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Reproductive ageing is one of the earliest human ageing phenotypes, and mitochondrial dysfunction has been linked to oocyte quality decline; however, it is not known which mitochondrial metabolic processes are critical for oocyte quality maintenance with age. To understand how mitochondrial processes contribute to Caenorhabditis elegans oocyte quality, we characterized the mitochondrial proteomes of young and aged wild-type and long-reproductive daf-2 mutants. Here we show that the mitochondrial proteomic profiles of young wild-type and daf-2 worms are similar and share upregulation of branched-chain amino acid (BCAA) metabolism pathway enzymes. Reduction of the BCAA catabolism enzyme BCAT-1 shortens reproduction, elevates mitochondrial reactive oxygen species levels, and shifts mitochondrial localization. Moreover, bcat-1 knockdown decreases oocyte quality in daf-2 worms and reduces reproductive capability, indicating the role of this pathway in the maintenance of oocyte quality with age. Notably, oocyte quality deterioration can be delayed, and reproduction can be extended in wild-type animals both by bcat-1 overexpression and by supplementing with vitamin B1, a cofactor needed for BCAA metabolism., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The transcription factor, known as basic leucine zipper ATF-like 3 (BATF3), is a crucial contributor to the development of conventional type 1 dendritic cells (cDC1), which is definitely required for priming CD8 + T cell-mediated immunity against intracellular pathogens and malignancies. In this respect, BATF3-dependent cDC1 can bring about immunological tolerance, an autoimmune response, graft immunity, and defense against infectious agents such as viruses, microbes, parasites, and fungi. Moreover, the important function of cDC1 in stimulating CD8 + T cells creates an excellent opportunity to develop a highly effective target for vaccination against intracellular pathogens and diseases. BATF3 has been clarified to control the development of CD8α + and CD103 + DCs. The presence of BATF3-dependent cDC1 in the tumor microenvironment (TME) reinforces immunosurveillance and improves immunotherapy approaches, which can be beneficial for cancer immunotherapy. Additionally, BATF3 acts as a transcriptional inhibitor of Treg development by decreasing the expression of the transcription factor FOXP3. However, when overexpressed in CD8 + T cells, it can enhance their survival and facilitate their transition to a memory state. BATF3 induces Th9 cell differentiation by binding to the IL-9 promoter through a BATF3/IRF4 complex. One of the latest research findings is the oncogenic function of BATF3, which has been approved and illustrated in several biological processes of proliferation and invasion., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Ideally, the evaluation of automated vehicles would involve the careful tracking of individual vehicles and recording of observed crash events. Unfortunately, due to the low frequency of crash events, such data would require many years to acquire, and potentially place the motorized public at risk if defective automated technologies were present. To acquire information on the safety effectiveness of automated vehicles more quickly, this paper uses the collective crash histories of a group of automated vehicles, and applies a duration modeling approach to the accumulated distances between crashes. To demonstrate the applicability of this approach as a method compare automated and conventional vehicles (human drivers), an empirical assessment was undertaken using two comparable sources of data. For conventional vehicles, police and non-police-reportable crashes were collected from the Second Strategic Highway Research Program's naturalistic driving study, and for automated vehicles, data from the California Department of Motor Vehicles Autonomous Vehicle Tester program were used (105 crashes from 59 permit holders driving ∼2.8 million miles were used for the analysis). The results of the empirical study showed that automated driving was safer at the 95% confidence level, with a higher number of miles between crashes, relative to their conventional vehicle counterparts. The findings indicate that the number of miles between crashes would be increased by roughly 27% when switching from conventional vehicles to automated vehicles. Despite limited data which mandated a group-vehicle approach, this study can be considered a reasonable initial approximation of automated vehicle safety., 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 Ltd. All rights reserved.)

Breast cancer is significantly influenced by endoplasmic reticulum (ER) stress, impacting both its initiation and progression. When cells experience an accumulation of misfolded or unfolded proteins, they activate the unfolded protein response (UPR) to restore cellular balance. In breast cancer, the UPR is frequently triggered due to challenging conditions within tumors. The UPR has a dual impact on breast cancer. On one hand, it can contribute to tumor growth by enhancing cell survival and resistance to programmed cell death in unfavorable environments. On the other hand, prolonged and severe ER stress can trigger cell death mechanisms, limiting tumor progression. Furthermore, ER stress has been linked to the regulation of non-coding RNAs (ncRNAs) in breast cancer cells. These ncRNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), play essential roles in cancer development by influencing gene expression and cellular processes. An improved understanding of how ER stress and ncRNAs interact in breast cancer can potentially lead to new treatment approaches. Modifying specific ncRNAs involved in the ER stress response might interfere with cancer cell survival and induce cell death. Additionally, focusing on UPR-associated proteins that interact with ncRNAs could offer novel therapeutic possibilities. Therefore, this review provides a concise overview of the interconnection between ER stress and ncRNAs in breast cancer, elucidating the nuanced effects of the UPR on cell fate and emphasizing the regulatory roles of ncRNAs in breast cancer progression., (© 2024. The Author(s).)

Competing Interests: Conflict of interest The authors declare that they have no conflict of interest.

Tolerogenic dendritic cells (TolDCs) are attractive therapeutic options for autoimmune disorders because they suppress autologous T-cell responses. Dendritic cells (DCs) are equipped with pattern recognition receptors (PRR), including nucleotide-binding and oligomerization domain-like receptors (NLRs) such as NLRP3. Abnormal NLRP3 activation has been reported to be correlated with the occurrence of autoimmune disorders. Accordingly, we hypothesized that glyburide treatment of DCs by blocking the ATP-sensitive K+ (kATP) channels generates TolDCs by inhibiting NLRP3. Insulin was even loaded on a group of glyburide-treated mature DCs (mDCs) to investigate the antigen (Ag) loading effects on glyburide-treated mDCs' phenotypical and functional features. Consequently, T lymphocytes' mediated responses ensuing co-culture of them with control mDCs, insulin loaded and unloaded glyburide treated mDCs were evaluated to determine generated TolDCs' capacity in inhibition of T cell responses that are inducer of destruction in insulin-producing pancreatic beta cells in Type 1 Diabetes Mellitus (T1DM). Our findings indicated that glyburide generates desirable TolDCs with decreased surface expression of maturation and Ag presentation related markers and diminished level of inflammatory but increased level of anti-inflammatory cytokines, which even insulin loading demonstrated more anti-inflammatory functions. In addition, co-cultured T cells showed regulatory or T helper 2 phenotype instead of T helper 1 features. Our findings suggested that insulin-loaded and unloaded glyburide-treated DCs are promising therapeutic approaches for autoimmune patients, specifically DCs loaded with insulin for T1DM patients. However, further research is required before this technique can be applied in clinical practice., 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 © 2023 Elsevier B.V. All rights reserved.)

Introduction: Colorectal cancer (CRC) ranks as the second leading cause of cancer-related deaths. This study aimed to predict survival outcomes of CRC patients using machine learning (ML) methods., Material and Methods: A retrospective analysis included 1853 CRC patients admitted to three prominent tertiary hospitals in Iran from October 2006 to July 2019. Six ML methods, namely logistic regression (LR), Naïve Bayes (NB), Support Vector Machine (SVM), Neural Network (NN), Decision Tree (DT), and Light Gradient Boosting Machine (LGBM), were developed with 10-fold cross-validation. Feature selection employed the Random Forest method based on mean decrease GINI criteria. Model performance was assessed using Area Under the Curve (AUC)., Results: Time from diagnosis, age, tumor size, metastatic status, lymph node involvement, and treatment type emerged as crucial predictors of survival based on mean decrease GINI. The NB (AUC = 0.70, 95% Confidence Interval [CI] 0.65-0.75) and LGBM (AUC = 0.70, 95% CI 0.65-0.75) models achieved the highest predictive AUC values for CRC patient survival., Conclusions: This study highlights the significance of variables including time from diagnosis, age, tumor size, metastatic status, lymph node involvement, and treatment type in predicting CRC survival. The NB model exhibited optimal efficacy in mortality prediction, maintaining a balanced sensitivity and specificity. Policy recommendations encompass early diagnosis and treatment initiation for CRC patients, improved data collection through digital health records and standardized protocols, support for predictive analytics integration in clinical decisions, and the inclusion of identified prognostic variables in treatment guidelines to enhance patient outcomes.

Background and Objectives: Isoniazid and rifampin are the first -line drugs against Mycobacterium tuberculosis. Resistance to these important drugs is a serious threat to human public health. Therefore, this study aimed at molecular detection of resistance to these valuable drugs., Materials and Methods: In this descriptive cross-sectional study, 111 non - duplicated clinical samples including sputum and Bronchoalveolar lavage (BAL) samples were collected from patients referred to the Ardabil Health Center between 2017 and 2020. The samples were first examined by microscopic method, then their DNA was extracted using the boiling method. Specific primers and MAS-PCR method were employed for the detection resistance to isoniazid and rifampin drugs and identification of MDR strain., Results: of 111 specimens, 15.3% belonged to NTM. In total, the resistance rate to isoniazid and rifampin was 17% and 27% respectively while the resistance rate to isoniazid and rifampin among NTM was 61.54% and 38.46%., Conclusion: In our study, the prevalence of resistance to isoniazid and rifampin among Mycobacterium tuberculosis complex(MTC) and non-tuberculous mycobacteria(NTM) was investigated using the MAS-PCR method. This work highlighted the high anti- tuberculosis resistance rate among NTM compared to MTC strains., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

A student support system (SSS) has a crucial role in the absorption, retention, and success of students in virtual learning. The purpose of this scoping review was to identify and map the available evidence regarding the dimensions and components of the SSS in virtual learning. This study was conducted in accordance with the methodology of the Joanna Briggs Institute (JBI) for scoping reviews. Our search strategy was based on using search engines, such as MEDLINE, EMBASE, Scopus, WoS, CINAHL, ERIC, PsycINFO, ProQuest, and Google Scholar. The articles were published in renowned medical education journals, including Medical Education, Medical Teacher, and Academic Medicine, and the reference lists of identified and reviewed articles were searched manually. The search results were imported into EndNote X20, and after removing duplicates and screenings, 42 studies met the inclusion criteria and were included in the review. A descriptive- analytical approach was employed, including a numerical count of study characteristics (quantitative) and template analysis (qualitative). Five dimensions were identified in the SSS in virtual learning: types of support, domains of support, stages of support, instigating of support, levels of support, and their components and subcomponents. The findings of this study depict a comprehensive roadmap and have an important contribution to the knowledge body of SSS in virtual learning. We suggest system developers, planners, and higher education officials to improve the quality of virtual learning by applying these findings in their planning and decision-making., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Education and Health Promotion.)

Purpose: Hemorrhoids are the most common benign anorectal diseases. Mucopexy strengthens the anal canal mucosa, which can be performed alone or in combination with Doppler-guided hemorrhoidal artery ligation (DG-HAL). In this study, we compared the postoperative complications between simple mucopexy plus HAL with and without a Doppler guide., Methods: This study was performed as a single-blinded randomized clinical trial. Patients referred to a tertiary colorectal referral clinic with grades 3 and 4 hemorrhoids who were candidates for surgical intervention entered the study. Thirty-six patients were randomly divided into 2 groups. Group A including 18 patients underwent mucopexy and DG-HAL and the other 18 patients (group B) underwent standard mucopexy and HAL without a Doppler guide. Postoperative pain score and the duration of oral analgesic consumption were recorded. Additionally, postoperative symptoms and complications were recorded and compared between the 2 methods., Results: There was no significant difference between the 2 groups in terms of pain score and the duration of postoperative analgesic consumption as well as the incidence of postoperative complications. Besides, the primary grade of hemorrhoids was not significantly associated with recurrence, but there was a significant association between body mass index and Wexner score (WS) with recurrence. The mean WS of patients showed a significant decrease in both groups postoperatively. However, the rate of WS reduction was not remarkably different between the 2 groups., Conclusion: Simple mucopexy with blind HAL (without Doppler guide) might be considered for the treatment of grades 3 and 4 hemorrhoids effectively.

Millions of people are grieving the loss of someone who died of COVID-19. The current study aims to validate a Kurdish version of the Pandemic Grief Scale which is a brief English-language mental health screener to identify cases of dysfunctional grief associated with a COVID-19 death. We recruited 501 participants. Participants completed the PGS, WSAS, PHQ-9, and Optimism scales. The factor structure, reliability, and validity of the PGS were analyzed. Using exploratory factor analysis ( N 1 = 300), we derived an one-factor structure. In confirmatory factor analysis ( N 2 = 201), the one-factor model showed good to excellent fitness. The PGS was positively correlated with PHQ-4, and WSAS and negatively correlated with optimism. The scale was internally consistent with a Cronbach's alpha of .79. These results support that the Kurdish version of the PGS is a valid and reliable assessment to assess the severity of dysfunctional grief associated with a COVID-19 death., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The aim of this study was to investigate the effect of vitamin D3 (VitD3) on inflammatory mechanisms, hyperphosphorylated tau (p-tau) in the hippocampus, and cognitive impairment of the mouse model of vascular dementia (VaD)., Methods: In this study, 32 male mice were randomly assigned to the control, VaD, VitD3 (300 IU/Kg/day), and VitD3 (500 IU/Kg/day) groups. VaD and VitD3 groups were gavaged daily for 4 weeks with a gastric needle. For biochemical assessments, blood samples and the hippocampus were isolated. IL-1β and TNF-α were analyzed by ELISA, and p-tau and other inflammatory molecules were measured by western blot., Results: VitD3 supplements significantly (P < 0.05) decreased the level of inflammatory factors in the hippocampus and prevented apoptosis. However, regarding p-tau in hippocampal tissue, this decrease was not statistically significant (P > 0.05). The results of behavioral assessments showed that VitD3 significantly improved the spatial memory of treated mice., Conclusion: These results suggest that the neuroprotective effects of VitD3 are mainly associated with their anti-inflammatory effects., 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 © 2023 Elsevier B.V. All rights reserved.)

The potential to carry out high-throughput assays in a whole organism in a small space is one of the benefits of C. elegans , but worm assays often require a large sample size with frequent physical manipulations, rendering them highly labor-intensive. Microfluidic assays have been designed with specific questions in mind, such as analysis of behavior, embryonic development, lifespan, and motility. While these devices have many advantages, current technologies to automate worm experiments have several limitations that prevent widespread adoption, and most do not allow analyses of reproduction-linked traits. We developed a miniature C. elegans lab-on-a-chip device, Ce Lab, a reusable, multi-layer device with 200 separate incubation arenas that allows progeny removal, to automate a variety of worm assays on both individual and population levels. Ce Lab enables high-throughput simultaneous analysis of lifespan, reproductive span, and progeny production, refuting assumptions about the disposable soma hypothesis. Because Ce Lab chambers require small volumes, the chip is ideal for drug screens; we found that drugs previously shown to increase lifespan also increase reproductive span, and we discovered that low-dose metformin increases both. Ce Lab reduces the limitations of escaping and matricide that typically limit plate assays, revealing that feeding with heat-killed bacteria greatly extends lifespan and reproductive span of mated animals. Ce Lab allows tracking of life history traits of individuals, which revealed that the nutrient-sensing mTOR pathway mutant, sgk-1 , reproduces nearly until its death. These findings would not have been possible to make in standard plate assays, in low-throughput assays, or in normal population assays.

Pedestrians and bicyclists from marginalized and underserved populations experienced disproportionate fatalities and injury rates due to traffic crashes in the US. This disparity among road users of different races and the increasing trend of traffic risk for underserved racial groups called for an urgent agenda for transportation policy making and research to ensure equity in roadway safety. Pedestrian and bicyclist crashes involved drivers and pedestrians/bicyclists; the latter were usually victims. Traditional safety studies did not account for the interaction between the two parties and assumed that they were independent from each other. In this study we paired the driver and pedestrian/bicyclist involved in the same crash to understand the socioeconomic and demographic make-up of the two parties involved in crashes and assessed the geographic distribution of these crashes and crash-contributing factors. For this purpose, we applied thelatent class clustering analysis (LCA) to classify different crash types and analyze the patterns of the crashes based on the income and ethnicity of both drivers and victims involved in pedestrian and bicyclist crashes. We then used random forest algorithms and partial dependence plots (PDPs) to model and interpreted the contributing factors of the clusters in both pedestrian and bicyclist models. The clustering results showed a pattern of social segregation in pedestrian and bicyclist crashes that drivers and victims with similar socioeconomic characteristics tend to be involved in one crash. Pedestrian/bicyclist exposure, driver's age, victim's age, year of the car in use, annual average daily traffic (AADT), speed limit, roadbed width, and lane width were the most influential factors contributing to this pattern. Crashes that involved drivers and victims with lower income and non-white ethnicity tended to happen in the location with higher pedestrian/bicyclist exposure, higher speed limit, and wider road. The findings of this research can help to inform the decision-making process for improving safety to ensure equitable and sustainable safety for all road users and communities., 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 © 2023 Elsevier Ltd. All rights reserved.)

Active transportation could be an effective way to promote healthy physical activity, especially during pandemics like COVID-19. A comprehensive evaluation of health outcomes derived from COVID-19 induced active transportation can assist multiple stakeholders in revisiting strategies and priorities for supporting active transportation during and beyond the pandemic. We performed a two-step reviewing process by combining a scoping review with a narrative review to summarize published literature addressing the influence of COVID-19 on mobility and the environment that can lead to various health pathways and health outcomes associated with active transportation. We summarized the COVID-19 induced changes in active transportation demand, built environment, air quality, and physical activity. The results demonstrated that, since the pandemic began, bike-sharing users dropped significantly while recreational bike trips and walking activities increased in some areas. Meanwhile, there have been favorable changes to the air quality and the built environment for active transportation users. We then discussed how these changes impact health outcomes during the pandemic and their implications for urban planning and policymaking. This review also suggests that walking and biking can make up for the reduced physical activities during the pandemic, helping people stay active and healthy., Competing Interests: Authors declare no conflict of interest., (© 2022 Elsevier Ltd. All rights reserved.)

While road navigation systems seek to determine the shortest routes between a given set of origin and destination points, there are certain situations in which the fastest route increases the risk of being involved in road crashes. This implies the necessity of integrating safe route-finding into road navigation systems. This study is designed to synthesize the literature on safe route-finding and identify the gaps in the literature for future research. Specifically, a scoping literature review methodology is applied to understand how safety is incorporated in route-finding, even beyond motor vehicle navigation systems. Three databases (Scopus, Web of Science, and IEEE Xplore) are explored, and controlling for inclusion criteria, 40 studies are included in this review. The findings of this review indicated five areas through which safety was considered in route-finding: motor vehicle navigation, public safety, public health, pedestrian and cyclist navigation, and hazardous material transportation. The measurement of safety was found challenging with inconsistencies in safety quantification approaches. The safe route-finding algorithms were investigated based on their predictive/reactive, static/dynamic, and centralized/decentralized characteristics. Based on the critical review of the safe route-finding algorithms, availability of real-time data sources, accurate real-time and disaggregated crash risk prediction models, trade-off between time and safety in road navigation tools, and centralized safe route-finding are highlighted as the requirements and challenges in considering safety in road navigation systems. This study outlines a research agenda to address the identified challenges in safe route-finding., 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., (Published by Elsevier Ltd.)

Scarring is associated with significant morbidity. The mechanical signaling factor yes-associated protein (YAP) has been linked to Engrailed-1 (En1)-lineage positive fibroblasts (EPFs), a pro-scarring fibroblast lineage, establishing a connection between mechanotransduction and fibrosis. In this study, we investigate the impact of micromechanical forces exerted through negative pressure wound therapy (NPWT) on the pathophysiology of fibrosis. Full-thickness excisional dorsal skin wounds were created on diabetic (db/db) mice which were treated with occlusive covering (control) or NPWT (continuous, −125 mmHg, 7 days; NPWT). Analysis was performed on tissue harvested 10 days after wounding. NPWT was associated with increased YAP (p = 0.04) but decreased En1 (p = 0.0001) and CD26 (p < 0.0001). The pro-fibrotic factors Vimentin (p = 0.04), α-SMA (p = 0.04) and HSP47 (p = 0.0008) were decreased with NPWT. Fibronectin was higher (p = 0.01) and collagen deposition lower in the NPWT group (p = 0.02). NPWT increased cellular proliferation (p = 0.002) and decreased apoptosis (p = 0.03). Western blotting demonstrated increased YAP (p = 0.02) and RhoA (p = 0.03) and decreased Caspase-3 (p = 0.03) with NPWT. NPWT uncouples YAP from EPF activation, through downregulation of Caspace-3, a pro-apoptotic factor linked to keloid formation. Mechanotransduction decreases multiple pro-fibrotic factors. Through this multifactorial process, NPWT significantly decreases fibrosis and offers promising potential as a mode to improve scar appearance.

Women's reproductive cessation is the earliest sign of human aging and is caused by decreasing oocyte quality. Similarly, C. elegans' reproduction declines in mid-adulthood and is caused by oocyte quality decline. Aberrant mitochondrial morphology is a hallmark of age-related dysfunction, but the role of mitochondrial morphology and dynamics in reproductive aging is unclear. We examined the requirements for mitochondrial fusion and fission in oocytes of both wild-type worms and the long-lived, long-reproducing insulin-like receptor mutant daf-2. We find that normal reproduction requires both fusion and fission, but that daf-2 mutants utilize a shift towards fission, but not fusion, to extend their reproductive span and oocyte health. daf-2 mutant oocytes' mitochondria are punctate (fissioned) and this morphology is primed for mitophagy, as loss of the mitophagy regulator PINK-1 shortens daf-2's reproductive span. daf-2 mutants maintain oocyte mitochondria quality with age at least in part through a shift toward punctate mitochondrial morphology and subsequent mitophagy. Supporting this model, Urolithin A, a metabolite that promotes mitophagy, extends reproductive span in wild-type mothers-even in mid-reproduction-by maintaining youthful oocytes with age. Our data suggest that promotion of mitophagy may be an effective strategy to maintain oocyte health with age., Competing Interests: The authors have declared that no competing interests exist.

For the first time, a bio-photo-catalyst is synthesized in a microfluidic platform. The microchannel, which is wall-coated by in situ synthesized bio-photo-catalyst is used as an opto-fluidic reactor for amoxicillin degradation. Analyses including SEM, XRD, FTIR, Raman, UV-Vis spectra, and DLS have been used to characterize samples. The structure and morphology of TiO 2 in microfluidic assisted synthesis are studied at 70-120 °C. The results show that both single-crystalline anatase sample and two-phase samples of anatase and rutile can be attained. According to SEM images, the smallest size and the narrowest particle size distribution (0.86 nm [Formula: see text]) is achieved by synthesis at 70 °C. Elemental mapping of Ti shows a uniform coating layer on inner walls. Raman signals besides the primary amines in FTIR results show the biological activity of the cross-linked Glucose oxidase (GOx), which is aimed for situ generation of H 2 O 2 . FTIR comparison of bulk and spiral microfluidic synthesized ZnO indicates identical bonds. SEM-coupled with performance experimentation reveal that by regulating the flowrate of spiral micromixer for ZnCl 2 at 25 µl/min and NaOH at 50 µl/min, the narrowest size distribution and best the bio-photo-catalytic performance of ZnO nanoparticles is observed., (© 2022. The Author(s).)

Abstract: Breast cancer due to its high incidence and mortality is the second leading cause of death among females. On the other hand, nanoparticle-based drug delivery is one of the most promising approaches in cancer therapy, nowadays. Hence, margetuximab- and polyethylene glycol-conjugated PAMAM G4 dendrimers were efficiently synthesized for targeted delivery of quercetin (therapeutic agent) to MDA-MB-231 breast cancer cells. Synthesized nano-complexes were characterized using analytical devices such as FT-IR, TGA, DLS, Zeta potential analyzer, and TEM. The size less than 40 nm, - 18.8 mV surface charge, efficient drug loading capacity (21.48%), and controlled drug release (about 45% of drug release normal pH after 8 h) were determined for the nano-complex. In the biomedical test, the cell viability was obtained 14.67% at 24 h of post-treatment for 800 nM concentration, and IC 50 was ascertained at 100 nM for the nano-complex. The expression of apoptotic Bax and Caspase9 genes was increased by more than eightfolds and more than fivefolds after treatment with an optimal concentration of nanocarrier. Also, more than threefolds of cell cycle arrest was observed at the optimal concentration synthetics, and 27.5% breast cancer cell apoptosis was detected after treatment with 100 nM nano-complex. These outputs have been indicating the potential capacity of synthesized nano-complex in inhibiting the growth of breast cancer cells., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© Korean Society of Medical and Biological Engineering 2022.)

Changes in biomechanical properties have profound impacts on human health. C. elegans might serve as a model for studying the molecular genetics of mammalian tissue decline. Previously, we found that collagens are required for insulin signaling mutants' long lifespan and that overexpression of specific collagens extends wild-type lifespan. However, whether these effects on lifespan are due to mechanical changes during aging has not yet been established. Here, we have developed two novel methods to study the cuticle: we measure mechanical properties of live animals using osmotic shock, and we directly perform the tensile test on isolated cuticles using microfluidic technology. Using these tools, we find that the cuticle, not the muscle, is responsible for changes in the "stretchiness" of C. elegans, and that cuticle stiffness is highly nonlinear and anisotropic. We also found that collagen mutations alter the integrity of the cuticle by significantly changing the elasticity. In addition, aging stiffens the cuticle under mechanical loads beyond the cuticle's healthy stretched state. Measurements of elasticity showed that long-lived daf-2 mutants were considerably better at preventing progressive mechanical changes with age. These tests of C. elegans biophysical properties suggest that the cuticle is responsible for their resilience., (Copyright © 2022 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Dupuytren's disease (DD) is a common, progressive fibroproliferative disease affecting the palmar fascia of the hands, causing fingers to irreversibly flex toward the palm with significant loss of function. Surgical treatments are limited; therefore, effective new therapies for DD are urgently required. To identify the key cellular and molecular pathways driving DD, we employed single-cell RNA sequencing, profiling the transcriptomes of 35,250 human single cells from DD, nonpathogenic fascia, and healthy dermis. We identify a DD-specific population of pathogenic PDPN + /FAP + mesenchymal cells displaying an elevated expression of fibrillar collagens and profibrogenic genes. In silico trajectory analysis reveals resident fibroblasts to be the source of this pathogenic population. To resolve the processes governing DD progression, genes differentially expressed during fibroblast differentiation were identified, including upregulated TNFRSF12A and transcription factor SCX. Knockdown of SCX and blockade of TNFRSF12A inhibited the proliferation and altered the profibrotic gene expression of cultured human FAP + mesenchymal cells, demonstrating a functional role for these genes in DD. The power of single-cell RNA sequencing is utilized to identify the major pathogenic mesenchymal subpopulations driving DD and the key molecular pathways regulating the DD-specific myofibroblast phenotype. Using this precision medicine approach, inhibition of TNFRSF12A has shown potential clinical utility in the treatment of DD., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: A few studies have been published on the clinical efficacy and safety of nasal tip defatting plus rhinoplasty, particularly among people with bulbous noses. Therefore, the present study aimed to assess the consequences of nasal tip defatting for skin thickness reduction. Methods: This quasi-experimental study was performed on 72 consecutive patients, candidates for aesthetic rhinoplasty. Twenty-seven patients were scheduled for nasal tip defatting with routine open rhinoplasty concomitantly. Besides, 45 patients underwent rhinoplasty without nasal tip defatting method. Tip and supra-tip skin thickness were assessed before and 12 months after the operation using ultrasonography. The patients' and surgeon's satisfaction with aesthetic results after the operation were also evaluated based on visual analog scaling (VAS). SPSS version 16.0 (SPSS Inc., Chicago, IL., USA) was used for the analyses. P values below 0.05 were considered statistically significant. Results: Seventy-two patients (4 men, 68 women; mean age 26.40 ± 4.61 years) entered the study. Twenty-seven candidates underwent rhinoplasty plus nasal tip defatting (group A). Open rhinoplasty alone was performed for the other 45 patients (group B). The mean nasal tip thickness was 3.98±0.84 mm in group A and 3.69±0.64 mm in group B before the surgery (p=0.059). Preoperative nasal supra-tip thickness of the patients was also assessed using ultrasonography (3.54±0.72 mm in group A versus 3.73±0.54 mm in group B; p=0.065). Both preoperative tip and supra-tip thickness did not statistically differ between the two groups. No significant difference in postoperative tip skin thickness was obtained between two groups after 12 months (3.24±1 mm in group A versus 3.25±0.625 mm in group B; p=0.960), while postoperative supra-tip skin thickness differed significantly according to ultrasonography assessments (2.86±0.60 mm in group A versus 3.25±0.71 mm in group B; p=0.016). Postoperative satisfaction of the candidates was obtained using theVAS scoring system 12 months after the operation in both groups (8±1 in group A, 7.5±1 in group B; p=0.021). Surgeon's satisfaction in terms of the aesthetic outcome was also assessed based on the VAS system which did not statistically differ between the two groups as well as the patients' satisfaction (7.84±1.42 in group A, 7±1.61 in group B; p=0.014). Conclusion: Nasal tip skin defatting is the main component in aesthetic rhinoplasty, but its significant effect on the reduction of tip skin thickness is controversial. However, in patients with moderate or thick nasal tip skin, such a procedure can result in higher postoperative satisfaction with the aesthetic outcome compared to rhinoplasty alone., (© 2021 Iran University of Medical Sciences.)

Caenorhabditis elegans is used as a model organism to study a wide range of topics in molecular and cellular biology. Conventional C. elegans assays often require a large sample size with frequent manipulations, rendering them labor-intensive. Automated high-throughput workflows may not be always the best solution to reduce benchwork labor, as they may introduce more complexity. Thus, most assays are carried out manually, where logging and digitizing experimental data can be as time-consuming as picking and scoring worms. Here we report the development of CeAid, C. elegans Application for inputting data, which significantly expedites the data entry process, utilizing swiping gestures and a voice recognition algorithm for logging data using a standard smartphone or Android device. This modular platform can also be adapted for a wide range of assays where recording data is laborious, even beyond worm research., (© The Author(s) 2021. Published by Oxford University Press on behalf of Genetics Society of America.)

Reproduction comes at a cost, including accelerated death. Previous studies of the interconnections between reproduction, lifespan, and fat metabolism in C. elegans were predominantly performed in low-reproduction conditions. To understand how increased reproduction affects lifespan and fat metabolism, we examined mated worms; we find that a Δ9 desaturase, FAT-7, is significantly up-regulated. Dietary supplementation of oleic acid (OA), the immediate downstream product of FAT-7 activity, restores fat storage and completely rescues mating-induced death, while other fatty acids cannot. OA-mediated lifespan restoration is also observed in C. elegans mutants suffering increased death from short-term mating, and in mated C. remanei females, indicating a conserved role of oleic acid in post-mating lifespan regulation. Our results suggest that increased reproduction can be uncoupled from the costs of reproduction from somatic longevity regulation if provided with the limiting lipid, oleic acid., 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 © 2021 Choi, Shi, Ashraf, Sohrabi and Murphy.)

Background: Health literacy, social support and self-efficacy are important concepts in mothers of preterm neonates. The purpose of study was to determine the association between health literacy, social support and self-efficacy of mothers of preterm neonates admitted to the neonatal intensive care unit., Methods: This descriptive correlational study was conducted from November 2017 to January 2019 on 200 mothers of preterm neonates admitted to the neonatal intensive care unit of selected hospitals affiliated with Iran University of Medical Sciences, Tehran, Iran. Data were collected using demographic, maternal health literacy, maternal self-efficacy and multidimensional scale of perceived social support questionnaires. Data were analyzed by descriptive statistics (mean and standard deviation) and inferential tests (Pearson correlation coefficient) using SPSS-PC (v.23) and R software., Results: The data showed 23.5% of mothers had high likelihood of low health literacy, 45.5% had possibility of low health literacy and 31% had adequate with mean score 2.57 ± 1.28. Also, 9.5% of participants had low perceived social support, 62.5% moderate perceived social support and 28% high perceived social support. Maternal self-efficacy score was 52.54 ± 8.06. Pearson's correlation coefficient analyses revealed a statistically significant positive correlation between maternal health literacy and social support ( r  = 0.304, p  < .001). Also maternal health literacy was positively correlated with the self-efficacy ( r  = 0.292, p  < .001) and self-efficacy was positively correlated with social support ( r  = 0.440, p  < .001)., Conclusion: Health literacy, social support and self-efficacy of mothers of preterm neonates admitted to the neonatal intensive care unit in Iran are related together. Therefore, neonatal care nurses need to note this in care of this clients and adopt strategies to enhance them.

Objective: The purpose of this study is to review the mammographic and the ultrasound features of triple negative breast cancer (TNBC) patients and to investigate the potential effect of BRCA mutations on the imaging features of these patients., Methods: One hundred and seven patients with TNBC were enrolled in a retrospective study following IRB approval and approval of waiver of informed consent. BRCA mutations were assessed using genetic testing. Imaging features on mammography and ultrasound (US) as well as pathology and clinical information were retrospectively reviewed and characterized according to the BI-RADS lexicon (fifth edition). The relationships between BRCA mutations and the imaging findings were examined., Results: TNBC commonly presented as an irregular mass with obscured margins on mammography and as an irregular hypoechoic mass with microlobulated or angular margins on US. Approximately two thirds of TNBC cases had a parallel orientation and approximately one third had posterior enhancement, features often associated with benign masses. There was no statistically significant difference in the mammographic and the US features of BRCA positive and BRCA negative triple negative tumors., Conclusion: TNBC may have a parallel orientation and posterior enhancement, which are features often seen with benign masses. BRCA mutations do not affect the imaging features of triple negative breast tumors., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Vehicle automation safety must be evaluated not only for market success but also for more informed decision-making about Automated Vehicles' (AVs) deployment and supporting policies and regulations to govern AVs' unintended consequences. This study is designed to identify the AV safety quantification studies, evaluate the quantification approaches used in the literature, and uncover the gaps and challenges in AV safety evaluation. We employed a scoping review methodology to identify the approaches used in the literature to quantify AV safety. After screening and reviewing the literature, six approaches were identified: target crash population, traffic simulation, driving simulator, road test data analysis, system failure risk assessment, and safety effectiveness estimation. We ran two evaluations on the identified approaches. First, we investigated each approach in terms of its input (required data, assumptions, etc.), output (safety evaluation metrics), and application (to estimate AVs' safety implications at the vehicle, transportation system, and society levels). Second, we qualitatively compared them in terms of three criteria: availability of input data, suitability for evaluating different automation levels, and reliability of estimations. This review identifies four challenges in AV safety evaluation: (a) shortcomings in AV safety evaluation approaches, (b) uncertainties in AV implementations and their impacts on AV safety, (c) potential riskier behavior of AV passengers as well as other road users, and (d) emerging safety issues related to AV implementations. This review is expected to help researchers and rulemakers to choose the most appropriate quantification method based on their goals and study limitations. Future research is required to address the identified challenges in AV safety evaluation., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

We recently linked branched-chain amino acid transferase 1 (BCAT1) dysfunction with the movement disorder Parkinson's disease (PD), and found that RNAi-mediated knockdown of neuronal bcat-1 in C. elegans causes abnormal spasm-like 'curling' behavior with age. Here we report the development of a machine learning-based workflow and its application to the discovery of potentially new therapeutics for PD. In addition to simplifying quantification and maintaining a low data overhead, our simple segment-train-quantify platform enables fully automated scoring of image stills upon training of a convolutional neural network. We have trained a highly reliable neural network for the detection and classification of worm postures in order to carry out high-throughput curling analysis without the need for user intervention or post-inspection. In a proof-of-concept screen of 50 FDA-approved drugs, enasidenib, ethosuximide, metformin, and nitisinone were identified as candidates for potential late-in-life intervention in PD. These findings point to the utility of our high-throughput platform for automated scoring of worm postures and in particular, the discovery of potential candidate treatments for PD.

Plant defensins are a group of small disulfide-rich cationic peptides that exhibit a broad spectrum of antimicrobial activities. In the present study, an antibacterial plant defensin peptide was successfully identified and characterized from the transcriptome of the oat (Avena sativa L.), and called AsDef1. The complete nucleotide sequence of AsDef1 was determined (321 bp) and found to contain an open reading frame (ORF) encoding a peptide of 77 aa with a putative 22 aa signal peptide sequence that addresses the mature defensin to the apoplast. Further in silico analyses revealed that the structure of the identified defensin (AsDef1) consists of the Knot1 functional domain with eight conserved cysteine residues and four disulfide bonds. The highest expression of AsDef1 was observed in the developing seeds of the A. sativa plant. AsDef1 also showed antibacterial activity against both Gram-positive and Gram-negative bacteria. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values ranged from 0.15625 μM to 0.625 μM. In this study, we identified and characterized an antibacterial defensin from A. sativa for the first time. The findings of the present study offer insights that can be used in producing pathogen-resistant transgenic plants and in developing potential antibacterial agents in the future using AsDef1 from A. sativa., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

In this work, the effect of environment and additives on the self-assembly and delivery of doxorubicin (DOX) have been studied. A microfluidic system with better control over molecular interactions and high surface to volume ratio has superior performance in comparison to the bulk system. Moreover, carbon nanotube (CNT) and CNT-doped structures have a high surface area to incorporate the DOX molecules into a polymer and the presence of functional groups can influence the polymer-drug interactions. In this work, the interactions of DOX with both the polymeric complex and the nanotube structure have been investigated. For quantification of the interactions, H-bonding, gyration radius, root-mean-square deviation (RMSD), Gibbs free energy, radial distribution function (RDF), energy, and Solvent Accessible Surface Area (SASA) analyses have been performed. The most stable micelle-DOX interaction is attributed to the presence of BCN in the microfluidic system according to the gyration radius and RMSD. Meanwhile, for DOX-doped CNT interaction the phosphorus-doped CNT in the microfluidic system is more stable. The highest electrostatic interaction can be seen between polymeric micelles and DOX in the presence of BCN. For nanotube-drug interaction, phosphorus-doped carbon nanotubes in the microfluidic system have the largest electrostatic interaction with the DOX. RDF results show that in the microfluidic system, nanotube-DOX affinity is larger than that of nanotube-micelle., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Metabolic dysfunction occurs in many age-related neurodegenerative diseases, yet its role in disease etiology remains poorly understood. We recently discovered a potential causal link between the branched-chain amino acid transferase BCAT-1 and the neurodegenerative movement disorder Parkinson's disease (PD). RNAi-mediated knockdown of Caenorhabditis elegans bcat-1 is known to recapitulate PD-like features, including progressive motor deficits and neurodegeneration with age, yet the underlying mechanisms have remained unknown. Using transcriptomic, metabolomic, and imaging approaches, we show here that bcat-1 knockdown increases mitochondrial respiration and induces oxidative damage in neurons through mammalian target of rapamycin-independent mechanisms. Increased mitochondrial respiration, or "mitochondrial hyperactivity," is required for bcat-1(RNAi) neurotoxicity. Moreover, we show that post-disease-onset administration of the type 2 diabetes medication metformin reduces mitochondrial respiration to control levels and significantly improves both motor function and neuronal viability. Taken together, our findings suggest that mitochondrial hyperactivity may be an early event in the pathogenesis of PD, and that strategies aimed at reducing mitochondrial respiration may constitute a surprising new avenue for PD treatment., Competing Interests: Competing interest statement: The method used for automated quantification of curling motor behavior was filed under Patent #62/989,317: C.T.M., S.S., D.E.M., R.K., W.K., “Novel High-Throughput Screening Method for Parkinson’s Phenotypes Using C. elegans.” This patent is specifically for the screening method, not for metformin treatment of Parkinson’s disease phenotypes., (Copyright © 2020 the Author(s). Published by PNAS.)

Despite the substantial role that chickens have played in human societies across the world, both the geographic and temporal origins of their domestication remain controversial. To address this issue, we analyzed 863 genomes from a worldwide sampling of chickens and representatives of all four species of wild jungle fowl and each of the five subspecies of red jungle fowl (RJF). Our study suggests that domestic chickens were initially derived from the RJF subspecies Gallus gallus spadiceus whose present-day distribution is predominantly in southwestern China, northern Thailand and Myanmar. Following their domestication, chickens were translocated across Southeast and South Asia where they interbred locally with both RJF subspecies and other jungle fowl species. In addition, our results show that the White Leghorn chicken breed possesses a mosaic of divergent ancestries inherited from other subspecies of RJF. Despite the strong episodic gene flow from geographically divergent lineages of jungle fowls, our analyses show that domestic chickens undergo genetic adaptations that underlie their unique behavioral, morphological and reproductive traits. Our study provides novel insights into the evolutionary history of domestic chickens and a valuable resource to facilitate ongoing genetic and functional investigations of the world's most numerous domestic animal.

Droplet-based microfluidic systems have been shown to be compatible with many chemical and biological reagents and capable of performing a variety of operations that can be rendered programmable and reconfigurable. This platform has dimensional scaling benefits that have enabled controlled and rapid mixing of fluids in the droplet reactors, resulting in decreased reaction times. This, coupled with the precise generation and repeatability of droplet operations, has made the droplet-based microfluidic system a potent high throughput platform for biomedical research and applications. In addition to being used as micro-reactors ranging from the nano- to femtoliter (10 -15 liters) range; droplet-based systems have also been used to directly synthesize particles and encapsulate many biological entities for biomedicine and biotechnology applications. For this, in the following article we will focus on the various droplet operations, as well as the numerous applications of the system and its future in many advanced scientific fields. Due to advantages of droplet-based systems, this technology has the potential to offer solutions to today's biomedical engineering challenges for advanced diagnostics and therapeutics., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Treatment of high-risk traumatic immature teeth due to incomplete root development is challenging. Apexogenesis is currently the ideal treatment option that allows normal root development. The purpose of this study was to evaluate the apexogenesis process of immature permanent teeth of dogs when co-administered with calcium hydroxide and photobiomodulation therapy (PBMT). A total of 36 immature permanent anterior and premolar teeth were selected from three 4-6-month-old dogs of Iranian mixed generation. The teeth were categorized into two groups, calcium hydroxide with laser irradiation (CHL) and calcium hydroxide without laser irradiation (CH). All the selected teeth received calcium hydroxide pulpotomy. After restoring teeth with amalgam, the CHL group received gallium‑aluminum-arsenide (GaAlAs) diode laser (810 nm, 4.2 J/cm 2 , 0.3 W, 9 s,CW) on apical one-third of both buccal and lingual roots. The irradiation was repeated every 48 h for fourteen days. Intravenous tetracycline was used to observe newly formed dentin in the first, third, seventh, and fourteenth days. The distance between tetracycline lines (DTL) was examined by Fluorescence microscopy. Generalized estimating equations (GEE) were used for data analysis. In all assessments, the mean DTL were greater in the CHL group. However, the two groups had no significant differences in the amount of deposited dentin between the first and third, third and seventh, and first and seventh lines. Meanwhile, there was a significant difference between the two groups in terms of the distances between lines 7 and 14, 1 and 14 and also 3 to 14 (P < .001). In other words, from the 7th day onwards, there was a significant difference between the two groups. Within the limitation of this study, the combination therapy of PBMT and pulpotomy with calcium hydroxide accelerated apexogenesis in immature permanent dogs' teeth., Competing Interests: Declaration of Competing Interest There is no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Transportation systems have an essential role in satisfying individuals' needs for mobility and accessibility. Yet, they have been linked to several adverse health impacts, with a large, but modifiable, burden of disease. Among the several transportation-related health risk factors, this study focused on transportation-related noise as an emerging exposure whose burden of disease remains partially recognized. We compared premature deaths potentially attributable to transportation-related noise with deaths from motor vehicle crashes, a well-researched and widely recognized transportation risk factor., Method: We employed a standard burden of disease assessment framework to quantify premature cardiovascular diseases mortality attributable to transportation-related (road and aviation) noise at the census tract level (n = 592) in Houston, Texas. The results were compared to motor vehicle crash fatalities, which are routinely observed and collected in the study area. We also investigated the distribution of premature deaths across the city and explored the relationship between household median income and premature deaths attributable to transportation-related noise., Results: We estimated 302 (95% CI: 185-427) premature deaths (adults 30-75 years old) attributable to transportation-related noise in Houston, compared to 330 fatalities from motor vehicle crashes (adults younger than 75 years old). Transportation-related noise and motor vehicle crashes were responsible for 1.7% and 1.9% of all-cause premature deaths in Houston, respectively. Households with lower median income had a higher risk of adverse exposure and premature deaths potentially attributable to transportation-related noise. A larger number of premature deaths was associated with living in the central business district and the vicinity of highways and airports., Conclusion: This study highlighted the significant contribution of transportation-related noise and motor vehicle crashes to premature deaths in the city of Houston. The analogy between the estimated premature deaths attributable to transportation-related noise and motor vehicle crashes showed that the health impacts of transportation-related noise were as significant as motor vehicle crashes. The estimated premature death rate attributable to transportation-related noise was also comparable to the death rate caused by suicide, influenza, or pneumonia in the US. There is an urgent need for imposing policies to reduce transportation noise emissions and human exposures and to equip health impact assessment tools with a noise burden of disease analysis function., 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 © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

With recent rapid urbanization, sustainable development is required to prevent health risks associated with adverse environmental exposures from the unsustainable development of cities. Ambient air pollution is the greatest environmental risk factor for human health and is responsible for considerable levels of mortality worldwide. Burden of disease assessment (BoD) of air pollution in and across cities, and how these estimates vary according to socioeconomic status and exposure to road traffic, can help city planners and health practitioners to mitigate adverse exposures and promote public health. In this study, we quantified the health impacts of air pollution exposure (PM 2.5 and NO 2 ) at the census tract level in Houston, Texas, employing a standard BoD assessment framework to estimate the premature deaths (adults 30 to 78 years old) attributable to PM 2.5 and NO 2 . We found that 631 (95% CI: 366-809) premature deaths were attributable to PM 2.5 in Houston, and 159 (95% CI: 0-609) were attributable to NO 2 , in 2010. Complying with the World Health Organization air quality guidelines (annual mean: 10 μg/m 3 for PM 2.5 ) and the US National Ambient Air Quality standard (annual mean: 12 μg/m 3 for PM 2.5 ) could save 82 (95% CI: 42-95) and 8 (95% CI: 6-10) lives in Houston, respectively. PM 2.5 was responsible for 7.3% of all-cause premature deaths in Houston, in 2010, which is higher than the death rate associated with diabetes mellites, Alzheimer's disease, or motor vehicle crashes in the US. Households with lower income had a higher risk of adverse exposure and attributable premature deaths. We also showed a positive relationship between health impacts attributable to air pollution and road traffic passing through census tracts, which was more prominent for NO 2 ., Competing Interests: The authors declare no conflict of interest.

Background: Ex situ liver resection and autotransplantation is among the most advanced techniques which has been introduced in recent years., Case Presentation: A 24-year-old male referred with chief complaints of abdominal pain, nausea, and vomiting from 1 month prior to admission. Computed tomography showed a large liver mass in the left lobe of the liver with involvement of retrohepatic inferior vena cava (IVC), in favor of hepatocellular carcinoma. After hepatectomy, the common bile duct was completely removed. A 4-cm Dacron graft was anastomosed to the inferior and top of the IVC. A temporary portocaval shunt was placed, and ex situ resection of the left lobe of the liver was done. Remnant of the liver was implanted. Reconstruction of the bile duct was done using a Roux-en-Y technique, and autotransplantation of the liver was then completed. During a 4-year follow-up, the patient had no complaints and is in good conditions., Conclusion: With appropriate consideration of patients, despite surgical complexities, ex situ resection of unresectable HCC can provide excellent prognosis.

A key knowledge gap blocking development of effective therapeutics for Alzheimer's disease (AD) is the lack of understanding of how amyloid beta (Aβ) peptide and pathological forms of the tau protein cooperate in causing disease phenotypes. Within a mouse tau-deficient background, we probed the molecular, cellular, and behavioral disruption triggered by the influence of wild-type human tau on human Aβ-induced pathology. We find that Aβ and tau work cooperatively to cause a hyperactivity behavioral phenotype and to cause downregulation of transcription of genes involved in synaptic function. In both our mouse model and human postmortem tissue, we observe accumulation of pathological tau in synapses, supporting the potential importance of synaptic tau. Importantly, tau reduction in the mice initiated after behavioral deficits emerge corrects behavioral deficits, reduces synaptic tau levels, and substantially reverses transcriptional perturbations, suggesting that lowering synaptic tau levels may be beneficial in AD., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Recent large-cohort sequencing studies have investigated the genomic landscape of meningiomas, identifying somatic coding alterations in NF2, SMARCB1, SMARCE1, TRAF7, KLF4, POLR2A, BAP1, and members of the PI3K and Hedgehog signaling pathways. Initial associations between clinical features and genomic subgroups have been described, including location, grade, and histology. However, further investigation using an expanded collection of samples is needed to confirm previous findings, as well as elucidate relationships not evident in smaller discovery cohorts., Methods: Targeted sequencing of established meningioma driver genes was performed on a multiinstitution cohort of 3016 meningiomas for classification into mutually exclusive subgroups. Relevant clinical information was collected for all available cases and correlated with genomic subgroup. Nominal variables were analyzed using Fisher's exact tests, while ordinal and continuous variables were assessed using Kruskal-Wallis and 1-way ANOVA tests, respectively. Machine-learning approaches were used to predict genomic subgroup based on noninvasive clinical features., Results: Genomic subgroups were strongly associated with tumor locations, including correlation of HH tumors with midline location, and non-NF2 tumors in anterior skull base regions. NF2 meningiomas were significantly enriched in male patients, while KLF4 and POLR2A mutations were associated with female sex. Among histologies, the results confirmed previously identified relationships, and observed enrichment of microcystic features among "mutation unknown" samples. Additionally, KLF4-mutant meningiomas were associated with larger peritumoral brain edema, while SMARCB1 cases exhibited elevated Ki-67 index. Machine-learning methods revealed that observable, noninvasive patient features were largely predictive of each tumor's underlying driver mutation., Conclusions: Using a rigorous and comprehensive approach, this study expands previously described correlations between genomic drivers and clinical features, enhancing our understanding of meningioma pathogenesis, and laying further groundwork for the use of targeted therapies. Importantly, the authors found that noninvasive patient variables exhibited a moderate predictive value of underlying genomic subgroup, which could improve with additional training data. With continued development, this framework may enable selection of appropriate precision medications without the need for invasive sampling procedures.

Background: A sore throat is one of the common causes behind visits to the physician and antibiotic overtreatment in the world, especially in Iran. There are six ways of approaching pharyngitis patients. It is necessary to perform a cost-effectiveness analysis and find the best approach in all situations on group A streptococcus (GAS) pharyngitis management to propose a pharyngitis guideline., Method: The decision tree of managing pharyngitis and its complications was drawn. The probability of every status and the branches of the tree were derived from the literature, and the cost of related diseases and complications were calculated based on the dossiers of the patients in two main pediatric central hospitals in Tehran, Iran. Further, cost-effectiveness, sensitivity, and threshold analyses were conducted to find out the best management strategy. Moreover, for a situation analysis of pharyngitis management in Iran, a questionnaire was designed and given to general practitioners and pediatricians; 130 subjects responded to it. The results were then analyzed., Results: The rapid test antigen (RTA) and culture strategy were proved to have the highest effect on the quality-adjusted life year. In addition, a less expensive strategy was solely observed to be the RTA. The worst effect gained (most quality-adjusted lost days) was, however, from the "treat none" strategy., Conclusion: According to our cost-effectiveness analysis, the best management of pharyngitis occurs in RTA alone, followed slightly by culture strategies; the "RTA then culture if needed" and "RTA and culture" approaches become possible options after them. The "treat all" and "treat none" approaches, however, were not proper strategies in any case., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 Journal of Family Medicine and Primary Care.)

Introduction: The oncological benefit of completion thyroidectomy (CT) following thyroid lobectomy (TL) is presumed to be similar to that of upfront total thyroidectomy(TT), from a patient's perspective the risk and inconvenience of further surgery adds significantly to the impact of the overall treatment. The aim of this study is to assess the impact of CT in terms of the duration of admission and associated complications., Methods: A study of consecutive patients with DTC identified from prospective MDT records of South-East Scotland from 2009 to 2015. Surgical data was extracted from electronic medical record., Results: Of 361 patients diagnosed with DTC, 161 (45%) had CT. The median postoperative stay was 1 day (range 1-5days). In total 22 patients (14%)suffered complications. Four patients (3%) developed postoperative haematoma. Two (1%) had an identified permanent nerve palsy on the completion side. 13 patients (8%) remained on calcium supplementation for more than 6 months postoperatively and three patients (2%) developed wound complications., Conclusions: Our study confirms that CT is regularly performed (45%). Recent changes in international guidelines recognize increasing number of patients as eligible for a conservative approach but recommend CT based on whether upfront TT would have been recommended if the TL pathology were known from the outset. Such an approach fails to consider the additional risk and inconvenience of CT on the overall patient experience. Due to a relatively high rate of complications, only those patients who are most likely to benefit from further surgery to facilitate adjuvant radioactive iodine should be offered additional surgery., (Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Introduction: Arterial tortuosity has emerged as a predictor of adverse outcomes in congenital aortopathies using 3D reconstructed images. We validated a new method to estimate aortic arch tortuosity on 2D CT. We hypothesize that arch tortuosity may identify bicuspid aortic valve (BAV) patients at high risk to develop thoracic aortic aneurysms or aortic dissections (TAD)., Methods: BAV subjects with chest CT scans were retrospectively identified in our clinical records and matched to tricuspid aortic valve (TAV) controls by age, gender, and presentation with TAD. Subjects with prior ascending aortic intervention were excluded. Measurements included aortic arch tortuosity, length, angle, width and height. Total aortic tortuosity was estimated in subjects with available abdominal images., Results: 120 BAV and 234 TAV subjects were included. Our 2D measurements were highly correlated with 3D midline arch measurements and had high inter- and intra-observer reliability. Compared to TAV, BAV subjects had increased arch tortuosity (median 1.76 [Q1-Q3: 1.62-1.95] vs. 1.63 [1.53-1.78], P < 0.01), length (149 [136-160] vs. 135 [122-152] mm, P < 0.01), height (46 [41-53] vs. 39 [34-47] mm, P < 0.01), and vertex acuity (70 [61-77] vs. 75 [68-81] degree, P < 0.01). In a multivariable analysis, arch tortuosity remained independently associated with BAV after adjusting for aortic diameter and other clinical characteristics., Conclusions: We found that aortic arch tortuosity is significantly increased in BAV and may identify BAV patients who are at increased risk for TAD. Further studies to evaluate the association between tortuosity and clinical outcomes are in progress., (Copyright © 2018 Elsevier B.V. All rights reserved.)