, highlights the importance of studies evaluating the risk factors and the disparities in the rate of incidence of CVD among immigrants. Canada is home to a diverse group of immigrants, each presenting with a risk profile that is unique to their ethnicity and country of birth. A variety of cardiac risk factors, such as dietary habits, physical activity, smoking, cultural traditions as well as preponderance to certain diseases like type II diabetes mellitus, hypertension, and high lipid levels act in concert and impact CVD risk and overall incidence. This narrative review focuses on CVD risks and how it is related to the immigration status among various ethnic groups in Canada.

Behavioral Problems in Fragile X Syndrome: A Review of Clinical Management.

Fragile X syndrome (FXS) is noted to be the leading cause of inherited intellectual disabilities and is caused by expansive cytosine-guanine-guanine (CGG) trinucleotide repeats in the fragile X mental retardation 1 gene (FMR1). FXS can display a wide range of behavioral problems in addition to intellectual and developmental issues. Management of these problems includes both pharmacological and non-pharmacological options and research on these different management styles has been extensive in recent years. This narrative review aimed to collate recent evidence on the various management options of behavioral problems in FXS, including the pharmacological and non-pharmacological treatments, and also to provide a review of the newer avenues in the FXS treatment.

Genetic manipulation of anti-nutritional factors in major crops for a sustainable diet in future.

The consumption of healthy food, in order to strengthen the immune system, is now a major focus of people worldwide and is essential to tackle the emerging pandemic concerns. Moreover, research in this area paves the way for diversification of human diets by incorporating underutilized crops which are highly nutritious and climate-resilient in nature. However, although the consumption of healthy foods increases nutritional uptake, the bioavailability of nutrients and their absorption from foods also play an essential role in curbing malnutrition in developing countries. This has led to a focus on anti-nutrients that interfere with the digestion and absorption of nutrients and proteins from foods. Anti-nutritional factors in crops, such as phytic acid, gossypol, goitrogens, glucosinolates, lectins, oxalic acid, saponins, raffinose, tannins, enzyme inhibitors, alkaloids, ß-N-oxalyl amino alanine (BOAA), and hydrogen cyanide (HCN), are synthesized in crop metabolic pathways and are interconnected with other essential growth regulation factors. Hence, breeding with the aim of completely eliminating anti-nutrition factors tends to compromise desirable features such as yield and seed size. However, advanced techniques, such as integrated multi-omics, RNAi, gene editing, and genomics-assisted breeding, aim to breed crops in which negative traits are minimized and to provide new strategies to handle these traits in crop improvement programs. There is also a need to emphasize individual crop-based approaches in upcoming research programs to achieve smart foods with minimum constraints in future. This review focuses on progress in molecular breeding and prospects for additional approaches to improve nutrient bioavailability in major crops.

Evaluating the stability and activity of dilute Cu-based alloys for electrochemical CO2 reduction.

Cu-based catalysts currently offer the most promising route to actively and selectively produce value-added chemicals via electrochemical reduction of CO2 (eCO2R); yet further improvements are required for their wide-scale deployment in carbon mitigation efforts. Here, we systematically investigate a family of dilute Cu-based alloys to explore their viability as active and selective catalysts for eCO2R through a combined theoretical-experimental approach. Using a quantum-classical modeling approach that accounts for dynamic solvation effects, we assess the stability and activity of model single-atom catalysts under eCO2R conditions. Our calculations identify that the presence of eCO2R intermediates, such as CO*, H*, and OH*, may dynamically influence the local catalyst surface composition. Additionally, we identify through binding energy descriptors of the CO*, CHO*, and OCCO* dimer intermediates that certain elements, such as group 13 elements (B, Al, and Ga), enhance the selectivity of C2+ species relative to pure Cu by facilitating CO dimerization. The theoretical work is corroborated by preliminary testing of eCO2R activity and selectivity of candidate dilute Cu-based alloy catalyst films prepared by electron beam evaporation in a zero-gap gas diffusion electrode-based reactor. Of all studied alloys, dilute CuAl was found to be the most active and selective toward C2+ products like ethylene, consistent with the theoretical predictions. We attribute the improved performance of dilute CuAl alloys to more favorable dimerization reaction energetics of bound CO species relative to that on pure Cu. In a broader context, the results presented here demonstrate the power of our simulation framework in terms of rational catalyst design.

Chemical Modifications of Ag Catalyst Surfaces with Imidazolium Ionomers Modulate H2 Evolution Rates during Electrochemical CO2 Reduction.

Bridging polymer design with catalyst surface science is a promising direction for tuning and optimizing electrochemical reactors that could impact long-term goals in energy and sustainability. Particularly, the interaction between inorganic catalyst surfaces and organic-based ionomers provides an avenue to both steer reaction selectivity and promote activity. Here, we studied the role of imidazolium-based ionomers for electrocatalytic CO2 reduction to CO (CO2R) on Ag surfaces and found that they produce no effect on CO2R activity yet strongly promote the competing hydrogen evolution reaction (HER). By examining the dependence of HER and CO2R rates on concentrations of CO2 and HCO3-, we developed a kinetic model that attributes HER promotion to intrinsic promotion of HCO3- reduction by imidazolium ionomers. We also show that varying the ionomer structure by changing substituents on the imidazolium ring modulates the HER promotion. This ionomer-structure dependence was analyzed via Taft steric parameters and density functional theory calculations, which suggest that steric bulk from functionalities on the imidazolium ring reduces access of the ionomer to both HCO3- and the Ag surface, thus limiting the promotional effect. Our results help develop design rules for ionomer-catalyst interactions in CO2R and motivate further work into precisely uncovering the interplay between primary and secondary coordination in determining electrocatalytic behavior.

Comparison of Antimicrobial Efficacy of Diode Laser, Ultrasonic Activated and Conventional Irrigation with 2.5% NaOCl during RCT: An Interventional Study.

AIM AND OBJECTIVE: The aim and objective of the study was to evaluate and compare the antimicrobial efficacy of a diode laser irradiation, ultrasonic activated and conventional irrigation with 2.5% NaOCl on obligatory and facultative anaerobic bacteria in single-rooted canals. MATERIALS AND METHODS: Total of 60 permanent maxillary and mandibular single-rooted (single canal) anterior teeth were selected. First microbial sample (S1) was collected after access opening and working length determination, using a sterile paper point. Cleaning and shaping were performed, with each instrument change accompanied by irrigation using 2 mL 2.5% NaOCl. After cleaning and shaping, disinfection protocol using diode laser (group1), ultrasonic activated irrigation with 2.5% NaOCl (group 2) and conventional irrigation with 2.5% NaOCl (group 3) was performed and second microbial sample (S2) was obtained. The colony characters of each type of growth on each media were noted and the organisms were identified using standard biochemical reactions. RESULT: Gram-positive and gram-negative facultative anaerobe were predominantly isolated from the culture, and the highest reduction of the microbial count was seen in diode laser group with 60.92% followed by the ultrasonic group with 47.22% reduction and least reduction was observed in conventional irrigation with the ultrasonic group with 37.97%. The results were statistically significant with p-value <0.05. CONCLUSION: Diode laser disinfection showed the highest reduction of microbial count compared to ultrasonic activated and conventional needle irrigation with 2.5% NaOCl group. CLINICAL SIGNIFICANCE: This study will help us to choose wisely between various irrigating methods and protocols. Diode laser in our study has shown superior disinfection of the root canals compared to others.

Electrocatalytic Hydrogenation of Biomass-Derived Organics: A Review.

Sustainable energy generation calls for a shift away from centralized, high-temperature, energy-intensive processes to decentralized, low-temperature conversions that can be powered by electricity produced from renewable sources. Electrocatalytic conversion of biomass-derived feedstocks would allow carbon recycling of distributed, energy-poor resources in the absence of sinks and sources of high-grade heat. Selective, efficient electrocatalysts that operate at low temperatures are needed for electrocatalytic hydrogenation (ECH) to upgrade the feedstocks. For effective generation of energy-dense chemicals and fuels, two design criteria must be met: (i) a high H:C ratio via ECH to allow for high-quality fuels and blends and (ii) a lower O:C ratio in the target molecules via electrochemical decarboxylation/deoxygenation to improve the stability of fuels and chemicals. The goal of this review is to determine whether the following questions have been sufficiently answered in the open literature, and if not, what additional information is required:(1)What organic functionalities are accessible for electrocatalytic hydrogenation under a set of reaction conditions? How do substitutions and functionalities impact the activity and selectivity of ECH?(2)What material properties cause an electrocatalyst to be active for ECH? Can general trends in ECH be formulated based on the type of electrocatalyst?(3)What are the impacts of reaction conditions (electrolyte concentration, pH, operating potential) and reactor types?