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A substantial amount of research, resources, and effort has been invested in the search for a 'holy grail' of twenty-first century leadership competencies. Ironically, despite the increasing significance of leadership and the substantial investments in uncovering the attributes of successful leaders, concerns persist regarding the quality of leadership worldwide. While the literature extensively outlines 'what' twenty-first century-ready leaders should embody, there remains a gap in outlining 'how' to nurture such leaders. We contrast existing practices that have focused on teaching functional content and relying on retrospective and deficit-based competency models by advocating for a strengths-based perspective. While there has been an increasing interest in positive psychology, which promotes a shift away from prevalent deficit correction approaches towards a framework that emphasises social-emotional and meta-cognitive strengths, character strengths have received little attention in corporate leader development programmes. We argue that nurturing character strengths offers a more sustainable, self-reinforcing process for twenty-first century leader development to overcome the limitations of short-lived leadership training results that fade over time. The Values in Action Classification of Character Strengths and Virtues provides a robust framework for identifying and nurturing these strengths. However, character strengths have traditionally been viewed as personal attributes, rather than leadership competencies. We challenge traditional views on leader development by arguing that character strengths reflect the competencies required of twenty-first century-ready leaders, as these more 'humane' characteristics remain relevant over time and valued across cultures because they represent qualities that are universally appreciated in defining 'what makes a good person'. [ABSTRACT FROM AUTHOR]

Significant effort has been invested previously to understand the effect of temperature and humidity on water uptake, water transport, structure, and proton conductivity of perfluorosulfonic acid (PFSA) ionomer membranes. One of the significant factors influencing the performance and durability of Nafion is its ability to retain and transport water. Water transport in Nafion is a strong function of sorption, ion exchange capacity, and transport properties of the membrane, which in turn, are functions of its structure and morphology. In addition to the operating conditions, pre-treatment conditions, additives, and the presence of cations significantly affect Nafion's morphology. Infrared spectroscopy (IR) is a powerful tool to gain insight into the properties of Nafion structure and properties. FTIR can monitor real-time changes in chemical interactions, molecular motions, and connectivity of ionic channels under varying operating conditions. FTIR has also been used to validate models developed to explain the dynamic behavior of polymer electrolyte membrane fuel cells. The potential of infrared spectroscopy to understand the impact of environmental changes on Nafion structure is immense but remains underutilized. This review provides a comprehensive summary of the assignment of vibrational modes of Nafion in various regions of the spectrum and sheds light on discrepancies concerning the allocation of vibrational modes to specific interactions. [ABSTRACT FROM AUTHOR]

NGS used to diagnose and treat NSCLC patient with initial concern for metaplastic breast cancer [ABSTRACT FROM AUTHOR]

Policymakers are liable to 'treasure what is measured' and overlook phenomena that are not. In an era of increased reliance on administrative data, existing policies also often determine what is measured in the first place. We explore this two-way interaction between measurement and policy in the context of the investment incomes and capital gains that are missing from the UK's official income statistics. We show that these 'missing incomes' change the established picture of economic inequality over the past decade, revealing rising top income shares during the period of austerity. The underestimation of these forms of income in official statistics has hidden the impact of tax policies that disproportionately benefit the wealthiest. We urge a renewed focus on how policy affects and is affected by measurement. [ABSTRACT FROM AUTHOR]

The possible association of Cytomegalovirus (CMV) with human colorectal adenocarcinomas was first reported in 1978 by Huang and Roche, who detected CMV DNA in 4 of 7 colonic adenocarcinomas by membrane complementary Ribonucleic AcidDeoxyribonucleic Acid (RNA-DNA) hybridisation. CMV earns its name from the characteristic cytomegalic appearance of intranuclear inclusions in infected cells, which include endothelial cells, histiocytes, macrophages, and epithelial cells. The most common site of CMV infection in the gastrointestinal tract is the colon (55%), followed by the sigmoid colon and rectum (35%) and the gastric antrum (25%). Here, a middle-aged female presenting with pain in the lower abdomen, which was insidious in onset and gradually progressive. Ultrasonography revealed a large intestine dilated and filled with multiple air-fluid levels, indicating bowel obstruction. Multidetector Computed Tomography (MDCT) showed circumferential wall thickening involving the distal half of the transverse colon and descending colon. The case was subjected to laparotomy. The resected segment of the colon was sent for histopathological evaluation, and microscopic examination showed adenocarcinoma and many mucosal ulcers, which on keen observation revealed viral inclusions. The diagnosis of colon adenocarcinoma, with a pathological staging of pT2N0Mx with CMV infection, was rendered. CMV infection was confirmed by immunohistochemistry. The patient was on post-surgery chemotherapy and receiving ganciclovir. On follow-up, the patient was recovering fine. Histopathology examination and IHC remain the gold standard in diagnosing CMV, and the concurrent occurrence of colitis and carcinoma should be kept in mind to assist in proper management. [ABSTRACT FROM AUTHOR]

Background and Purpose: Activated fibroblasts deposit fibrotic matrix in chronic kidney disease (CKD) and G‐protein coupled receptors (GPCRs) are the most druggable therapeutic targets. Here, we set out to establish a transcriptional profile that identifies activated kidney fibroblasts and the GPCRs that they express. Experimental Approach: RNA sequencing and single cell qRT‐PCR were performed on mouse kidneys after unilateral ureteral obstruction (UUO). Candidate expression was evaluated in mice with UUO or diabetes or injected with adriamycin or folic acid. Intervention studies were conducted in mice with diabetes or UUO. Correlative histology was performed in human kidney tissue. Key Results: Transcription factor 21 (Tcf21)+ cells that expressed 2 or 3 of Postn, Acta2 and Pdgfra were highly enriched for fibrogenic genes and were defined as activated kidney fibroblasts. Tcf21+ α‐smooth muscle actin (α‐SMA)+ interstitial cells accumulated in kidneys of mice with UUO or diabetes or injected with adriamycin or folic acid, whereas renin‐angiotensin system blockade attenuated increases in Tcf21 in diabetic mice. Fifty‐six GPCRs were up‐regulated in single Tcf21+ kidney fibroblasts, the most up‐regulated being Adgra2 and S1pr3. Adenosine receptors, Adora2a/2b, were up‐regulated in Tcf21+ fibroblasts and the adenosine receptor antagonist, caffeine decreased Tcf21 upregulation and kidney fibrosis in UUO mice. TCF21, ADGRA2, S1PR3 and ADORA2A/2B were each detectable in α‐SMA+ interstitial cells in human kidney samples. Conclusion and Implications: Tcf21 is a marker of kidney fibroblasts that are enriched for fibrogenic genes in CKD. Further analysis of the GPCRs expressed by these cells may identify new targets for treating CKD. LINKED ARTICLES: This article is part of a themed issue on Translational Advances in Fibrosis as a Therapeutic Target. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.22/issuetoc [ABSTRACT FROM AUTHOR]

The feasibility of measuring the surface potential decay of polystyrene (PS) film is investigated at room temperature by using Kelvin probe force microscopy (KPFM). The PS film was charged by an ion injection method utilizing Bruker's atomic force microscope (AFM) Nanoman module with a pulse duration of 1 ms, SCM‐PIT electrically conductive probe, and a voltage pulse of −250 mV. The surface potential decayed linearly on a semi‐log scale with time, where the time decay constant was quantified for relative humidity (RH) = 5% by KPFM at room temperature. The surface potential decayed due to the interaction of the PS film with the hydronium ions available in the environment. Furthermore, the effect of the material forms (film vs. microspheres) on the time decay constant at RH = 5% was investigated. The time decay constants measured using different methods exhibited excellent correlation with the AFM‐KPFM. This also confirmed that the results are independent of the material form (microspheres vs. film form). As a result, the proposed method can be used to measure the effect of RH for any PS surface (i.e., particles of various sizes and films) exposed to these environmental conditions. [ABSTRACT FROM AUTHOR]

DNA methylation provides a crucial epigenetic mark linking genetic variations to environmental influence. We have analyzed array-based DNA methylation profiles of 160 human retinas with co-measured RNA-seq and >8 million genetic variants, uncovering sites of genetic regulation in cis (37,453 methylation quantitative trait loci and 12,505 expression quantitative trait loci) and 13,747 DNA methylation loci affecting gene expression, with over one-third specific to the retina. Methylation and expression quantitative trait loci show non-random distribution and enrichment of biological processes related to synapse, mitochondria, and catabolism. Summary data-based Mendelian randomization and colocalization analyses identify 87 target genes where methylation and gene-expression changes likely mediate the genotype effect on age-related macular degeneration. Integrated pathway analysis reveals epigenetic regulation of immune response and metabolism including the glutathione pathway and glycolysis. Our study thus defines key roles of genetic variations driving methylation changes, prioritizes epigenetic control of gene expression, and suggests frameworks for regulation of macular degeneration pathology by genotype–environment interaction in retina. Here, the authors perform genome-wide mapping of DNA methylation and expression quantitative trait loci, revealing associations among genotype, epigenome and transcriptome, uncovering genes and gene-environment interactions contributing to age-related macular degeneration (AMD). [ABSTRACT FROM AUTHOR]

Objectives: Tonsillectomy is the most common operation performed by otolaryngologists in the UK, despite this we have a poor understanding of the post‐operative recovery. We aimed to investigate post‐operative bleeding and pain following paediatric tonsillectomy using a patient diary. Design: Prospective observational cohort study. Setting: Multi‐centre study involving 12 secondary and tertiary otolaryngology units across the North of England. Patients were recruited from 1st March 2020 to 30th June 2022. Multilevel ordered logistic regression model statistics were performed. Participants: Children (≥4 years, ≤16 years) undergoing tonsillectomy (with or without adenoidectomy) for benign pathology. Main Outcome Measures: Frequency and severity of post‐operative bleeding.Intensity and pattern of post‐operative pain. Results: In total 297 children were recruited, with 91 (30.6%) diaries eligible for analysis. Post‐operative bleeding occurred in 44% of children. Most frequently blood in the saliva was reported (82.9%). Increasing age significantly increased bleeding odds by 17% per year (p =.001). Bleeding frequency decreased with higher surgeon grade (p =.003) and when performing intracapsular coblation tonsillectomy (p =.02) compared with other techniques. Lower age and intracapsular coblation tonsillectomy, against other techniques, significantly reduced rates of pain post‐operatively (p <.0001 and p =.0008). Conclusion: A high level of low‐level post‐operative bleeding was observed. Pain scores remained high for 5 days post‐operatively then gradually reduce to normal by day 13. Intracapsular coblation tonsillectomy appears to be superior to all other techniques in terms of reducing post‐operative bleeding and pain. These findings should be used to guide patients in the consent process to inform them of the expected nature of post‐surgical recovery. [ABSTRACT FROM AUTHOR]

Wastewater surveillance of coronavirus disease 2019 (COVID-19) commonly applies reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to quantify severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA concentrations in wastewater over time. In most applications worldwide, maximal sensitivity and specificity of RT-qPCR has been achieved, in part, by monitoring two or more genomic loci of SARS-CoV-2. In Ontario, Canada, the provincial Wastewater Surveillance Initiative reports the average copies of the CDC N1 and N2 loci normalized to the fecal biomarker pepper mild mottle virus. In November 2021, the emergence of the Omicron variant of concern, harboring a C28311T mutation within the CDC N1 probe region, challenged the accuracy of the consensus between the RT-qPCR measurements of the N1 and N2 loci of SARS-CoV-2. In this study, we developed and applied a novel real-time dual loci quality assurance and control framework based on the relative difference between the loci measurements to the City of Ottawa dataset to identify a loss of sensitivity of the N1 assay in the period from July 10, 2022 to January 31, 2023. Further analysis via sequencing and allele-specific RT-qPCR revealed a high proportion of mutations C28312T and A28330G during the study period, both in the City of Ottawa and across the province. It is hypothesized that nucleotide mutations in the probe region, especially A28330G, led to inefficient annealing, resulting in reduction in sensitivity and accuracy of the N1 assay. This study highlights the importance of implementing quality assurance and control criteria to continually evaluate, in near real-time, the accuracy of the signal produced in wastewater surveillance applications that rely on detection of pathogens whose genomes undergo high rates of mutation. [ABSTRACT FROM AUTHOR]

The aim of this study is to assess the potential of Spherical Cap Studs (SCS) as a substitute for conventional speed bumps, with a focus on limiting two wheeler speed while minimizing discomfort to riders by comparing the speed reduction capabilities and discomfort levels associated with SCS and speed bumps. The study uses experimental approach to compare the speed limiting ability and discomfort caused to rider by the proposed SCS and a standard speed bump. Speed profiles were developed for two wheelers passing over both SCS and speed bump. The parameter employed to compare speed profiles is the Mean Absolute Percentage Difference (MAPD), offering valuable insights into how effectively the two traffic calming measures reduce two wheeler speeds. To compare discomfort, the study calculates the 'Vibration Dose Value' (VDV) experienced by riders when traversing both speed bump and SCS. Additionally, 'Static Compressive Stress' (Se) applied to the spinal cord is also calculated in both scenarios. The analysis of speed profiles reveals an MAPD value of 13.70% indicating that SCS exhibits speed reduction capabilities comparable to traditional speed bump. In terms of discomfort, the VDV for two wheelers passing over a speed bump is measured at 5.92 m/s1.75, whereas the VDV for SCS is found to be 5.16 m/s1.75. Similarly, the Static Compressive Stress (Se) experienced at a speed bump is 0.60 MPa, in contrast to the 0.33 MPa recorded for SCS. This data underscores a noteworthy 12.8% reduction in VDV and a substantial 45.57% reduction in Se. The study's findings support the potential adoption of SCS as an effective alternative to conventional speed bumps for controlling two wheeler speeds. SCS demonstrate a speed reduction capability similar to that of traditional speed bumps while significantly alleviating discomfort for riders. SCS is expected to be a promising solution for traffic calming purposes in various settings, such as markets, residential areas, institutional campuses, and parking lots. [ABSTRACT FROM AUTHOR]

Background: Sodium glucose linked transporter 2 (SGLT2) inhibition not only reduces morbidity and mortality in patients with diagnosed heart failure but also prevents the development of heart failure hospitalization in those at risk. While studies to date have focused on the role of SGLT2 inhibition in left ventricular failure, whether this drug class is efficacious in the treatment and prevention of right heart failure has not been explored. Hypothesis: We hypothesized that SGLT2 inhibition would reduce the structural, functional, and molecular responses to pressure overload of the right ventricle. Methods: Thirteen-week-old Fischer F344 rats underwent pulmonary artery banding (PAB) or sham surgery prior to being randomized to receive either the SGLT2 inhibitor: dapagliflozin (0.5 mg/kg/day) or vehicle by oral gavage. After 6 weeks of treatment, animals underwent transthoracic echocardiography and invasive hemodynamic studies. Animals were then terminated, and their hearts harvested for structural and molecular analyses. Results: PAB induced features consistent with a compensatory response to increased right ventricular (RV) afterload with elevated mass, end systolic pressure, collagen content, and alteration in calcium handling protein expression (all p < 0.05 when compared to sham + vehicle). Dapagliflozin reduced RV mass, including both wet and dry weight as well as normalizing the protein expression of SERCA 2A, phospho-AMPK and LC3I/II ratio expression (all p < 0.05). Significance: Dapagliflozin reduces the structural, functional, and molecular manifestations of right ventricular pressure overload. Whether amelioration of these early changes in the RV may ultimately lead to a reduction in RV failure remains to be determined. [ABSTRACT FROM AUTHOR]

BACKGROUND: Maintenance therapy for acute lymphoblastic leukemia (ALL) in young adults Includes a backbone of daily oral 6-mercaptopurine (6-MP) and weekly oral methotrexate (MTX). Oral 6-MP and MTX are associated with large interpersonal variations in drug bioavailability and tolerability and frequently cause adverse events. National Comprehensive Cancer Network guidelines recommend following dose modifications per the chosen treatment regimen, but data regarding the tolerability of oral chemotherapy and frequency of dose modifications during the maintenance phase in adults are lacking. OBJECTIVES: To describe real-world dose adjustments of MTX and 6-MP during the maintenance therapy in young adults, to describe the adverse events related to treatment with 6-MP and MTX, and to assess the incidence of relapse. METHODS: This was a single-center, retrospective, descriptive study of young adults with ALL. We reviewed the medical records of all patients aged 18 to 39 years who were initiated on standard-of-care treatment with CALGB 10403 (C10403) between January 1, 2015, and January 1, 2020, and received maintenance therapy. RESULTS: A total of 12 of the 13 included patients had adverse events requiring a dose adjustment. Overall, there were 130 dose adjustments. Dose interruptions most frequently resulted from grade >2 hepatotoxicity or grade >3 neutropenia. The agents were restarted at lower doses in approximately 50% of the cases, including 8 cases after the first episode of hematologic adverse events or hepatotoxicity. Dose escalations primarily occurred after previous interruption and resumption at a lower dose as a result of adverse events and were well tolerated, with a median of 15% increase per escalation. Of the 13 patients, 4 had disease relapse, 3 of which occurred during maintenance therapy. CONCLUSION: Adverse events leading to dose adjustments were common in the young adults with ALL who received maintenance treatment at our institution, but treatment modifications varied from recommendations in C10403, highlighting the challenges with tolerability and patient and physician protocol compliance in young adults. Additional studies that optimize monitoring, dose modifications, and maintenance dose intensity in adolescents and young adults are warranted. [ABSTRACT FROM AUTHOR]

Primary open-angle glaucoma (POAG), characterized by retinal ganglion cell death, is a leading cause of irreversible blindness worldwide. However, its molecular and cellular causes are not well understood. Elevated intraocular pressure (IOP) is a major risk factor, but many patients have normal IOP. Colocalization and Mendelian randomization analysis of >240 POAG and IOP genome-wide association study (GWAS) loci and overlapping expression and splicing quantitative trait loci (e/sQTLs) in 49 GTEx tissues and retina prioritizes causal genes for 60% of loci. These genes are enriched in pathways implicated in extracellular matrix organization, cell adhesion, and vascular development. Analysis of single-nucleus RNA-seq of glaucoma-relevant eye tissues reveals that the POAG and IOP colocalizing genes and genome-wide associations are enriched in specific cell types in the aqueous outflow pathways, retina, optic nerve head, peripapillary sclera, and choroid. This study nominates IOP-dependent and independent regulatory mechanisms, genes, and cell types that may contribute to POAG pathogenesis. The molecular and cellular causes of glaucoma are not well understood. Here, the authors integrate GWAS with genetic regulation and single cell expression from multiple eye tissues to identify genes and key cell types that affect glaucoma pathogenesis. [ABSTRACT FROM AUTHOR]

A model along with experimental validation is presented for fiber re-orientation within the flow of a thin fluid layer down an inclined plane. Unlike the usual approach (Jeffery), the model accommodates the fast-changing velocity gradient defying linearization and the flow constraints due to the thin thickness of the fluid film. Model equations are formulated, and the algorithm for the fiber rotation is developed. The velocity field within the channel is obtained, using COMSOLTM multiphase simulation. The formulated model equations are used to track the orientation of a single fiber. The spatial fiber orientation state is described in terms of the second order tensor by tracking multiple individual fibers with different initial orientations. To validate the model's predictions, an experimental setup was fabricated to record individual fiber kinematics during the flow and to describe the orientation of fibers in the open channel. A novel benchmark for assessing fiber re-orientation models is presented, wherein the dynamics of fiber orientation is observed in response to a semicircular obstacle within the fluid flow. The experimental results are compared to model predictions and are in reasonable agreement. Despite the simplified approach, both the dynamic of single fiber and the development of fiber orientation distribution due to the obstacle can be reasonably predicted. [ABSTRACT FROM AUTHOR]

The chemical durability of perfluorosulfonic acid (PFSA) membranes is a topic of growing interest to meet Department of Energy (DOE) durability targets for heavy‐duty vehicle (HDV) applications. State‐of‐the‐art membranes like Nafion, rely on the use of cerium, heteropolyacids, and other inorganic additives to increase PFSA chemical durability. A less explored avenue for the oxidative stabilization of PFSA and hydrocarbon membranes is the use of organic antioxidants. No reversible organic antioxidant has been demonstrated to date which can enhance membrane lifetime by factors comparable to cerium. Here, ellagic acid (EA) is demonstrated as a promising radical scavenger for PFSA's. It is found that the incorporation of EA enhances the chemical durability of Nafion by 160%. EA, when incorporated with cerium as an electron donorenhances Nafion durability by at least 80% compared to a membrane incorporated with just cerium in DOE‐defined durability tests. EA is found to be reversible in acidic conditions like those of fuel cells and its reversibility could be further enhanced by the use of suitable co‐antioxidants. [ABSTRACT FROM AUTHOR]

Background: Patients with mantle cell lymphoma (MCL) exhibit a wide variation in clinical presentation and outcome. However, the commonly used prognostic models are outdated and inadequate to address the needs of the current multidisciplinary management of this disease. This study aims to investigate the clinical and pathological features of MCL in the immunochemotherapy era and improve the prognostic models for a more accurate prediction of patient outcomes. Methods: The North American Mantle Cell Lymphoma Project is a multi-institutional collaboration of 23 institutions across North America to evaluate and refine prognosticators for front-line therapy. A total of 586 MCL cases diagnosed between 2000 and 2012 are included in this study. A comprehensive retrospective analysis was performed on the clinicopathological features, treatment approaches, and outcomes of these cases. The establishment of novel prognostic models was based on in-depth examination of baseline parameters, and subsequent validation in an independent cohort of MCL cases. Results: In front-line strategies, the use of hematopoietic stem cell transplantation was the most significant parameter affecting outcomes, for both overall survival (OS, p < 0.0001) and progression-free survival (PFS, p < 0.0001). P53 positive expression was the most significant pathological parameter correlating with inferior outcomes (p < 0.0001 for OS and p = 0.0021 for PFS). Based on the baseline risk factor profile, we developed a set of prognostic models incorporating clinical, laboratory, and pathological parameters that are specifically tailored for various applications. These models, when tested in the validation cohort, exhibited strong predictive power for survival and showed a stratification resembling the training cohort. Conclusions: The outcome of patients with MCL has markedly improved over the past two decades, and further enhancement is anticipated with the evolution of clinical management. The innovative prognostic models developed in this study would serve as a valuable tool to guide the selection of more suitable treatment strategies for patients with MCL. [ABSTRACT FROM AUTHOR]

During period of the ongoing COVID-19 pandemic, the unexpected outbreak and worldwide spread of monkeypox has gained global attention. Monkeypox is a viral zoonotic disease caused by MPXV, which is an enveloped, linear, double-stranded DNA virus belonging to the Orthopoxvirus genus, of the Chordopoxvirinaesubfamily, within the Poxviridaefamily. Monkeypox virus (MPXV) is transmitted from human-to-human through direct contact with infectious skin or mucosal skin lesions, respiratory droplets, or indirect contact with contaminated objects or materials, as well as mother-to-child vertical transmission. It is also possibly sexually transmitted through semen/vaginal fluid, and the possibility of community transmission cannot be ruled out. The typical presentation of monkeypox includes prodromal symptoms, followed by a rash that usually begins within13 days of symptom onset, and the skin lesions can last for 24 weeks and then gradually resolve. A definite diagnosis of monkeypox virus infection requires nucleic acid amplification testing via the polymerase chain reaction method. Supportive care is essential along with treatment of complications affecting multiple organs of the body. [ABSTRACT FROM AUTHOR]

Polybenzoxazine thermoset resins exhibit significant potential as precursors for carbon–carbon composites, owing to their high char yield upon pyrolysis. During pyrolysis, the resin is converted to an amorphous carbon‐rich material through a series of mechanisms, resulting in a linear increase of the glass transition temperature (TG) from 133 to 396°C at 0.48 pyrolytic conversion. To better understand this relationship, a non‐isothermal kinetic model was integrated, enabling the prediction of the TG onset, inflection, and endpoint based on the heat treatment protocol (process temperature (TP) vs. time) and the total volume of pyrolytic gases generated. By considering the TG behavior and anticipated gas effects, three distinct mechanisms were identified: (1) gas accumulation and matrix expansion leading to increased sample thickness (TG < TP), (2) crack network formation caused by gas‐pressure‐induced brittle failure (TG > TP), and (3) sample thickness reduction due to gas venting through the crack network (TG < TP). To validate this theory, thermal mechanical analysis was performed during pyrolysis, and changes in thickness (±ΔL/L0) were attributed to gas pressure‐related matrix deformation. Conversely, no change in ΔL/L0 indicated the formation of an interconnected crack network through which gases could vent without building a measurable internal pressure. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases (NDDs) and neuropsychiatric disorders (NPDs) are two common causes of death in elderly people, which includes progressive neuronal cell death and behavioral changes. NDDs include Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, and motor neuron disease, characterized by cognitive defects and memory impairment, whereas NPDs include depression, seizures, migraine headaches, eating disorders, addictions, palsies, major depressive disorders, anxiety, and schizophrenia, characterized by behavioral changes. Mounting evidence demonstrated that NDDs and NPDs share an overlapping mechanism, which includes post-translational modifications, the microbiota–gut–brain axis, and signaling events. Mounting evidence demonstrated that various drug molecules, namely, natural compounds, repurposed drugs, multitarget directed ligands, and RNAs, have been potentially implemented as therapeutic agents against NDDs and NPDs. Herein, we highlighted the overlapping mechanism, the role of anxiety/stress-releasing factors, cytosol-to-nucleus signaling, and the microbiota–gut–brain axis in the pathophysiology of NDDs and NPDs. We summarize the therapeutic application of natural compounds, repurposed drugs, and multitarget-directed ligands as therapeutic agents. Lastly, we briefly described the application of RNA interferences as therapeutic agents in the pathogenesis of NDDs and NPDs. Neurodegenerative diseases and neuropsychiatric diseases both share a common signaling molecule and molecular phenomenon, namely, pro-inflammatory cytokines, γCaMKII and MAPK/ERK, chemokine receptors, BBB permeability, and the gut–microbiota–brain axis. Studies have demonstrated that any alterations in the signaling mentioned above molecules and molecular phenomena lead to the pathophysiology of neurodegenerative diseases, namely, Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, and neuropsychiatric disorders, such as bipolar disorder, schizophrenia, depression, anxiety, autism spectrum disorder, and post-traumatic stress disorder. [ABSTRACT FROM AUTHOR]

The transformation of abundantly available bioresources into specialty chemicals, particularly as consumer products, remains an important pursuit in chemical research. In this sense, the valorization of bio‐oil strategies that utilize stable and easy‐to‐handle chemical entity not only creates application‐oriented products but also helps in avoiding the usage of toxic and hazardous chemical sources. Recently, the valorization of α‐pinene (readily/naturally available terpenic compounds) has been explored to prepare a wide range of processes to access perfumery products and remains fast‐growing research for industrial and societal applications. Considering the valorization of α‐pinene, challenges for the synthetic and selective preparation of perfumery chemicals are centered around the design of the catalyst and the setting up of the precise reaction conditions. Extensive research is employed using diverse catalytic approaches to utilize α‐pinene to prepare important perfumery intermediates. In this review, the state‐of‐the‐art, recent advances and challenges in the utilization of α‐pinene are reviewed, emphasizing two main products, i.e., α‐campholenic aldehyde and carveol via α‐pinene oxide isomerization, and discussed the pertinent role of various homogeneous and heterogeneous catalytic systems. [ABSTRACT FROM AUTHOR]

Autoclave consolidation is used to manufacture continuous fiber composites in applications that have strict part porosity requirements. The applied positive pressure in this process is attractive for reduction in part porosity. However, some part geometries can cause porosity issues even under positive pressure. One is the concave corner seen in an L-bracket geometry. Higher porosity is seen in areas of high curvature, hindering part quality. Since the autoclave process takes several hours and prepreg material is expensive, trial-and-error methods of resolving issues are not practical. In this work, a unique physics-based viscoelastic model is proposed to describe the mechanical behavior of uncured continuous fiber thermoset prepreg undergoing consolidation under hydrostatic pressure. This model considers stress due to compaction of the fiber network, compression of voids in the resin, and viscous stress from resin flow relative to fibers. The constitutive expressions for these are coupled to important mechanisms that occur during autoclave consolidation. The viscoelastic model is incorporated into the finite element analysis software ABAQUS/Standard using a UMAT subroutine. Numerical results are validated by analytic solutions and experimental comparison for flat and L-bracket geometries. A parametric study identifies important process and material parameters that influence the quality of the manufactured part. [ABSTRACT FROM AUTHOR]

Background: Blalock-Taussig (BT) is a palliative procedure that preserves blood circulation to the lungs and alleviates cyanosis in patients with congenital heart diseases and reduced pulmonary blood flow. BT shunt remains a routinely performed procedure in developing countries before definitive surgery. However, evidence on predictor factors of mortality after this procedure is still scarce in Indonesia. This study evaluated the predictive factors of mortality after the BT shunt procedure.Methods: This retrospective study evaluated the medical record data of all postoperative BT shunt patients at Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia, from 2016 to 2020. We performed univariate and multivariate analyses to identify the predictors of in-hospital mortality.Results: The total subjects in this study were 197 children, 107 (54.3%) boys and 90 (45.7%) girls. The median values for age and body weight at the time of surgery were 20 months (11 days – 32 years) and 7.9 (2.7– 42) kg. The most prevalent diagnosis was the Tetralogy of Fallot, found in 80 (40.6%) patients. In-hospital postoperative mortality was 20.8% (41 patients). Based on multivariate analysis, predictors associated with mortality were weight < 4.25 kg (OR 20.9; 95% CI 7.4– 59.0; p < 0.0001) and emergency procedures (OR 3.5; 95% CI 1.3– 9.5; p = 0.016).Conclusion: The mortality rate after BT shunt at PJT Rumah Sakit Cipto Mangunkusumo was 20.8%. Based on multivariate analysis, weight < 4.25 kg and emergency procedures are two predictors of mortality in BT shunt. [ABSTRACT FROM AUTHOR]

Featured Application: Predict race-tracking strength in an RTM process using minimal pressure sensor measurements and position the sensors optimally throughout the preform in order to do so. A Bayesian inference formulation is applied to the Resin Transfer Moulding process to estimate bulk permeability and race-tracking effects using measured values of pressure at discrete sensor locations throughout a preform. The algorithm quantifies uncertainty in both the permeability and race-tracking effects, which decreases when more sensors are used or the preform geometry is less complex. We show that this approach becomes less reliable with a smaller resin exit vent. Numerical experiments show that the formulation can accurately predict race-tracking effects with few measurements. A Bayesian A-optimality formulation is used to develop a method for producing optimal sensor locations that reduce the uncertainty in the permeability and race-tracking estimates the most. This method is applied to two numerical examples which show that optimal designs reduce uncertainty by up to an order of magnitude compared to a random design. [ABSTRACT FROM AUTHOR]

Structural composites supercapacitors are manufactured by converting commercial carbon fabrics into electrodes by applying a surface treatment without changing their sizing chemistry, integrating electrolytes with single and hybrid material components in the forms of solution, gel, and film, with glass fabrics as a separator to prevent short-circuit in the system. Carbon fabrics are treated by applying stepwise dip-coating method including graphene oxide (GO) coating, Fe2O3 treatment and reduction steps in aqueous medium. Four configured supercapacitors are tested by changing electrodes and electrolytes. Supercapacitor with reduced GO (rGO) and rGO-Fe2O3 coated carbon fabric electrodes with mesoporous PVA-KOH film electrolyte in the laminated structure covered by insulator films demonstrates 46% charge retention at 1 V after 30 s, 21 Ω charge transfer resistance, 120 mWh/kg energy density, 3.12 W/kg power density, and 0.35 mF/g specific capacitance. Electrolytes in gel and solution forms do not display any capacitance behavior in cyclic voltammetry analysis and exhibit lower energy densities compared to the film electrolyte. PVA-KOH film electrolyte provides a synergistic effect with resized commercial grade carbon fabric electrodes through its homogenous impregnation on electrode surfaces which is responsible for the enhancement of charge-storage behavior of the fabricated structural supercapacitors. [ABSTRACT FROM AUTHOR]

Background Older patients with myelodysplastic syndromes (MDS), particularly those with no or one cytopenia and no transfusion dependence, typically have an indolent course. Approximately, half of these receive the recommended diagnostic evaluation (DE) for MDS. We explored factors determining DE in these patients and its impact on subsequent treatment and outcomes. Patients and Methods We used 2011-2014 Medicare data to identify patients ≥66 years of age diagnosed with MDS. We used Classification and Regression Tree (CART) analysis to identify combinations of factors associated with DE and its impact on subsequent treatment. Variables examined included demographics, comorbidities, nursing home status, and investigative procedures performed. We conducted a logistic regression analysis to identify correlates associated with receipt of DE and treatment. Results Of 16 851 patients with MDS, 51% underwent DE. patients with MDS with no cytopenia (n = 3908) had the lowest uptake of DE (34.7%). Compared to patients with no cytopenia, those with any cytopenia had nearly 3 times higher odds of receiving DE [adjusted odds ratio (AOR), 2.81: 95% CI, 2.60-3.04] and the odds were higher for men than for women [AOR, 1.39: 95%CI, 1.30-1.48] and for Non-Hispanic Whites [vs. everyone else (AOR, 1.17: 95% CI, 1.06-1.29)]. The CART showed DE as the principal discriminating node, followed by the presence of any cytopenia for receiving MDS treatment. The lowest percentage of treatment was observed in patients without DE, at 14.6%. Conclusion In this select older patients with MDS, we identified disparities in accurate diagnosis by demographic and clinical factors. Receipt of DE influenced subsequent treatment but not survival. [ABSTRACT FROM AUTHOR]

Background: Glycaemic control of Type 1 Diabetes Mellitus (T1DM) remains a challenge due to hypoglycaemic episodes and the burden of insulin self-management. Advancements have been made with the development of automated insulin delivery (AID) devices, yet, previous reviews have only assessed the use of AID over days or weeks, and potential benefits with longer time of AID use in this population remain unclear. Methods: We performed a systematic review and meta-analysis of randomised controlled trials comparing AID (hybrid and fully closed-loop systems) to usual care (sensor augmented pumps, multiple daily insulin injections, continuous glucose monitoring and predictive low-glucose suspend) for adults and children with T1DM with a minimum duration of 3 months. We searched PubMed, Embase, Cochrane Central, and Clinicaltrials.gov for studies published up until April 4, 2023. Main outcomes included time in range 70–180 mg/dL as the primary outcome, and change in HbA1c (%, mmol/mol), glucose variability, and psychosocial impact (diabetes distress, treatment satisfaction and fear of hypoglycaemia) as secondary outcomes. Adverse events included diabetic ketoacidosis (DKA) and severe hypoglycaemia. Statistical analyses were conducted using mean differences and odds ratios. Sensitivity analyses were performed according to age, study duration and type of AID device. The protocol was registered in PROSPERO, CRD42022366710. Results: We identified 25 comparisons from 22 studies (six crossover and 16 parallel designs) including a total of 2376 participants (721 in adult studies, 621 in paediatric studies, and 1034 in combined studies) which were eligible for analysis. Use of AID devices ranged from 12 to 96 weeks. Patients using AID had 10.87% higher time in range [95% CI 9.38 to 12.37; p < 0.0001, I2 = 87%) and 0.37% (4.77 mmol/mol) lower HbA1c (95% CI − 0.49% (− 6.39 mmol/mol) to – 0.26 (− 3.14 mmol/mol); p < 0·0001, I2 = 77%]. AID systems decreased night hypoglycaemia, time in hypoglycaemia and hyperglycaemia and improved patient distress, with no increase in the risk of DKA or severe hypoglycaemia. No difference was found regarding treatment satisfaction or fear of hypoglycaemia. Among children, there was no difference in glucose variability or time spent in hypoglycaemia between the use of AID systems or usual care. In sensitivity analyses, results remained consistent with the overall analysis favouring AID. Conclusion: The use of AID systems over 12 weeks, regardless of technical or clinical differences, improved glycaemic outcomes and diabetes distress without increasing the risk of adverse events in adults and children with T1DM. [ABSTRACT FROM AUTHOR]

Using anonymized administrative data on the population of UK taxpayers, we show that—in line with high-profile anecdotes about the tax affairs of the rich—effective average tax rates (EATRs) decline at the top of the distribution of income and capital gains. We also document substantial variation in EATRs within remuneration level: a quarter of those in the top 1 per cent pay headline rates, while another quarter pay at least 9pp less than the headline rate. Most of this effect is driven by the composition of remuneration, with investment income having lower tax rates and capital gains having lower rates still. If all individuals with income above £100,000 paid the headline rates, this would raise tax revenue on income and gains by £23 billion on a static basis, an increase of 27 per cent in the tax paid by this group. [ABSTRACT FROM AUTHOR]

Background and Aim: Each team discipline presents a specific physiological and anthropometric profile because of some particular needs and functions. The primary aim of the study was to analyze the vertical jump power (squat jump, countermovement jump, and countermovement jump with arm swing), Closed Kinetic Chain Upper Extremity Stability test (CKCUES test), throwing ball velocity, and handgrip strength among volleyball, basketball, and handball players, and the secondary aim was to find out the correlation of handgrip strength with all these parameters. Materials and Methods: This was a cross-sectional study where 75 university male volleyball (Group A, n = 25), basketball (Group B, n = 25), and handball (Group C, n = 25) players participated. Throwing ball velocity was measured with SRA3000 Radar Gun, vertical jump power was assessed by force platform (Kinematic Measurement System), and handgrip strength was measured by using a digital handheld dynamometer (CAMRY EH101). Results: By using SPSS version 21, one-way analysis of variance and Pearson correlation were found. Group A showed significantly higher scores in handgrip strength, vertical jump power, and CKCUES test as compared to Group B and Group C. Handgrip strength showed a positive correlation with throwing ball velocity, vertical jump power, and CKCUES test (P < 0.05). Conclusion: Significant differences in fitness and strength parameters were found among all the groups, and there was a positive correlation of handgrip with upper- and lower-limb strength. These findings will empower the coaches for objective selection of players on the basis of strength and fitness baselines as well as better understanding of injury risks. [ABSTRACT FROM AUTHOR]

Andrea Wright's book, "Between Dreams and Ghosts: Indian Migration and Middle Eastern Oil," challenges common narratives about Indian migrant labor in the Persian Gulf. The book explores the complex factors that contribute to the exploitative conditions faced by these workers, including the kafala system, Gulf political culture, labor surpluses in India, and the history of oil companies. Wright's research includes extensive fieldwork and interviews with workers, their families, recruiting agents, and managers. The book also examines the role of gold in Indian kinship relations and the layers of subcontracting firms used by oil companies. While the book could further explore the relationship between colonial and postcolonial practices, it provides valuable insights into the experiences of Indian migrant workers in the Gulf. [Extracted from the article]

Introduction: Medical colleges globally have student organizations that serve to enable students' involvement in research. However, details of their approach and activities are seldom published to serve as learning for student organizations in other settings. The Student Research Forum (SRF), a student organization based at a private medical school in Pakistan aims to facilitate students in acquiring research skills. Following the observation of a downward trajectory of student initiative and interest, SRF leadership restructured the organization and improve its impact. This study describes the development and implementation evaluation of the interventions. Methodology: The operational framework was revised using the Theory of Change by the core group. Major interventions included enhanced social media and outreach coordination, research workshops, journal clubs, and mentorship to increase research output, mentorship opportunities, and knowledge of medical research; ultimately improving quality in research. The outcomes generated over the course of the study's duration from July 2019 to September 2021 were analyzed using the process metrics of reach, adoption, and efficacy. Results: As a result of the interventions, SRF expanded its reach by conducting a total of 41 events during the duration of the study, facilitated by social media growth on each of SRF's online platforms, with a 300% increase in followers on Facebook, and a nationwide network of 91 student ambassadors. An annual workshop series taught research skills to more than 3800 participants. Students leading their own events, SRF featuring international speakers, and the abstracts submitted to SRF's annual conference, along with the conference's reach of 10,000 students, are seen as improvements in the ToC-informed interventions' adoption. The efficacy of the interventions manifested as the REACH program allocated 56 research projects to vetted applicants. Conclusion: The applied interventions have accelerated SRF's progress towards achieving its long-term outcome of increased quality in research as translated by increased research output quantity, mentorship, and knowledge of medical research. Further evaluation is required to assess the success of the ToC. As SRF continues to grow, a continued analysis of the implementation outcomes is imperative to gauge its effectiveness. [ABSTRACT FROM AUTHOR]

Summary: There remains no one standard induction for nodal‐based peripheral T‐cell lymphoma (PTCL). We conducted a phase II study of lenalidomide plus CHOEP as a novel induction strategy. Patients received CHOEP at standard doses in combination with 10 mg of lenalidomide on days 1–10 of a 21‐day cycle for six cycles of therapy followed by observation, high‐dose therapy with autologous stem cell rescue, or maintenance lenalidomide per provider preference. Among 39 patients evaluable for efficacy, the objective response rate after six cycles was 69%, with complete response in 49%, partial response in 21%, stable disease in 0% and progressive disease in 13%. Thirty‐two patients (82%) completed full induction, and seven patients (18%) discontinued for toxicity, primarily hematologic. Any grade hematologic toxicity occurred in over 50% of patients, with grade 3 or 4 febrile neutropenia occurring in 35% of patients despite mandated growth factors. With a median followup of surviving patients of 21.3 months, the estimated 2‐year progression‐free and overall survival were 55% (95% CI 37%–70%) and 78% (95% CI 59%–89%), respectively. In sum, six cycles of lenalidomide plus CHOEP resulted in a modest response rate primarily due to hematologic toxicity, which prevented all patients from completing planned induction. [ABSTRACT FROM AUTHOR]

In this study, we sought to determine the role of tRNA‐derived fragments in the regulation of gene expression during skeletal muscle cell proliferation and differentiation. We employed cell culture to examine the function of mt‐Ty 5' tiRNAs. Northern blotting, RT‐PCR as well as RNA‐Seq, were performed to determine the effects of mt‐Ty 5' tiRNA loss and gain on gene expression. Standard and transmission electron microscopy (TEM) were used to characterize cell and sub‐cellular structures. mt‐Ty 5'tiRNAs were found to be enriched in mouse skeletal muscle, showing increased levels in later developmental stages. Gapmer‐mediated inhibition of tiRNAs in skeletal muscle C2C12 myoblasts resulted in decreased cell proliferation and myogenic differentiation; consistent with this observation, RNA‐Seq, transcriptome analyses, and RT‐PCR revealed that skeletal muscle cell differentiation and cell proliferation pathways were also downregulated. Conversely, overexpression of mt‐Ty 5'tiRNAs in C2C12 cells led to a reversal of these transcriptional trends. These data reveal that mt‐Ty 5'tiRNAs are enriched in skeletal muscle and play an important role in myoblast proliferation and differentiation. Our study also highlights the potential for the development of tiRNAs as novel therapeutic targets for muscle‐related diseases. [ABSTRACT FROM AUTHOR]

Optimizing the pharmacokinetics (PK) of a drug candidate to support oral dosing is a key challenge in drug development. PK parameters are usually estimated from the concentration–time profile following intravenous administration; however, traditional methods are time-consuming and expensive. In recent years, quantitative structure–pharmacokinetic relationship (QSPKR), an in silico tool that aims to develop a mathematical relationship between the structure of a molecule and its PK properties, has emerged as a useful alternative to experimental testing. Due to the complex nature of the various processes involved in dictating the fate of a drug, the development of adequate QSPKR models that can be used in real-world pre-screening situations has proved challenging. Given the crucial role played by a molecule's ionization state in determining its PK properties, this work aims to build predictive QSPKR models for PK parameters in humans using an ionization state-based strategy. We divide a high-quality dataset into clusters based on ionization state at physiological pH and build global and ion subset-based 'local' models for three major PK parameters: plasma clearance (CL), steady-state volume of distribution (VDss), and half-life (t1/2). We use a robust methodology developed in our lab entitled 'EigenValue ANalySis' that accounts for the stereospecificity in drug disposition and use the support vector machine algorithm for model building. Our findings suggest that categorizing compounds in accordance with ionization state does not result in improved QSPKR models. The narrow ranges in the endpoints along with redundancies in the data adversely affect the ion subset-based QSPKR models. We suggest alternative approaches such as elimination route-based models that account for drug–transporter interactions for CL and chemotype-specific QSPKR for VDss. [ABSTRACT FROM AUTHOR]

Chloride is a vital ion for all forms of life. Protein-based fluorescent biosensors can enable researchers to visualize chloride in cells but remain underdeveloped. Here, we demonstrate how a single point mutation in an engineered microbial rhodopsin results in ChloRED-1-CFP. This membrane-bound host is a far-red emitting, ratiometric sensor that provides a reversible readout of chloride in live bacteria at physiological pH, setting the stage to investigate the roles of chloride in diverse biological contexts. [ABSTRACT FROM AUTHOR]

Selecting regions of interest (ROI) is a common step in medical image analysis across all imaging modalities. An ROI is a subset of an image appropriate for the intended analysis and identified manually by experts. In modern pathology, the analysis involves processing multidimensional and high resolution whole slide image (WSI) tiles automatically with an overwhelming quantity of structural and functional information. Despite recent improvements in computing capacity, analyzing such a plethora of data is challenging but vital to accurate analysis. Automatic ROI detection can significantly reduce the number of pixels to be processed, speed the analysis, improve accuracy and reduce dependency on pathologists. In this paper, we present an ROI detection method for WSI and demonstrated it for human epidermal growth factor receptor 2 (HER2) grading for breast cancer patients. Existing HER2 grading relies on manual ROI selection, which is tedious, time-consuming and suffers from inter-observer and intra-observer variability. This study found that the HER2 grade changes with ROI selection. We proposed an ROI detection method using Vision Transformer and investigated the role of image magnification for ROI detection. This method yielded an accuracy of 99% using 20 × WSI and 97% using 10 × WSI for the ROI detection. In the demonstration, the proposed method increased the diagnostic agreement to 99.3% with the clinical scores and reduced the time to 15 seconds for automated HER2 grading. [ABSTRACT FROM AUTHOR]

Silicoalumiophosphates (SAPOs) are microporous crystalline materials extensively utilized as adsorbents and catalysts. The present work utilized two strategies to synthesize nanocrystalline SAPO‐11. The first strategy involves a surfactant as a mesoporogen to reduce the crystallite size and increase the surface area for the materials synthesized at 200 °C in 2 days. In the second strategy, the synthesis temperature and time were significantly reduced to 160 °C and 3 h using propylene oxide as a pH accelerator. The reduction in the particle size and the improvement in the surface area were achieved using propyltriethoxysilane, which inhibited the growth of SAPO‐11 particles. The materials were thoroughly characterized using XRD, N2‐sorption, FTIR, pyridine‐adsorbed FTIR, electron microscopy, XPS, and NMR. The surfactant‐assisted synthesis formed a nanorod morphology with a large external and BET surface area. The low‐temperature synthesis involving silane as a growth inhibitor and propylene oxide as a pH modulator demonstrated a rectangular nanoplatelet morphology with a large surface area. The synthesis was scaled up to 10 g with no change in the experimental parameters. A synthesis strategy facilitating nuclei formation and retarding the growth of particle size will attract academia and industrial researchers to utilize these strategies for the manufacturing of zeolites of different frameworks on a large scale. [ABSTRACT FROM AUTHOR]

We study the effects of audits on long run compliance behavior using a random audit program covering more than 53,000 tax returns. We find that audits raise reported tax liabilities for five years after audit, effects are longer-lasting for more stable sources of income, and only individuals found to have made errors respond to audit. A total of 60%–65% of revenue from audit comes from the change in reporting behavior. Extending the standard model of rational tax evasion, we show that these results are best explained by information revealed by audits constraining future misreporting. Together these imply that more resources should be devoted to audits, audit targeting should account for reporting responses, and performing audits has additional value beyond merely threatening them. [ABSTRACT FROM AUTHOR]