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Shohreh Ghorbani,* Hosein Aghayan Golkashani,* Nicholas IYN Chee, Teck Boon Teo, Andrew Roshan Dicom, Gizem Yilmaz, Ruth LF Leong, Ju Lynn Ong, Michael WL Chee Centre for Sleep and Cognition, Yong Loo Lin School of Medicine, National University of Singapore, Singapore*These authors contributed equally to this workCorrespondence: Michael WL Chee, Centre for Sleep and Cognition, Yong Loo Lin School of Medicine, National University of Singapore, MD1 Level 13 Rm 05B, 117549, Singapore, Tel +65 66013199, Email michael.chee@nus.edu.sgPurpose: To evaluate the benefits of applying an improved sleep detection and staging algorithm on minimally processed multi-sensor wearable data collected from older generation hardware.Patients and Methods: 58 healthy, East Asian adults aged 23– 69 years (M = 37.10, SD = 13.03, 32 males), each underwent 3 nights of PSG at home, wearing 2nd Generation Oura Rings equipped with additional memory to store raw data from accelerometer, infra-red photoplethysmography and temperature sensors. 2-stage and 4-stage sleep classifications using a new machine-learning algorithm (Gen3) trained on a diverse and independent dataset were compared to the existing consumer algorithm (Gen2) for whole-night and epoch-by-epoch metrics.Results: Gen 3 outperformed its predecessor with a mean (SD) accuracy of 92.6% (0.04), sensitivity of 94.9% (0.03), and specificity of 78.5% (0.11); corresponding to a 3%, 2.8% and 6.2% improvement from Gen2 across the three nights, with Cohen’s d values > 0.39, t values > 2.69, and p values < 0.01. Notably, Gen 3 showed robust performance comparable to PSG in its assessment of sleep latency, light sleep, rapid eye movement (REM), and wake after sleep onset (WASO) duration. Participants < 40 years of age benefited more from the upgrade with less measurement bias for total sleep time (TST), WASO, light sleep and sleep efficiency compared to those ≥ 40 years. Males showed greater improvements on TST and REM sleep measurement bias compared to females, while females benefitted more for deep sleep measures compared to males.Conclusion: These results affirm the benefits of applying machine learning and a diverse training dataset to improve sleep measurement of a consumer wearable device. Importantly, collecting raw data with appropriate hardware allows for future advancements in algorithm development or sleep physiology to be retrospectively applied to enhance the value of longitudinal sleep studies.Keywords: consumer wearable, sleep tracking, validation, sleep staging, sleep detection

Copyright of Journal of Mahani Mathematical Research Center is the property of Shahid Bahonar University of Kerman, Department of Pure Mathematics and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The extracellular matrix (ECM) plays an important role in the central nervous system (CNS), shaping tissue structure and functions as well as contributing to the pathology of chronic diseases such as multiple sclerosis (MS). ECM components, including fibulin-2 (FBLN2) and chondroitin sulfate proteoglycans (CSPGs), may impact neuroinflammation and remyelination. We investigated the capacity of FBLN2 to modulate immune responses and evaluated its interaction with CSPGs in experimental autoimmune encephalomyelitis (EAE), a common model for MS. We show that FBLN2 deficiency in EAE mice reduced microglial pro-inflammatory activity, while effects on monocyte-derived macrophages and border-associated macrophages were less pronounced. Targeting FBLN2 and CSPGs individually, using FBLN2 -/- mice and the CSPG-synthesis inhibitor difluorosamine (DIF), respectively, enhanced recovery of disability and reduced neuroinflammation in EAE mice. However, their combined targeting did not result in additive therapeutic effects beyond either alone. This study underscores the complex regulatory roles of ECM components on neuroinflammation and provides insights into potential therapeutic strategies for neuroinflammatory diseases., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Advances in biofabrication have enabled the generation of freeform perfusable networks mimicking vasculature. However, key challenges remain in the effective endothelialization of these complex, vascular-like networks, including cell uniformity, seeding efficiency, and the ability to pattern multiple cell types. To overcome these challenges, we present an integrated fabrication and endothelialization strategy to directly generate branched, endothelial cell-lined networks using a diffusion-based, embedded 3D bioprinting process. In this strategy, a gelatin microparticle sacrificial ink delivering both cells and crosslinkers is extruded into a crosslinkable gel precursor support bath. A self-supporting, perfusable structure is formed by diffusion-induced crosslinking, after which the sacrificial ink is melted to allow cell release and adhesion to the printed lumen. This approach produces a uniform cell lining throughout networks with complex branching geometries, which are challenging to uniformly and efficiently endothelialize using conventional perfusion-based approaches. Furthermore, the biofabrication process enables high cell viability (>90%) and the formation of a confluent endothelial layer providing vascular-mimetic barrier function and shear stress response. Leveraging this strategy, we demonstrate for the first time the patterning of multiple endothelial cell types, including arterial and venous cells, within a single arterial-venous-like network. Altogether, this strategy enables the fabrication of multi-cellular engineered vasculature with enhanced geometric complexity and phenotypic heterogeneity., (© 2025 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Background: Intracerebral hemorrhage (ICH) causes prominent deposition of extracellular matrix molecules, particularly the chondroitin sulphate proteoglycan (CSPG) member neurocan. In tissue culture, neurocan impedes the properties of oligodendrocytes. Whether therapeutic reduction of neurocan promotes oligodendrogenesis and functional recovery in ICH is unknown., Methods: Mice were retro-orbitally injected with adeno-associated virus (AAV-CRISPR/Cas9) to reduce neurocan deposition after ICH induction by collagenase. Other groups of ICH mice were treated with vehicle or a drug that reduces CSPG synthesis, 4-4-difluoro-N-acetylglucosamine (difluorosamine). Rota-rod and grip strength behavioral tests were conducted over 7 or 14 days. Brain tissues were investigated for expression of neurocan by immunofluorescence microscopy and western blot analysis. Brain cryosections were also stained for microglia/macrophage phenotype, oligodendrocyte lineage cells and neuroblasts by immunofluorescence microscopy. Tissue structural changes were assessed using brain magnetic resonance imaging (MRI)., Results: The adeno-associated virus (AAV)-reduction of neurocan increased oligodendrocyte numbers and functional recovery in ICH. The small molecule inhibitor of CSPG synthesis, difluorosamine, lowered neurocan levels in lesions and elevated numbers of oligodendrocyte precursor cells, mature oligodendrocytes, and SOX2 + nestin + neuroblasts in the perihematomal area. Difluorosamine shifted the degeneration-associated functional state of microglia/macrophages in ICH towards a regulatory phenotype. MRI analyses showed better fiber tract integrity in the penumbra of difluorosamine mice. These beneficial difluorosamine results were achieved with delayed (2 or 3 days) treatment after ICH., Conclusion: Reducing neurocan deposition following ICH injury is a therapeutic approach to promote histological and behavioral recovery from the devastating stroke., Competing Interests: Declarations. Ethics approval and consent to participate: All animal experiments were performed with ethics approval (protocol number AC21-0073) from the Animal Care Committee at the University of Calgary under regulations of the Canadian Council of Animal Care. Consent for publication: Not applicable. Competing interests: PZ, CCL and VWY are co-inventors in a US Provisional Patent application (US 63/720,938) titled: Fluorinated glucosamine analogs to reduce injury and promote recovery in neurological disorders., (© 2025. The Author(s).)

Mechanized tunneling in harsh environments faces many hazards, which can stop tunneling operations for a long time. Due to the high investment volume in tunneling projects, it is imperative to predict and assess the geotechnical hazards. This research has tried to evaluate and introduce the most dangerous section of the Kerman water conveyance tunnel (KWCT) using multi-index decision-making techniques including PROMETHEE II, WASPAS, and CoCoSo models. For this purpose, at first, the most important hazards in the tunnel route including dealing with fault zones, water inflow into the tunnel, rock abrasivity, and squeezing potential were identified. Then, the most dangerous sections of the tunnel were determined using empirical and analytical methods. In the next step, the weight of each criterion at most dangerous sections was determined using Shannon's entropy method. The results showed that using PROMETHEE II, WASPAS, and CoCoSo models, section Hz11 of the tunnel is the most dangerous section among all sections from a geotechnical point of view. Finally, this study suggests the PROMETHEE II-entropy, WASPAS-entropy, and CoCoSo-entropy models as the suitable methods with more accuracy among MCDM techniques for evaluating the geotechnical and geological hazards in a real situation of tunneling projects., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background and Objective: Dental implant therapy faces challenges in patients with Type 1 and Type 2 Diabetes Mellitus (T1DM and T2DM) due to adverse effects on bone metabolism and immune response. Despite advancements, diabetic patients face higher risks of peri-implantitis and compromised osseointegration. This review assesses the impact of anti-diabetic medications on implant outcomes, offering insights to bridge the gap between animal studies and clinical practice. By evaluating pharmacotherapeutic strategies in preclinical models, this review guides future research designs to improve implant success rates in diabetic individuals., Method: A comprehensive literature review identified 21 animal studies examining the impact of anti-diabetic medications on dental and bone implants. These studies explored diabetes models, medication regimens, and designs to assess outcomes related to bone metabolism, osseointegration, and peri-implant tissue responses. The findings are systematically summarized, highlighting the scope, design, and procedures of each study. An example includes placing a dental implant in the molar region of a mouse, providing insight into preclinical approaches., Results: Twenty-one animal studies, primarily using rodents, investigate various anti-diabetic medications on dental and bone implants. Interventions include insulin, aminoguanidine, voglibose, sitagliptin, exenatide, and metformin, analyzing outcomes like bone-implant contact (BIC), bone volume (BV), and counter-torque values in T1DM and T2DM models. The impacts of these medications on implant osseointegration under diabetic conditions are detailed, with their benefits and shortcomings assessed., Discussion: The findings and challenges of existing animal studies on diabetes mellitus (DM) and implant osseointegration are presented. Despite T2DM prevalence, research primarily focuses on T1DM models due to easier experimental practicalities, limiting applicability. Inconsistent protocols in studies compromise reliability regarding anti-diabetic treatments' effectiveness on osseointegration. Standardized methodologies and long-term assessments of local drug delivery alongside systemic anti-DM treatments are crucial to manage DM-related complications in implant dentistry., Conclusion: Insulin administration in short-term T1DM animal studies enhances implant osseointegration. However, the efficacy of non-insulin medications remains inconclusive. Rigorous experimental designs are needed to address inconsistencies and assess long-term impacts. Larger-sized (e.g., porcine) animal studies across various intraoral implant scenarios are required. Future research should focus on enhancing clinical applicability and improving implant stability in evolving conditions., Competing Interests: Author DW was employed by DWA Energy Limited but the company does not trade in the medical and pharmaceutical fields and provided no funding for this study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ghorbani, Minasyan, Ansari, Ghorbani, Wood, Yeremyan, Ghorbani and Minasian.)

Purpose: To conduct a systematic review and meta-analysis to provide an outline of available data on the association between serum vitamin D levels and vernal keratoconjunctivitis (VKC) and to determine the possible relationship in children., Methods: Systematic research on all articles published until July 2023 was conducted in PubMed, SCOPUS, Web of Science, and Embase. All observational-analytical studies that measured vitamin D levels in patients with VKC were included. Extracted data were included in two separate meta-analyses: 1) a meta-analysis on the standardized mean difference (SMD) of vitamin D levels between VKC patients and the control group and 2) a meta-analysis on the prevalence of vitamin D deficiency in VKC patients., Results: Seven relevant studies that included 316 patients, with the mean age of 10.8 3 ± 1.14 years, with VKC were included in this meta-analysis. The mean serum vitamin D level was significantly lower in the patients with VKC as compared with the control group (SMD: -0.92; 95% CI -1.15, -0.69, p  < 0.001). The overall prevalence of vitamin D deficiency among VKC patients was 63.7% (95% CI 42.5%-80.7%, p < 0.001). VKC patients spent significantly less time outdoors during daylight compared to healthy individuals (SMD = -0.90, 95%CI -1.28, -0.52, p  < 0.001)., Conclusion: VKC patients have lower serum vitamin D than healthy controls. This finding underscores the potential role of vitamin D in the immunopathogenesis of VKC.

Background: Bladder cancer (BC) is the tenth most common cancer with the highest mortality rate. Since the etiological role of viral infection in the development of BC is less known, the aim of the present study was to examine the pooled prevalence and possible relationship between viral infection and BC., Methods: A systematic search of major online databases was conducted to investigate relevant studies. We estimated the pooled odds ratio (OR), 95 % confidence interval (CI), and heterogeneity for all studies by using meta-analysis and forest plots. All data were analyzed using Stata Software v.14.1., Results: We analyzed 87 articles (97 datasets), which included 59 case-control and 38 cross-sectional designs. The pooled prevalence of viral infection among BC patients was 17.59 % (95 % CI: 13.09-22.55 %; I 2 = 96.34 %). Our subgroup analysis indicated that the pooled prevalence of human herpesvirus (HHV), papillomavirus (HPV), polyomavirus, and adenovirus was 33.67 %, 15.18 %, 7.46 %, and 30.14 %, respectively. We detected a significant relationship between viral infection and BC [summary OR 2.34 (95 % CI 1.56-3.51; I 2 = 58.0 %)]., Conclusions: This possible association was exhibited for Epstein-Barr virus (EBV) and HPV. Our finding indicated that HPV and EBV infections with significant associations with BC can be considered as possible risk factors for BC. Although the specific molecular mechanism of the role of viruses in the development of BC has not been identified, persistent viral infection, oncogenic protein expression, apoptosis inhibition, cell cycle promotion, and disruption of signaling pathways in bladder tissue are possible pathways for the role of viruses in the development of BC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Cyclophosphamide, a chemotherapy drug, increases oxidative stress in sperm and testicular tissue. This study evaluated the effect of silymarin, a potent antioxidant, on the quality of sperm and testicular tissue in mice treated with cyclophosphamide. NMRI adult male mice were divided into four groups: control; cyclophosphamide (intraperitoneal injection, 100 mg/kg, once a week); cyclophosphamide + silymarin; and silymarin (intraperitoneal injection, 200 mg/kg, every other day). After a 35-day treatment period, the caudal region of the epididymis was examined for sperm parameters, the right testis was used for stereological studies, and the left testis was used to assess biochemical factors. The data were statistically analyzed using SPSS software, one-way ANOVA and Tukey's test. In the cyclophosphamide group, there was a significant reduction in the mean total volume of testicular tissue, the average volume of seminiferous tubules and their components, and the average volume of interstitial tissue. Additionally, there was a notable decrease (p < 0.001) in the average number of Leydig cells, Sertoli cells, and sperm parameters. The mean concentration of testosterone hormone (p < 0.05) and total antioxidant capacity (TAC) level (p < 0.01) also significantly decreased, while the malondialdehyde (MDA) level increased significantly (p < 0.05). However, these adverse changes were mitigated in the cyclophosphamide + silymarin group compared to the cyclophosphamide group. Our results showed that silymarin as an antioxidant can mitigate the adverse effects of cyclophosphamide on testicular tissue and sperm parameters., Competing Interests: Declaration of Competing Interest The authors state that they have no conflicts of interest., (Copyright © 2024 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier B.V. All rights reserved.)

Purpose: This study investigates the determinants of smoking behavior among young adults in Khuzestan province, southwest Iran, using two-level count regression models. Given the high prevalence of smoking-related diseases and the social impact of smoking, understanding the factors influencing smoking habits is crucial for effective public health interventions., Methods: We conducted a cross-sectional analysis of 1,973 individuals aged 18-35 years, using data from the Daily Smoking Consumption Survey (DSCS) in Khuzestan province collected in 2023. A variety of count regression models, including Poisson, Negative Binomial, Conway-Maxwell Poisson, and their zero-inflated counterparts, were evaluated. The best-fitting model was selected based on goodness-of-fit indices., Results: Approximately 90% of participants were non-smokers. Among smokers, the prevalence of light, moderate, and heavy smoking was 47.7, 19.0, and 33.3%, respectively. The two-level Zero-Inflated Conway-Maxwell Poisson (ZICMP) model provided the appropriate fit for the data. Key determinants of daily cigarette consumption included gender, age, education, and Body Mass Index (BMI). Men consumed 3.24 times more cigarettes per day than women. Higher education levels were inversely related to smoking intensity, with MSc/PhD holders having significantly lower smoking rates. Age and BMI also significantly influenced smoking behavior, with younger and obese individuals showing lower smoking rates., Conclusion: The use of advanced count models capable of handling numerous zeros and overdispersion is crucial for accurately analyzing trends in cigarette consumption across different population groups. The results indicate that factors such as older age, lower education levels, and gender differences influence smoking behavior. Therefore, prevention strategies aimed at delaying the onset of smoking, particularly among men, and promoting education among adolescents can effectively reduce smoking rates. However, further research should consider additional socioeconomic variables and encompass a broader age range to enhance the understanding of smoking behavior., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Satyar, Ahmadi Angali, Ghorbani, Kamyari and Seyedtabib.)

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is the most prevalent chronic liver condition worldwide, affecting over 25% of the population. Fatty infiltration in MASLD leads to hemodynamic changes in hepatic circulation, which can be quantitatively assessed using Color Doppler Ultrasonography (US). In this study, we aimed to investigate the correlation of Color Doppler US findings of the portal, hepatic, and splenic venous system within various degrees of MASLD., Methods and Materials: Between 2021 and 2024, 104 patients referred to Mousavi Hospital at Zanjan University of Medical Sciences were enrolled. Participants were divided into four groups based on the degree of hepatic fatty infiltration on biopsy results: normal, grade 1, grade 2, and grade 3, with 26 subjects in each group (13 men and 13 women). All patients were biopsy proved. Gray-scale and Color Doppler US were used to assess portal and splenic vein peak systolic velocity (PSV), portal and splenic vein diameter, hepatic vein waveform, and spleen size. The Spearman rank correlation was employed to evaluate the relationship between these variables under non-parametric conditions., Results: A significant negative correlation was found between portal vein PSV and MASLD grade (r = - 0.499, p = 0.000). A significant difference was also observed in hepatic venous waveform abnormality between different grades of MASLD (p = 0.043). Accordingly, portal vein PSV and splenic vein PSV had a significantly positive correlation (r = 0.209, p = 0.033). We also observed a positive correlation between the portal vein and splenic diameter (r = 0.210, p = 0.032)., Conclusion: Increasing MASLD severity is associated with reduced portal vein PSV and more pronounced abnormalities in hepatic vein flow. Routine assessment of portal and hepatic vein flow using Color Doppler US is recommended to accurately diagnose and monitor the effects of MASLD on hepatic circulation, potentially improving disease management and patient outcomes., Competing Interests: Declarations Conflict of interest The authors declare that they have no scientific or commercial conflicts of interest. The authors have no relevant financial or non-financial interests to disclose. Ethical approval The study received approval from the Ethics Committee of Zanjan University of Medical Sciences in Zanjan, Iran (reference number ZUMS.REC.1396.224). Consent to participate All participants were fully informed about the study's purpose, requirements, and timeline. They provided written informed consent before participating. Consent to publish Written informed consent for publication of data was received from all participants., (© 2024. Società Italiana di Ultrasonologia in Medicina e Biologia (SIUMB).)

Adding plant extracts to sausage and other meat products is very important to improve their quality, safety, and durability. The aim of this study was to evaluate the microbiological properties of beef sausage enriched with roselle ( Hibiscus sabdariffa L.) sepal extract. The total content of phenolic and flavonoid compounds in hydroalcoholic extract of Roselle sepals was measured by Folin-Ciocalteu test and aluminum chloride colorimetric method, and antioxidant activity was measured by DPPH method. Pectin was used to encapsulate the extract. The characteristics of capsules, including particle size, zeta potential, and capsule efficiency were measured. Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) of extracts were performed by tube dilution method. Microbial tests were performed on sausage treatment samples. Analysis of the obtained data was done using SPSS and Excel software. The study revealed that the total phenolic and flavonoid compounds in the extract were 174.6 mg of gallic acid per gram and 16.8368 mg of quercetin, respectively. The extract displayed the highest antioxidant activity at elevated concentrations. Particle size ranged from 16.833 to 640.534 μm. The zeta potential and capsule efficiency were found to be satisfactory. Compared to the encapsulated extract, the free roselle extract better inhibited Staphylococcus aureus ( s. aureus ), Salmonella typhimurium ( S. typhimurium ), and Escherichia coli ( E.coli ). During storage until day 20, these bacteria did not grow in the free or encapsulated extract groups. However, S. aureus appeared in the free extract group from day 25 and the encapsulated extract group from day 20. Roselle extract has antimicrobial properties that can improve the quality and safety of beef sausage during storage., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Food Science & Nutrition published by Wiley Periodicals LLC.)

Purpose: To evaluate clinical presentations, computed tomography (CT) findings, and various prognostic factors affecting the surgical outcomes of trapdoor fractures., Methods: This retrospective multi-center study reviewed medical records and orbital CT scans of patients under 21 years old, diagnosed with isolated trapdoor fractures. The study was conducted across multiple medical centers, including emergency and clinical departments in Isfahan, Shiraz, and Tehran-Iran. The characteristics and outcomes following surgical intervention were assessed., Results: 45 patients with isolated trapdoor fractures were included in the study, with a mean age of 11.67 ± 4.69 years, predominantly male (84.4%). Vehicle accidents was the major cause of fractures (31.1%). 44 patients (97.8%) had orbital floor fracture, and one patient (2.2%) had medial wall involvement. Nausea/vomiting were reported in 41 patients (91.1%). Surgical intervention within 2 days, resulted in 85.0% of patients experiencing no postoperative diplopia. Delayed surgery beyond 2 days showed increased odds of diplopia, although not statistically significant. CT scan findings suggested a lower risk of diplopia in patients with soft tissue entrapment compared to muscle involvement (OR: 0.336, 95% CI: 0.077-1.462, p = 0.146). Shorter time to surgery (within 2 days) was significantly associated with normal postoperative eye movements (p = 0.002). Nausea/vomiting were more prevalent in patients with muscle entrapment (p < 0.05)., Conclusion: Surgical intervention within 48 h is crucial for improving ocular motility following trapdoor fractures. Extraocular symptoms, including nausea/vomiting, should raise suspicion for trapdoor fractures in cases of orbital trauma associated with ocular movement impairment., Clinical Trial Number: Not applicable., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Aim: Several microRNAs (miRNAs) are differentially expressed and serve as tumor suppressors in glioblastoma (GBM). The present study aimed to elucidate the function of exosomal microRNA-4731-5p (miR-4731-5p) from adipose tissue-derived mesenchymal stem cells (AD-MSCs) in the activity of human GBM cell lines., Method: First, GBM-related miRNAs, their expression, and potential target genes and cytokines of miR-4731-5p were identified using bioinformatic datasets. Subsequently, purified AD-MSCs were transfected with a miRNA-4731-5p expression plasmid, and exosomes were isolated and characterized. Next, the transfection process was confirmed and the 50% inhibitory concentration (IC50) of the overexpressed exosomal miRNA-4731-5p was inhibited for cancer cells. The probable anticancer action of exosomal miRNA-4731-5p on U-87 and U-251 GBM cell lines was verified by flow cytometry, DAPI staining, cell cycle, real-time PCR, and wound healing assays., Results: A concentration of 50 ng/mL of miRNA-4731-5p-transfected exosomes was the safe dose for anticancer settings. The results showed that the exosomal miR-4731-5p exerted an inhibitory effect on the cell cycle and migration and induced apoptosis in GBM cell lines by regulating the phosphoinositide-3-kinase-AKT (PI3K-AKT) and nuclear factor-kB (NF-kB) signaling pathways., Conclusion: This study reveals that the expression of exosomal miRNA-4731-5p has favorable antitumor properties for the treatment of GBM cell lines and may be a fundamental therapeutic option for this type of brain tumor., (Copyright © 2024. Published by Elsevier Inc.)

Given the large number of genes significantly associated with risk for neuropsychiatric disorders, a critical unanswered question is the extent to which diverse mutations --sometimes impacting the same gene-- will require tailored therapeutic strategies. Here we consider this in the context of rare neuropsychiatric disorder-associated copy number variants (2p16.3) resulting in heterozygous deletions in NRXN1 , a pre-synaptic cell adhesion protein that serves as a critical synaptic organizer in the brain. Complex patterns of NRXN1 alternative splicing are fundamental to establishing diverse neurocircuitry, vary between the cell types of the brain, and are differentially impacted by unique (non-recurrent) deletions. We contrast the cell-type-specific impact of patient-specific mutations in NRXN1 using human induced pluripotent stem cells, finding that perturbations in NRXN1 splicing result in divergent cell-type-specific synaptic outcomes. Via distinct loss-of-function (LOF) and gain-of-function (GOF) mechanisms, NRXN1 +/- deletions cause decreased synaptic activity in glutamatergic neurons, yet increased synaptic activity in GABAergic neurons. Reciprocal isogenic manipulations causally demonstrate that aberrant splicing drives these changes in synaptic activity. For NRXN1 deletions, and perhaps more broadly, precision medicine will require stratifying patients based on whether their gene mutations act through LOF or GOF mechanisms, in order to achieve individualized restoration of NRXN1 isoform repertoires by increasing wildtype, or ablating mutant isoforms. Given the increasing number of mutations predicted to engender both LOF and GOF mechanisms in brain disorders, our findings add nuance to future considerations of precision medicine., Competing Interests: Ethics declarations / Competing interest statement. All authors have no competing interests to declare.

Background: The association of serum FABP4 and other biochemical-related parameters is important to determine complications of hypothyroidism. This study aimed to evaluate serum FABP-4 levels in hypothyroidism patients in comparison with a control group., Materials and Methods: Forty-five patients with hypothyroidism and 45 healthy volunteers were included in this study. Liver function tests, thyroid hormones panel, lipid profile and serum FABP-4 levels were measured and compared in both groups, and their correlations were analysed., Results: Serum FABP-4 levels were significantly higher in patients with hypothyroidism compared to the control group (p = 0.002), and serum FABP-4 level in males was higher than it in females (p = 0.022). There was a significant difference between patients with hypothyroidism and the control group in the levels of AST (p = 0.012). Moreover, serum FABP-4 levels were negatively correlated with age (p = 0.016) and positively correlated with weight (p = 0.044)., Conclusion: In our study, there was a notable increase in serum FABP-4 concentration among hypothyroidism subjects. The data suggest that FABP-4 could potentially be a superior diagnostic indicator for hypothyroidism when contrasted with a control cohort in future studies., (© 2024 The Author(s). Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)

Background: Healthcare program monitoring can play a key role in evaluating their implementation and identifying their strengths and weaknesses., Methods: This study was performed with the exploratory sequential mixed methods design in 2023 at Tehran, Iran. The information was categorized into indicators, refining, analysis, interpretation, reporting, and proposed challenges and recommendations., Results: Medical Sciences Department of Public Health (TUMSDoPH) evaluation of its public health programs revealed a comprehensive approach covering a wide spectrum from disease management to health promotion, emphasizing electronic health records, targeted disease interventions, and strategies for non-communicable diseases, alongside efforts to enhance community health., Conclusion: There is a need for initiating "the monitoring committee" under the supervision of the deputy chancellor for public health to monitor key performance indicators and policies to discover the problems of each part of the health system and provide recommendations., (Copyright© 2024 Ehsani et al. Published by Tehran University of Medical Sciences.)

Background: Major psychotic disorders (MPD), including schizophrenia (SCZ) and schizoaffective disorder (SAD), are severe neuropsychiatric conditions with unclear causes. Understanding their pathophysiology is essential for better diagnosis, treatment, and prognosis. Recent research highlights the role of inflammation and the immune system, particularly the Interleukin 17 (IL-17) family, in these disorders. Elevated IL-17 levels have been found in MPD, and human IL-17 A antibodies are available. Changes in chemokine levels, such as CCL20, are also noted in SCZ. This study investigates the relationship between serum levels of IL-17 A and CCL20 in MPD patients and their clinical characteristics., Method: We conducted a case-control study at the Ibn Sina Psychiatric Hospital (Mashhad, Iran) in 2023. The study involved 101 participants, of which 71 were MPD patients and 30 were healthy controls (HC). The Positive and Negative Symptom Scale (PANSS) was utilized to assess the symptoms of MPD patients. Serum levels of CCL20 and IL-17 A were measured using Enzyme-Linked Immunosorbent Assay (ELISA) kits. We also gathered data on lipid profiles and Fasting Blood Glucose (FBS)., Results: The mean age of patients was 41.04 ± 9.93 years. The median serum levels of CCL20 and IL-17 A were significantly elevated in MPD patients compared to HC (5.8 (4.1-15.3) pg/mL and 4.2 (3-5) pg/mL, respectively; p < 0.001). Furthermore, CCL20 and IL-17 A levels showed a positive correlation with the severity of MPD. MPD patients also had significantly higher FBS, cholesterol, and Low-Density Lipoprotein (LDL) levels, and lower High-Density Lipoprotein (HDL) levels compared to HC. No significant relationship was found between PANSS components and blood levels of IL17 and CCL20., Conclusion: The current study revealed that the serum levels of IL-17 A and CCL20 in schizophrenia patients are higher than those in the control group. Metabolic factors such as FBS, cholesterol, HDL, and LDL also showed significant differences between MPD and HC. In conclusion, the findings suggest that these two inflammatory factors could serve as potential therapeutic targets and prognostic biomarkers for schizophrenia., (© 2024. The Author(s).)

Trace elements (TEs) play a crucial role in metabolism through their biochemical and catalytic effects, and alterations in their levels have been observed in various malignancies. Given that chemotherapy is a common treatment for cancer, it is important to understand how it may affect the levels of TEs in the body. By investigating changes in TEs levels before and after chemotherapy, this study aims to provide insights into the potential impact of chemotherapy on TEs levels in cancer patients. In the present study, analyses were performed on the serum level of some elements including Zn, Cu, Cd, and Se in 69 patients with leukemia, lymphoma, prostate and breast cancers before and after three courses of chemotherapy. The serum TEs were measured by atomic absorption spectroscopy. The serum Zn levels in patients with leukemia, lymphoma, and breast cancer significantly decreased after chemotherapy (P < 0.05). Significant reductions were also observed in the post-chemotherapy serum level of Cd in patients with prostate (P = 0.020) and breast cancer (P = 0.013). Moreover, the Se serum level significantly decreased after chemotherapy compared to before it in the breast cancer patients (P < 0.001). In contrast, the serum level of Cu was higher before than after chemotherapy in all the patients, but no significant difference was found (P > 0.05). The results show that chemotherapy can alter the level of TEs. The assessment of TEs in cancer patients may provide information about the side effects of chemotherapy as well as the use of appropriate strategies to better manage the clinical conditions of patients., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Diabetes is the most prevalent metabolic disease globally. Correct and effective healthcare management requires up-to-date and accurate information at the local level. This level of information allows managers to determine whether the health system has achieved its desired goals in this area. This study aimed to evaluate the adequacy and quality of care for Type 2 diabetes mellitus (T2DM) patients using the Lot quality assurance sampling (LQAS) technique to provide evidence for decision-making at the local level, prioritizing and allocating resources., Methods: A descriptive-analytical study was conducted in 12 supervision areas (SAs)/health facilities in northwestern Iran involving 240 patients with T2DM in primary health care. The selection of patients and determination of SAs were done randomly using the LQAS technique. Glycated Hemoglobin (HbA 1 c) was used to evaluate patients' blood sugar control in each SA. Multiple linear regression analysis was used to estimate predictors of HbA 1 c in T2DM., Results: The overall average of HbA1c value was 7.84%. The HbA 1 c level was > 7% in 148 (61.6%) of the patients. Among the 12 SAs, the LQAS identified unacceptable quality of care in 5 SAs. In the final analysis, each unit increase in fasting blood sugar (FBS), High-density lipoprotein (HDL), Low-density lipoprotein (LDL), and Thyroglobulin (TG) values resulted in an increased in HbA 1 c levels by 0.43, 0.183, 0.124, and 0.182 times, respectively. However, with a one-unit increase in the care of a family physician and nutritionist, along with regular physical activity, HbA 1 c levels decreased by - 0.162, -0.74, and - 0.11 times, respectively., Conclusions: The quality of care for diabetic patients needs improvement in some SAs. Findings indicated that the LQAS technique effectively identifies centers/areas with substandard diabetes care quality and efficiently allocates resources to those in need. It is recommended to implement corrective measures in areas with inadequate care quality., (© 2024. The Author(s).)

Background: Arm contouring has been a challenging issue for many years. Patients request contouring of their arms without incisions and with a shorter recovery time. Making an incision on the arm does not always lead to a nice scar, and in case of complications, it may be catastrophic. The use of "arm net suture" can replace the incision during the arm contour surgery., Objectives: The author has developed a simple technique of arm contouring with arm net suture that leads to eliminating the need for making an incision, preventing of sagging in the proximal part of the arm, and a shorter recovery time., Methods: A retrospective study was conducted on 157 patients who underwent arm contouring surgery. Through a small 5 mm incision in the medial elbow, normal saline solution containing Xylocaine (Fresenius Kabi, Bad Homburg, Germany) and adrenaline was infiltrated. After 20 min, liposuction was started from the most superficial layer with a 3 mm cannula, and then, deeper layers superficial to the fascia were suctioned with a 4 mm cannula. The author usually utilizes traditional suction-assisted lipectomy or power-assisted lipectomy. After completing liposuction, the laxity of the skin along the arm was checked. Most of the laxity of the skin occurred in the proximal third of the arm; while the assistant pulled the skin of the proximal part lateral and downward, the net sutures were inserted. On the third or fourth day (based on the severity of laxity of the skin), the sutures start to be removed from the distal rows, with all sutures removed by the fifth to sixth day. The follow-up times were between 3 and 12 months., Results: All patients were female, and their age range was from 19 to 62 years (mean, 40.45 years). The volume of liposuction was from a minimum of 1200 cc to a maximum of 2500 cc (mean, 1645 cc), and the reduction of the arm diameter was occurred in the range of 6 to 14 cm. No immediate postoperative problems were observed in the patients. Revision was not needed for any patients., Conclusions: Arm net suture is a simple and safe method to replace the incision during arm contour surgery., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Aesthetic Society.)

Purpose: The perception of a clinical condition or disorder can vary across patients from different cultural-linguistic backgrounds. There is insufficient evidence to inspect this potential impact on the perception of vocal fatigue (VF) as a common condition perceived by patients with voice disorders. In order to more comprehensively explore this phenomenon, a systematic review was carried out to investigate the differences in perceived VF in a variety of cultural-linguistic contexts, based on a standard self-assessment instrument-the Vocal Fatigue Index (VFI), as translated in different languages., Method: A thorough search was done in MEDLINE, CENTRAL, Web of Science, and Google Scholar by March 2024. Cross-sectional studies investigating the accuracy of the VFI to detect perceived VF in all available languages were considered. The VFI has three distinct parts or factors assessing: (a) tiredness of voice, (b) physical discomfort associated with voicing, and (c) improvement of symptoms with rest. The cutoff points and sensitivity and specificity of each factor were submitted to meta-analysis, and the summary receiver operating characteristic curves were used to determine pooled sensitivity and specificity of each factor of the VFI., Results: Eight papers that examined the diagnostic accuracy of the VFI in English, Malayalam, Turkish, German, Mandarin Chinese, Polish, Cantonese, and Finnish languages were identified as being eligible for this meta-analysis. The pooled sensitivity and specificity along with their confidence intervals (CIs) were as follows: 0.91 CI [0.80, 0.96] and 0.88 CI [0.78, 0.94] for Factor 1, 0.83 CI [0.69, 0.91] and 0.84 CI [0.76, 0.89] for Factor 2, and 0.75 CI [0.67, 0.82] and 0.77 CI [0.59, 0.89] for Factor 3., Conclusions: The present research demonstrates medium to high but heterogeneous accuracy of the VFI for detecting perceived VF across cultural-linguistic contexts. Given the promising results, future studies should focus on (a) further investigating the underlying factors for the observed heterogeneity in diagnostic accuracy and (b) adapting and validating the VFI in more languages toward establishing its validity as a cross-linguistic diagnostic tool for the perception of VF., Supplemental Material: https://doi.org/10.23641/asha.26397106.

Introduction: Congenital lung anomalies (CLA) are a group of anomalies, including congenital cystic adenomatoid malformation (CCAM), bronchopulmonary sequestrations (BPS), congenital lobar emphysema (CLE), and bronchogenic cysts (BC). The prevalence of these rare anomalies has risen in recent years, according to various population-based studies due to advances in fetal ultrasound technology., Method: This retrospective study examines the diagnosis of CLA, and was conducted on 72 patients between March 2014 and March 2024 at Taleghani Pediatric Hospital in Gorgan, Iran., Result: The average age was 18.8 ± 30.3 months, with the majority being boys (62.5%). Most participants had CCAM (41.7%), followed by CLE (18.1%), BPS (16.7%), pulmonary hypoplasia (9.7%), BC (8.3%), and hybrid lesion (5.6%). The majority of patients were Fars (62.5%), and the average hospitalization days was 9.4 ± 4.5 days. Cardiac anomalies were observed in 19.4% of the patients. 62 patients (86.1%) exhibited respiratory symptoms, and prenatal screening during pregnancy led to the diagnosis in 51 patients (70.8%). Most patients had left lung anomalies (43; 59.7%), and the majority (90.3%) survived. There is a statistically significant relation between needed for surgical treatment and patients' type of pulmonary lesions (p-value: 0.02). In addition, there was a significant relation between the Fars ethnicity and the presence of cardiac anomalies (p-value: 0.04)., Conclusion: Some CLAs remain undiagnosed or untreated due to the rare nature of congenital lung anomalies. Nevertheless, improvements in ultrasound and other imaging methods will make diagnosing and managing these anomalies during the prenatal period more prevalent, resulting in enhanced understanding., (© 2024. The Author(s).)

Objective: The objective of this study was to evaluate the effectiveness of Hibiscus sabdariffa L. extract (HS) as an adjunct to valsartan in the treatment of high blood pressure in patients with mild chronic kidney disease (CKD)., Materials and Methods: This trial was conducted in Gorgan, Iran. Seventy-two participants with CKD and high blood pressure were randomly assigned to either the HS group, receiving a 350 mg pill every 12 hr for 90 days along with 40 mg of valsartan every 12 hr, or the control group (40 mg valsartan + 12.5 mg hydrochlorothiazide). The primary objective was to assess the improvement of hypertension, while secondary objectives included the evaluation of proteinuria, albuminuria, kidney function, lipid profile, and electrolyte levels. Molecular docking analysis was performed to examine the mechanisms of action of the isolated components of HS., Results: Out of 80 initial participants, 72 were included in the analysis. Both groups showed a significant reduction in blood pressure (p<0.001). The HS group demonstrated a statistically significant decrease in lipid profile (p<0.001). There were no statistically significant differences between the groups regarding the reduction of renal markers. Molecular docking analysis revealed that the compounds present in HS, particularly its anthocyanins and flavonoids, exhibited greater angiotensin-converting enzyme (ACE) inhibitory potential than hydrochlorothiazide in both domains. Moreover, the compounds met the criteria for drug likeness and Lipinski rules., Conclusion: Adjunctive therapy with HS showed promising results in reducing hypertension and improving lipid profile in patients with CKD., Competing Interests: Mohammad Hadi Soleimani is the CEO of Giah Essence Phytopharmaceutical Co

A promising research direction in the field of biological engineering is the design and functional programming of three-dimensional (3D) biointerfaces designed to support living cell functionality and growth in vitro, offering a route to precisely regulate cellular behaviors and phenotypes for addressing therapeutic challenges. While traditional two-dimensional (2D) biointerfaces have provided valuable insights, incorporating specific signaling cues into a 3D biointeractive microenvironment at the right locations and time is now recognized as crucial for accurately programming cellular decision-making and communication processes. This approach aims to engineer cell-centric microenvironments with the potential to recapitulate complex biological functions into a finite set of growing cellular organizations. Additionally, they provide insights into the hierarchical logic governing the relationship between molecular components and higher-order multicellular functionality. The functional live cell-based microenvironment engineered through such innovative biointerfaces has the potential to be used as an in vitro model system for expanding our understanding of cellular behaviors or as a therapeutic habitat where cellular functions can be reprogrammed., (2024 Published under an exclusive license by the AVS.)

Introduction: Reinfection and hospital readmission due to COVID-19 were significant and costly during the pandemic. This study aimed to assess the rate and risk factors of SARS-Cov-2 reinfection, recurrence, and hospital readmission, by analyzing the national data registry in Iran., Methods: This study was a retrospective cohort conducted from March 2020 to May 2021. A census method was used to consider all of the possible information in the national Medical Care Monitoring Center (MCMC) database obtained from the Ministry of Health and Medical Education; the data included information from all confirmed COVID-19 patients who were hospitalized and diagnosed using at least one positive Polymerase Chain Reaction (PCR) test by nasopharyngeal swab specimens. Univariate and multivariable Cox regression analyses were performed to assess the factors related to each studied outcome., Results: After analyzing data from 1,445,441 patients who had been hospitalized due to COVID-19 in Iran, the rates of overall reinfection, reinfection occurring at least 90 days after the initial infection, recurrence, and hospital readmission among hospitalized patients were 67.79, 26.8, 41.61, and 30.53 per 1000 person-years, respectively. Among all cases of hospitalized reinfection (48292 cases), 38.61% occurred more than 90 days from the initial SARS-Cov-2 infection. Getting infected with COVID-19 in the fifth wave of the disease compared to getting infected in the first wave (P<0.001), having cancer (P<0.001), chronic kidney disease (P<0.001), and age over 80 years (P<0.001) were respectively the most important risk factors for overall reinfection. In contrast, age 19-44 years (P<0.001), intubation (P<0.001), fever (P<0.001), and cough (P<0.001) in the initial admission were the most important protective factors of overall reinfection, respectively., Conclusion: Reinfection and recurrence of COVID-19 after recovery and the rate of hospital readmission after discharge were remarkable. Advanced or young age, as well as having underlying conditions like cancer and chronic kidney disease, increase the risk of infection and readmission., Competing Interests: The authors declare that they have no competing interests.

Introduction: The present study aims to compare the risk factors, clinical presentation, and severity of coronary artery involvement in young compared to elderly CAD patients to assess the cardiovascular health status for better disease management and control of these specific patients., Methods: This registry-based cross-sectional study was conducted using Coronary Angiography and Angioplasty Registry (CAAR) patients in east of Tehran, Iran. The data were extracted from 330 patients with confirmed CAD recorded by the CAAR during July 2021 to August 2023., Results: The majority of patients in MCAD (68.2%) and VECAD (80%) were male, while the majority of PCAD patients were female (51.8%). Among PCAD patients, the prevalence of diabetes (38.1%) was higher than in other groups. The presence of IHD history in the father (38.1%) and mother (26.3%) was higher in the VECAD group. The mean total cholesterol, LDL, and LDL/HDL ratio were higher in the VECAD group. Among MCAD group (75.4%) compared to PCAD (58.1%) and VECAD (47.2%) groups, the multi-vessel disease was more common.MCAD patients had the highest median Gensini score compared to PCAD and VECAD patients. Also, in male compared to female the mean Gensini score was higher by 8 units (ß = 8.26, 95%CI = 0.24, 16.28)., Conclusion: Modifiable risk factors in young CAD patients are common. High LDL-C levels and smoking were the common modifiable CVD risk factors in young patients, indicating the significant role of these traditional risk factors in early atherosclerosis development alongside inheritable risk-factors such as positive family history that were more common in young CAD patients. While, the severity of coronary artery involvement in individuals with MCAD was higher, but the priority of involvement based on the type of vessel was almost the same in all CAD groups., Competing Interests: The authors declare that they have no competing interests., (© 2024 Published by Elsevier Inc.)

Background: Cancer is one of the main causes of death in the worldwide. Pancreatic Cancer (PC) is prevalent in developed and increasing in developing countries. PC is important because of its low survival rate, high fatality, and increasing incidence. Therefore, identifying risk factors to prevent its development is necessary. This study aimed to determine incidence of PC and its risk factors in the Golestan Cohort Study (GCS) in Iran., Method: This study is a prospective population-based cohort study in the frame of GCS with 15 years of follow-up for PC. GCS was launched in the Golestan province of Iran with 50045 participants who were 40 to 75 years old. variables included: age, gender, education status, smoking, alcohol consumption, opium usage, type of blood group, dyslipidemia, body mass index (BMI), waist circumference (WC), family history (FH) of PC, ethnicity, and history of diabetes mellitus (DM)., Result: Among 50045 participants of GCS during 15 years of follow up, 100 people were diagnosed PC. PC incidence was 0.2%. Age-standardized incidence rate (ASR) of PC in the study population was 11.12 per 100,000 person-years. People with age ≥60 years were 46, in 50-59 years old group were 36, and 18 of them were <50 years (p<0.001). The smoking rate in PC group was 27% (p<0.01). Univariate model of cox regression analysis showed age 50-59, ≥60 years compared to <50 years [HR:3.006, 95%CI (1.707-5.294), p<0.001], [HR: 6.727, 95% CI (3.899-11.608), p<0.001], male gender [HR:1.541, 95%CI (1.041-2.281), p = 0.031], opium use [HR:1.436, 95% CI (0.887-2.324), p = 0.141], and smoking [HR:1.884, 95%CI (1.211-2.929), p = 0.005] were predictors for PC. In the multivariate model after adjusting, age 50-59 [HR:2.99, 95% CI (1.698-5.265), p<0.001], and ≥60 years [HR: 6.564, 95% CI (3.797-11.346), p<0.001] was the only predictor for PC., Conclusion: This study revealed an incidence of PC 0.2% in GCS in Iran. Main risk factor for PC was older age., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Mirzamohamadi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Goal and Aims: To test sleep/wake transition detection of consumer sleep trackers and research-grade actigraphy during nocturnal sleep and simulated peri-sleep behavior involving minimal movement., Focus Technology: Oura Ring Gen 3, Fitbit Sense, AXTRO Fit 3, Xiaomi Mi Band 7, and ActiGraph GT9X., Reference Technology: Polysomnography., Sample: Sixty-three participants (36 female) aged 20-68., Design: Participants engaged in common peri-sleep behavior (reading news articles, watching videos, and exchanging texts) on a smartphone before and after the sleep period. They were woken up during the night to complete a short questionnaire to simulate responding to an incoming message., Core Analytics: Detection and timing accuracy for the sleep onset times and wake times., Additional Analytics and Exploratory Analyses: Discrepancy analysis both including and excluding the peri-sleep activity periods. Epoch-by-epoch analysis of rate and extent of wake misclassification during peri-sleep activity periods., Core Outcomes: Oura and Fitbit were more accurate at detecting sleep/wake transitions than the actigraph and the lower-priced consumer sleep tracker devices. Detection accuracy was less reliable in participants with lower sleep efficiency., Important Additional Outcomes: With inclusion of peri-sleep periods, specificity and Kappa improved significantly for Oura and Fitbit, but not ActiGraph. All devices misclassified motionless wake as sleep to some extent, but this was less prevalent for Oura and Fitbit., Core Conclusions: Performance of Oura and Fitbit is robust on nights with suboptimal bedtime routines or minor sleep disturbances. Reduced performance on nights with low sleep efficiency bolsters concerns that these devices are less accurate for fragmented or disturbed sleep., Competing Interests: Declaration of conflicts of interest Oura Health Oy funded the data collection for the evaluation of its new sleep staging algorithm (OSSA 2.0), but the company did not influence the design of the study, analyses, its interpretation, or data presentation. All other equipment was contributed by the Sleep and Cognition Laboratory., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The ability to accurately classify accents and assess accentedness in non-native speakers are challenging tasks due primarily to the complexity and diversity of accent and dialect variations. In this study, embeddings from advanced pretrained language identification (LID) and speaker identification (SID) models are leveraged to improve the accuracy of accent classification and non-native accentedness assessment. Findings demonstrate that employing pretrained LID and SID models effectively encodes accent/dialect information in speech. Furthermore, the LID and SID encoded accent information complement an end-to-end (E2E) accent identification (AID) model trained from scratch. By incorporating all three embeddings, the proposed multi-embedding AID system achieves superior accuracy in AID. Next, leveraging automatic speech recognition (ASR) and AID models is investigated to explore accentedness estimation. The ASR model is an E2E connectionist temporal classification model trained exclusively with American English (en-US) utterances. The ASR error rate and en-US output of the AID model are leveraged as objective accentedness scores. Evaluation results demonstrate a strong correlation between scores estimated by the two models. Additionally, a robust correlation between objective accentedness scores and subjective scores based on human perception is demonstrated, providing evidence for the reliability and validity of using AID-based and ASR-based systems for accentedness assessment in non-native speech. Such advanced systems would benefit accent assessment in language learning as well as speech and speaker assessment for intelligibility, quality, and speaker diarization and speech recognition advancements., (© 2024 Acoustical Society of America.)

Impairment of oligodendrocytes and myelin contributes to neurological disorders including multiple sclerosis (MS), stroke, and Alzheimer's disease. Regeneration of myelin (remyelination) decreases the vulnerability of demyelinated axons, but this repair process commonly fails with disease progression. A contributor to inefficient remyelination is the altered extracellular matrix (ECM) in lesions, which remains to be better defined. We have identified fibulin-2 (FBLN2) as a highly upregulated ECM component in lesions of MS and stroke and in proteome databases of Alzheimer's disease and traumatic brain injury. Focusing on MS, the inhibitory role of FBLN2 was suggested in the experimental autoimmune encephalomyelitis (EAE) model, in which genetic FBLN2 deficiency improved behavioral recovery by promoting the maturation of oligodendrocytes and enhancing remyelination. Mechanistically, when oligodendrocyte progenitors were cultured in differentiation medium, FBLN2 impeded their maturation into oligodendrocytes by engaging the Notch pathway, leading to cell death. Adeno-associated virus deletion of FBLN2 in astrocytes improved oligodendrocyte numbers and functional recovery in EAE and generated new myelin profiles after lysolecithin-induced demyelination. Collectively, our findings implicate FBLN2 as a hitherto unrecognized injury-elevated ECM, and a therapeutic target, that impairs oligodendrocyte maturation and myelin repair.

Purpose: Human adenoviruses (HAdVs) have always been suggested as one of the main causes of gastroenteritis in children. However, no comprehensive report on the global epidemiology of these viruses in pediatric gastroenteritis is available., Methods: A systematic search was conducted to obtain published papers from 2003 to 2023 in three main databases PubMed, Scopus, and Web of Science., Results: The estimated global pooled prevalence of HAdV infection in children with gastroenteritis was 10% (95% CI: 9-11%), with a growing trend after 2010. The highest prevalence was observed in Africa (20%, 95% CI: 14-26%). The prevalence was higher in inpatients (11%; 95% CI: 8-13%) and patients aged 5 years old and younger (9%; 95% CI: 7-10%). However, no significant difference was observed between male and female patients (P = 0.63). The most prevalent species was found to be the species F (57%; 95% CI: 41-72%). The most common HAdVs observed in children with gastroenteritis were types 40/41, 38, and 2. Analysis of case-control studies showed an association between HAdV and gastroenteritis in children (OR: 2.28, 95% CI; 1.51-3.44)., Conclusion: This study provided valuable insights into the importance of HAdVs in children with gastroenteritis, especially in hospitalized and younger children. The results can be used in future preventive measurements and the development of effective vaccines., (© 2024. The Author(s).)

Introduction: This study assessed the incidence and severity of side effects associated with coronavirus disease 2019 (COVID-19) vaccination among healthcare workers registered with the Medical Council of the Islamic Republic of Iran., Methodology: A retrospective cohort study was conducted on the healthcare workers focusing on the side-effects of COVID-19 vaccines from March to June 2021. Data were collected using online questionnaires. Multivariable logistic regression was used to assess the association between side effects of the vaccines and demographic variables, comorbidities, vaccine type, and history of COVID-19., Results: Out of 42,018 people who were included, 55.85% reported at least one side effect after receiving the first vaccine dose. 4.59% of those with side effects sought diagnostic intervention or were referred to treatment centers. Multivariable logistic regression indicated that being a woman, higher education, having a history of COVID-19 infection, and having comorbidities increased the risk of side effects. The AstraZeneca vaccine significantly increased the risk of side effects compared to the Sputnik vaccine, while the Sinopharm vaccine decreased this risk. The risk of developing a side effect decreased with age. The risk of moderate and severe side effects was significantly associated with gender, younger age, comorbidities, and a history of COVID-19 infection. Moderate and severe side effects were less reported by those who received the Sinopharm vaccine., Conclusions: Clinical complications after COVID-19 vaccination, directly or indirectly caused by the vaccines, are common. However, the benefits of COVID-19 vaccines greatly outweigh the risk of reversible side effects, especially among the high-risk population., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2024 Hassan Roudgari, Koorosh Etemad, Manoochehr Karami, Farideh Mostafavi, Sahar Sotoodeh Ghorbani, Kosar Farhadi Babadi, Elham Rahimi, Niloufar Taherpour, Seyed Mahmood Fattahi Masoom, Masoud Habibi, Hossein Kermanpour, Reza Laripour, Omid Manoochehri, Mohammad Raeeszadeh, Alireza Salimi, Babak Shekarchi, Ali Tajernia, Mohammad Reza Zafarghandi, Alireza Zali, Afshin Zarghi, Seyed Saeed Hashemi Nazari.)

Tissue damage elicits a wound healing response of inflammation and remodeling aimed at restoring homeostasis. Dysregulation of wound healing leads to accumulation of effector cells and extracellular matrix (ECM) components, collectively termed fibrosis, which impairs organ functions. Fibrosis of the central nervous system, neurofibrosis, is a major contributor to the lack of neural regeneration and it involves fibroblasts, microglia/macrophages and astrocytes, and their deposited ECM. Neurofibrosis occurs commonly across neurological conditions. This review describes processes of wound healing and fibrosis in tissues in general, and in multiple sclerosis in particular, and considers approaches to ameliorate neurofibrosis to enhance neural recovery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lozinski, Ghorbani and Yong.)

Cell-based therapy, as a promising regenerative medicine approach, has been a promising and effective strategy to treat or even cure various kinds of diseases and conditions. Generally, two types of cells are used in cell therapy, the first is the stem cell, and the other is a fully differentiated cell. Initially, all cells in the body are derived from stem cells. Based on the capacity, potency and differentiation potential of stem cells, there are four types: totipotent (produces all somatic cells plus perinatal tissues), pluripotent (produces all somatic cells), multipotent (produces many types of cells), and unipotent (produces a particular type of cells). All non-totipotent stem cells can be used for cell therapy, depending on their potency and/or disease state/conditions. Adult fully differentiated cell is another cell type for cell therapy that is isolated from adult tissues or obtained following the differentiation of stem cells. The cells can then be transplanted back into the patient to replace damaged or malfunctioning cells, promote tissue repair, or enhance the targeted organ's overall function. With increasing science and knowledge in biology and medicine, different types of techniques have been developed to obtain efficient cells to use for therapeutic approaches. In this study, the potential and opportunity of use of all cell types, both stem cells and fully differentiated cells, are reviewed., Competing Interests: Declaration of competing interest Authors have no conflict of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

Aims: Evaluate the performance of 6 wearable sleep trackers across 4 classes (EEG-based headband, research-grade actigraphy, iteratively improved consumer tracker, low-cost consumer tracker)., Focus Technology: Dreem 3 headband, Actigraph GT9X, Oura Ring Gen3, Fitbit Sense, Xiaomi Mi Band 7, Axtro Fit3., Reference Technology: In-lab polysomnography with 3-reader, consensus sleep scoring., Sample: Sixty participants (26 males) across 3 age groups (18-30, 31-50, and 51-70years)., Design: Overnight in a sleep laboratory from habitual sleep time to wake time., Core Analytics: Discrepancy and epoch-by-epoch analyses for sleep/wake (2-stage) and sleep-stage (4-stage; wake/light/deep/rapid eye movement) classification (devices vs. polysomnography)., Core Outcomes: EEG-based Dreem performed the best (2-stage kappa=0.76, 4-stage kappa=0.76-0.86) with the lowest total sleep time, sleep efficiency, sleep onset latency, and wake after sleep onset discrepancies vs. polysomnography. This was followed by the iteratively improved consumer trackers: Oura (2-stage kappa=0.64, 4-stage kappa=0.55-0.70) and Fitbit (2-stage kappa=0.58, 4-stage kappa=0.45-0.60) which had comparable total sleep time and sleep efficiency discrepancies that outperformed accelerometry-only Actigraph (2-stage kappa=0.47). The low-cost consumer trackers had poorest overall performance (2-stage kappa<0.31, 4-stage kappa<0.33)., Important Additional Outcomes: Proportional biases were driven by nights with poorer sleep (longer sleep onset latencies and/or wake after sleep onset)., Core Conclusion: EEG-based Dreem is recommended when evaluating poor quality sleep or when highest accuracy sleep-staging is required. Iteratively improved non-EEG sleep trackers (Oura, Fitbit) balance classification accuracy with well-tolerated, and economic deployment at-scale, and are recommended for studies involving mostly healthy sleepers. The low-cost trackers, can log time in bed but are not recommended for research use., Competing Interests: Declaration of conflicts of interest Oura Health Oy funded the data collection for the evaluation of its new sleep staging algorithm (OSSA 2.0), but the company did not influence the design of the study, analyses, its interpretation or data presentation. All other equipment was contributed by the Sleep and Cognition Laboratory., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The extracellular matrix (ECM) of the central nervous system (CNS) is an interconnected network of proteins and sugars with critical roles in both homeostasis and disease. In neurological diseases, excessive ECM deposition and remodeling impact both injury and repair. CNS lesions of multiple sclerosis (MS), a chronic inflammatory and degenerative disease, cause prominent alterations of the ECM. However, there are a lack of data investigating how the multitude of ECM members change in relation to each other and how this affects the MS disease course. Here, we evaluated ECM changes in MS lesions compared to a control brain using databases generated in-house through spatial mRNA-sequencing and through a public resource of single-nucleus RNA sequencing previously published by Absinta and colleagues. These results underline the importance of publicly available datasets to find new targets of interest, such as the ECM. Both spatial and public datasets demonstrated widespread changes in ECM molecules and their interacting proteins, including alterations to proteoglycans and glycoproteins within MS lesions. Some of the altered ECM members have been described in MS, but other highly upregulated members, including the SPARC family of proteins, have not previously been highlighted. SPARC family members are upregulated in other conditions by reactive astrocytes and may influence immune cell activation and MS disease course. The profound changes to the ECM in MS lesions deserve more scrutiny as they impact neuroinflammation, injury, and repair.

Objectives: This study aimed to examine the incidence of distal radius fractures in patients aged 55 and above who had also experienced hip fractures. Osteoporosis-associated fractures, particularly hip fractures, are common and serious in older individuals with reduced bone density. Previous research has suggested a relationship between hip fractures and distal radius fractures., Methods: The study included patients over 55 years old who had presented with hip fractures at Akhtar Hospital in the past five years. Patients with a history of hip fractures more than five years before experiencing the distal radius fracture were excluded. Personal information was extracted from medical records, and the collected data were analyzed in SPSS software using statistical methods, such as t-tests and paired t-tests., Results: This study involved 1,745 patients with hip fractures and 183 individuals without fractures. The average age of the patients was 75.8±10.4 years old, with the majority being female (59.6%). Among the hip fractures, 59.6%, 34.5%, and 5.9% were intertrochanteric fractures, neck of femur fractures, and subtrochanteric fractures, respectively. Overall, 15.8% of individuals with hip fractures also had distal radius fractures. The average age and gender distribution of the patients were similar in both groups, with no significant difference. However, the prevalence of distal radius fractures was significantly higher in the hip fracture group, compared to the control group., Conclusion: It was found that individuals over the age of 55 with distal radius fractures, especially females, are more susceptible to hip fractures. Distal radius fractures have a significant impact on the occurrence of hip fractures in patients. Therefore, older individuals with osteoporosis should be cautious and avoid high-risk activities that could lead to falls and fractures., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (2024 © BY THE ARCHIVES OF BONE AND JOINT SURGERY.)

Background: Inflammation-exacerbated secondary brain injury and limited tissue regeneration are barriers to favourable prognosis after intracerebral haemorrhage (ICH). As a regulator of inflammation and lipid metabolism, Liver X receptor (LXR) has the potential to alter microglia/macrophage (M/M) phenotype, and assist tissue repair by promoting cholesterol efflux and recycling from phagocytes. To support potential clinical translation, the benefits of enhanced LXR signalling are examined in experimental ICH., Methods: Collagenase-induced ICH mice were treated with the LXR agonist GW3965 or vehicle. Behavioural tests were conducted at multiple time points. Lesion and haematoma volume, and other brain parameters were assessed using multimodal MRI with T2-weighted, diffusion tensor imaging and dynamic contrast-enhanced MRI sequences. The fixed brain cryosections were stained and confocal microscopy was applied to detect LXR downstream genes, M/M phenotype, lipid/cholesterol-laden phagocytes, oligodendrocyte lineage cells and neural stem cells. Western blot and real-time qPCR were also used. CX3CR1 CreER : Rosa26 iDTR mice were employed for M/M-depletion experiments., Results: GW3965 treatment reduced lesion volume and white matter injury, and promoted haematoma clearance. Treated mice upregulated LXR downstream genes including ABCA1 and Apolipoprotein E, and had reduced density of M/M that apparently shifted from proinflammatory interleukin-1β + to Arginase1 + CD206 + regulatory phenotype. Fewer cholesterol crystal or myelin debris-laden phagocytes were observed in GW3965 mice. LXR activation increased the number of Olig2 + PDGFRα + precursors and Olig2 + CC1 + mature oligodendrocytes in perihaematomal regions, and elevated SOX2 + or nestin + neural stem cells in lesion and subventricular zone. MRI results supported better lesion recovery by GW3965, and this was corroborated by return to pre-ICH values of functional rotarod activity. The therapeutic effects of GW3965 were abrogated by M/M depletion in CX3CR1 CreER : Rosa26 iDTR mice., Conclusions: LXR agonism using GW3965 reduced brain injury, promoted beneficial properties of M/M and facilitated tissue repair correspondent with enhanced cholesterol recycling., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)