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Physiotherapy is a treatment that may be required permanently by many patients. As a result, a robot that can execute physiotherapy exercises for the legs like a professional therapist with adequate performance and acceptable safety may be efficient and widely used. In this study, a robust control system for a Stewart platform with six degrees of freedom is provided. First, the Newton-Euler approach is used in conjunction with a methodology and some simplification tools to achieve explicit dynamics formulation for the Stewart platform. For the primary application of this research, which is to follow the specified trajectory of ankle rehabilitation, computed torque control law (CTCL) and polynomial chaos expansion (PCE) were used to examine and consider any uncertainty in geometric and physical parameters. In fact, this strategy integrated the uncertainties with CTCL using PCE. The suggested PCE-based CTCL eliminates the system's nonlinearity by applying feedback linearization to evaluate generalized driving forces; hence, the nondeterministic multi-body system follows the desired direction. Uncertainties in the patient's foot as well as the main diameter parameters of the moment of inertia of the upper platform of the Stewart robot with various uniform, beta, and normal distributions, have been analyzed. The PCE technique's results were compared to the Monte Carlo method's outcomes, and the strengths and weaknesses of each method were investigated. In brief, the PCE method operated far better than the Monte Carlo (MC) method in speed, accuracy, and numerical volume. [ABSTRACT FROM AUTHOR]

Background and Goals: Peptic ulcer disease is the most frequent cause of upper gastrointestinal bleeding. We sought to establish the epidemiology and hemostasis success rate of the different treatment modalities in this setting. Methods: Retrospective cohort study using the National Inpatient Sample. Non-elective adult admissions with a principal diagnosis of ulcer bleeding were included. The primary outcome was endoscopic, radiologic and surgical hemostasis success rate. Secondary outcomes were patients' demographics, in-hospital mortality and resource utilization. On subgroup analysis, gastric and duodenal ulcers were studied separately. Confounders were adjusted for using multivariate regression analysis. Results: A total of 136,425 admissions (55% gastric and 45% duodenal ulcers) were included. The mean patient age was 67 years. The majority of patients were males, Caucasians, of lower income and high comorbidity burden. The endoscopic, radiological and surgical therapy and hemostasis success rates were 33.6, 1.4, 0.1, and 95.1%, 89.1 and 66.7%, respectively. The in-hospital mortality rate was 1.9% overall, but 2.4% after successful and 11.1% after failed endoscopic hemostasis, respectively. Duodenal ulcers were associated with lower adjusted odds of successful endoscopic hemostasis, but higher odds of early and multiple endoscopies, endoscopic therapy, overall and successful radiological therapy, in-hospital mortality, longer length of stay and higher total hospitalization charges and costs. Conclusions: The ulcer bleeding endoscopic hemostasis success rate is 95.1%. Rescue therapy is associated with lower hemostasis success and more than a ten-fold increase in mortality rate. Duodenal ulcers are associated with worse treatment outcomes and higher resource utilization compared with gastric ulcers. [ABSTRACT FROM AUTHOR]

Workplace spirituality is a psycho-theological phenomenon understood generally as employees’ inner drive to connect with fellows at work and become mindful of one’s inner consciousness, while pursuing a purposeful work. However, there exists an inherent probability that what is promoted as workplace spirituality is truly a cloaked version of psychological conformity on part of the employees. The present study incorporates an argumentative analysis to deconstruct how workplace spirituality in its present form is more inclined toward material pursuits rather than spiritual nourishment. Moreover, the study also provides a compilation of authentic nourishers who, when cultivated thoroughly in the workplace, can be amenable toward spiritual flourishing. In addition to explaining the significance of number 17 amongst spiritual traditions, the paper explores 17 different fragments which are required for spiritual nourishment. [ABSTRACT FROM AUTHOR]

Aims: Renal insufficiency is a common comorbidity in patients with haematological malignancies. This study aimed to assess how end‐stage renal disease (ESRD) might affect the pharmacokinetics of venetoclax, a Bcl‐2 inhibitor, in participants with ESRD undergoing haemodialysis. Methods: Venetoclax was administered as a single 100‐mg dose to 6 female participants with ESRD (estimated glomerular filtration rate <15 mL/min) both prior to haemodialysis and between haemodialysis days and 7 healthy female participants with normal renal function (estimated glomerular filtration rate >90 mL/min). Intensive pharmacokinetic and protein binding samples were collected from all participants. Arterial and venous samples were collected from ESRD participants during haemodialysis to assess the effect of haemodialysis on venetoclax pharmacokinetics. Pharmacokinetic parameters were estimated using noncompartmental methods. Results: There was no difference in plasma venetoclax concentrations between arterial and venous samples, suggesting that haemodialysis did not affect the pharmacokinetics of venetoclax. The fraction unbound (fu) of venetoclax was ~2‐fold higher for participants with ESRD compared to participants with normal renal function. The unbound maximum plasma concentration and area under the plasma concentration–time curve from time 0 to 48 h were comparable between ESRD and normal function groups. The mean half‐life ranged from 10.4 to 12.2 h across groups, demonstrating that ESRD did not affect the half‐life of venetoclax. No new safety signals were observed during this study. Conclusion: ESRD and dialysis do not alter unbound venetoclax plasma concentrations. No pharmacokinetics driven dose adjustment is needed for patients with renal insufficiency. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the frequency of anemia and its risk factor among female students. Study Design: Cross Sectional study. Setting: PUMHSW, Nawabshah. Period: September 2019 to February 2020. Material & Methods: Three hundred and fifty female students were included from various departments and academic years. Data was collected on prescribed performed with their consent, than statistically analyzed with SPSS. Results: Sample size of the study was 350. The age group 18 to 21 years 194 (55.4%) was dominating in the study, Further, hostlers were 207(59.1%, p=.004), married 5 (1.4%), belonged to middle socioeconomic status 327 (93.4%), literacy level of the parents, and dietary habits were major risk factors among study subjects. Furthermore, Anemic were 139 (39.7%), in which mild anemia found in 79 (22.6%), moderate anemia in 53(15.1%) and severe anemia in 7(2.0%). Conclusion: Current study identified the high prevalence of anemia among students. This study concluded the frequency of anemia in health sciences student of PUMHSW Nawabshah was 39.7%. Further; this study also determined risk factors associated with anemic status, and explored the dietary risk factors of anemia. [ABSTRACT FROM AUTHOR]

Recent research has pointed to the modern nature of the state that Islamists posit in contrast to medieval Islamic notions of political authority. This paper argues that a conceptual framework derived from romantic aesthetics underpinned the Islamist thought of Sayyid Qutb, who was for many years a secular literary writer. The aesthetic framework made possible the notion of human freedom and progress as the enactment of the general or collective will, which is the source of the state. Classical formulations of the general will in Rousseau, Kant, and Hegel are closely related to contemporaneous aesthetic notions of freedom as creative expression of interiority. Qutb participated in this line of thinking. The vitalist metaphysics and expressivist aesthetic theory of his literary period led him to later formulate an account of the general will that is embodied in Islamic law, the sharīʿa, which he identified with the state. He presented the Islamic state on this basis as resolving the fundamental contradiction of western modernity that romantic aesthetics had identified in the context of establishing the redemptive value of art. This contradiction, the disunity of the spiritual and the material, was equated by Qutb with the separation of church and state. Islamic law as the state is thus justified on aesthetic grounds as the reconciliation of humanity and nature now divided by Western materialism. Qutb's thought in the context of its aesthetic genesis provides valuable insight into the nature of modern notions of individual and collective will. [ABSTRACT FROM AUTHOR]

This study is the first study to incorporate a novel approach to single-implant-retained mandibular overdenture with a bar attachment on a single implant in the symphysis region. The use of a single-implant-retained bar overdenture significantly improved patients' chewing efficiency, indicating enhanced overdenture retention and stability. Materials and Methods: Ten maxillary and mandibular completely edentulous patients were enrolled in the study. A complete denture was fabricated for them. On completion, bite force, retention force, and bone change were recorded. Bite force was recorded with the strain gauge, retention force with the force measurement gauge, and bone changes with radiographs. Conclusion: Single-implant-supported bar mandibular overdenture (SISBOD) can be a suitable standard economic option for edentulous mandible and can greatly improve the quality of life of patients. [ABSTRACT FROM AUTHOR]

What happens when an emerging programme of medical research overlaps with a surging social movement? In this article we draw on the anthropological term 'chemosociality' to describe forms of sociality born of shared chemical exposure. Psychedelic administration in the context of recent clinical trials appears to have been particularly chemosocial in nature. We argue that one consequence is that psychedelic-assisted therapy (PAT) clinical research trials tend to breach key assumptions underlying the logic of causal inference used to establish efficacy. We propose the concept of dark loops to describe forms of sociality variously emerging from, and impacting participant experiences in, PAT trials. These dark loops are not recorded, let alone incorporated into the causal pathways in the interpretation of psychedelic trial data to date. We end with three positions which researchers might adopt in response to these issues: chemosocial minimisation where research is designed to attenuate or eliminate the effects of dark loops in trials; chemosocial description where dark loops (and their impacts) are openly and candidly documented and chemosocial valorisation where dark loops are hypothesised to contribute to trial outcomes and actively drawn upon for positive effect. Our goal is to fold in an appreciation of how the increasingly-discussed hype surrounding psychedelic research and therapeutics continues to shape the phenomena under study in complex ways, even as trials become larger and more rigorous in their design. [ABSTRACT FROM AUTHOR]

With the rapid industry development in the last decades, air pollution has increased with the increase in carbon dioxide (CO2). Adsorbents are considered a good candidate for capturing CO2 owing to their many advantages, such as reusability, low cost, easy operation, and scale-up synthesis. In this study, the synthesis of mesoporous cobalt oxide (Co3O4) nanoparticles (NPs) in deep eutectic solvent (DES) is reported by the ultrasound-assisted method to improve the CO2 adsorption performance. The synthesized Co3O4 NPs were characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), and Brunauer–Emmett–Teller (BET) for investigating morphology, crystallinity, and porosity. CO2 and N2 adsorption isotherms of Co3O4 NPs synthesized in DES and synthesized in water were measured by quartz crystal microbalance (QCM) at a temperature range of 288.15–308.15 K and pressures of up to 5 bar. In addition, CO2/N2 selectivity adsorption on the Co3O4 NPs was investigated. Furthermore, adsorption isotherms were correlated to the Langmuir isotherm model. The results reveal that the adsorption performance of Co3O4 NPs synthesized in DES improved in comparison with Co3O4 NPs synthesized in water. The Co3O4 NPs' molar enthalpy of adsorption showed that the CO2 adsorption process is exothermic. [ABSTRACT FROM AUTHOR]

As a common data-driven method, artificial neural networks have been widely used in electricity spot price forecasting. To improve the accuracy of short-term forecasts, this paper proposes an optimized artificial neural network model for monthly electricity spot prices forecasting. A genetic algorithm is applied to regulate the weights and biases parameters of the artificial neural network structure. This study uses various historical dataset at monthly periods selected from Nordic electricity spot prices. For efficiency comparison, one-step ahead forecast method based on Schwartz-Smith stochastic model and two other prediction models, artificial neural network trained by Levenberg–Marquardt and particle swarm optimization algorithms are also presented. The comparison results show that the prediction model based on the genetic optimization algorithm is more accurate than the other prediction models. The proposed forecasting model can be considered as an alternative technique for the electricity spot price forecasting in the Nordic regions. [ABSTRACT FROM AUTHOR]

To improve the CO2/N2 separation performance of metal–organic frameworks (MOFs), amine functionalized deep eutectic solvents (DESs) (choline chloride/ethanolamine (DES1), choline chloride/ethanolamine/diethanolamine (DES2), and choline chloride/ethanolamine/methyldiethanolamine (DES3)) confined in the NH2-MIL-53(Al). NH2-MIL-53(Al) impregnated with DES was synthesized and characterized using N2-sorption analysis and Fourier transform infrared (FTIR) spectroscopy. Morphology of the synthesized MOFs was investigated using scanning electron microscopy (SEM). Also, elemental analysis was determined by energy-dispersive X-ray spectroscopy (EDX). CO2 adsorption isotherms of amine-functionalized DESs impregnated NH2-MIL-53(Al) were measured at temperatures range of 288.15–308.15 K and pressures up to 5 bar. The results reveal that the impregnated MOF with functional group of amine DES improves separation performance NH2-MIL-53(Al). CO2 adsorption capacity of DES1/NH2-MILS-53(Al) was twofold respect to of pristine NH2-MIL-53(Al) at 5 bar and 298.15 K; which helps to guide the logical design of new mixtures for gas separation applications. Also, the heat of adsorption for the synthesized NH2-MIL-53(Al) and DESs/NH2-MIL-53(Al) were estimated. Most importantly, CO2 chemisorption by NH2 group in the sorbent structure has a significant effect on the adsorption mechanism. [ABSTRACT FROM AUTHOR]

Key Clinical Message: This case report describes the benefits of a unique tape‐splinting technique to serve as a nonsurgical tarsorrhaphy in the management of exposure keratopathy in a patient who refuses surgical intervention. [ABSTRACT FROM AUTHOR]

Peer learning is the method of students learning with and from each other. However, it is not completely developed or studied in online and blended higher education. In this paper, an Educational Game Theory method called EGT-Moodle is proposed to establish a peer learning in an online-learning environment. This method is implemented in Moodle (an open-source learning management system) environment. The method is a quasi-experimental study with a post-test design consisting of the experimental and control groups. A total of 152 students of the Discrete Mathematics course in computer engineering constitute the experimental and control groups randomly at 76. The Mann–Whitney two-independent group is applied to compare the post-tests of the subject groups. The result indicates that there is a significant difference (U = 1319, p =.000) between post-tests for the experimental group compared to the control which indicates the positive effect of EGT-Moodle on learning enhancement. [ABSTRACT FROM AUTHOR]

Refugia have been perceived as a major role in structuring species biodiversity, and understanding the impacts of this force in a community assembly with prey–predator species is a difficult task because refuge process can interact with different ecological components and may show counterintuitive effects. To understand this problem, we used a simple two-species model incorporating a functional response inspired by a Holling type-II equation and a prey refuge mechanism that depends on prey and predator population densities (i.e., density-dependent prey refuge). We then perform the co-dimension one and co-dimension two bifurcation analysis to examine steady states and its stability, together with the bifurcation points as different parameters change. As the capacity of prey refuge is varied, there occur critical values i.e., saddle-node and supercritical Hopf bifurcations. The interaction between these two co-dimension one bifurcations engenders distinct outcomes of ecological system such as coexistence of species, bistability phenomena and oscillatory dynamics. Additionally, we construct a parameter space diagram illustrating the dynamics of species interactions as prey refuge intensity and predation pressure vary; as the two saddle-node move nearer to one another, these bifurcations annihilate tangentially in a co-dimension two cusp bifurcation. We also realised several contrasting observations of refuge process on species biodiversity: for instance, while it is believed that some refuge processes (e.g., constant proportion of prey refuge) would result in exclusion of predator species, our findings show that density-dependent prey refuge is beneficial for both predator and prey species, and consequently, promotes the maintenance of species biodiversity. [ABSTRACT FROM AUTHOR]

Prunus necrotic ringspot virus (PNRSV) is a pathogen that infects Prunus species worldwide, causing major economic losses. Using one and two-step RT-PCR and multiplex RT-PCR, the whole genome of the PNRSV-infecting apricot was obtained and described in this study. Computational approaches were used to investigate the participation of several regulatory motifs and domains of the Replicase1, Replicase2, MP, and CP. A single degenerated reverse and three forward oligo primers were used to amplify PNRSV's tripartite genome. The size of RNA1 was 3.332 kb, RNA2 was 2.591 kb, and RNA3 was 1.952 kb, according to the sequencing analysis. The Sequence Demarcation Tool analysis determined a percentage pair-wise identity ranging between 91 and 99% for RNA1 and 2, and 87–98% for RNA3. Interestingly, the phylogenetic analysis revealed that closely related RNA1, RNA2, and RNA3 sequences of PNRSV strains from various geographical regions of the world are classified into distinct clades or groups. This is the first report on the characterization of the whole genome of PNRSV from India, which provides the cornerstone for further studies on the molecular evolution of this virus. This study will assist in molecular diagnostics and management of the diseases caused by PNRSV. [ABSTRACT FROM AUTHOR]

Introduction. While cerebrospinal fluid (CSF) core biomarkers have been considered diagnostic biomarkers for a long time, special attention has been recently dedicated to lipoproteins and metabolites that could be potentially associated with Alzheimer's disease (AD) neurodegeneration. Herein, we aimed to investigate the relationship between the levels of CSF core biomarkers including Aβ-42, TAU, and P-TAU and plasma lipoproteins and metabolites of patients with AD from the baseline cohort of the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Method. Using the ADNI database, fourteen subclasses of lipoproteins as well as a number of lipids and fatty acids and low-molecular metabolites including amino acids, ketone bodies, and glycolysis-related metabolites in blood samples were measured as potential noninvasive markers, and their association with the CSF core biomarkers was statistically investigated controlling for age and gender. Results. A total number of 251 AD subjects were included, among whom 71 subjects were negative for the Apo-E ε4 allele and 150 were positive. There was no significant difference between the two groups regarding cognitive assessments, CSF core biomarkers, and lipoproteins and metabolites except the level of Aβ-42 (p < 0.001) and phenylalanine (p = 0.049), which were higher in the negative group. CSF TAU and P-TAU were significantly correlated with medium and small HDL in the negative group, and with extremely large VLDL in the positive group. Our results also indicated significant correlations of metabolites including unsaturated fatty acids, glycerol, and leucine with CSF core biomarkers. Conclusion. Based on our findings, a number of lipoproteins and metabolites were associated with CSF core biomarkers of AD. These correlations showed some differences in Apo-E ε4 positive and negative groups, which reminds the role of Apo-E gene status in the pathophysiology of AD development. However, further research is warranted to explore the exact association of lipoproteins and other metabolites with AD core biomarkers and pathology. [ABSTRACT FROM AUTHOR]

In this work, the CO2 adsorption performance of metal–organic frameworks (MOFs) impregnated with ionic liquids (ILs) was studied using quartz crystal microbalance (QCM) at the temperature of 298.15 K and pressures up to 5 bar. The hybrid composites consist of aluminum terephthalate metal–organic framework (AlTp) impregnated of 1-butyl-4-methyl pyridinium and 1-butyl-3-methylimidazolium–based ionic liquids (ILs) with different anions, viz. tetrafluoroborate ([BF4]−), thiocyanate ([SCN]−), chloride ([Cl]−), and bromide ([Br]−). ILs-impregnated AlTp synthesized was characterized using scanning electron microscopy (SEM), X-ray diffraction analysis (XRD), the thermogravimetry analysis (TGA) and Fourier transform infrared (FTIR) spectroscopy. CO2 adsorption isotherms of the IL/AlTp composites and AlTp were measured to evaluate the ILs effect on the CO2 adsorption of the AlTp. Comparison of CO2 adsorption in ILs/AlTp with different anion ([Cl]−, [Br]−, [SCN]−, [BF4]−) reveals that CO2 adsorption in ILs/AlTp was increased in the order as: [BF4]− < [SCN]− < [Br]− < [Cl]−. The results show that [BMPyr][Cl]/AlTp the highest CO2 adsorption capacity, 2.6 times higher than that of AlTp at 5 bar and 298.15 K which helps to guide the logical design of new mixtures for gas separation applications. Also, adsorption/desorption test show that regeneration performance of [BMPyr][Cl]/AlTp is 96.53% after five consecutive cycles adsorption/desorption. [ABSTRACT FROM AUTHOR]

These data help in advance genotyping and imaging with a detailed clinical history of patients in dermatology and psychiatry.[[5]] No implications of artificial intelligence are reported on psychodermatological practice. Dear Editor, Psychodermatology is an emerging discipline of medicine that focuses on the mind-skin connection and its disorders.[1] Roberts et al.[2] described psychodermatology as dermatologic manifestations caused by psychiatric disorders, psychiatric symptoms caused by dermatologic disorders, and the effects of psychological stressors and the physiologic response to dermatological disorders. [Extracted from the article]

In this paper, we propose a numerical scheme of the predictor–corrector type for solving nonlinear fractional initial value problems; the chosen fractional derivative is called the Atangana–Baleanu derivative defined in Caputo sense (ABC). This proposed method is based on Lagrangian quadratic polynomials to approximate the nonlinearity implied in the Volterra integral, which is obtained by reducing the given fractional differential equation via the properties of the ABC‐fractional derivative. Through this technique, we get corrector formula with high accuracy, which is implicit, as well as predictor formula, which is explicit and has the same precision order as the corrective formula. On the other hand, the so‐called memory term is computed only once for both prediction and correction phases, which indicates the low cost of the proposed method. Also, the error bound of the proposed numerical scheme is offered. Furthermore, numerical experiments are presented in order to assess the accuracy of the new method on two differential equations. Moreover, a case study is considered where the proposed predictor–corrector scheme is used to obtain approximate solutions of a coupled nonautonomous ABC‐fractional differential system. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is a highly lethal disease. Therapeutic resistance to chemotherapy is a major cause of treatment failure and recurrence in pancreatic cancer. Organoids derived from cancer stem cells (CSC) are promising models for the advancement of personalised therapeutic responses to inform clinical decisions. However, scaling-up of 3D organoids for high-throughput screening is time-consuming and costly. Here, we successfully developed organoid-derived cell lines (2.5D) from 3D organoids; the cells were then expanded and recapitulated back into organoids known as cell line organoids (CLOs). The 2.5D lines were cultured long term into 2D established cell lines for downstream comparison analysis. Experimental characterisation of the models revealed that the proliferation of CLOs was slightly faster than that of parental organoids. The therapeutic response to chemotherapeutic agents in 3D CLOs and organoids showed a similar responsive profile. Compared to 3D CLOs and organoids, 2D cell lines tended to be less responsive to all the drugs tested. Stem cell marker expression was higher in either 3D CLOs or organoids compared to 2D cell lines. An in vivo tumorigenicity study found CLOs form tumours at a similar rate to organoids and retain enhanced CSC marker expression, indicating the plasticity of CSCs within the in vivo microenvironment. [ABSTRACT FROM AUTHOR]

The ward round has traditionally been a learning activity in medical education. Apart from education, ward rounds have multiple roles including patient care and communication. Some studies have described the ward round as an ideal place to learn patient management while others reported that little learning happens on rounds due to lack of time and patient volume. This study aimed to develop a deeper understanding of ward round learning from the perspective of postgraduate trainees. A constructivist grounded theory approach was used and data was collected during focus group discussions. Data were analyzed by initial coding, then grouped into focused codes and development of a theoretical framework by the process of constant comparison. Six categories evolved which contributed to the framework. Postgraduate trainees perceive the ward round as an important space where they use different learning activities to acquire knowledge, attitude and skills required of a specialist doctor. They progress from novices to experts under supervision of faculty who lead ward rounds. The round can achieve its full learning potential if planned and organized well but can become a missed opportunity if the learning environment is unfriendly. Patient- and learner-related barriers exist that hinder ward round learning. The framework explains how ward round learning occurs in postgraduate medical education from a trainee perspective. The findings can guide interventions to improve the learning experience. Studies comparing perspectives of teachers to those of learners are needed to further understand the complex learning milieu of the ward round. [ABSTRACT FROM AUTHOR]

DevOps (development and operations) is a collective and multidisciplinary organizational effort used by many software development organizations to build high-quality software on schedule and within budget. Implementing DevOps is challenging to implement in software organizations. The DevOps literature is far away from providing a guideline for effectively implementing DevOps in software organizations. This study is conducted with the aim to develop a readiness model by investigating the DevOps-related factors that could positively or negatively impact DevOps activities in the software industry. The identified factors are further categorized based on the internal and external aspects of the organization, using the SWOT (strengths, weaknesses, opportunities, threats) framework. This research work is conducted in three different phases: (1) investigating the factors, (2) categorizing the factors using the SWOT framework, and finally, (3) developing an analytic hierarchy process (AHP)-based readiness model of DevOps factors for use in software organizations. The findings would provide a readiness model based on the SWOT framework. The proposed framework could provide a roadmap for organizations in the software development industry to evaluate and improve their implementation approaches to implement a DevOps process. [ABSTRACT FROM AUTHOR]

Background: Congenital cataract is causing one‐third of blindness worldwide. Congenital cataract is heterogeneous in its inheritance patterns. The current study is aimed to explore the unknown genetic causes underlying congenital cataracts. Methods: Blood samples from affected and normal individuals of n = 25 Pakistani families identified with congenital cataracts were collected. Genomic DNA was extracted and Sanger sequencing was performed to identify novel pathogenic variants in the FYCO1 (MIM#607182) gene. Later structural bioinformatics tools and molecular dynamics simulations were performed to analyze the impact of these variants on protein structure and function. Results: Sanger sequencing resulted in the identification of a novel splice site mutation (NM_024513.3: c.3151‐29_3151‐7del) segregating in an autosomal recessive manner. This novel variant was confirmed to be absent in the n = 300 population controls. Further, bioinformatics tools revealed the formation of a mutant protein with a loss of the Znf domain. In addition, we also found a previously known (c.4127 T > C; p.Leu1376Pro) mutation in four families. We also report a novel heterozygous variant (c.3419G > A; p.Arg1140Gln) in another family. Conclusions: In conclusion, we report a novel deletion (NM_024513.3: c.3151‐29_3151‐7del) in one family and a frequent homozygous missense mutation (c.4127 T > C; p.Leu1376Pro) in four Pakistani families. The current research highlights the importance of autophagy in lens development and maintaining its transparency. [ABSTRACT FROM AUTHOR]

Stock markets around the world are growing rapidly, and vulnerability created by default risk of option holders has become a serious issue. In such circumstances, this paper suggests the pricing of vulnerable European and barrier options, when the underlying asset and asset held by the option writer follow the geometric Liu process and uncertain mean-reverting process, respectively. According to the uncertainty theory, we present closed-form analytic formulas of these option prices and use the residual method to estimate the model parameters. In order to estimate the model parameters, the genetic algorithm to solve the generalized moment estimation problem derived by the residual method is suggested. From the uncertain hypothesis test, we then evaluate whether the proposed uncertain stock models fit the observed data. Ultimately, based on the estimated parameters, we evaluate the effect of the vulnerable option parameters on its price. [ABSTRACT FROM AUTHOR]

Correction for 'Improved the CO2 adsorption performance in cobalt oxide nanoparticles in the presence of DES' by Narmin Noorani et al., New J. Chem., 2023, 47, 16748–16755, https://doi.org/10.1039/D3NJ02469E. [ABSTRACT FROM AUTHOR]

In this study, the solubility of carbon dioxide gas in a series of 1-alkyl-4-methyl pyridinium and 1-alkyl-3-methylimidazolium-based ionic liquids with various anions, viz. thiocyanate ([SCN]−), chloride ([Cl]−) and bromide ([Br]−) was investigated using a quartz crystal microbalance at 298.15 K and pressures up to 0.4 MPa. CO2 solubility in the ionic liquids correlates well with the non-random two-liquid (NRTL) model. The results indicate that the cation alkyl chain length and the type of anion have the main effects on the solubility of carbon dioxide in ionic liquids. CO2 solubility in both 1-alkyl-4-methyl pyridinium and 1-alkyl-3-methylimidazolium-based ionic liquids increased with increasing alkyl chain length of the cation. Also, CO2 solubility was strongly dependent on the selection of the anion. CO2 solubility in both 1-alkyl-4-methyl pyridinium and 1-alkyl-3-methylimidazolium-based ionic liquids increased as follows: [SCN]− > [Cl]− > [Br]−. The solubility of CO2 in some of ionic liquids (ILs) was measured. CO2 solubility in ILs with different alkyl chain lengths in the cation increased with increasing alkyl chain length. Also, CO2 solubility increased with increasing anion basicity. [ABSTRACT FROM AUTHOR]

A survey was conducted to know the incidence of viruses in apricot growing in the Srinagar and Shopian regions of Jammu and Kashmir during May 2015. A total of 52 leaf samples were obtained and virus infection was confirmed using nucleic acid spot hybridization (NASH) and reverse transcription-polymerase chain reaction (RT-PCR). The infectivity of cherry virus A (CVA) and prunus necrotic ringspot virus (PNRSV) was found to be 44% and 98% by NASH and 36% and 77% by RT-PCR, respectively. Based on the sequence variability of RdRp, CVA isolates found globally have been grouped into six phylogroups (Group 1–6), whereas PNRSV isolates from India have been divided into three phylogroups (Group 1, Group 2A and Group 2B) based on coat protein gene. Our findings prove that PNRSV and CVA are the two significant viruses of apricot, with PNRSV being the leading cause of apricot necrosis in old orchards. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate a three-compartmental semi-physiological model for analysis of uptake clearance and efflux from brain tissue of the hydrophilic markers sucrose and mannitol, compared to non-compartmental techniques presuming unidirectional uptake. Methods: Stable isotope-labeled [13C]sucrose and [13C]mannitol (10 mg/kg each) were injected as IV bolus into the tail vein of awake young adult mice. Blood and brain samples were taken after different time intervals up to 8 h. Plasma and brain concentrations were quantified by UPLC-MS/MS. Brain uptake clearance (Kin) was analyzed using either the single-time point analysis, the multiple time point graphical method, or by fitting the parameters of a three-compartmental model that allows for symmetrical exchange across the blood-brain barrier and an additional brain efflux clearance. Results: The three-compartment model was able to describe the experimental data well, yielding estimates for Kin of sucrose and mannitol of 0.068 ± 0.005 and 0.146 ± 0.020 μl.min−1.g−1, respectively, which were significantly different (p < 0.01). The separate brain efflux clearance had values of 0.693 ± 0.106 (sucrose) and 0.881 ± 0.20 (mannitol) μl.min−1.g−1, which were not statistically different. Kin values obtained by single time point and multiple time point analyses were dependent on the terminal sampling time and showed declining values for later time points. Conclusions: Using the three-compartment model allows determination of Kin for small molecule hydrophilic markers with low blood-brain barrier permeability. It also provides, for the first time, an estimate of brain efflux after systemic administration of a marker, which likely represents bulk flow clearance from brain tissue. [ABSTRACT FROM AUTHOR]

The proliferation of emerging pollutants (EPs), encompassing a range of substances such as phthalates, phenolics, pharmaceuticals, pesticides, personal care products, surfactants, and disinfection agents, has become a significant global concern due to their potential risks to the environment and human well-being. Over the past two decades, numerous research studies have investigated the presence of EPs in wastewater and aquatic ecosystems, with the United States Environmental Protection Agency (USEPA) categorizing these newly introduced chemical compounds as emerging contaminants due to their poorly understood impact. EPs have been linked to adverse health effects in humans, including genotoxic and cytotoxic effects, as well as conditions such as obesity, diabetes, cardiovascular disease, and reproductive abnormalities, often associated with their estrogenic action. Microalgae have shown promise in the detoxification of both inorganic and organic contaminants, and several large-scale microalgal systems for wastewater treatment have been developed. However, the progress of algal bioremediation can be influenced by accidental contaminations and operational challenges encountered in pilot-scale research. Microalgae employ various processes, such as bioadsorption, biouptake, and biodegradation, to effectively remediate EPs. During microalgal biodegradation, complex chemical compounds are transformed into simpler substances through catalytic metabolic degradation. Integrating algal bioremediation with existing treatment methodologies offers a viable approach for efficiently eliminating EPs from wastewater. This review focuses on the use of algal-based biological remediation processes for wastewater treatment, the environmental impacts of EPs, and the challenges associated with implementing algal bioremediation systems to effectively remove emerging pollutants. [Display omitted] • Innovation in phycoremediation to remove emerging pollutants (EPs) from wastewater. • Deep evaluation of the negative impacts of EPs on human health and the environment. • Phycoremediation is combined with modern techniques to remove EPs effectively. • Potential of microalgae to catalyse the metabolic breakdown of complex EPs. [ABSTRACT FROM AUTHOR]

Orexin receptors expressed in basolateral amygdala (BLA) have been proposed for memory processing and hippocampal plasticity. There are several investigations about the effect of the adrenergic system in BLA on memory enhancement. However, there is no information about the molecular basis of this effect. Adrenergic and orexinergic fibers are found in BLA. In this study, the effects of both adrenergic and orexinergic systems were investigated on the amygdala function. To this end, the selective beta 2 adrenergic agonist (clenbuterol) and orexin receptors' antagonists (OX1R and OX2R, SB-334867-A and TCS-OX2-29, respectively) were administered into the BLA, then the high frequency stimulation (200-Hz) was applied to the perforant pathway and the synaptic plasticity of the dentate granular cells was studied in anaesthetized rats. Clenbuterol injection into the BLA enhanced the population spike (PS) component of LTP in the dentate gyrus (DG), as compared to that observed after dimethyl sulfoxide treatment. In addition, after orexin 1 or 2 receptor antagonists (SB-334867-A and TCS-OX2-29, respectively) injecting into the BLA, the enhancing effect of clenbuterol on PS was reduced. Moreover, the population excitatory post-synaptic potential also decreased in the SB-clenbuterol and TCS- clenbuterol experimental groups. However, the PS amplitude was also decreased in the group treated only by SB or TCS relative to the clenbuterol treated group. The PS amplitude or EPSP slope in the groups treated by both application of orexin receptors' antagonists and clenbuterol was considerably lower relative to the groups treated only by orexin receptors' antagonists. It is concluded that the BLA orexinergic system modulates hippocampal plasticity in relation with the adrenergic system. [Display omitted] • The roles of the orexin receptors (type 1 and 2) and β2 adrenergic receptors on LTP. • The beta-adrenergic activation of BLA potentiated LTP induction inside DG. • Antagonism of the OX1R of BLA impaired LTP induction in DG induced by clenbuterol. • Antagonism of the OX2R of BLA impaired LTP induction in DG induced by clenbuterol. [ABSTRACT FROM AUTHOR]

In recent years, the liberalization of energy markets (especially electricity) by many countries has led to much attention being paid to their modeling. The energy market modeling under the framework of probability theory is valuable when the distribution function is close enough to the actual frequency. However, due to the complexity and variability of the world, economic reasons and changing government policies, this assumption is not applicable in some cases. Under such circumstances, we propose an uncertain two-factor model based on uncertain differential equations to evaluate the electricity spot price dynamics. Then, several essential indicators of electricity are investigated and generalized moment estimation for unknown parameters is also provided. Two case studies by using electricity data from the Oslo and Stockholm regions illustrate our approach. We also compare the proposed model with one-factor uncertain model driven by Liu process and the electricity stochastic model. A detailed numerical study illustrates the efficiency of the proposed model to evaluate electricity spot prices. [ABSTRACT FROM AUTHOR]

A reaction-diffusion system can be represented by the Gray-Scott model. In this study, we discuss a one-dimensional time-fractional Gray-Scott model with Liouville-Caputo, Caputo-Fabrizio-Caputo, and Atangana-Baleanu-Caputo fractional derivatives. We utilize the fractional homotopy analysis transformation method to obtain approximate solutions for the time-fractional Gray-Scott model. This method gives a more realistic series of solutions that converge rapidly to the exact solution. We can ensure convergence by solving the series resultant. We study the convergence analysis of fractional homotopy analysis transformation method by determining the interval of convergence employing the ℏ u , v -curves and the average residual error. We also test the accuracy and the efficiency of this method by comparing our results numerically with the exact solution. Moreover, the effect of the fractionally obtained derivatives on the reaction-diffusion is analyzed. The fractional homotopy analysis transformation method algorithm can be easily applied for singular and nonsingular fractional derivative with partial differential equations, where a few terms of series solution are good enough to give an accurate solution. [ABSTRACT FROM AUTHOR]

Over the past decade and a half, psychedelic drug-induced experiences have been returning to psychiatry as promising new healing modalities. The case of psychedelic-assisted psychotherapy can inform how we think about the context of drug use because psychedelics are commonly considered to be sensitive to the '[mind] set and setting' of their use. As such, epistemic and therapeutic concerns among psychedelic researchers and therapists over the importance of set and setting are interwoven. My ethnography of psychedelic therapeutics both inside and outside of the clinical trials on the east coast of the United States from 2015 to 2019 suggests that there are added political and economic imperatives to contain psychedelic use. Working with this insight, I suggest psychedelic researchers and therapists are producing immense experiences that tend to overflow the attempts at their containment. I also identify two qualities central to the set and setting of the emerging modality of psychedelic-assisted psychotherapy. The first is a labor of protecting spaces which reveals an attentiveness to disconnection that can be read as in tension with the more commonly evoked emphasis on connection found within psychedelic discourses. The second is how psychedelic experiences (as 'mind-manifesting') are understood to reflect the self, and in so doing re-present epistemic disagreements about the nature of the self thus reflected. Taken together, I propose that these two qualities of psychedelic containment offer an analytics for reading the contemporary cultural politics of psychedelic use. [ABSTRACT FROM AUTHOR]

Introduction: the Coronavirus Disease 2019 pandemic has affected residency training globally. The aim of this study was to understand how the pandemic affected teaching and learning in residency programs in low resource settings where residents and faculty were working on the front line treating patients with the disease. Methods: this qualitative study enrolled residents and faculty from the Aga Khan University in Tanzania who were providing front line care during the pandemic. Purposeful sampling was used and data was collected using focus group discussions and in-depth interviews between August and September 2020. Analysis was done using qualitative content analysis. Results: twelve residents and six faculty members participated in this study. Two main themes emerged. The first was: "New and unfamiliar teaching and learning experiences." Residents and faculty had to adapt to changes in the learning environment and the academic program. Residents had increased responsibilities, including providing front line care and working with reduced supervision. The second theme was: "Learning opportunities amidst crisis." There were opportunities to improve critical care and procedural skills. They also had opportunities to improve non-technical skills like teamwork and communication. Conclusion: residents and faculty had to adapt to changes in teaching and learning. Residents also had to take up additional responsibilities. Support systems are required to help them adapt to the changes and settle in their new roles. There were opportunities to learn new skills, and training should be restructured to maximize the use of these opportunities. [ABSTRACT FROM AUTHOR]

Poly (ionic liquid)s attracted enormous attention as adsorbents for the CO2 separation from natural gas. Hence, in this work poly (1-butyl-3-vinylimidazolium bromide), P[VBIm][Br], poly (1-butyl-3-vinylimidazolium thiocyanate), P[VBIm][SCN], and poly (1-butyl-3-vinylimidazolium tetrafluoroborate), P[VBIm][BF4] were synthesized and evaluated their CO2 adsorption performance. The synthesized poly(ionic liquid)s were characterized by 1H NMR, FT-IR spectroscopy, and differential scanning calorimetery (DSC) analysis. The CO2 adsorption was studied at various temperatures and pressures by quartz crystal microbalance (QCM) and experimental data were correlated by a model of dual-mode. The Henry and Langmuir contributions in CO2 adsorption were evaluated. The obtained thermodynamics and kinetics parameters of CO2 adsorption reveal that CO2 adsorption has an exothermic and physisorption nature. Also, density functional theory (DFT) computations were done in order to assess interactions between poly(ionic liquid)s with CO2 gas. DFT computations corroborated that interaction of P[VBIm][SCN] with CO2 is stronger than those of other poly(ionic liquid)s. [ABSTRACT FROM AUTHOR]

The brain is the most important organ in our body requiring its unique microenvironment. By the virtue of its function, the blood-brain barrier poses a significant hurdle in drug delivery for the treatment of neurological diseases. There are also different theories regarding how molecules are typically effluxed from the brain. In this review, we comprehensively discuss how the different pharmacokinetic techniques used for measuring brain uptake/permeability of small molecules have evolved with time. We also discuss the advantages and disadvantages associated with these different techniques as well as the importance to utilize the right method to properly assess CNS exposure to drug molecules. Even though very strong advances have been made we still have a long way to go to ensure a reduction in failures in central nervous system drug development programs. [ABSTRACT FROM AUTHOR]

A reaction-diffusion system can be represented by the Gray-Scott model. In this study, we discuss a one-dimensional time-fractional Gray-Scott model with Liouville-Caputo, Caputo-Fabrizio-Caputo, and Atangana-Baleanu-Caputo fractional derivatives. We utilize the fractional homotopy analysis transformation method to obtain approximate solutions for the time-fractional Gray-Scott model. This method gives a more realistic series of solutions that converge rapidly to the exact solution. We can ensure convergence by solving the series resultant. We study the convergence analysis of fractional homotopy analysis transformation method by determining the interval of convergence employing the ℏ u , v -curves and the average residual error. We also test the accuracy and the efficiency of this method by comparing our results numerically with the exact solution. Moreover, the effect of the fractionally obtained derivatives on the reaction-diffusion is analyzed. The fractional homotopy analysis transformation method algorithm can be easily applied for singular and nonsingular fractional derivative with partial differential equations, where a few terms of series solution are good enough to give an accurate solution. [ABSTRACT FROM AUTHOR]

Background: The blood–brain barrier (BBB) plays a critical role in protecting the central nervous system (CNS) from blood-borne agents and potentially harmful xenobiotics. Our group's previous data has shown that tobacco smoke (TS) and electronic cigarettes (EC) affect the BBB integrity, increase stroke incidence, and are considered a risk factor for multiple CNS disorders. Metformin was also found to abrogate the adverse effects of TS and EC. Methods: We used sucrose and mannitol as paracellular markers to quantitatively assess TS and EC's impact on the BBB in-vitro. Specifically, we used a quantitative platform to determine the harmful effects of smoking on the BBB and study the protective effect of metformin. Using a transwell system and iPSCs-derived BMECs, we assessed TS and EC's effect on sucrose and mannitol permeability with and without metformin pre-treatment at different time points. Concurrently, using immunofluorescence (IF) and Western blot (WB) techniques, we evaluated the expression and distribution of tight junction proteins, including ZO-1, occludin, and claudin-5. Results: Our data showed that TS and EC negatively affect sucrose and mannitol permeability starting after 6 h and up to 24 h. The loss of barrier integrity was associated with a reduction of TEER values. While the overall expression level of ZO-1 and occludin was not significantly downregulated, the distribution of ZO-1 was altered, and discontinuation patterns were evident through IF imaging. In contrast to occludin, claudin-5 expression was significantly decreased by TS and EC, as demonstrated by WB and IF data. Conclusion: In agreement with previous studies, our data showed the metformin could counteract the negative impact of TS and EC on BBB integrity, thus suggesting the possibility of repurposing this drug to afford cerebrovascular protection. [ABSTRACT FROM AUTHOR]

Objective: Common surgical treatments for trigeminal neuralgia (TN) include microvascular decompression (MVD) and percutaneous procedures (glycerol rhizolysis; thermocoagulation; and balloon compression). Although the efficacy of each procedure has been documented, direct comparisons of their relative efficacies for TN are lacking. We aimed to directly compare long-term outcomes after first-time MVD with percutaneous surgery in primary (idiopathic and classical) TN and identify predictors of outcome. Methods: We conducted a retrospective analysis of prospectively collected data on 185 patients undergoing MVD and 129 undergoing percutaneous surgery. Procedures were performed by one of two neurosurgeons in a single centre; an independent observer collected long-term follow-up data by interviews, using the same outcome measures for all procedures. Results: MVD patients were younger than those undergoing percutaneous surgery (P <.001). MVD provided superior initial pain relief (P <.001): 87.0% had Barrow Neurological Institute class I or II pain scores after MVD compared with 67.2% after percutaneous surgery. The complication rate for percutaneous procedures was 35.7% and for MVDs was 24.9% (P =.04), including minor and transient complications. Kaplan-Meier analysis demonstrated that MVD provided longer pain relief than percutaneous procedures (P <.001); 25% of patients had recurrence at 96 months following MVD compared with 12 months after percutaneous surgery. Subgroup analysis showed that balloon compression provided more durable relief amongst percutaneous procedures. Multivariate analysis revealed that post-operative numbness and age were prognostic factors for percutaneous procedures (P =.03 and.01, respectively). Conclusions: MVD provides better initial pain relief and longer durability of relief than percutaneous surgery, although carrying a small risk of major complications. Amongst percutaneous procedures, balloon compression gave the most durable relief from pain. Older age and post-operative numbness were predictors of good outcome from percutaneous surgery. These results can help clinicians to counsel patients with primary TN on neurosurgical treatment selection for pain relief. [ABSTRACT FROM AUTHOR]

In this article, we introduce a new type of conformable derivative and integral which involve the time scale power function G ˆ η (t , a) for t , a ∈ T . The time scale power function takes the form (t − a) η for T = R which reduces to the definition of conformable fractional derivative defined by Khalil et al. (2014). For the discrete time scales, it is completely novel, where the power function takes the form (t − a) (η) which is an increasing factorial function suitable for discrete time scales analysis. We introduce a new conformable exponential function and study its properties. Finally, we consider the conformable dynamic equation of the form ▽ a γ y (t) = y (t , f (t)) , and study the existence and uniqueness of the solution. As an application, we show that the conformable exponential function is the unique solution to the given dynamic equation. We also examine the analogue of Gronwall's inequality and its application on time scales. [ABSTRACT FROM AUTHOR]

Ionic liquids have received special attention as CO2 adsorbents from natural gas. This article has investigated the adsorption of CO2 onto three polyvinyl chloride–ionic liquid ionomers (polyvinyl chloride–1–vinyl–3–butyilimidazolium bromide, PVC–g–P[VBIm][Br]; polyvinyl chloride–1–vinyl–3–butyilimidazolium thiocyanate, PVC–g–P[VBIm][SCN]; polyvinyl chloride–1–vinyl–3–butyilimidazolium tetrafluoroborate, PVC–g–P[VBIm][BF4]) using quartz crystal microbalance (QCM) at various temperatures and pressures. The non-linear pseudo-second-order model was used to obtain the CO2 adsorption kinetic parameters. The thermodynamic parameters of CO2 adsorption were evaluated by fitting the experimental adsorption data with the dual-mode model. The obtained thermodynamic and kinetic parameters indicated that CO2 adsorption had exothermic and physisorption nature. The PVC–g–P [VBIm][SCN] ionomer had a better performance in adsorbing the carbon dioxide gas. The density functional theory (DFT) method was also employed to confirm adsorption energy of CO2 onto three polyvinyl chloride–ionic liquid ionomers with different anions. [ABSTRACT FROM AUTHOR]

Flood early warning systems (FLEWSs) contribute remarkably to reducing economic and life losses during a flood. The theory of critical slowing down (CSD) has been successfully used as a generic indicator of early warning signals in various fields. A new tool called persistent homology (PH) was recently introduced for data analysis. PH employs a qualitative approach to assess a data set and provide new information on the topological features of the data set. In the present paper, we propose the use of PH as a preprocessing step to achieve a FLEWS through CSD. We test our proposal on water level data of the Kelantan River, which tends to flood nearly every year. The results suggest that the new information obtained by PH exhibits CSD and, therefore, can be used as a signal for a FLEWS. Further analysis of the signal, we manage to establish an early warning signal for ten of the twelve flood events recorded in the river; the two other events are detected on the first day of the flood. Finally, we compare our results with those of a FLEWS constructed directly from water level data and find that FLEWS via PH creates fewer false alarms than the conventional technique. [ABSTRACT FROM AUTHOR]

Partial b -metric spaces are characterised by a modified triangular inequality and that the self-distance of any point of space may not be zero and the symmetry is preserved. The spaces with a symmetric property have interesting topological properties. This manuscript paper deals with the existence and uniqueness of fixed point points for contraction mappings using triangular weak α -admissibility with regard to η and C -class functions in the class of partial b -metric spaces. We also introduce an example to demonstrate the obtained results. [ABSTRACT FROM AUTHOR]

Carbon dioxide (CO 2) capture from flue gas is of utmost importance in mitigating greenhouse gas emissions. This study focuses on enhancing the CO 2 adsorption capacity of activated carbon (AC) composites through the incorporation of metal oxides. AC, AC/Fe 3 O 4 , and AC/MgO composites were synthesized and characterized using various analytical techniques including Raman and FTIR spectroscopy, TGA, SEM, EDX, XRD, AFM, BET, and VSM analysis. The CO2 adsorption isotherms of the AC/MgO and AC/Fe 3 O 4 composites were measured at different temperatures and pressures using quartz crystal microbalance (QCM). The Langmuir model was successfully employed to fit the experimental data, with AC/MgO and AC/Fe 3 O 4 exhibiting adsorption capacities of 38.567 mmol g− 1 and 71.963 mmol g− 1, respectively, at 298.15 K and 5 bar. These results demonstrate the significant enhancement of CO 2 adsorption capacity achieved by incorporating metal oxides into the AC composite structure. Furthermore, the regeneration efficiency of the adsorbents was evaluated through multiple adsorption/desorption cycles, revealing that AC, AC/MgO, and AC/Fe 3 O 4 maintained adsorption capacities of 94.1%, 97.9%, and 96.5%, respectively, after six consecutive cycles. This confirms their stability and reusability under practical conditions. These findings contribute to our understanding of CO 2 capture using activated pyrolytic coke and metal oxide nanoparticle composites, highlighting the promising potential of AC/MgO composites as effective adsorbents for CO 2 capture applications. Further investigation and optimization of composite structures and synthesis methods are warranted to enhance their overall performance and applicability [Display omitted] [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is characterized by neuronal loss and accumulation of b-amyloid-protein (Ab) in the brain parenchyma. Sleep impairment is associated with AD and affects about 25-40% of patients in the mild-to-moderate stages of the disease. Sleep deprivation leads to increased Ab production; however, its mechanism remains largely unknown. We hypothesized that the increase in core body temperature induced by sleep deprivation may promote Ab production. Here, we report temperature-dependent regulation ofAb production. We found that an increase in temperature, from 37 °C to 39 °C, significantly increased Ab production in amyloid precursor proteinoverexpressing cells. We also found that high temperature (39 °C) significantly increased the expression levels of heat shock protein 90 (Hsp90) and the C-terminal fragment of presenilin 1 (PS1-CTF) and promoted g-secretase complex formation. Interestingly, Hsp90 was associated with the components of the premature g-secretase complex, anterior pharynx-defective- 1 (APH-1), and nicastrin (NCT) but was not associated with PS1-CTF or presenilin enhancer-2. Hsp90 knockdown abolished the increased level of Ab production and the increased formation of the g-secretase complex at high temperature in culture. Furthermore, with in vivo experiments, we observed increases in the levels of Hsp90, PS1-CTF, NCT, and the g-secretase complex in the cortex of mice housed at higher room temperature (30 °C) compared with those housed at standard roomtemperature (23 °C). Our results suggest that high temperature regulates Ab production by modulating g-secretase complex formation through the binding of Hsp90 to NCT/APH-1. [ABSTRACT FROM AUTHOR]