Up-regulation of GINS1 highlighted a good diagnostic and prognostic potential of survival in three different subtypes of human cancer / A regulação positiva de GINS1 destacou um bom potencial diagnóstico e prognóstico de sobrevivência em três subtipos diferentes de câncer humano

Abstract Cancer is a fatal malignancy and its increasing worldwide prevalence demands the discovery of more sensitive and reliable molecular biomarkers. To investigate the GINS1 expression level and its prognostic value in distinct human cancers using a series of multi-layered in silico approach may help to establish it as a potential shared diagnostic and prognostic biomarker of different cancer subtypes. The GINS1 mRNA, protein expression, and promoter methylation were analyzed using UALCAN and Human Protein Atlas (HPA), while mRNA expression was further validated via GENT2. The potential prognostic values of GINS1 were evaluated through KM plotter. Then, cBioPortal was utilized to examine the GINS1-related genetic mutations and copy number variations (CNVs), while pathway enrichment analysis was performed using DAVID. Moreover, a correlational analysis between GINS1 expression and CD8+ T immune cells and a the construction of gene-drug interaction network was performed using TIMER, CDT, and Cytoscape. The GINS1 was found down-regulated in a single subtypes of human cancer while commonly up-regulated in 23 different other subtypes. The up-regulation of GINS1 was significantly correlated with the poor overall survival (OS) of Liver Hepatocellular Carcinoma (LIHC), Lung Adenocarcinoma (LUAD), and Kidney renal clear cell carcinoma (KIRC). The GINS1 was also found up-regulated in LIHC, LUAD, and KIRC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of GINS1 in two diverse pathways, while few interesting correlations were also documented between GINS1 expression and its promoter methylation level, CD8+ T immune cells level, and CNVs. Moreover, we also predicted few drugs that could be used in the treatment of LIHC, LUAD, and KIRC by regulating the GINS1 expression. The expression profiling of GINS1 in the current study has suggested it a novel shared diagnostic and prognostic biomarker of LIHC, LUAD, and KIRC.

Resumo O câncer é uma doença maligna fatal e sua crescente prevalência mundial exige a descoberta de biomarcadores moleculares mais sensíveis e confiáveis. Investigar o nível de expressão de GINS1 e seu valor prognóstico em cânceres humanos distintos, usando uma série de abordagens in silico em várias camadas, pode ajudar a estabelecê-lo como um potencial biomarcador de diagnóstico e prognóstico compartilhado de diferentes subtipos de câncer. O mRNA de GINS1, a expressão da proteína e a metilação do promotor foram analisados ​​usando UALCAN e Human Protein Atlas (HPA), enquanto a expressão de mRNA foi posteriormente validada via GENT2. Os valores prognósticos potenciais de GINS1 foram avaliados por meio do plotter KM. Em seguida, o cBioPortal foi utilizado para examinar as mutações genéticas relacionadas ao GINS1 e as variações do número de cópias (CNVs), enquanto a análise de enriquecimento da via foi realizada usando DAVID. Além disso, uma análise correlacional entre a expressão de GINS1 e células imunes T CD8 + e a construção de uma rede de interação gene-droga foi realizada usando TIMER, CDT e Cytoscape. O GINS1 foi encontrado regulado negativamente em um único subtipo de câncer humano, enquanto comumente regulado positivamente em 23 outros subtipos diferentes. A regulação positiva de GINS1 foi significativamente correlacionada com a sobrevida global pobre (OS) de Carcinoma Hepatocelular de Fígado (LIHC), Adenocarcinoma de Pulmão (LUAD) e Carcinoma de Células Claras Renais de Rim (KIRC). O GINS1 também foi encontrado regulado positivamente em pacientes LIHC, LUAD e KIRC de diferentes características clínico-patológicas. A análise de enriquecimento de vias revelou o envolvimento de GINS1 em duas vias diversas, enquanto poucas correlações interessantes também foram documentadas entre a expressão de GINS1 e seu nível de metilação do promotor, nível de células imunes T CD8 + e CNVs. Além disso, também previmos poucos medicamentos que poderiam ser usados ​​no tratamento de LIHC, LUAD e KIRC, regulando a expressão de GINS1. O perfil de expressão de GINS1 no estudo atual sugeriu que é um novo biomarcador de diagnóstico e prognóstico compartilhado de LIHC, LUAD e KIRC.

Effects of Solanum lycopersicum L. (tomato) against isoniazid and rifampicin induced hepatotoxicity in wistar albino rats / Efeitos de Solanum lycopersicum L. (tomate) contra hepatotoxicidade induzida por isoniazida e rifampicina em ratos albinos wistar

Anti-tuberculosis drugs are reported to cause hepatotoxicity, which varies from asymptomatic rise of the hepatic enzymes. Hepatoprotective plants plays important role to protect liver. This study investigated the hepatoprotective potential of the Solanum lycopersicum in rats intoxicated with Isoniazid and Rifampicin (INH+RIF) to induce hepatotoxicity. Thirty wistar albino rats were divided into five groups of six animals each. Group 1 rats were kept control while groups II, III, IV and V were administered with INH+RIF (75+150 mg/kg) orally, for seven consecutive days. For treatment, rats in group III received silymarin while animals in group IV and V were provided with 40 mg/kg and 80 mg/kg of Solanum lycopersicum extract, respectively. On day 0 and 8th blood samples were collected for the analysis of hepatic biomarkers. The data were subjected to one-way ANOVA and Bonferroni's post hoc test for statistical analysis. Hepatotoxicity induced by INH+RIF resulted in significant elevation of serum hepatic enzymes including Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), and total bilirubin while decreased the albumin level. The Solanum lycopersicum at dose of 80 mg/kg significantly reduced the hepatic enzymes AST, ALT, ALP and bilirubin while the albumin level was significantly increased. The treatment had non-significant effect on body and liver weight. Drug induced hepatotoxicity can be effectively treated with Solanum lycopersicum at 80 mg/kg dose.

As drogas antituberculose são relatadas como causadoras de hepatotoxicidade, ocasionando o aumento assintomático das enzimas hepáticas. As plantas hepatoprotetoras desempenham um papel importante na proteção do fígado. Este estudo investigou o potencial hepatoprotetor de Solanum lycopersicum em ratos que foram intoxicados com isoniazida e rifampicina (INH + RIF) para induzir hepatotoxicidade. Trinta ratos wistar albinos foram divididos em cinco grupos de seis animais cada. Os ratos do grupo 1 representaram o grupo controle, enquanto os ratos dos grupos II, III, IV e V receberam INH + RIF (75 + 150 mg/kg) por via oral, por sete dias consecutivos. Para o tratamento, os ratos do grupo III receberam silimarina, enquanto os animais do grupo IV e V receberam 40 mg/kg e 80 mg/kg de extrato de S. lycopersicum, respectivamente. Nos dias 0 e 8, foram coletadas amostras de sangue para análise de biomarcadores hepáticos. Os dados foram submetidos a teste unilateral (ANOVA) e post hoc de Bonferroni para análise estatística. A hepatotoxicidade induzida por INH + RIF resultou em elevação significativa das enzimas hepáticas séricas, incluindo aspartato aminotransferase (AST), alanina aminotransferase (ALT), fosfatase alcalina (ALP) e bilirrubina total, enquanto houve a diminuição do nível de albumina. O S. lycopersicum, na dose de 80 mg / kg, reduziu significativamente as enzimas hepáticas AST, ALT, ALP e bilirrubina, enquanto o nível de albumina aumentou de forma significativa. O tratamento não teve efeito significativo no peso corporal e hepático. A hepatotoxicidade induzida por drogas pode ser tratada de forma eficaz com S. lycopersicum na dose de 80 mg/kg.

Comparing the Safety and Effectiveness of Ketamine Versus Benzodiazepine/Opioid Combination for Procedural Sedation in Emergency Medicine: A Comprehensive Review and Meta-Analysis.

Procedural sedation is essential in the ED to conduct painful procedures effectively. Ketamine and benzodiazepines/opioids are commonly used, with ketamine providing adequate analgesia and preserving airway muscle tone. However, ketamine is associated with adverse effects while benzodiazepines/opioids can lead to respiratory depression. This study compares the safety and efficacy of ketamine and midazolam/fentanyl. Two search methods were used to identify studies related to our topic, including a database search and a manual search involving screening reference lists of articles retrieved by the database search. A methodological quality appraisal was conducted on the articles suitable for inclusion using Cochrane's risk of bias tool in the Review Manager software (Review Manager (RevMan) (Computer program). Version 5.4, The Cochrane Collaboration, 2020). Moreover, pooled analysis was performed using the Review manager software. The study analyzed 1366 articles, of which seven were included for analysis. Pooled data showed that ketamine and midazolam/fentanyl had similar effects on pain scores during procedures and sedation depth measured by the University of Michigan sedation scale. However, the Modified Ramsay Sedation Score showed significantly more profound sedation in the ketamine group. The only significant adverse events were vomiting and nausea, which had a higher incidence in the ketamine group. Our data suggest that ketamine is as effective as the midazolam/fentanyl combination for procedural sedation but is associated with higher incidences of adverse events. Therefore, midazolam/fentanyl can be recommended for procedural sedation in the ED. However, it should be provided in the presence of a physician comfortable with airway management due to high incidences of oxygen desaturation.

Alternative splicing: transcriptional regulatory network in agroforestry.

Alternative splicing (AS) in plants plays a key role in regulating the expression of numerous transcripts from a single gene in a regulatory pathway. Variable concentrations of growth regulatory hormones and external stimuli trigger alternative splicing to switch among different growth stages and adapt to environmental stresses. In the AS phenomenon, a spliceosome causes differential transcriptional modifications in messenger RNA (mRNAs), resulting in partial or complete retention of one or more introns as compared to fully spliced mRNA. Differentially expressed proteins translated from intron-retaining messenger RNA (mRNAir) perform vital functions in the feedback mechanism. At the post-transcriptional level, AS causes the remodeling of transcription factors (TFs) by the addition or deletion of binding domains to activate and/or repress transcription. In this study, we have summarized the specific role of AS in the regulation of gene expression through repression and activation of the transcriptional regulatory network under external stimuli and switch among developmental stages.

Interplay of silymarin and clove fruit extract effectively enhances cadmium stress tolerance in wheat (Triticum aestivum).

Introduction: Osmoprotectant supplementation can be used as a useful approach to enhance plant stress tolerance. However, the effect of silymarin and clove fruit extract (CFE) on wheat plants grown under cadmium (Cd) stress has not been studied. Methods: Wheat seeds were planted in plastic pots filled with ions-free sand. A ½-strength Hoagland's nutrient solution was used for irrigation. Pots were treated with eight treatments thirteen days after sowing: 1) Control, 2) 0.5 mM silymarin foliar application [silymarin], 3) 2% CFE foliar application [CFE], 4) CFE enriched with silymarin (0.24 g silymarin L-1 of CFE) [CFE-silymarin], 5) Watering wheat seedlings with a nutritious solution of 2 mM Cd [Cd]. 6) Cadmium + silymarin, 7) Cadmium + CFE, and 8) Cadmium + CFE-silymarin. The experimental design was a completely randomized design with nine replicates. Results and discussion: The Cd stress decreased grain yield, shoot dry weight, leaf area, carotenoids, chlorophylls, stomatal conductance, net photosynthetic rate, transpiration rate, membrane stability index, nitrogen, phosphorus, and potassium content by 66.9, 60.6, 56.7, 23.8, 33.5, 48.1, 41.2, 48.7, 42.5, 24.1, 39.9, and 24.1%, respectively. On the other hand, Cd has an Application of CFE, silymarin, or CEF-silymarin for wheat plants grown under Cd stress, significantly improved all investigated biochemical, morphological, and physiological variables and enhanced the antioxidant enzyme activities. Applying CFE and/or silymarin enhanced plant tolerance to Cd stress more efficiently. Our findings suggest using CFE-silymarin as a meaningful biostimulator for wheat plants to increase wheat plants' tolerance to Cd stress via enhancing various metabolic and physiological processes.

Quiescent optical solitons with complex Ginzburg-Landau equation having a dozen forms of self-phase modulation.

The current study focuses on the recovery of quiescent optical solitons through the use of the complex Ginzburg-Landau equation when the chromatic dispersion is rendered to be nonlinear. A dozen forms of self-phase modulation structures are taken into consideration. The utilization of the enhanced Kudryashov's scheme has led to the emergence of singular, dark, and bright soliton solutions. The existence of such solitons is subject to certain parametric restrictions, which are also discussed in this paper.

Evaluation of synergistic approach of spinel cadmium-copper nanoferrites as magnetic catalysts for promoting wastewater decontamination: Impact of Ag ions doping.

Metal substitution is an efficient strategy to improve the catalytic activity of ferrite-based catalysts. In this study, Cd0.5Cu0.5-xAgxFe2O4 (where 0 ≤ x ≤ 0.5) ferrites were fabricated via a simple co-precipitation method. The influence of the silver ions on the structural, magnetic, and catalytic characteristics of the spinel nanoparticles, as well as on their morphology, was examined. X-ray diffractograms revealed a crystalline cubic spinel structure with crystallite sizes in the nanoregime (7-15 nm). The saturation magnetization reduced from 29.8 to 2.80 emu as the Ag+ doping increased. Two prominent absorption bands were visible in Fourier-transform infrared spectra at 600 cm-1 and 400 cm-1, respectively, and they belonged to the tetrahedral (A) and octahedral (B) sites. The samples were then used as catalysts for the oxidative breakdown of the typical organic contaminant indigo carmine dye (IC). The catalytic process followed the first-order kinetic model, and the rate constant increased from 0.007 to 0.023 min-1 with increasing of Ag+ doping. Cd0.5Cu0.5-xAgxFe2O4 exhibited excellent catalytic performance in the pH range of 2-11, which means that they are promising efficient and stable materials for Fenton-based alkaline wastewater treatment. Finally, the pathway includes, HO•, HO2-•, and O2-• as oxidants resulted from the synergistic effects of Fe3+, Cu2+, and Ag+, with H2O2 and surface hydroxyl groups have been proposed.

Translation machinery captured in motion.

Translation accuracy is one of the most critical factors for protein synthesis. It is regulated by the ribosome and its dynamic behavior, along with translation factors that direct ribosome rearrangements to make translation a uniform process. Earlier structural studies of the ribosome complex with arrested translation factors laid the foundation for an understanding of ribosome dynamics and the translation process as such. Recent technological advances in time-resolved and ensemble cryo-EM have made it possible to study translation in real time at high resolution. These methods provided a detailed view of translation in bacteria for all three phases: initiation, elongation, and termination. In this review, we focus on translation factors (in some cases GTP activation) and their ability to monitor and respond to ribosome organization to enable efficient and accurate translation. This article is categorized under: Translation > Ribosome Structure/Function Translation > Mechanisms.

Scaffold hopping of N-benzyl-3,4,5-trimethoxyaniline: 5,6,7-Trimethoxyflavan derivatives as novel potential anticancer agents modulating hippo signaling pathway.

Scaffold hopping of N-benzyl-3,4,5-trimethoxyaniline afforded 5,6,7-trimethoxyflavan derivatives that were efficiently synthesized in four linear steps. As lung cancer is the most lethal cancer, twenty-three synthesized compounds were evaluated against a panel of lung cancer cells. Amongst, compounds 8q and 8e showed interesting activity. Hence, compounds 8q and 8e were evaluated against panels of diverse cancers. Compounds 8q and 8e showed broad spectrum anticancer activity. However, compound 8q was more effective and, hence, was advanced for potency evaluation and characterization. Compound 8q showed comparable potencies to gefitinib, and oxaliplatin against lung and colorectal cancers, respectively, and superior potencies to temozolomide, dacarbazine, cisplatin, enzalutamide, methotrexate, imatinib against brain, skin, ovary, prostate, breast, and blood cancers, respectively. Compound 8q increased cleaved PARP, caspase 3, and 7 inducing apoptosis. In addition, it inhibited cyclins A, B1, H and cdc25c, and increased p53 triggering cell cycle arrest in G2/M phase. Moreover, it decreased YAP and increased LATS1 and p-mob1/mob1 activating hippo signaling. Furthermore, it decreased p-PI3K/PI3k, p-mTOR/mTOR and p-P70S6K/P70S6K inhibiting PI3k pathway. Together, these findings present compound 8q as a potential anticancer lead compound for further development of potential agents.

Voltage-dependent anion channels: Key players in viral infection.

Viruses control the host cell by exploiting its molecular machinery to facilitate viral replication and propagation. Understanding different viral mechanisms and biochemical pathways is crucial for finding promising therapeutic solutions to viral infections. The mitochondrion is a vital organelle targeted by various types of viruses. More specifically, viruses interact with the voltage-dependent anion channel (VDAC), a porin protein found in the outer mitochondrial membrane. VDAC controls metabolite flux, regulates reactive oxygen species production, and promotes mitochondrial-mediated apoptosis by releasing pro-apoptotic proteins. Hence, a common pathogenic strategy used by many viruses seems to exploit natural pathways that VDAC regulates. This review aims to address the inhibition and enhancement roles of VDAC in viral pathogenesis and outlines multiple links and interactions between VDAC and viral proteins as potential antiviral targets.

A Novel c.100C > G Mutation in the FST Gene and Its Relation With the Reproductive Traits of Awassi Ewes.

Reproductive traits are affected by many factors, including ovarian function, hormones, and genetics. Genetic polymorphisms of candidate genes are associated with reproductive traits. Several candidate genes are associated with economic traits, including the follistatin (FST) gene. Thus, this study aimed to evaluate whether the genetic variations in the FST gene are associated with the reproductive traits in Awassi ewes. The genomic DNA was extracted from 109 twin ewes and 123 single-progeny ewes. Therefore, 4 sequence fragments from the FST gene were amplified using polymerase chain reaction (PCR) (exon 2/240, exon 3/268, exon 4/254, and exon 5/266 bp, respectively). For a 254 bp amplicon, 3 genotypes were identified: CC, CG, and GG. Sequencing revealed a novel mutation in CG genotypes c.100C > G. The statistical analysis of c.100C > G showed an association with reproductive characteristics. Ewes carrying the c.100C > G had significantly (P ⩽ .01) lower litter sizes, twinning rates, lambing rates, and more days to lambing compared with CG and CC genotypes. Logistic regression analysis confirmed that the c.100C > G single-nucleotide polymorphism (SNP) is responsible for decreasing litter size. According to these results, the variant c.100C > G negatively affects the traits of interest and is associated with lower reproductive traits in Awassi sheep. As a result of this study, ewes carrying the c.100C > G SNP have lower litter size and are less prolific.

Magnitude of A1C improvement in relation to baseline A1C and amount of weight loss in response to intensive lifestyle intervention in real-world diabetes practice: 13 years of observation.

BACKGROUND: Effect of intensive lifestyle intervention (ILI) on A1C in participants with diabetes is underestimated. A1C improvement is presumed to be dependent on the amount of weight loss. Here, we evaluate the magnitude of A1C change in relation to baseline A1C and the amount of weight loss in participants with diabetes who underwent ILI over 13 years in real-world clinical practice. METHODS: A total of 590 participants with diabetes were enrolled in the Weight Achievement and Intensive Treatment (Why WAIT) program, a 12-week multidisciplinary ILI program designed for real-world clinical practice between September 2005 and May 2018. We stratified participants based on baseline A1C into three groups: group A: A1C ≥ 9%, group B: A1C 8 to <9%, and group C: A1C ≥6.5% to <8%. RESULTS: After 12-weeks of intervention, body weight decreased in all groups, and pairwise comparisons of A1C changes showed that: group A had 1.3% greater A1C reduction than group B (p = 0.0001) and 2% greater than group C (p = 0.0001), while group B had 0.7% greater A1C reduction than group C (p = 0.0001). CONCLUSION: We conclude that ILI may decrease A1C by up to 2.5% in participants with diabetes. At similar magnitude of weight loss, A1C reduction was more prominent in participants with higher baseline A1C. This may be valuable for clinicians to set a realistic expectation of A1C change in response to ILI.

Fundamental Aspects of Skin Cancer Drugs via Degree-Based Chemical Bonding Topological Descriptors.

Due to significant advancements being made in the field of drug design, the use of topological descriptors remains the primary approach. When combined with QSPR models, descriptors illustrate a molecule's chemical properties numerically. Numbers relating to chemical composition topological indices are structures that link chemical composition to physical characteristics. This research concentrates on the analysis of curvilinear regression models and degree-based topological descriptors for thirteen skin cancer drugs. The physicochemical characteristics of the skin cancer drugs are examined while regression models are built for computed index values. An analysis is performed for several significant results based on the acquired data.

The medicinal activity of lyophilized aqueous seed extract of Lepidium sativum L. in an androgenic alopecia model.

This study evaluated the topical effect of Lepidium sativum lyophilized seed extract (LSLE) towards Sustanon-induced alopecia in male adult Wistar albino rats in vivo, compared to minoxidil topical reference standard drug (MRD). LC-MS/MS together with molecular networking was used to profile the metabolites of LSLE. LSLE treated group revealed significant changes in alopecia related biomarkers, perturbation of androgenic markers; decline in testosterone level and elevation in 5α-reductase (5-AR); decline in the cholesterol level. On the other hand, LSLE treated group showed improvement in vascular markers; CTGF, FGF and VEGF. Groups treated topically with minoxidil and LSLE showed significant improvement in hair length. LC-MS/MS profile of LSLE tentatively identified 17 constituents: mainly glucosinolates, flavonoid glycosides, alkaloids and phenolic acids. The results point to the potential role of LSLE in the treatment of alopecia through decreasing 5(alpha)-dihydrotestosterone levels. Molecular docking was attempted to evaluate the probable binding mode of identified compounds to androgen receptor (PDB code: 4K7A).

Antiviral activity of some benzo[g]quinazolines against coxsackievirus B4: biological screening and docking study.

BACKGROUND: Serotype coxsackievirus B (CVB) infection has been linked to viral myocarditis, dilated cardiomyopathy, meningitis, and pancreatitis in children and young adults. As of yet, no antiviral drug has been authorized for the treatment of coxsackievirus infection. Therefore, there is perpetual demand for new therapeutic agents and the improvement of existing ones. Benzo[g]quinazolines, the subject of several well-known heterocyclic systems, have risen to prominence and played a significant role in the development of antiviral agents, particularly those for anti-coxsackievirus B4 infection. METHODS: This study investigated the cytotoxicity of the target benzo[g]quinazolines (1-16) in the BGM cells line as well as their anti-coxsackievirus B4 activity. Determination of CVB4 titers using a plaque assay. RESULTS: Most of the target benzoquinazolines exhibited antiviral activity, however, compounds 1-3 appeared to be the most effective (reduction percentages of 66.7, 70, and 83.3%, respectively). The binding mechanisms and interactions of the three most active 1-3 with the constitutive amino acids in the active site of the multi-target of coxsackievirus B4 (3Clpro and RdRp) targets were also investigated using molecular docking. CONCLUSION: The anti coxsackievirus B4 activity has resulted, and the top three active benzoquinazolines (1-3) have bonded to and interacted with the constitutive amino acids in the active region of the multi-target coxsackievirus B4 (RdRp and 3Clpro). Further research is required in the lab. to determine the exact benzoquinazolines mechanism of action.

A Novel ANO1 Gene Variant is Associated with Intestinal Dysmotility Syndrome Masquerading as Hirschsprung Disease: A Case Report.

Anoctamin 1 (ANO1)-related intestinal dysmotility syndrome (OMIM: 620045) is an extremely rare disorder with only 2 cases reported in the medical literature. We present the clinical scenario of a 2-month-old male infant that presented to our center with diarrhea, vomiting, and abdominal distension. Routine investigations did not yield a clear diagnosis. Whole-exome sequencing showed a novel homozygous nonsense ANO1 pathogenic variant (c.1273G>T) with a protein alternation of p.Glu425Ter that fits the patient's phenotype. Sanger sequencing revealed the same ANO1 variant in both parents in a heterozygous form confirming an autosomal recessive mode of inheritance. The patient experienced multiple bouts of diarrhea-related metabolic acidosis, dehydration, and severe electrolyte imbalances that required intensive care unit monitoring. The patient was managed conservatively and being followed regularly in an outpatient setting.

Search for Lepton-Flavor-Violating τ Decays to a Lepton and an Invisible Boson at Belle II.

We search for lepton-flavor-violating τ^{-}→e^{-}α and τ^{-}→µ^{-}α decays, where α is an invisible spin-0 boson. The search uses electron-positron collisions at 10.58 GeV center-of-mass energy with an integrated luminosity of 62.8 fb^{-1}, produced by the SuperKEKB collider and collected with the Belle II detector. We search for an excess in the lepton-energy spectrum of the known τ^{-}→e^{-}ν[over ¯]_{e}ν_{τ} and τ^{-}→µ^{-}ν[over ¯]_{µ}ν_{τ} decays. We report 95% confidence-level upper limits on the branching-fraction ratio B(τ^{-}→e^{-}α)/B(τ^{-}→e^{-}ν[over ¯]_{e}ν_{τ}) in the range (1.1-9.7)×10^{-3} and on B(τ^{-}→µ^{-}α)/B(τ^{-}→µ^{-}ν[over ¯]_{µ}ν_{τ}) in the range (0.7-12.2)×10^{-3} for α masses between 0 and 1.6 GeV/c^{2}. These results provide the most stringent bounds on invisible boson production from τ decays.

A Fast Loss Model for Cascode GaN-FETs and Real-Time Degradation-Sensitive Control of Solid-State Transformers.

This paper proposes a novel, degradation-sensitive, adaptive SST controller for cascode GaN-FETs. Unlike in traditional transformers, a semiconductor switch's degradation and failure can compromise its robustness and integrity. It is vital to continuously monitor a switch's health condition to adapt it to mission-critical applications. The current state-of-the-art degradation monitoring methods for power electronics systems are computationally intensive, have limited capacity to accurately identify the severity of degradation, and can be challenging to implement in real time. These methods primarily focus on conducting accelerated life testing (ALT) of individual switches and are not typically implemented for online monitoring. The proposed controller uses accelerated life testing (ALT)-based switch degradation mapping for degradation severity assessment. This controller intelligently derates the SST to (1) ensure robust operation over the SST's lifetime and (2) achieve the optimal degradation-sensitive function. Additionally, a fast behavioral switch loss model for cascode GaN-FETs is used. This proposed fast model estimates the loss accurately without proprietary switch parasitic information. Finally, the proposed method is experimentally validated using a 5 kW cascode GaN-FET-based SST platform.

A Decade's Perspective on the Orthopedic Workforce in Saudi Arabia.

Background The orthopedic surgery workforce constitutes a vital role in the healthcare system, with data being scarce. Therefore, through this study, we share an overview of the orthopedic workforce distribution, demographic trends, and changes over the past decade in Saudi Arabia. Methods All practicing orthopedic surgeons in Saudi Arabia from January 1, 2010, to December 31, 2021, were included in the study. Data regarding orthopedic surgeons' demographics and numbers were obtained from the Saudi Commission for Health Specialties (SCFHS), whereas the data related to the geographical distribution of orthopedic surgeons was obtained from the Ministry of Health Statistical Yearbook of 2020. Results The ratio of orthopedic surgeons per 100,000 people was 5.42 in 2010, which grew subsequently to 12.29 in 2021. The number of Saudi orthopedic surgeons has been noticeably rising through the years, while a slowly growing pattern can be seen among non-Saudi orthopedic surgeons. In addition, the highest ratios of orthopedic surgeons per 100,000 were in Makkah (1.72), Riyadh (1.26), and the Eastern Region (1.06). Conclusion In this study, we demonstrate the progress of the orthopedic workforce in Saudi Arabia over a period of 12 years. The number of orthopedic surgeons per 100,000 people showed a significant rise due to several factors, one of which is road traffic accidents. Also, although the number of female orthopedic surgeons has been rising lately, they are still much fewer than males in this field. In addition, Saudi Arabia has been developing a new healthcare system via the privatization of some of the governmental hospitals, which will lead to changes in the future workforce and its accommodations.

Cellulitis in Hajj Pilgrims: Role of Environmental Temperature and Population Size of Pilgrims as a Contributory Factor.

Background Cellulitis is a common infection of the skin and subcutaneous tissue. Meteorological and environmental temperatures were previously identified as potential risk factors for causation and the patient's odds of hospitalization. In this regard, we aim to study the pattern of cellulitis during 10 Hajj seasons and examine the impact of changing seasonal temperatures and overall pilgrim populations as potential risk factors. Methodology In-hospital cellulitis was studied within the context of the Hajj. A retrospective review of pilgrim patients coded for cellulitis was undertaken for the Hajj seasons between 2004 and 2012. Possible roles of environmental temperatures, pilgrim population sizes, and ethnicity were examined as potential risk factors. Results A total of 381 patients belonging to 42 nationalities were identified, with 285 (75%) males and 96 (25%) females with a mean age of 63 years. On average, cellulitis accounted for 23.5% of general surgical admissions with proportional increases from 2004 to 2012 (r= 0.73, p= 0.016), which significantly correlated with the rise in seasonal temperatures (r = 0.7, p= 0.023). Conclusions The findings of this study identified cellulitis as a significant health risk during the Hajj, which is likely to be prevalent in warmer seasons. Our results may assist clinicians in educating Hajj pilgrims of different nationalities about the increased risk of cellulitis during warm seasons and possible predisposing environmental factors of infection.