Uptake of Cascade Genetic Testing for Hereditary Breast and Ovarian Cancer: A Systematic Review and Meta-Analysis.

This is a systematic review and meta-analysis evaluating the uptake of cascade genetic testing for hereditary breast and ovarian cancer syndrome. Among 30 studies included for meta-analysis, the uptake of cascade genetic testing was 33% (95% CI 25%-42%), with higher uptake rates among females compared with male relatives, and among first-degree compared with second-degree relatives. These findings indicate suboptimal uptake of cascade genetic testing among people at risk for hereditary breast and ovarian cancer syndrome, representing a missed opportunity for cancer prevention and early detection. There is a need for interventions to improve uptake rates.

Transcriptome analysis of high- and low-selenium genotypes identifies genes responsible for selenium absorption, translocation, and accumulation.

Introduction: Selenium is an essential micronutrient the human body requires, which is closely linked to health. Rice, a primary staple food globally, is a major source of human selenium intake. To develop selenium-enriched rice varieties, it is imperative to understand the mechanisms behind selenium's absorption and transport within rice, alongside identifying the key genes involved in selenium uptake, transport, and transformation within the plant. Methods: This study conducted transcriptome sequencing on four types of rice materials (two with low-selenium and two with high-selenium contents) across roots, stems, leaves, and panicles to analyze the gene expression differences. Results and discussion: Differential gene expression was observed in the various tissues, identifying 5,815, 6,169, 7,609, and 10,223 distinct genes in roots, stems, leaves, and panicles, respectively. To delve into these differentially expressed genes and identify the hub genes linked to selenium contents, weighted gene co-expression network analysis (WGCNA) was performed. Ultimately, 10, 8, 7, and 6 hub genes in the roots, stems, leaves, and panicles, respectively, were identified. The identification of these hub genes substantially aids in advancing our understanding of the molecular mechanisms involved in selenium absorption and transport during the growth of rice.

Infection detection revolution: Harnessing AI-powered image analysis to combat infectious diseases.

Infectious diseases wield significant influence on global mortality rates, largely due to the challenge of gauging their severity owing to diverse symptomatology. Each nation grapples with its unique obstacles in combatting these diseases. This study delves into three distinct decision-making methodologies for medical diagnostics employing Neutrosophic Hypersoft Set (NHSS) and Plithogenic Hypersoft Set (PHSS), extensions of the Hypersoft set. It introduces state-of-the-art AI-driven techniques to enhance the precision of medical diagnostics through the analysis of medical imagery. By transforming these images into the aforementioned sets, the analysis becomes more refined, facilitating more accurate diagnoses. The study advocates various courses of action, including isolation, home or specialized center quarantine, or hospitalization for further treatment. The novelty in this study utilizes cutting-edge AI methods to enhance medical imaging, transforming them into accurate diagnostic tools, marking a significant change in how infectious diseases are addressed. By combining machine learning and pattern recognition, it offers the potential to overhaul healthcare worldwide, facilitating accurate diagnoses and customized treatment plans, ultimately reducing the global burden of infectious diseases on mortality rates.

Efficacy of Berberis vulgaris and Berberis integerrima on glycemic indices and weight profile in type 2 diabetic patients: A systematic review and meta-analysis of randomized controlled trials.

Type 2 diabetes mellitus (T2DM) is a multifactorial lifelong condition. Berberis vulgaris (BV) and Berberis integerrima (BI) regulate glucose levels with minimal adverse effects. In this systematic review and meta-analysis, we evaluate the effect of BV and BI on glycemic indices, weight, and body mass index (BMI) against placebo. Four electronic databases were searched till September 24, 2023. Inclusion criteria for studies were: (a) T2DM patients; (b) berberis (vulgaris/integerrima) therapy as intervention; (c) control group of placebo or metformin; (d) outcomes including fasting blood glucose (FBG) levels, glycated hemoglobin (HbA1c%), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), fasting serum insulin (FSI), 2-h postprandial glucose (2hPPG), fructosamine, weight, and BMI; (e) randomized controlled trials (RCTs). Data was pooled using a random-effects analysis model on Review Manager. The inverse variance statistical method was applied keeping weighted mean difference (WMD) as the effect measure. The Cochrane risk of bias tool evaluated the risk of bias. A p-value of less than 0.05 was considered significant. Nine RCTs comprising 547 patients were included. Significant reduction was noted with berberis therapy in FBG (WMD: -14.52; 95% CI = -22.97, -6.07; P = 0.0008); HbA1c % (WMD: -0.30; 95% CI = -0.53, -0.07; P = 0.01); HOMA-IR (WMD: -0.97; 95% CI = -1.56, 0.37; P = 0.001). No significant differences were noted between the two groups in 2hPPG (WMD: 6.52; 95% CI = -21.57, 34.61; P = 0.65); FSI (WMD: -0.79; 95% CI = -1.80, 0.22, P = 0.13); Fructosamine (WMD: -12.57; 95% CI = -40.74, 15.60; P = 0.38); Weight (WMD: -1.89; 95% CI = -4.55, 0.76; P = 0.16) and BMI (WMD: -0.12; 95% CI = -0.90, 0.65; P = 0.76). The data showed significant reduction in FBG and improved insulin levels but limited effects were observed in other glycemic indexes. More extensive RCTs are required globally to achieve a holistic comprehension of the connection between berberis and T2DM.

TCP BBR-n interplay with modern AQM in Wireless-N/AC networks: Quest for the golden pair.

Effective congestion control on the internet has been a problem since its inception. Transmission Control Protocol (TCP), being the most widely used transport layer protocol tries to mitigate it using a variety of congestion control algorithms. Cubic, Reno, and Bottleneck Bandwidth and Round-trip propagation time (BBR) are the most deployed congestion controls. BBR v2 is leading the congestion control race with its superior performance in terms of better throughput and lower latency. Furthermore, Active Queue Management (AQM) algorithms try to mitigate the congestion control at the network layer through active buffer control to avoid bufferbloat. The most efficient congestion control occurs when TCP and AQM work together. Indeed, it is the TCP-AQM algorithm "Golden pair" that can result in the most efficient performance. This paper proposes such a novel pair based on our previously tested and published BBR-n (BBR new) with the most effective of the modern AQMs, that completely gels together to provide lower latency in wireless networks based on Wireless N/AC. Real-time experiments were performed using Flent on our physical testbed with BBR-n and modern AQMs such as Fair Queuing (FQ), Constrained Delay (CoDel), Proportional Integral controller Enhanced (PIE), Common Applications Kept Enhanced (Cake) and Flow Queuing Controlled Delay (FQ_CoDel). Various tests done on our physical testbed helped us identify CAKE as the most optimum AQM that fits with our proposed BBR-n while providing optimum throughput and lower latency in 802.11N/AC-based wireless networks.

Protocol for Health Risk Information Technology-Assisted Genetic Evaluation (HeRITAGE): a randomised controlled trial of digital genetic cancer risk assessment in a diverse underserved gynaecology clinic.

INTRODUCTION: In the USA, up to 95% of individuals harbouring cancer-predisposing germline pathogenic variants have not been identified despite recommendations for screening at the primary care level. METHODS AND ANALYSIS: Our primary objective is to use a two-arm, single-institution randomised controlled trial to compare the proportion of eligible patients that are recommended genetic testing for hereditary cancer syndromes using a digital tool versus clinician interview for genetic cancer risk assessment in an urban academic gynaecology clinic. New gynaecology patients will be consented and randomised 1:1 to either the intervention arm, in which a digital tool is used for genetic cancer risk assessment, or usual care, in which the clinician performs genetic cancer risk assessment. Individuals will be considered eligible for hereditary cancer syndrome genetic testing if criteria set forth by the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology are met. Eligible patients are 18 years or older, speak and read English, have not yet undergone hereditary cancer genetic testing and have access to a smartphone. The study aims to enrol 50 patients in each arm to allow for 80% power with two-tailed alpha of 5% to detect a 20% difference in proportion of eligible patients recommended for genetic testing. The primary outcome is the proportion of eligible individuals recommended genetic testing in the digital tool arm versus usual care arm, analysed using the χ2 or Fisher's exact test as appropriate for sample size. The secondary outcome is completion of genetic testing, as well as exploration of patient factors, particularly social determinants of health, which may affect the receipt, utilisation and experience with genetic services. ETHICS AND DISSEMINATION: This study has been approved by the Weill Cornell Institutional Review Board (Protocol No. 21-11024123). Participants will be informed of the benefits and risks of participation prior to consent. Dissemination of data will be deidentified and conducted through academic conferences and journals. Patients identified to be eligible for genetic testing who did not receive counselling from their providers will be contacted; participants will not receive direct notification of trial results. REGISTRATION DETAILS: This trial is registered at clinicaltrials.gov (NCT05562778) in September 2022. PROTOCOL VERSION: This is protocol version 1, as of 22 May 2024. COUNTRIES OF RECRUITMENT AND RECRUITMENT STATUS: USA, currently recruiting. HEALTH CONDITIONS/PROBLEMS STUDIED: Genetic predisposition to cancers such as breast, ovarian, uterine and pancreatic. DEIDENTIFIED INDIVIDUAL CLINICAL TRIAL PARTICIPANT-LEVEL DATA IDP SHARING STATEMENT: IDP will not be shared. TRIAL REGISTRATION NUMBER: NCT05562778.

Simvastatin alleviates glymphatic system damage via the VEGF-C/VEGFR3/PI3K-Akt pathway after experimental intracerebral hemorrhage.

Current clinical practice primarily relies on surgical intervention to remove hematomas in patients with intracerebral hemorrhage (ICH), given the lack of effective drug therapies. Previous research indicates that simvastatin (SIM) may enhance hematoma absorption and resolution in the acute phase of ICH, though the precise mechanisms remain unclear. Recent findings have highlighted the glymphatic system (GS) as a crucial component in intracranial cerebrospinal fluid circulation, playing a significant role in hematoma clearance post-ICH. This study investigates the link between SIM efficacy in hematoma resolution and the GS. Our experimental results show that SIM alleviates GS damage in ICH-induced rats, resulting in improved outcomes such as reduced brain edema, neuronal apoptosis, and degeneration. Further analysis reveals that SIM's effects are mediated through the VEGF-C/VEGFR3/PI3K-Akt pathway. This study advances our understanding of SIM's mechanism in promoting intracranial hematoma clearance and underscores the potential of targeting the GS for ICH treatment.

A Strategy to Mitigate Jahn Teller Effect of Mn-Rich NASICON Framework for Sodium-Ion Batteries.

Mn-based sodium superionic conductors have driven attention to the low-cost advanced cathode materials for sodium-ion batteries (SIBs). However, low-rate capability and unsatisfactory cyclic performance due to the Jahn teller effect of Mn3+ redox couple which occurs from the change in Mn-O bond length at the octahedral site of crystal structure during charge-discharge, eventually limiting their application. Herein, a disordered and sodium deficient NASICON Na4-xMn(FeVCrTi)0.25(PO4)3 (termed as Na4-xMn(HE)) is synthesized to mitigate this Jahn teller effect to achieve high rate and ultrastable cathode material. Interestingly, the as-prepared Na3.5Mn(HE) shows five reversible electron reactions (i.e., Ti3+/Ti4+, Fe2+/Fe3+, V3+/V4+, Mn2+/Mn3+, and Mn3+/Mn4+) and demonstrates 141 mA h g-1 at 0.2 C with 80% capacity retention at 1 C after 500 cycles which is far superior to its counterparts binary Mn-based materials. The excellent cyclic performance is due to the remediation of the Jahn teller effect in sodium-deficient entropy-stabilized material. The structural reversibility, enhanced kinetics, and electronic properties are further studied in detail by in situ X-ray diffraction (XRD), ex situ X-ray photoelectron spectroscopy (XPS), and first principal calculations. Na3.5Mn(HE)//HC full cell delivered 89.7 mAh g-1 capacity at 0.2 C. This work sheds light on designing Mn-based cathodes with superior electrochemical performance for wide energy storage applications.

Design and numerical simulation of lead-free inorganic perovskites (Cs2BiAgI6) solar cell through computation method.

Cs2BiAgI6 is a lead-free inorganic perovskite material exhibits exceptional photoelectric characteristics and great environmental stability. HTL/Cs2BiAgI6is/ETLs solar cells was investigated numerically by using SCAPS 1-D Capacitance Simulator. IGZO, TiO2, WO3, MoO3, and SnO2 have been chosen as ETLs, while CuO, CuI, and MoO3 are as HTLs. The values of electrical parameters were calculated as function of thickness of the absorber layer, ETLs, HTLs, interface defect densities, doping densities, and working temperature. Comparative study shows that best configuration of obtain solar cell is MoO3/Cs2BiAgI6/IGZO. The obtain value of Jsc, Voc, FF and PCE are 23.80 mA/cm2, 1.193 V, 83.46 %, 23.711 % respectively. The value of quantum efficiency is 80-90 % in the range of 350-750 nm. These results will open the door for the widespread use of stable and environmentally friendly perovskite solar cells by providing theoretical recommendations for high performance of Cs2BiAgI6 based photovoltaic solar cells (PSCs).

Silicon nanoparticles and indole butyric acid positively regulate the growth performance of Freesia refracta by ameliorating oxidative stress under chromium toxicity.

Chromium (Cr) toxicity hampers ornamental crops' growth and post-harvest quality, especially in cut flower plants. Nano-enabled approaches have been developing with phenomenal potential towards improving floricultural crop production under heavy metal-stressed conditions. The current pot experiment aims to explore the ameliorative impact of silicon nanoparticles (Si-NPs; 10 mM) and indole butyric acid (IBA; 20 mM) against Cr stress (0.8 mM) in Freesia refracta. The results showed that Cr stress significantly reduced morphological traits, decreased roots-stems biomass, abridged chlorophyll (14.7%) and carotenoid contents (27.2%), limited gas exchange attributes (intercellular CO2 concentration (Ci) 24.8%, stomatal conductance (gs) 19.3% and photosynthetic rate (A) 28.8%), condensed proline (39.2%) and total protein (40%) contents and reduced vase life (15.3%) of freesia plants by increasing oxidative stress. Contrarily, antioxidant enzyme activities, MDA and H2O2 levels, and Cr concentrations in plant parts were remarkably enhanced in Cr-stressed plants than in the control. However, foliar supplementation of Si-NPs + IBA (combined form) to Cr-stressed plants increased defense mechanism and tolerance as revealed by improved vegetative and reproductive traits, increased biomass, photosynthetic pigments (chlorophyll 30.3%, carotenoid 57.2%) and gaseous exchange attributes (Ci 33.3%, gs 25.6%, A 31.1%), proline (54.5%), total protein (55.1%), and vase life (34.9%) of metal contaminated plants. Similarly, the improvement in the activities of peroxidase, catalase, and superoxide dismutase was recorded by 30.8%, 52.4%, and 60.8%, respectively, compared with Cr-stressed plants. Meanwhile, MDA (54.3%), H2O2 (32.7%) contents, and Cr levels in roots (43.3), in stems (44%), in leaves (52.8%), and in flowers (78.5%), were remarkably reduced due to combine application of Si-NPs + IBA as compared with Cr-stressed nontreated freesia plants. Thus, the hypothesis that the synergistic application of Si-NPs + IBA will be an effective approach in ameliorating Cr stress is authenticated from the results of this experiment. Furthermore, the study will be significant since it will demonstrate how Si-NPs and IBA can work synergistically to combat Cr toxicity, and even when added separately, they can improve growth characteristics both under stressed and un-stressed conditions.

Experimental development of lightweight manipulators with improved design cycle time that leverages off-the-shelf robotic arm components.

The growing market for lightweight robots inspires new use-cases, such as collaborative manipulators for human-centered automation. However, widespread adoption faces obstacles due to high R&D costs and longer design cycles, although rapid advances in mechatronic engineering have effectively narrowed the design space to affordable robot components, turning the development of lightweight robots into a component selection and integration challenge. Recognizing this transformation, we demonstrate a practical framework for designing lightweight industrial manipulators using a case-study of indigenously developed 5 Degrees-of-Freedom (DOF) cobot prototype. Our framework incorporates off-the-shelf sensors, actuators, gears, and links for Design for Manufacturing and Assembly (DFMA), along with complete virtual prototyping. The design cycle time is reduced by approximately 40% at the cost of cobot real-time performance deviating within 2.5% of the target metric. Our physical prototype, having repeatability of 0.05mm calculated as per the procedure defined in ISO 9283:1998, validates the cost-effective nature of the framework for creating lightweight manipulators, benefiting robotic startups, R&D organizations, and educational institutes without access to expensive in-house fabrication setups.

DEL-Thyroid: deep ensemble learning framework for detection of thyroid cancer progression through genomic mutation.

Genes, expressed as sequences of nucleotides, are susceptible to mutations, some of which can lead to cancer. Machine learning and deep learning methods have emerged as vital tools in identifying mutations associated with cancer. Thyroid cancer ranks as the 5th most prevalent cancer in the USA, with thousands diagnosed annually. This paper presents an ensemble learning model leveraging deep learning techniques such as Long Short-Term Memory (LSTM), Gated Recurrent Units (GRUs), and Bi-directional LSTM (Bi-LSTM) to detect thyroid cancer mutations early. The model is trained on a dataset sourced from asia.ensembl.org and IntOGen.org, consisting of 633 samples with 969 mutations across 41 genes, collected from individuals of various demographics. Feature extraction encompasses techniques including Hahn moments, central moments, raw moments, and various matrix-based methods. Evaluation employs three testing methods: self-consistency test (SCT), independent set test (IST), and 10-fold cross-validation test (10-FCVT). The proposed ensemble learning model demonstrates promising performance, achieving 96% accuracy in the independent set test (IST). Statistical measures such as training accuracy, testing accuracy, recall, sensitivity, specificity, Mathew's Correlation Coefficient (MCC), loss, training accuracy, F1 Score, and Cohen's kappa are utilized for comprehensive evaluation.

Factors Contributing to Rapid Early Infarct Expansion in Acute Ischemic Stroke Patients With Large Vessel Occlusion.

Background Acute ischemic stroke, particularly in cases involving large vessel occlusion (LVO), poses a significant challenge due to the potential for rapid infarct expansion in the early phase. Such expansion, if not managed promptly, can lead to severe neurological deficits and poor clinical outcomes. Understanding the contributing factors that accelerate early infarct expansion is crucial for optimizing treatment strategies and improving patient prognosis. The main aim of the study is to determine the factors contributing to rapid early infarct expansion in acute ischemic stroke patients with LVO. Methodology The retrospective study was conducted at Liaquat National Hospital in Karachi from August 2023 to December 2023. Data were collected from 685 patients with anterior circulation LVO-related acute stroke with witnessed stroke onset and baseline perfusion imaging. Extracted clinical data included age, gender, medical history (hypertension, diabetes, etc.), and baseline National Institutes of Health Stroke Scale (NIHSS) scores. Results The mean age of the included patients was 67.4 years, with a relatively balanced gender distribution, i.e., 48.5% male (n = 332) and 51.5% female (n = 353). The mean baseline NIHSS score was 14.2, reflecting initial neurological severity. Imaging parameters revealed that 294 (42.6%) patients exhibited infarct expansion, with an average penumbra size of 23.5 mL. Hypoperfusion intensity ratio (HIR) quartiles demonstrated a notable association with progression rates, escalating from 27 (4%) patients in the first quartile to approximately 527 (77%) patients in the fourth quartile, highlighting a significant correlation between HIR and infarct expansion (p < 0.001). Conclusions HIR emerged as a pivotal factor strongly associated with rapid infarct expansion, underscoring its significance in predicting the trajectory of ischemic injury.

Women and Cardiovascular Health: Unraveling Gender-Specific Factors, Risks, and Therapeutic Approaches in Contemporary Medicine.

Background and objective Cardiovascular diseases (CVDs) constitute a significant global health challenge, causing millions of deaths annually and straining healthcare systems worldwide. This study aimed to investigate and elucidate gender-specific factors, risks, and therapeutic approaches related to cardiovascular health in women within the context of contemporary medicine. Methodology We conducted a prospective observational study spanning one year (November 2022 to October 2023) at the Peshawar Medical Complex Hospital, to meticulously explore the field of women's cardiovascular health. With a diverse cohort of 435 women (age range: 18-55 years), representing various socioeconomic backgrounds and geographic locations, our study aimed to elicit comprehensive insights. Through structured interviews covering reproductive history, lifestyle, and psychosocial aspects, coupled with clinical assessments, we gathered multifaceted data. Statistical analysis was done using SPSS Statistics version 23.0 (IBM Corp., Armonk, NY). By employing descriptive and t-tests for quantitative analysis and by thematically analyzing qualitative insights, our approach ultimately sought to provide a nuanced understanding of gender-specific factors impacting women's cardiovascular health. Results The study, involving 435 women, revealed various prevalent cardiovascular risk factors. Notable findings include a high incidence of a family history of CVD (n=213, 48.96%, p=0.013), hypertension (n=207, 47.58%), hypercholesterolemia (n=114, 26.21%), elevated triglycerides (n=162, 37.24%), and diabetes (n=64, 14.71%). Physical inactivity was also significantly more common (53.56%, p=0.004) compared to those engaging in regular activity. Women-specific risk factors comprised miscarriage (n=191, 43.91%). Therapeutic preferences varied, with a majority opting for lifestyle modifications (n=263, 60.39%) and pharmacological interventions (n=331, 76.33%). Conclusions This study provides a comprehensive understanding of prevalent cardiovascular risk factors, distinctive women-specific contributors, and diverse therapeutic preferences, highlighting the importance of personalized and targeted interventions to optimize women's cardiovascular health outcomes in contemporary medicine.

Cost-effectiveness of BRCA1 testing at time of obstetrical prenatal carrier screening for cancer prevention.

BACKGROUND: Improved technologies paired with an increase in access to genetic testing have led to the availability of expanded carrier screening evaluating hundreds of disorders. Currently, most autosomal dominant mutations, such as BRCA1, are not included in expanded carrier assays. Screening pregnant or preconception reproductive-aged women for BRCA1 may present a unique opportunity to perform population-based screening for patients at a time when precancer screening, chemoprevention, and/or risk-reducing surgery may be beneficial. OBJECTIVE: This study aimed to inform clinical decision-making as to whether the universal incorporation of BRCA1 testing at the time of obstetrical prenatal carrier screening is cost-effective. STUDY DESIGN: A decision analysis and Markov model was created. The initial decision point in the model was BRCA1 testing at the time of expanded carrier screening. Model probabilities, cost, and utility values were derived from published literature. For BRCA1-positive patients, the model simulated breast cancer screening and risk-reducing surgical interventions. A cycle length of 1 year and a time horizon of 47 years were used to simulate the lifespan of patients. The setting was obstetrical clinics in the United States, and the participants were a theoretical cohort of 1,429,074 pregnant patients who annually underwent expanded carrier screening. RESULTS: Among our cohort, BRCA1 testing resulted in the identification of an additional 3716 BRCA1-positive patients, the prevention of 1394 breast and ovarian cancer cases, and 1084 fewer deaths. BRCA1 testing was a cost-effective strategy compared with no BRCA1 testing with an incremental cost-effectiveness ratio of $86,001 per quality-adjusted life years. In a 1-way sensitivity analysis, we varied the prevalence of BRCA1 in the population from 0.00% to 20.00% and found that BRCA1 testing continued to be the cost-effective strategy until the prevalence rate was reduced to 0.16%. Multiple additional sensitivity analyses did not substantially affect the cost-effectiveness. CONCLUSION: The addition of BRCA1 testing to obstetrical prenatal carrier screening is a cost-effective management strategy to identify at-risk women at a time when cancer screening and preventive strategies can be effective. Despite the burden of additional genetic counseling, prenatal care represents a unique opportunity to implement population-based genetic testing.