Can AI Answer My Questions? Utilizing Artificial Intelligence in the Perioperative Assessment for Abdominoplasty Patients.

BACKGROUND: Abdominoplasty is a common operation, used for a range of cosmetic and functional issues, often in the context of divarication of recti, significant weight loss, and after pregnancy. Despite this, patient-surgeon communication gaps can hinder informed decision-making. The integration of large language models (LLMs) in healthcare offers potential for enhancing patient information. This study evaluated the feasibility of using LLMs for answering perioperative queries. METHODS: This study assessed the efficacy of four leading LLMs-OpenAI's ChatGPT-3.5, Anthropic's Claude, Google's Gemini, and Bing's CoPilot-using fifteen unique prompts. All outputs were evaluated using the Flesch-Kincaid, Flesch Reading Ease score, and Coleman-Liau index for readability assessment. The DISCERN score and a Likert scale were utilized to evaluate quality. Scores were assigned by two plastic surgical residents and then reviewed and discussed until a consensus was reached by five plastic surgeon specialists. RESULTS: ChatGPT-3.5 required the highest level for comprehension, followed by Gemini, Claude, then CoPilot. Claude provided the most appropriate and actionable advice. In terms of patient-friendliness, CoPilot outperformed the rest, enhancing engagement and information comprehensiveness. ChatGPT-3.5 and Gemini offered adequate, though unremarkable, advice, employing more professional language. CoPilot uniquely included visual aids and was the only model to use hyperlinks, although they were not very helpful and acceptable, and it faced limitations in responding to certain queries. CONCLUSION: ChatGPT-3.5, Gemini, Claude, and Bing's CoPilot showcased differences in readability and reliability. LLMs offer unique advantages for patient care but require careful selection. Future research should integrate LLM strengths and address weaknesses for optimal patient education. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Application of Near-Infrared Spectroscopy for Screening of Chlorothiazide Sodium Vials.

Chlorothiazide sodium for injection, USP, is a diuretic and antihypertensive medication in the form of a white or practically white, sterile, lyophilized powder. Each vial contains 500 mg of chlorothiazide sodium, equivalent to 500 mg of chlorothiazide, and 250 mg of mannitol as an inactive ingredient. The pH is adjusted with sodium hydroxide. Chlorothiazide sodium has a molecular weight of 317.71 amu. Since 2020 there have been multiple national shortages of chlorothiazide. Recent studies target chlorothiazide's low bioavailability, aiming to enhance it through nanoparticle production via a supercritical method. The drug's solubility in supercritical carbon dioxide (scCO2) is vital, with measurements ranging from 0.417×10-5 to 1.012×10-5 mole fraction under specific conditions. Adding co-solvents, like ethanol, DMSO, and acetone, to scCO2 boosts solubility, with ethanol proving most effective, enhancing solubility by 2.02-11.75 times. Intra-lot variability was discovered in a sample of a lot of chlorothiazide sodium by the University of Kentucky Drug Quality Task Force. Two vials of six screened in one lot were displaced from the center of the lot by 4.0 and 4.2 SDs, respectively. Inter-lot variability was confirmed in the near-IR spectra of 204 vials obtained from 28 different lots of chlorothiazide sodium. Using full spectrum BEST analysis 13 vials (6.4%) were outliers.

Dietary Super-Doses of Cholecalciferol Fed to Aged Laying Hens Illustrates Limitation of 24,25-Dihydroxycholecalciferol Conversion.

Background: Older humans taking high concentrations of vitamin D3 supplementation for a prolonged time may be at risk of vitamin D toxicity. It is unclear how dietary super-doses (10,000 times greater than the requirement) can affect vitamin D3 status in aged animals. Aged laying hens could be a model to compare vitamin D3 supplementation effects with women in peri- or postmenopausal stages of life. Objectives: We investigated the dietary super-dose impacts of cholecalciferol (vitamin D3) on vitamin D3 status in aged laying hens in production. Methods: Forty-eight 68-wk-old Hy-Line Brown laying hens were individually housed in cages with 8 hens per dietary treatment for 11 wk. Hens were randomly assigned to 1 of 6 treatment groups of dietary vitamin D3 supplementation and consumed ad libitum. Supplementation concentrations were 400, 800, 7400, 14,000, 20,000, and 36,000 IU D3/kg of feed. At the end of the study, all hens were sacrificed, and tissue samples and feces were collected. Plasma and egg yolk vitamin D3 metabolites, calcium and phosphorus composition of eggshells, ileal digesta, and feces were measured. Duodenal, ileal, liver, and kidney gene expression levels were also measured. Results: We observed that increasing dietary vitamin D3 increased plasma vitamin D3 and egg yolk vitamin D3 (P < 0.0001 for both sites). We also observed an increase in plasma 24,25-dihydroxycholecalciferol as dietary vitamin D3 concentrations increased (P < 0.0001). The plasma 25-hydroxycholecalciferol:24,25-dihydroxycholecalciferol ratio exhibited an asymptotic relationship starting at the 14,000 IU/kg D3 treatment. Conclusions: Dietary super-doses of vitamin D3 led to greater plasma and egg yolk vitamin D3 concentrations, which shows that aged laying hens can deposit excess vitamin D3 in egg yolk. We suggest future research should explore how 24-hydroxylation mechanisms are affected by vitamin D3 supplementation. Further understanding of 24-hydroxylation can help ascertain ways to reduce the risk of vitamin D toxicity.

Spread-out Bragg peak measurements using a compact quality assurance range calorimeter at the Clatterbridge cancer centre.

Objective.The superior dose conformity provided by proton therapy relative to conventional x-ray radiotherapy necessitates more rigorous quality assurance (QA) procedures to ensure optimal patient safety. Practically however, time-constraints prevent comprehensive measurements to be made of the proton range in water: a key parameter in ensuring accurate treatment delivery.Approach.A novel scintillator-based device for fast, accurate water-equivalent proton range QA measurements for ocular proton therapy is presented. Experiments were conducted using a compact detector prototype, the quality assurance range calorimeter (QuARC), at the Clatterbridge cancer centre (CCC) in Wirral, UK for the measurement of pristine and spread-out Bragg peaks (SOBPs). The QuARC uses a series of 14 optically-isolated 100 × 100 × 2.85 mm polystyrene scintillator sheets, read out by a series of photodiodes. The detector system is housed in a custom 3D-printed enclosure mounted directly to the nozzle and a numerical model was used to fit measured depth-light curves and correct for scintillator light quenching.Main results.Measurements of the pristine 60 MeV proton Bragg curve found the QuARC able to measure proton ranges accurate to 0.2 mm and reduced QA measurement times from several minutes down to a few seconds. A new framework of the quenching model was deployed to successfully fit depth-light curves of SOBPs with similar range accuracy.Significance.The speed, range accuracy and simplicity of the QuARC make the device a promising candidate for ocular proton range QA. Further work to investigate the performance of SOBP fitting at higher energies/greater depths is warranted.

The Preservation of Umbilical Blood Supply in Combined Ventral Hernia Repair and Abdominoplasty: A Narrative Review.

INTRODUCTION: Combined ventral hernia repair and abdominoplasty treat risk factors such as high body mass index and weak abdominal musculature, providing excellent intraoperative exposure and improved patient outcomes. Unfortunately, a combination of traditional procedures is unfeasible as the umbilical blood supply would be compromised, leading to increased umbilical necrosis risk. This narrative review aimed to identify new techniques and solidify evidence in preserving umbilical blood supply and associated level of evidence. METHODS: Two authors conducted a thorough literature search on PubMed, Scopus and Cochrane CENTRAL databases from January 1901 to July 2023, adhering to the methodologies of the preferred reporting items for systematic reviews and meta-analyses. Studies were reviewed for their surgical technique and quality of evidence. The primary outcomes of interest consisted of umbilical complications of this combined procedure. RESULTS: Six techniques were identified that included laparoscopic, pre-rectus, unilateral, distal bilateral, proximal bilateral, and inferior midline approaches. All techniques demonstrated as viable options in preserving umbilical blood supply as reported complications were few, minor, and compounded by risk factors. However, all included techniques were limited to low-to-moderate-quality evidence. CONCLUSION: Despite the lack of high-quality evidence, all techniques remain viable options for combined ventral hernia repair and abdominoplasty. Large-scale high-quality RCTs are required to compare the effectiveness of various approaches with additional outcomes of hernia recurrence rates, intraoperative time, and patient- and surgeon-reported satisfaction. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Systems genetics approach uncovers associations between host amylase locus, gut microbiome and metabolic traits in hyperlipidemic mice.

The molecular basis for how host genetic variation impacts gut microbial community and bacterial metabolic niches remain largely unknown. We leveraged 90 inbred hyperlipidemic mouse strains from the Hybrid Mouse Diversity Panel (HMDP), previously studied for a variety of cardio-metabolic traits. Metagenomic analysis of cecal DNA followed by genome-wide association analysis identified genomic loci that were associated with microbial enterotypes in the gut. Among these we detected a genetic locus surrounding multiple amylase genes that was associated with abundances of Firmicutes (Lachnospiraceae family) and Bacteroidetes (Muribaculaceae family) taxa encoding distinct starch and sugar metabolism functions. We also found that lower amylase gene number in the mouse genome was associated with higher gut Muribaculaceae levels. Previous work suggests that modulation of host amylase activity impacts the availability of carbohydrates to the host and potentially to gut bacteria. The genetic variants described above were associated with distinct gut microbial communities (enterotypes) with different predicted metabolic capacities for carbohydrate degradation. Mendelian randomization analysis revealed host phenotypes, including liver fibrosis and plasma HDL-cholesterol levels, that were associated with gut microbiome enterotypes. This work reveals novel relationships between host genetic variation, gut microbial enterotypes and host physiology/disease phenotypes in mice.

Milk exosomes anchored with hydrophilic and zwitterionic motifs enhance mucus permeability for applications in oral gene delivery.

Exosomes have emerged as a promising tool for the delivery of drugs and genetic materials, owing to their biocompatibility and non-immunogenic nature. However, challenges persist in achieving successful oral delivery due to their susceptibility to degradation in the harsh gastrointestinal (GI) environment and impeded transport across the mucus-epithelium barrier. To overcome these challenges, we have developed high-purity bovine milk exosomes (mExo) as a scalable and efficient oral drug delivery system, which can be customized by incorporating hydrophilic and zwitterionic motifs on their surface. In our study, we observed significantly improved transport rates by 2.5-4.5-fold in native porcine intestinal mucus after the introduction of hydrophilic and zwitterionic surface modifications, as demonstrated by transwell setup and fluorescence recovery after photobleaching (FRAP) analysis. Remarkably, mExo functionalized by a block peptide (BP), consisting of cationic and anionic amino acids arranged in blocks at the two ends, demonstrated superior tolerability in the acidic gastric environment (with a protein recovery rate of 84.8 ± 7.7%) and exhibited a 2.5-fold increase in uptake by intestinal epithelial cells. Furthermore, both mExo and mExo-BP demonstrated successful intracellular delivery of functional siRNA, resulting in up to 65% suppression of the target green fluorescence protein (GFP) gene expression at a low dose of siRNA (5 pmol) without causing significant toxicity. These findings highlight the immense potential of modifying mExo with hydrophilic and zwitterionic motifs for effective oral delivery of siRNA therapies.

Screening for quality with process analytical technology in a health-system pharmacy: A primer.

PURPOSE: The University of Kentucky Drug Quality Study team briefly reviews the growing concerns over pharmaceutical manufacturing quality in the globalized environment, reviews the historical approach by the US Food and Drug Administration (FDA) that prioritizes process over product in enforcing quality with manufacturers, reviews the science of process analytical technology (PAT) such as near-infrared (NIR) spectroscopy, illustrates the use of PAT methods for assessing uniformity and quality in injectable pharmaceuticals, and demonstrates the application of NIR spectroscopy in a health-system pharmacy setting while maintaining current good practice quality guidelines and regulations (cGxP). SUMMARY: Given that the current approach to monitoring quality in pharmaceutical manufacturing was developed in the late 1960s at a time when manufacturing was mostly domestic, the current approach prioritizes process over product, and the global footprint of manufacturing is straining federal resources to fulfill their task of monitoring quality, an approach to augment the quality monitoring process has been developed. PAT methodologies are supported by FDA for monitoring quality and offer a fast, low-cost, nondestructive solution. Given that the Accreditation Council for Pharmacy Education has not required qualitative/quantitative analysis and drug assaying in the pharmacy curriculum for several decades, the authors spend time explaining the science behind one of these PAT methodologies, NIR spectroscopy. This primer reviews the application of this technology in the health-system pharmacy setting and the relevant clinical applications. CONCLUSION: Utilizing PAT methodologies such as NIR spectroscopy, health-system pharmacies can gain insights about whether process controls are in place or lacking in FDA-approved formulations.

Shaping human gut community assembly and butyrate production by controlling the arginine dihydrolase pathway.

The arginine dihydrolase pathway (arc operon) present in a subset of diverse human gut species enables arginine catabolism. This specialized metabolic pathway can alter environmental pH and nitrogen availability, which in turn could shape gut microbiota inter-species interactions. By exploiting synthetic control of gene expression, we investigated the role of the arc operon in probiotic Escherichia coli Nissle 1917 on human gut community assembly and health-relevant metabolite profiles in vitro and in the murine gut. By stabilizing environmental pH, the arc operon reduced variability in community composition across different initial pH perturbations. The abundance of butyrate producing bacteria were altered in response to arc operon activity and butyrate production was enhanced in a physiologically relevant pH range. While the presence of the arc operon altered community dynamics, it did not impact production of short chain fatty acids. Dynamic computational modeling of pH-mediated interactions reveals the quantitative contribution of this mechanism to community assembly. In sum, our framework to quantify the contribution of molecular pathways and mechanism modalities on microbial community dynamics and functions could be applied more broadly.

Pre-rehabilitation interventions for patients with head and neck cancers: A systematic review and meta-analysis.

OBJECTIVE: To investigate the effect of pre-rehabilitation interventions such as nutrition and exercise for patients with head and neck cancer (HNC). METHODS: Web of Science, PubMed, Scopus, Google Scholar, and Cochrane databases were searched up to December 2022. Quality of life, length of hospital stay, postoperative complications, change in body mass index or muscle mass, and functional assessments were the primary outcomes. PRISMA guidelines were adhered to, and the study was registered on PROSPERO. The Cochrane Collaboration tool and Newcastle Ottawa scale assessed the quality of included studies. Pooled data are presented as odds ratios (OR) and 95% confidence intervals (CI). Analysis was conducted using RevMan5.4. RESULTS: A total of 31 articles were included for quantitative analysis and 15 for qualitative synthesis. Nutrition alone resulted in significant weight retention (2.60; 2.32, 2.88, p < 0.00001), length of stay (-4.00; -6.87, -1.13), p = 0.0006) and complications (0.64; 0.49, 0.83, p = 0.0009). Nutrition and psychoeducation resulted in a significant reduction in mortality rate (0.70; 0.49, 1.00, p = 0.05 and 0.60; 0.48, 0.74, p < 0.00001), and exercise resulted in a significant reduction in dysphagia (0.55; 0.35, 0.87, p = 0.01). Exercise with nutrition resulted in significant improvements in weight loss, length of stay, complications, and dysphagia. Randomized controlled trials (RCTs) had a moderate risk of bias and cohort studies were of fair to good quality. CONCLUSION: Prehabilitation programs based on exercise, nutrition, or psychoeducation demonstrated improved post-interventional outcomes in HNC, such as quality of life, and mortality and morbidity. Studies with longer follow-ups and larger sample sizes, and investigations comparing nutritional supplements with exercise programs are needed.

Chest pain due to coronary artery compression in an adult with CHD.

A 47-year-old with repaired ventricular septal defect and pulmonary valve stenosis as a child presents with chronic intermittent chest pain. CT evaluation for transcatheter pulmonary valve replacement revealed right coronary artery compression between a sternal wire and dilated right ventricle. Removal of the sternal wire resulted in improved symptoms.

Improving Visualization of Intramuscular Perforator Course: Augmented Reality Headsets for DIEP Flap Breast Reconstruction.

Background: Augmented reality (AR) technology, exemplified by devices such as the Microsoft HoloLens 2, has gained interest for its potential applications in preoperative guidance. This study explores the use of AR technology for perforator identification during deep inferior epigastric artery perforator (DIEP) flap breast reconstruction. Methods: A case series of five patients where an AR device was used to identify perforators during DIEP flap breast reconstruction is presented. The device was utilized to recognize preoperative perforators and map their extra- and intramuscular routes. Sound and/or color Doppler confirmation was used to verify the findings. Results: In all five cases, the AR device successfully identified preoperative perforators and delineated their extra- and intramuscular routes. AR technology in perioperative visualization of vasculature offers the potential to enhance surgical precision and reduce operative times. By providing an augmented three-dimensional overlay of patients' vascular structures, AR can facilitate a more comprehensive understanding of individual anatomy, ultimately improving surgical outcomes. Conclusions: AR technology shows promise in enhancing perforator identification efficiency and deepening understanding of perforator trajectories during preoperative planning. Nonetheless, additional research is needed to establish whether the advantages of AR technology warrant its widespread adoption for perforator identification.

Use of Artificial Intelligence in the Advancement of Breast Surgery and Implications for Breast Reconstruction: A Narrative Review.

BACKGROUND: Breast reconstruction is a pivotal part of the recuperation process following a mastectomy and aims to restore both the physical aesthetic and emotional well-being of breast cancer survivors. In recent years, artificial intelligence (AI) has emerged as a revolutionary technology across numerous medical disciplines. This narrative review of the current literature and evidence analysis explores the role of AI in the domain of breast reconstruction, outlining its potential to refine surgical procedures, enhance outcomes, and streamline decision making. METHODS: A systematic search on Medline (via PubMed), Cochrane Library, Web of Science, Google Scholar, Clinical Trials, and Embase databases from January 1901 to June 2023 was conducted. RESULTS: By meticulously evaluating a selection of recent studies and engaging with inherent challenges and prospective trajectories, this review spotlights the promising role AI plays in advancing the techniques of breast reconstruction. However, issues concerning data quality, privacy, and ethical considerations pose hurdles to the seamless integration of AI in the medical field. CONCLUSION: The future research agenda comprises dataset standardization, AI algorithm refinement, and the implementation of prospective clinical trials and fosters cross-disciplinary partnerships. The fusion of AI with other emergent technologies like augmented reality and 3D printing could further propel progress in breast surgery.

Reactive Extrusion of Nonmigratory Active and Intelligent Packaging.

The environmental and economic burden of food waste demands new preservation technologies to reduce the degradative actions of spoilage such as moisture, oxygen, and microorganisms. Direct food additives can help maintain product quality; however, the limited life span of these additives combined with consumer desire for "clean label" products has motivated research into new food manufacturing technologies like active and intelligent packaging that can prevent and detect food spoilage. In this work, curcumin was grafted to polypropylene (PP-g-Cur) via reactive extrusion to produce nonmigratory active and intelligent packaging through a solvent-free, efficient, and continuous method. Immobilization of curcumin was confirmed by a standard migration assay exhibiting a maximum of 0.011 mg/cm2 migration, significantly below the EU migratory limit for food contact materials (0.1 mg/cm2). Compared to native PP films, PP-g-Cur films blocked 93% of UV light while retaining 64% transparency in the visible region, allowing for desirable product visibility while inhibiting UV degradation of packaged goods. While the ability of PP-g-Cur to inhibit growth of E. coli and L. monocytogenes was insignificant compared to control PP, free curcumin exhibited poor bacterial inhibition as well, suggesting that without hydrophilic modification, native curcumin has limited antimicrobial efficacy. PP-g-Cur films displayed significant radical scavenging in both organic (11.71 ± 3.02 TroloxEq (nmol/cm2)) and aqueous (3.18 ± 1.04 TroloxEq (nmol/cm2)) matrices, exhibiting potential for antioxidant behavior in both lipophilic and hydrophilic applications. Finally, when PP-g-Cur films were exposed to ammonia, an indicator of microbial growth, the color visually and quantitatively changed from yellow to red, demonstrating potential to indicate spoilage. These findings demonstrate the potential of a scalable technology to produce active and intelligent packaging to limit food waste and advance the capabilities of functional materials in a variety of applications.

The Evolution of Longitudinal Strain Across Various Univentricular Morphologies Prior to Superior Cavopulmonary Anastomosis.

BACKGROUND: Infants with single-ventricle physiology have increased morbidity, mortality, and ventricular dysfunction in the pre-superior cavopulmonary anastomosis (pre-SCPA) period. Echocardiography-derived longitudinal strain (LS) is emerging as a reliable marker of single-ventricle performance. We aim to assess evolution of LS during the pre-SCPA period across univentricular morphologies and explore associations of LS with modifiable and nonmodifiable factors. METHODS: Ninety-four term infants (36 females) with univentricular physiology who were discharged home prior to stage 2 palliation were serially analyzed for LS (single apical view) and other echo measures at initial hospital discharge and the last pre-SCPA encounter. Ventricular myocardium was tracked for strain along the septum and respective lateral wall for single right ventricular (RV) and left ventricular (LV) groups, and along both right and left lateral walls in functionally univentricular hearts with biventricular (BiV) morphology. Clinical data were obtained from the medical record. RESULTS: Longitudinal strain improved in the total cohort during the pre-SCPA period (16.48% ± 3.31% to 17.57% ± 3.81%, P = .003). Longitudinal strain improved between encounters in the single LV (P = .04) and BiV groups (P = .02). However, LS failed to improve in the RV group (P = .7) with lower LS at both visits compared with the other groups. The RV group, mostly composed of hypoplastic left heart syndrome patients-87% of cases-had a higher incidence of arrhythmias (57%) and unplanned reinterventions (60%), most of which were arch reinterventions. A subanalysis based on arch reintervention showed that LS improves between encounters in the single LV group needing arch reintervention (P = .05) compared with the single RV group needing arch reintervention (P = .89). Lower LS was independently associated with unplanned reinterventions at both encounters (P = .008 and .02). CONCLUSIONS: Single-ventricle LS evolves differently across ventricular morphologies during the pre-SCPA period and is related to the need for unplanned cardiac reinterventions. Lower LS is noted in the single RV group, who mostly have hypoplastic left heart syndrome.

Modelling cybersecurity regulations for automated vehicles.

Technological advancements in Connected and Automated Vehicles (CAVs), particularly the integration of diverse stakeholder groups (communication service providers, road operators, automakers, repairers, CAV consumers, and the general public) and the pursuit of new economic opportunities, have resulted in the emergence of new technical, legal, and social challenges. The most pressing challenge is deterring criminal behaviour in both the physical and cyber realms through the adoption of CAV cybersecurity protocols and regulations. However, the literature lacks a systematic decision tool to analyze the impact of the potential cybersecurity regulations for dynamically interacting stakeholders, and to identify the leverage points to minimise the cyber-risks. To address this knowledge gap, this study uses systems theory to develop a dynamic modelling tool to analyze the indirect consequences of potential CAVs cybersecurity regulations in the medium to long term. It is hypothesized that CAVs Cybersecurity Regulatory Framework (CRF) is the property of the entire ITS stakeholders. The CRF is modelled using the System Dynamic based Stock-and-Flow-Model (SFM) technique. The SFM is founded on five critical pillars: the Cybersecurity Policy Stack, the Hacker's Capability, Logfiles, CAV Adopters, and intelligence-assisted traffic police. It is found that decision-makers should focus on three major leverage points: establishing a CRF grounded on automakers' innovation; sharing risks in eliminating negative externalities associated with underinvestment and knowledge asymmetries in cybersecurity; and capitalising on massive CAV-generated data in CAV operations. The formal integration of intelligence analysts and computer crime investigators to strengthen traffic police capabilities is pivotal. Recommendations for automakers include data-profiteering in CAV design, production, sales, marketing, safety enhancements and enabling consumer data transparency.Furthermore, CAVs-CRF necessitate a balanced approach to the trade-off between: i) data accessibility constraints on CAV automakers and ITS service providers; ii) regulator command and control thresholds; iii) automakers' business investment protection; and iv) consumers' data privacy guard.

A multinational empirical study of perceived cyber barriers to automated vehicles deployment.

The digital transformation of Automated Vehicles (AVs) has raised concerns in the cyber realm among prospective AV consumers. However, there is a dearth of empirical research on how cyber obstacles may impact the operation of AVs. To address this knowledge gap, this study examines the six critical cyber impediments (data privacy, AV connectivity, ITS infrastructure, lack of cybersecurity regulations, AV cybersecurity understanding, and AV cyber-insurance) that influence the deployment of AVs. The impact of gender, age, income level, and individual AV and cybersecurity knowledge on these obstacles are statistically assessed using a sample of 2061 adults from the United States, the United Kingdom, New Zealand, and Australia. The research revealed intriguing empirical findings on all cyber barriers in the form of a trichotomy: participants' education level, understanding of AVs, and cybersecurity knowledge. As education levels increase, the significance of a cyber barrier to AV deployment decreases; however, as AV comprehension and cybersecurity knowledge increase, the perception of a cyber barrier becomes significantly more important. In addition, the study demonstrates differences in perceptions of cyber barriers and AV deployments based on gender, age, income, and geographic location. This study's findings on cyber barriers and AV deployment have implications for academia and industry.

The combined effect and mechanism of antiangiogenic drugs and PD-L1 inhibitor on cell apoptosis in triple negative breast cancer.

Background: Breast cancer is the most common cancer worldwide, and triple-negative breast cancer (TNBC) has the worst prognosis. Standard systemic treatment includes chemotherapy and immunotherapy. Poly ADP-ribose polymerase (PARP) inhibitors are considered in breast cancer (BRCA) susceptibility genes mutated tumors. The role of antiangiogenic drugs is controversial. Immunotherapy with immune checkpoint inhibitor is now a standard of care for TNBC in the US, but its use in combination with anlotinib, an inhibitor of angiogenesis, on TNBC cells was never investigated. Methods: We tested the effects of anlotinib and programmed cell death-ligand 1 (PD-L1) inhibitor on the proliferation, apoptosis, migration, and invasion of MDA-MB-468 and BT-549 TNBC cells through 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT) assays, cell apoptosis assay, wound healing and transwell matrix assays, and verified whether the combination of the two drugs had synergistic effect. Western blotting was used to detect the effect of anlotinib and PD-L1 inhibitor on the protein expression levels of PI3K, p-PI3K, AKT, p-AKT, Bcl-xl in MDA-MB-468 and BT-549 cells. The effects of anlotinib, PD-L1 inhibitor and the combination of the two drugs on the transplanted tumor of TNBC mice were tested by animal experiments. Results: Anlotinib and PD-L1 inhibitor inhibited the proliferation and promote cell apoptosis of MDA-MB-468 and BT-549 cells, and the combination demonstrated the synergetic effect. Anlotinib and PD-L1 inhibitor inhibited cell migration and invasion, and the effect was strongest in the combination group. Both anlotinib and PD-L1 inhibitor reduced the expression of p-PI3K, p-AKT and Bcl-xl proteins in cells and the effects were the strongest in the combination group. Both anlotinib and PD-L1 inhibitor inhibited the growth of transplanted tumors in mice, and the combined group demonstrated the strongest growth suppression. Conclusions: Anlotinib and PD-L1 inhibitor can inhibit cell proliferation, migration, and invasion of TNBC and promote cell apoptosis, and the two drugs show combined anti-tumor effects in vivo and in vitro. The combination of anlotinib and PD-L1 inhibitor may promote apoptosis of TNBC cells through PI3K/AKT/Bcl-xl signaling pathways, which might offer potential clinical treatment roles for these.

Assessment of Vecuronium Quality Using Near-Infrared Spectrometry.

This study employed Fourier Transform near-infrared spectrometry to assess the quality of vecuronium bromide, a neuromuscular blocking agent. Spectral data from two lots of vecuronium were collected and analyzed using the BEST metric, principal component analysis (PCA) and other statistical techniques. The results showed that there was variability between the two lots and within each lot. Several outliers in the spectral data suggested potential differences in the chemical composition or sample condition of the vials. The outliers were identified and their spectral features were examined. A total of eight unique outliers were found in the PC space from PCs 1 to 9, so 22% of the total vials were outliers. The study findings suggest that the manufacturing process of vecuronium bromide may have been operating outside of a state of process control. Further investigation is needed to determine the source of these variations and their impact on the safety and efficacy of the drug product.