PROTACs as Therapeutic Modalities for Drug Discovery in Castration-Resistant Prostate Cancer.

Castration-resistant prostate cancer (CRPC) presents significant challenges in clinical management due to its resistance to conventional androgen receptor (AR)-targeting therapies. The advent of proteolysis targeting chimeras (PROTACs) has revolutionized cancer therapy by enabling the targeted degradation of key molecular players implicated in CRPC progression. In this review we discuss the developments of PROTACs for CRPC treatment, focusing on AR and other CRPC-associated regulators. We provide an overview of the strategic trends in AR PROTAC development from the aspect of targeting site selection and preclinical antitumor evaluation, as well as updates on AR degraders in clinical applications. Additionally, we briefly address the current status of selective AR degrader development. Furthermore, we review new developments in PROTACs as potential CRPC treatment paradigms, highlighting those targeting chromatin modulators BRD4, EZH2, and SWI/SNF; transcription regulator SMAD3; and kinases CDK9 and PIM1. Given the molecular targets shared between CRPC and neuroendocrine prostate cancer (NEPC), we also discuss the potential of PROTACs in addressing NEPC.

Trastuzumab deruxtecan in patients with HER2-positive advanced colorectal cancer (DESTINY-CRC02): primary results from a multicentre, randomised, phase 2 trial.

BACKGROUND: Trastuzumab deruxtecan has shown encouraging activity in patients with treatment-refractory HER2-positive, RAS wild-type and BRAF wild-type metastatic colorectal cancer. Dose optimisation and further antitumour assessments in patients with RAS mutations and those with previous anti-HER2 therapy are warranted. We aimed to evaluate two doses of trastuzumab deruxtecan (5·4 mg/kg and 6·4 mg/kg) to establish the recommended dose in patients with pretreated HER2-positive, RAS wild-type or mutant metastatic colorectal cancer. METHODS: DESTINY-CRC02 was a multicentre, randomised, two-stage, two-arm, phase 2 study done in 53 research hospitals and medical centres in Australia, Belgium, France, Italy, Japan, South Korea, Spain, Taiwan, the UK, and the USA. Eligible patients were aged 18 years and older or 20 years and older (depending on region) with pretreated pathologically documented, unresectable, recurrent, or metastatic HER2-positive, and RAS wild-type or mutant colorectal cancer. Patients were required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and have received previous chemotherapy, and anti-EGFR, anti-VEGF, or anti-PD-L1 therapy, if clinically indicated. In stage 1, patients were randomly assigned (1:1), via a secure interactive response technology system, to receive 5·4 mg/kg or 6·4 mg/kg trastuzumab deruxtecan administered intravenously every 21 days. Stratification factors were ECOG performance status, HER2 status, and RAS status. In stage 2, patients were assigned into the 5·4 mg/kg treatment group only. The primary endpoint was confirmed objective response rate by blinded independent central review, assessed in all patients for whom treatment was assigned (full analysis set). Safety was assessed in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT04744831, and is ongoing (not recruiting). FINDINGS: Between March 5, 2021, and March 29, 2022, 135 patients were centrally screened, 122 of whom were enrolled. In stage 1, 40 patients each were randomly assigned to receive trastuzumab deruxtecan 5·4 mg/kg and 6·4 mg/kg. In stage 2, an additional 42 patients were enrolled in the 5·4 mg/kg group. 64 (52%) participants were male and 58 (48%) were female. The median duration of follow-up was 8·9 months (IQR 6·7-10·5) in the 5·4 mg/kg group and 10·3 months (5·9-12·7) in the 6·4 mg/kg group. The confirmed objective response rate by blinded independent central review was 37·8% (31/82 [95% CI 27·3-49·2]) in the 5·4 mg/kg group and 27·5% (11/40 [14·6-43·9]) in the 6·4 mg/kg group. 34 (41%) of 83 patients in the 5·4 mg/kg group and 19 (49%) of 39 in the 6·4 mg/kg group had grade 3 or worse drug-related treatment-emergent adverse events. The most common grade 3 or worse drug-related treatment-emergent adverse events were neutrophil count decreased (13 [16%] of 83 patients), anaemia (six [7%]), nausea (six [7%]), and white blood cell count decreased (five [6%]) in the 5·4 mg/kg group; and were neutrophil count decreased (10 [26%] of 39 patients), anaemia (eight [21%]), platelet count decreased (four [10%]), and white blood cell count decreased (four [10%]) in the 6·4 mg/kg group. Drug-related serious adverse events occurred in 11 (13%) of 83 patients in the 5·4 mg/kg group and six (15%) of 39 patients in the 6·4 mg/kg group; the most common in the 5·4 mg/kg group was nausea (three [4%] patients) and the most common in the 6·4 mg/kg group were fatigue (two [5%] patients), neutropenia (two [5%]), and thrombocytopenia (two [5%]). A drug-related treatment-emergent adverse event related to death occurred in one (1%) patient in the 5·4 mg/kg group (due to hepatic failure). Adjudicated drug-related interstitial lung disease or pneumonitis events were observed in seven (8%) patients in the 5·4 mg/kg group (all grade 1 or 2) and in five (13%) patients in the 6·4 mg/kg group (four grade 1 or 2; one grade 5). INTERPRETATION: The promising antitumour activity and favourable safety profile support trastuzumab deruxtecan 5·4 mg/kg as the optimal single-agent dose for patients with pretreated HER2-positive metastatic colorectal cancer, including those with RAS mutations, previous anti-HER2 therapy, or both. FUNDING: Daiichi Sankyo and AstraZeneca.

Differences between atrial fibrillation diagnosed before and after stroke: A large real-world cohort study.

The clinical characteristics and long-term outcomes of patients with ischemic stroke (IS) and atrial fibrillation detected after stroke (AFDAS) have not been clearly established. Previous studies evaluating patients with AFDAS were limited by the low prescription rates of anticoagulants and short follow-up periods. Consecutive patients hospitalized for IS between 2014 and 2017 were identified from a National Health Insurance Research Database. The included patients were categorized into three groups: (1) known diagnosis of AF (KAF) before the index stroke, (2) AFDAS, and (3) without AF (non-AF). Univariable and multivariable Cox regression analyses were performed to estimate the hazard ratio (HR) for independent variables and recurrent IS, hemorrhagic stroke, or all-cause mortality. We identified 158,909 patients with IS of whom 16,699 (10.5%) had KAF and 7,826 (4.9%) had AFDAS. The patients with AFDAS were younger, more often male, and had lower CHA2DS2-VASc scores (3.8 ± 1.9 versus 4.9 ± 1.8, p < 0.001) than the patients with KAF. Anticoagulant treatment significantly reduced the risks of all outcomes. The standardized mortality rates were 40.4, 28.6, and 18.4 (per 100 person-years) for the patients with KAF, AFDAS, and non-AF, respectively. Compared with AFDAS, KAF was associated with lower risks of recurrent IS [hazard ratio (HR): 0.91, 95% confidence interval (CI): 0.86-0.97, p < 0.01] and hemorrhagic stroke (HR: 0.88, 95% CI: 0.79-0.99, p < 0.01) and a higher risk of all-cause mortality (HR: 1.11, 95% CI: 1.07-1.16, p < 0.001). The risks of recurrent IS and hemorrhagic stroke were higher and of all-cause mortality was lower for patients with AFDAS than with KAF. There is a strong need to refine treatment modalities to reduce the high mortality in patients with KAF and AFDAS.

Large-Area Perovskite Solar Module Produced by Introducing Self-Assembled L-Histidine Monolayer at TiO2 and Perovskite Interface.

Perovskite solar cells have been proven to enhance cell characteristics by introducing passivation materials that suppress defect formation. Defect states between the electron transport layer and the absorption layer reduce electron extraction and carrier transport capabilities, leading to a significant decline in device performance and stability, as well as an increased probability of non-radiative recombination. This study proposes the use of an amino acid (L-Histidine) self-assembled monolayer material between the transport layer and the perovskite absorption layer. Surface analysis revealed that the introduction of L-Histidine improved both the uniformity and roughness of the perovskite film surface. X-ray photoelectron spectroscopic analysis showed a reduction in oxygen vacancies in the lattice and an increase in Ti4+, indicating that L-Histidine successfully passivated trap states at the perovskite and TiO2 electron transport layer interface. In terms of device performance, the introduction of L-Histidine significantly improved the fill factor (FF) because the reduction in interface defects could suppress charge accumulation and reduce device hysteresis. The FF of large-area solar modules (25 cm2) with L-Histidine increased from 55% to 73%, and the power conversion efficiency (PCE) reached 16.5%. After 500 h of aging tests, the PCE still maintained 91% of its original efficiency. This study demonstrates the significant impact of L-Histidine on transport properties and showcases its potential for application in the development of large-area perovskite module processes.

Cyclin dependent kinase 9 inhibition reduced programmed death-ligand 1 expression and improved treatment efficacy in hepatocellular carcinoma.

The anti-programmed death-ligand 1 (PD-L1) antibody is a standard therapy for advanced hepatocellular carcinoma (HCC). Tumor expression of PD-L1 can be induced upon stimulus. Because cyclin-dependent kinase 9 (CDK9) inhibition reduces the expression of inducible proteins, we explored the influence of CDK9 inhibition on PD-L1 expression in HCC cells. We found that PD-L1 expression was low in HCC cells; however, IFN-γ treatment increased this expression. CDK9 inhibitors AZD4573 and atuveciclib reduced the IFN-γ induced PD-L1 expression in a dose-dependent manner. CDK9 knockdown yielded similar results, but CDK9 overexpression reversed the influence of the CDK9 inhibitors. In the orthotopic mouse model, mice treated with a CDK9 inhibitor and an anti-PD-L1 antibody had significantly smaller tumors and exhibited longer survival than mice treated with either agent. In conclusion, CDK9 inhibition could reduce the expression of PD-L1 in HCC cells. Using both CDK9 inhibitors and anti-PD-L1 antibodies is more effective than using either agent alone.

Query-Based Multiview Detection for Multiple Visual Sensor Networks.

In IoT systems, the goal of multiview detection for multiple visual sensor networks is to use multiple camera perspectives to address occlusion challenges with multiview aggregation being a crucial component. In these applications, data from various interconnected cameras are combined to create a detailed ground plane feature. This feature is formed by projecting convolutional feature maps from multiple viewpoints and fusing them using uniform weighting. However, simply aggregating data from all cameras is not ideal due to different levels of occlusion depending on object positions and camera angles. To overcome this, we introduce QMVDet, a new query-based learning multiview detector, which incorporates an innovative camera-aware attention mechanism for aggregating multiview information. This mechanism selects the most reliable information from various camera views, thus minimizing the confusion caused by occlusions. Our method simultaneously utilizes both 2D and 3D data while maintaining 2D-3D multiview consistency to guide the multiview detection network's training. The proposed approach achieves state-of-the-art accuracy on two leading multiview detection benchmarks, highlighting its effectiveness for IoT-based multiview detection scenarios.

Influence of Varied Dietary Cholesterol Levels on Lipid Metabolism in Hamsters.

Syrian hamsters are valuable models for studying lipid metabolism due to their sensitivity to dietary cholesterol, yet the precise impact of varying cholesterol levels has not been comprehensively assessed. This study examined the impact of varying dietary cholesterol levels on lipid metabolism in Syrian hamsters. Diets ranging from 0% to 1% cholesterol were administered to assess lipid profiles and oxidative stress markers. Key findings indicate specific cholesterol thresholds for inducing distinct lipid profiles: below 0.13% for normal lipids, 0.97% for elevated LDL-C, 0.43% for increased VLDL-C, and above 0.85% for heightened hepatic lipid accumulation. A cholesterol supplementation of 0.43% induced hypercholesterolemia without adverse liver effects or abnormal lipoprotein expression. Furthermore, cholesterol supplementation significantly increased liver weight, plasma total cholesterol, LDL-C, and VLDL-C levels while reducing the HDL-C/LDL-C ratio. Fecal cholesterol excretion increased, with stable bile acid levels. High cholesterol diets correlated with elevated plasma ALT activities, reduced hepatic lipid peroxidation, and altered leptin and CETP levels. These findings underscore Syrian hamsters as robust models for hyperlipidemia research, offering insights into experimental methodologies. The identified cholesterol thresholds facilitate precise lipid profile manipulation, enhancing the hamster's utility in lipid metabolism studies and potentially informing clinical approaches to managing lipid disorders.

Stabilization of polyacrylonitrile-based fiber with a quasi-traveling microwave applicator.

This study introduces a novel microwave applicator and optimized processing conditions to enhance the stability of Polyacrylonitrile (PAN)-based precursor fiber (PF). The innovative microwave applicator facilitates the propagation of the electromagnetic (EM) field akin to a quasi-traveling wave, thus circumventing standing wave nodes. This ensures a uniform thermal distribution and broadens the heating zone. Utilizing this applicator, the PF undergoes thermal stabilization in a streamlined two-step process, completing in just 13 min, a significant improvement over the conventional 90-min process. This not only saves manufacturing time, promoting energy efficient manufacturing but also aligns with the global trend towards green energy and lightweight carbon fiber-reinforced polymer matrix composites, potentially catalyzing rapid economic growth. Fiber characterization through Raman spectroscopy (RS), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and complex permittivity measurements reveals that the microwave-processed fiber meets the standard of commercial stabilization fiber (SF).

SLC11A1 predicts the overall survival of patients with colorectal cancer.

Colorectal cancer (CRC) remains a significant contributor to cancer-related mortality, emphasizing the critical need for identifying biomarkers that can improve clinical management and patient outcomes. In this retrospective study, we analyzed tumor samples from 25 patients with metastatic CRC, categorized based on long-term (> 50 months) or short-term (< 10 months) survival. Employing the PanCancer Immune Profile Panel, encompassing 770 genes, in the discovery dataset, we identified 54 differentially expressed genes (DEGs) within the tumor microenvironment of metastatic CRC. Validation of potential biomarkers was performed using two publicly available RNA-based sequencing datasets (TCGA 1 (n=371) and TCGA 2 (n=566)). Univariate COX regression unveiled that three significant biomarkers were associated with overall survival in CRC within the discovery dataset, which were SLC11A1 (hazard ratio (HR): 4.09, P=0.012), TNFSF11 (HR: 3.67, P=0.02), and MEF2C (HR: 0.34, P=0.037). Kaplan-Meier survival curve analyses confirmed the correlation between SLC11A1 expression and overall survival in CRC across the discovery set (P=0.0071) and the two independent datasets (TCGA 1 (P=0.0016) and TCGA 2 (P=0.025)). Receiver operating characteristic curve analysis demonstrated an area under the curve ranging from 0.64 to 0.76, with sensitivity of 59% to 87% and specificity of 60% to 73% for predicting CRC overall survival. Immunohistochemistry staining further validated the strong expression of SLC11A1 protein in CRC tumor cells, with high expression correlating with short-term survival. These findings suggest that SLC11A1 serves as a predictive biomarker for overall survival in CRC patients.

Atomically Resolved Defect-Engineering Scattering Potential in 2D Semiconductors.

Engineering atomic-scale defects has become an important strategy for the future application of transition metal dichalcogenide (TMD) materials in next-generation electronic technologies. Thus, providing an atomic understanding of the electron-defect interactions and supporting defect engineering development to improve carrier transport is crucial to future TMDs technologies. In this work, we utilize low-temperature scanning tunneling microscopy/spectroscopy (LT-STM/S) to elicit how distinct types of defects bring forth scattering potential engineering based on intervalley quantum quasiparticle interference (QPI) in TMDs. Furthermore, quantifying the energy-dependent phase variation of the QPI standing wave reveals the detailed electron-defect interaction between the substitution-induced scattering potential and the carrier transport mechanism. By exploring the intrinsic electronic behavior of atomic-level defects to further understand how defects affect carrier transport in low-dimensional semiconductors, we offer potential technological applications that may contribute to the future expansion of TMDs.

Low Levels of IgM Recognizing 4-Hydroxy-2-Nonenal-Modified Apolipoprotein A-I Peptide and Its Association with the Severity of Coronary Artery Disease in Taiwanese Patients.

Autoantibodies against apolipoprotein A-I (ApoA-I) are associated with cardiovascular disease risks. We aimed to examine the 4-hydroxy-2-nonenal (HNE) modification of ApoA-I in coronary artery disease (CAD) and evaluate the potential risk of autoantibodies against their unmodified and HNE-modified peptides. We assessed plasma levels of ApoA-I, HNE-protein adducts, and autoantibodies against unmodified and HNE-peptide adducts, and significant correlations and odds ratios (ORs) were examined. Two novel CAD-specific HNE-peptide adducts, ApoA-I251-262 and ApoA-I70-83, were identified. Notably, immunoglobulin G (IgG) anti-ApoA-I251-262 HNE, IgM anti-ApoA-I70-83 HNE, IgG anti-ApoA-I251-262, IgG anti-ApoA-I70-83, and HNE-protein adducts were significantly correlated with triglycerides, creatinine, or high-density lipoprotein in CAD with various degrees of stenosis (<30% or >70%). The HNE-protein adduct (OR = 2.208-fold, p = 0.020) and IgM anti-ApoA-I251-262 HNE (2.046-fold, p = 0.035) showed an increased risk of progression from >30% stenosis in CAD. HNE-protein adducts and IgM anti-ApoA-I251-262 HNE may increase the severity of CAD at high and low levels, respectively.

Symmetry-breaking of Dibenzo[b,d]thiophene Sulfone Enhancing Polaron Generation for Boosted Photocatalytic Hydrogen Evolution.

The current bottleneck in the development of efficient photocatalysts for hydrogen evolution is the limited availability of high-performance acceptor units. Over the past nine years, dibenzo[b,d]thiophene sulfone (DBS) has been the preferred choice for the acceptor unit. Despite extensive exploration of alternative structures as potential replacements for DBS, a superior substitute remains elusive. In this study, a symmetry-breaking strategy was employed on DBS to develop a novel acceptor unit, BBTT-1SO. The asymmetric structure of BBTT-1SO proved beneficial for increasing multiple moment and polarizability. BBTT-1SO-containing polymers showed higher efficiencies for hydrogen evolution than their DBS-containing counterparts by up to 166 %. PBBTT-1SO exhibited an excellent hydrogen evolution rate (HER) of 222.03 mmol g-1 h-1 and an apparent quantum yield of 27.5 % at 500 nm. Transient spectroscopic studies indicated that the BBTT-1SO-based polymers facilitated electron polaron formation, which explains their superior HERs. PBBTT-1SO also showed 14 % higher HER in natural seawater splitting than that in deionized water splitting. Molecular dynamics simulations highlighted the enhanced water-PBBTT-1SO polymer interactions in salt-containing solutions. This study presents a pioneering example of a substitute acceptor unit for DBS in the construction of high-performance photocatalysts for hydrogen evolution.

Fusion of memristor and digital compute-in-memory processing for energy-efficient edge computing.

Artificial intelligence (AI) edge devices prefer employing high-capacity nonvolatile compute-in-memory (CIM) to achieve high energy efficiency and rapid wakeup-to-response with sufficient accuracy. Most previous works are based on either memristor-based CIMs, which suffer from accuracy loss and do not support training as a result of limited endurance, or digital static random-access memory (SRAM)-based CIMs, which suffer from large area requirements and volatile storage. We report an AI edge processor that uses a memristor-SRAM CIM-fusion scheme to simultaneously exploit the high accuracy of the digital SRAM CIM and the high energy-efficiency and storage density of the resistive random-access memory memristor CIM. This also enables adaptive local training to accommodate personalized characterization and user environment. The fusion processor achieved high CIM capacity, short wakeup-to-response latency (392 microseconds), high peak energy efficiency (77.64 teraoperations per second per watt), and robust accuracy (<0.5% accuracy loss). This work demonstrates that memristor technology has moved beyond in-lab development stages and now has manufacturability for AI edge processors.

Clinical characteristics and genetic HLA marker for patients with oxaliplatin-induced adverse drug reactions.

BACKGROUND: Oxaliplatin is commonly used to treat gastrointestinal malignancies. However, its applications are limited due to potential adverse drug reactions (ADRs), particularly severe anaphylactic shock. There is no method to predict or prevent ADRs caused by oxaliplatin. Therefore, we aimed to investigate the genetic HLA predisposition and immune mechanism of oxaliplatin-induced ADRs. METHODS: A retrospective review was performed for 154 patients with ADRs induced by oxaliplatin during 2016-2021 recorded in our ADR notification system. HLA genotyping was conducted for 47 patients with oxaliplatin-induced ADRs, 1100 general population controls, and 34 oxaliplatin-tolerant controls in 2019-2023. The in vitro basophil activation test (BAT) was performed and oxaliplatin-specific IgE levels were determined. RESULTS: The incidence of oxaliplatin-induced ADRs and anaphylactic shock in our cohort was 7.1% and 0.15%, respectively. Of the 154 patients, 67.5% suffered rash/eruption; 26.0% of the patients who could not undergo oxaliplatin rechallenge were considered to show oxaliplatin-induced immune-mediated hypersensitivity reactions (HRs). The genetic study found that the HLA-DRB∗12:01 allele was associated with oxaliplatin-induced HRs compared to the general population controls (sensitivity = 42.9%; odds ratio [OR] = 3.4; 95% CI = 1.4-8.2; P = 0.008) and tolerant controls (OR = 12; 95% CI = 2.3-63.7; P = 0.001). The in vitro BAT showed higher activation of CD63+ basophils in patients with oxaliplatin-induced HRs compared to the tolerant controls (P < 0.05). Only four patients (8.5%) with oxaliplatin-induced ADRs were positive for oxaliplatin-specific IgE. CONCLUSIONS: This study found that 26.0% of patients with oxaliplatin-induced ADRs could not undergo oxaliplatin rechallenge. HLA-DRB∗12:01 is regarded as a genetic marker for oxaliplatin-induced hypersensitivity.

Linalool, a Fragrance Compound in Plants, Protects Dopaminergic Neurons and Improves Motor Function and Skeletal Muscle Strength in Experimental Models of Parkinson's Disease.

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the gradual loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), resulting in reduced dopamine levels in the striatum and eventual onset of motor symptoms. Linalool (3,7-dimethyl-1,6-octadien-3-ol) is a monoterpene in aromatic plants exhibiting antioxidant, antidepressant, and anti-anxiety properties. The objective of this study is to evaluate the neuroprotective impacts of linalool on dopaminergic SH-SY5Y cells, primary mesencephalic and cortical neurons treated with 1-methyl-4-phenylpyridinium ion (MPP+), as well as in PD-like mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Cell viability, α-tubulin staining, western blotting, immunohistochemistry and behavioral experiments were performed. In MPP+-treated SH-SY5Y cells, linalool increased cell viability, reduced neurite retraction, enhanced antioxidant defense by downregulation of apoptosis signaling (B-cell lymphoma 2 (Bcl-2), cleaved caspase-3 and poly ADP-ribose polymerase (PARP)) and phagocyte NADPH oxidase (gp91phox), as well as upregulation of neurotrophic signaling (brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF)) and nuclear factor-erythroid 2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. In MPP+-treated primary mesencephalic neurons, linalool enhanced the expressions of tyrosine hydroxylase (TH), Sirtuin 1 (SirT1), and parkin. In MPP+-treated primary cortical neurons, linalool upregulated protein expression of SirT1, γ-Aminobutyric acid type A-α1 (GABAA-α1), and γ-Aminobutyric acid type B (GABAB). In PD-like mice, linalool attenuated the loss of dopamine neurons in SNpc. Linalool improved the motor and nonmotor behavioral deficits and muscle strength of PD-like mice. These findings suggest that linalool potentially protects dopaminergic neurons and improves the impairment symptoms of PD.

Hardware implementation of memristor-based artificial neural networks.

Artificial Intelligence (AI) is currently experiencing a bloom driven by deep learning (DL) techniques, which rely on networks of connected simple computing units operating in parallel. The low communication bandwidth between memory and processing units in conventional von Neumann machines does not support the requirements of emerging applications that rely extensively on large sets of data. More recent computing paradigms, such as high parallelization and near-memory computing, help alleviate the data communication bottleneck to some extent, but paradigm- shifting concepts are required. Memristors, a novel beyond-complementary metal-oxide-semiconductor (CMOS) technology, are a promising choice for memory devices due to their unique intrinsic device-level properties, enabling both storing and computing with a small, massively-parallel footprint at low power. Theoretically, this directly translates to a major boost in energy efficiency and computational throughput, but various practical challenges remain. In this work we review the latest efforts for achieving hardware-based memristive artificial neural networks (ANNs), describing with detail the working principia of each block and the different design alternatives with their own advantages and disadvantages, as well as the tools required for accurate estimation of performance metrics. Ultimately, we aim to provide a comprehensive protocol of the materials and methods involved in memristive neural networks to those aiming to start working in this field and the experts looking for a holistic approach.

Association between personality types and low anterior resection syndrome in rectal cancer patients following surgery.

PURPOSE: Low anterior resection syndrome (LARS) has had many impacts on the lives of patients and substantial differences in emotional and social functions. The aim of this study was to investigate the correlation analysis of different personality traits in rectal cancer patients with LARS after undergoing curative surgery. METHODS: This study was designed as a prospective cohort study. The inclusion criteria included (1) participants diagnosed with rectal cancer who underwent surgical resection of malignant tumors and (2) ECOG 0-1. The primary outcome was the correlation between different personality traits and low anterior resection syndrome in rectal cancer patients after radical surgery. Low anterior resection syndrome incidence rates were estimated by questionnaires and personality groups by the Type A and Type D Scale-14 Personality Inventory. RESULTS: For all 161 participants in this study, the presence of a tumor at the lower anal verge and the receipt of neoadjuvant CCRT had a statistically significant positive correlation with the LARS score at 1 month, 6 months, and 1 year (Pearson correlation coefficient = -0.283, -0.374, and - 0.205, respectively), with a p value of less than 0.05. Personalities with Type A, Type D, and Type D-SI scores had a statistically significant positive correlation with LARS score at 1 month (Pearson correlation coefficient = 0.172, 0.162, and 0,164, p value = 0.03, 0.04, and 0.04). CONCLUSION: Type A and Type D personalities are highly linked to LARS. Personalized support approaches can ultimately assist rectal cancer patients in overcoming difficulties after surgery and recovery and enhance their functional outcomes.

Factors associated with sleep quality in patients undergoing cardiac surgery: A longitudinal study.

BACKGROUND: Poor sleep quality is associated with multiple factors in cardiac surgery patients. AIM: To examine the trajectory of sleep quality and its associated factors over 3 months in Taiwanese patients undergoing cardiac surgery. STUDY DESIGN: A longitudinal study. This study enrolled 95 patients undergoing cardiac surgery in northern Taiwan. Sleep quality was measured using the Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale before surgery, at discharge, and at 1 month and 3 months postsurgery. RESULTS: The majority of participants reported poor sleep quality before cardiac surgery (76.8%) and at discharge (81.6%), and they showed significant improvements in sleep quality at 1 month (B = -0.93, p = .023) and 3 months postsurgery (B = -1.50, p < .001). Significant daytime sleepiness was reported by 25.3% of patients before cardiac surgery, and this proportion significantly decreased at 3 months postsurgery (B = -2.59, p < .001). The significant predictors of sleep quality in cardiac surgery patients were symptom distress, sleep medications, occupation, left ventricular ejection fraction, ACE-I drugs and potassium ions, which explained 53.7% of the total variance in sleep quality. Having a nap habit was an independent predictor of daytime sleepiness in cardiac surgery patients, which could explain 3.7% of the total variation. CONCLUSION: Poor sleep quality was common in patients undergoing cardiac surgery and was associated with multiple factors, including symptom distress, cardiac function, medications, and psychosocial and environmental factors. RELEVANCE TO CLINICAL PRACTICE: Poor sleep quality was observed in cardiac surgical patients before surgery and at discharge postsurgery. Patient education on symptom management, medication adherence and sleep hygiene are suggested to improve sleep quality in patients undergoing cardiac surgery.

Proteomic analysis of exosomal proteins associated with bone healing speed in a rat tibial fracture model.

This study investigates the impact of exosomes on bone fracture healing in a rat tibial model, distinguishing between fast and slow healing processes. Bone healing and protein expression were assessed through X-ray examinations, hematoxylin and eosin staining, and immunohistochemical staining. Exosomes were isolated, characterized and subjected to liquid chromatography-mass spectrometry for protein analysis. Molecular differences were explored using differentially expressed protein analysis, Kyoto Encyclopedia of Genes and Genomes pathway enrichment and protein-protein interaction networks. Differential bone healing patterns and protein expressions were observed between the control and model groups. Exosomes were successfully isolated and characterized, revealing 2004 identified proteins, including distinct expression profiles. Notably, ribosomal proteins, ferritin and beta-actin emerged as pivotal players in bone fracture healing. This study unveils dynamic changes in bone healing and underscores the role of exosomes in the process. Identified proteins and pathways offer valuable insights for developing innovative therapeutic strategies for bone healing.