Biogenic synthesis and physicochemical characterization of metal nanoparticles based on Calotropis procera as promising sustainable materials against skin cancer.

The UAE harbors a rich diversity of wild medicinal plants, such as Calotropis procera (CP), that are renowned for their extensive use in traditional medicine due to their abundance of bioactive phytochemicals. Zinc and iron metals possess significant pharmacological effects including antioxidant and anticancer properties. In this study, nanoparticles (NPs) containing zinc and iron were green synthesized utilizing ethanolic and aqueous extracts of CP aerial parts. UV-Vis spectra revealed absorption peaks around 270-275 nm, while FT-IR analysis confirmed successful coating of the NPs with plant's phytochemicals. SEM/EDX analysis indicated a more potent reducing effect of the aqueous extract, whereas the alcoholic extract demonstrated more effective coating of the NPs. DLS showed monodispersed NPs with average sizes of 32.67-202 nm. The alcoholic extract-based zinc and iron NPs exhibited the highest phenolic and flavonoid contents (51.06 ± 2.82 µg of GAE/mg of DW and 66.26 ± 1.12 µg of Qu/mg of DW, respectively) and the strongest antioxidant effect against ABTS and DPPH radicals (IC50 = 52.81 and 148.46 µg/mL, respectively). The aqueous extract-based zinc NPs demonstrated the greatest cytotoxicity against A-431 cell lines (IC50 = 188.97 µg/mL). The findings highlight promising potential of these sustainable materials for therapeutic applications, indicating a need for continued research and development in this area.

A Predefined Rule-Based Multi-Factor Risk Stratification Is Associated With Improved Outcomes at a Rural Primary Care Practice.

This study built a predefined rule-based risk stratification paradigm using 19 factors in a primary care setting that works with rural communities. The factors include medical and nonmedical variables. The nonmedical variables represent 3 demographic attributes and one other factor represents transportation availability. Medical variables represent major clinical variables such as blood pressure and BMI. Many risk stratification models are found in the literature but few integrate medical and nonmedical variables, and to our knowledge, no such model is designed specifically for rural communities. The data used in this study contain the associated variables of all medical visits in 2021. Data from 2022 were used to evaluate the model. After our risk stratification model and several interventions were adopted in 2022, the percentage of patients with high or medium risk of deteriorating health outcomes dropped from 34.9% to 24.4%, which is a reduction of 30%. The medium-complex patient population size, which had been 29% of all patients, decreased by about 4% to 5.7%. According to the analysis, the total risk score showed a strong correlation with 3 risk factors: dual diagnoses, the number of seen providers, and PHQ9 (0.63, 0.54, and 0.45 correlation coefficients, respectively).

Innovate and Validate: Design-Led Simulation Optimization to Test Centralized Registration Feasibility in a Multispecialty Clinic.

OBJECTIVE: This study utilizes a design-led simulation-optimization process (DLSO) to refine a hybrid registration model for a free-standing outpatient clinic. The goal is to assess the viability of employing DLSO for innovation support and highlight key factors influencing resource requirements. BACKGROUND: Manual registration in healthcare causes delays, impacting patient services and resource allocation. This study addresses these challenges by optimizing a hybrid centralized registration and adopting technology for efficiency. METHOD: An iterative methodology with simulation optimization was designed to test a proof of concept. Configurations of four and five registration options within a hybrid centralized system were explored under preregistration adoption rates of 30% and 50%. Three self-service kiosks served as a baseline during concept design and test fits. RESULTS: Centralized registration accommodated a daily throughput of 2,000 people with a 30% baseline preregistration rate. Assessing preregistration impact on seating capacity showed significant reductions in demand and floor census. For four check-in stations, a 30%-50% preregistration increase led to a 32% seating demand reduction and a 26% decrease in maximum floor census. With five stations, a 50% preregistration reduced seating demand by 23% and maximum floor census by 20%. CONCLUSION: Innovating introduces complexity and uncertainties requiring buy-in from diverse stakeholders. DLSO experimentation proves beneficial for validating novel concepts during design.

Green Synthesis of Zinc Oxide Nanoparticles from Althaea officinalis Flower Extract Coated with Chitosan for Potential Healing Effects on Diabetic Wounds by Inhibiting TNF-α and IL-6/IL-1ß Signaling Pathways.

Background: Diabetes Mellitus is a multisystem chronic pandemic, wound inflammation, and healing are still major issues for diabetic patients who may suffer from ulcers, gangrene, and other wounds from uncontrolled chronic hyperglycemia. Marshmallows or Althaea officinalis (A.O.) contain bioactive compounds such as flavonoids and phenolics that support wound healing via antioxidant, anti-inflammatory, and antibacterial properties. Our study aimed to develop a combination of eco-friendly formulations of green synthesis of ZnO-NPs by Althaea officinalis extract and further incorporate them into 2% chitosan (CS) gel. Method and Results: First, develop eco-friendly green Zinc Oxide Nanoparticles (ZnO-NPs) and incorporate them into a 2% chitosan (CS) gel. In-vitro study performed by UV-visible spectrum analysis showed a sharp peak at 390 nm, and Energy-dispersive X-ray (EDX) spectrometry showed a peak of zinc and oxygen. Besides, Fourier transforms infrared (FTIR) was used to qualitatively validate biosynthesized ZnO-NPs, and transmission electron microscope (TEM) showed spherical nanoparticles with mean sizes of 76 nm and Zeta potential +30mV. The antibacterial potential of A.O.-ZnO-NPs-Cs was examined by the diffusion agar method against Gram-positive (Staphylococcus aureus and Bacillus subtilis) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). Based on the zone of inhibition and minimal inhibitory indices (MIC). In addition, an in-silico study investigated the binding affinity of A.O. major components to the expected biological targets that may aid wound healing. Althaea Officinalis, A.O-ZnO-NPs group showed reduced downregulation of IL-6, IL-1ß, and TNF-α and increased IL-10 levels compared to the control group signaling pathway expression levels confirming the improved anti-inflammatory effect of the self-assembly method. In-vivo study and histopathological analysis revealed the superiority of the nanoparticles in reducing signs of inflammation and wound incision in rat models. Conclusion: These biocompatible green zinc oxide nanoparticles, by using Althaea Officinalis chitosan gel ensure an excellent new therapeutic approach for quickening diabetic wound healing.

Revolutionizing Psoriasis Topical Treatment: Enhanced Efficacy Through Ceramide/Phospholipid Composite Cerosomes Co-Delivery of Cyclosporine and Dithranol: In-Vitro, Ex-Vivo, and in-Vivo Studies.

Purpose: Improving the treatment of psoriasis is a serious challenge today. Psoriasis is an immune-mediated skin condition affecting 125 million people worldwide. It is commonly treated with cyclosporine-A (CsA) and dithranol (DTH). CsA suppresses the activation of T-cells, immune cells involved in forming psoriatic lesions. Meanwhile, DTH is a potent anti-inflammatory and anti-proliferative drug that effectively reduces the severity of psoriasis symptoms such as redness, scaling, and skin thickness. CsA and DTH belong to BCS class II with limited oral bioavailability. We aim to develop a drug delivery system for topical co-delivery of CsA and DTH, exploring its therapeutic potential. Methods: Firstly, we developed a niosomal drug delivery system based on ceramide IIIB to form Cerosomes. Cerosomes were prepared from a mixture of Ceramide, hyaluronic acid, and edge activator using a thin-film hydration technique. To co-deliver CsA and DTH topically for the treatment of psoriasis. These two hydrophobic drugs encapsulated into our synthesized positively charged particle cerosomes. Results:  Cerosomes had an average particle size of (222.36 nm± 0.36), polydispersity index of (0.415±0.04), Entrapment Efficiency of (96.91%± 0.56), and zeta potential of (29.36±0.38mV) for selected formula. In vitro, In silico, in vivo, permeation, and histopathology experiments have shown that cerosomes enhanced the skin penetration of both hydrophobic drugs by 66.7% compared to the CsA/DTH solution. Imiquimod (IMQ) induced psoriatic mice model was topically treated with our CsA/DTH cerosomes. We found that our formulation enhances the skin penetration of both drugs and reduces psoriasis area and severity index (PASI score) by 2.73 times and 42.85%, respectively, compared to the CsA/DTH solution. Moreover, it reduces the levels of proinflammatory cytokines, TNF-α, IL-10, and IL-6 compared to CsA/DTH solution administration. Conclusion: The Cerosomes nano-vesicle-containing CsA/DTH represents a more promising topical treatment for psoriasis, giving new hope to individuals with psoriasis, compared to commercial and other conventional alternatives.

A systematic review on Nb2O5-based photocatalysts: Crystallography, synthetic methods, design strategies, and photocatalytic mechanisms.

With the increasing popularity of photocatalytic technology and the highly growing issues of energy scarcity and environmental pollution, there is an increasing interest in extremely efficient photocatalytic systems. The widespread immense attention and applicability of Nb2O5 photocatalysts can be attributed to their multiple benefits, including strong redox potentials, non-toxicity, earth abundance, corrosion resistance, and efficient thermal and chemical stability. However, the large-scale application of Nb2O5 is currently impeded by the barriers of rapid recombination loss of photo-activated electron/hole pairs and the inadequacy of visible light absorption. To overcome these constraints, plentiful design strategies have been directed at modulating the morphology, electronic band structure, and optical properties of Nb2O5. The current review offers an extensive analysis of Nb2O5-based photocatalysts, with a particular emphasis on crystallography, synthetic methods, design strategies, and photocatalytic mechanisms. Finally, an outline of future research directions and challenges in developing Nb2O5-based materials with excellent photocatalytic performance is presented.

Treatment of Internal Mammary Nodes is Associated With Improved Overall Survival in Breast Cancer: A Meta-Analysis.

INTRODUCTION: The role of internal mammary nodal irradiation (IMNI) as a component of regional nodal radiotherapy is a controversial issue in breast radiation oncology with conflicting results presented in recent landmark trials. We thus created a meta-analysis of available data to better ascertain the potential benefit of IMNI. We hypothesize that with the increased power available within a meta-analysis, IMNI will prove to improve overall survival (OS) in breast cancer. METHODS: Literature search was conducted for prospective studies comparing IMNI to no IMNI. Primary endpoint was OS and secondary endpoints included local recurrence, regional recurrence, disease-free survival (DFS), breast cancer mortality (BCM), distant metastasis-free survival (DMFS), grade 2+ skin toxicity, cardiac events, and pneumonitis events. Subgroup analyses were performed for tumor location (medial/central vs. lateral), and nodal status (pN+ vs. pN0). Fixed-effect model was used if there was no heterogeneity, random-effects model otherwise. RESULTS: Four studies with a total of 5258 patients (IMNI: n=2592; control: n=2666) were included in the study. Pooled results showed IMNI significantly improved OS for all-comers (hazard ratio [HR]=0.89; 95% CI 0.81-0.97; P =0.008), as well as subgroups of pN+ with medial/central tumor location (HR=0.84; 95% CI 0.73-0.96; P =0.01) and pN+ with lateral tumor location (HR=0.87; 95% CI 0.77-0.99; P =0.04). There was no significant difference in OS for subgroups of pN0 and medial/central tumor location. There was no difference in local recurrence, but regional recurrence was significantly improved ( P =0.04). Endpoints of DFS (HR 0.91, 95% CI 0.84-0.99 P =0.03), BCM (HR 0.87, 95% CI 0.77-0.98, P =0.03), and DMFS (HR=0.87; 95% CI, 0.78-0.98; P =0.02) were all improved with IMNI. Grade 2+ skin toxicity, cardiac events and pneumonitis events were not significantly different between patient in the IMNI and no IMNI groups. CONCLUSION: Inclusion of IMN irradiation improves OS, DFS, BCM, and DMFS in breast cancer. Largest effect on OS was noted in the subgroup of patients with pN+ and medial/central tumor location.

Development of canagliflozin nanocrystals sublingual tablets in the presence of sodium caprate permeability enhancer: formulation optimization, characterization, in-vitro, in silico, and in-vivo study.

Canagliflozin (CFZ) is a sodium-glucose cotransporter-2 inhibitor (SGLT2) that lowers albuminuria in type-2 diabetic patients, cardiovascular, kidney, and liver disease. CFZ is classified as class IV in the Biopharmaceutical Classification System (BCS) and is characterized by low permeability, solubility, and bioavailability, most likely attributed to hepatic first-pass metabolism. Nanocrystal-based sublingual formulations were developed in the presence of sodium caprate, as a wetting agent, and as a permeability enhancer. This formulation is suitable for children and adults and could enhance solubility, permeability, and avoid enterohepatic circulation due to absorption through the sublingual mucosa. In the present study, formulations containing various surfactants (P237, P338, PVA, and PVP K30) were prepared by the Sono-homo-assisted precipitation ion technique. The optimized formula prepared with PVP-K30 showed the smallest particle size (157 ± 0.32 nm), Zeta-potential (-18 ± 0.01), and morphology by TEM analysis. The optimized formula was subsequently formulated into a sublingual tablet containing Pharma burst-V® with a shorter disintegration time (51s) for the in-vivo study. The selected sublingual tablet improved histological and biochemical markers (blood glucose, liver, and kidney function), AMP-activated protein kinase (AMPK), and protein kinase B (AKT) pathway compared to the market formula, increased CFZ's antidiabetic potency in diabetic rabbits, boosted bioavailability by five-fold, and produced faster onset of action. These findings suggest successful treatment of diabetes with CFZ nanocrystal-sublingual tablets.

Explainable Artificial Intelligence to Identify Dosimetric Predictors of Toxicity in Patients with Locally Advanced Non-Small Cell Lung Cancer: A Secondary Analysis of RTOG 0617.

PURPOSE: Dosimetric predictors of toxicity in patients treated with definitive chemoradiation for locally advanced non-small cell lung cancer are often identified through trial and error. This study used machine learning (ML) and explainable artificial intelligence to empirically characterize dosimetric predictors of toxicity in patients treated as part of a prospective clinical trial. METHODS AND MATERIALS: A secondary analysis of the Radiation Therapy Oncology Group (RTOG) 0617 trial was performed. Multiple ML models were trained to predict grade ≥3 pulmonary, cardiac, and esophageal toxicities using clinical and dosimetric features. Model performance was evaluated using the area under the curve (AUC). The best performing model for each toxicity was explained using the Shapley Additive Explanation (SHAP) framework; SHAP values were used to identify relevant dosimetric thresholds and were converted to odds ratios (ORs) with confidence intervals (CIs) generated using bootstrapping to obtain quantitative measures of risk. Thresholds were validated using logistic regression. RESULTS: The best-performing models for pulmonary, cardiac, and esophageal toxicities, outperforming logistic regression, were extreme gradient boosting (AUC, 0.739), random forest (AUC, 0.706), and naive Bayes (AUC, 0.721), respectively. For pulmonary toxicity, thresholds of a mean dose >18 Gy (OR, 2.467; 95% CI, 1.049-5.800; P = .038) and lung volume receiving ≥20 Gy (V20) > 37% (OR, 2.722; 95% CI, 1.034-7.163; P = .043) were identified. For esophageal toxicity, thresholds of a mean dose >34 Gy (OR, 4.006; 95% CI, 2.183-7.354; P < .001) and V20 > 37% (OR, 3.725; 95% CI, 1.308-10.603; P = .014) were identified. No significant thresholds were identified for cardiac toxicity. CONCLUSIONS: In this data set, ML approaches validated known dosimetric thresholds and outperformed logistic regression at predicting toxicity. Furthermore, using explainable artificial intelligence, clinically useful dosimetric thresholds might be identified and subsequently externally validated.

Development of thermosensitive hydrogel of Amphotericin-B and Lactoferrin combination-loaded PLGA-PEG-PEI nanoparticles for potential eradication of ocular fungal infections: In-vitro, ex-vivo and in-vivo studies.

The most prevalent conditions among ocular surgery and COVID-19 patients are fungal eye infections, which may cause inflammation and dry eye, and may cause ocular morbidity. Amphotericin-B eye drops are commonly used in the treatment of ocular fungal infections. Lactoferrin is an iron-binding glycoprotein with broad-spectrum antimicrobial activity and is used for the treatment of dry eye, conjunctivitis, and ocular inflammation. However, poor aqueous stability and excessive nasolacrimal duct draining impede these agens' efficiency. The aim of this study was to examine the effect of Amphotericin-B, as an antifungal against Candida albicans, Fusarium, and Aspergillus flavus, and Lactoferrin, as an anti-inflammatory and anti-dry eye, when co-loaded in triblock polymers PLGA-PEG-PEI nanoparticles embedded in P188-P407 ophthalmic thermosensitive gel. The nanoparticles were prepared by a double emulsion solvent evaporation method. The optimized formula showed particle size (177.0 ± 0.3 nm), poly-dispersity index (0.011 ± 0.01), zeta-potential (31.9 ± 0.3 mV), and entrapment% (90.9 ± 0.5) with improved ex-vivo pharmacokinetic parameters and ex-vivo trans-corneal penetrability, compared with drug solution. Confocal laser scanning revealed valuable penetration of fluoro-labeled nanoparticles. Irritation tests (Draize Test), Atomic force microscopy, cell culture and animal tests including histopathological analysis revealed superiority of the nanoparticles in reducing signs of inflammation and eradication of fungal infection in rabbits, without causing any damage to rabbit eyeballs. The nanoparticles exhibited favorable pharmacodynamic features with sustained release profile, and is neither cytotoxic nor irritating in-vitro or in-vivo. The developed formulation might provide a new and safe nanotechnology for treating eye problems, like inflammation and fungal infections.

Biosynthesis and Characterization of Gold and Copper Nanoparticles from Salvadora persica Fruit Extracts and Their Biological Properties.

Introduction: Metal nanoparticle synthesis using plant has emerged as an eco-friendly, clean, and viable strategy alternative to chemical and physical approaches. Methods: The fruit extract of Salvadora persica (SP) was utilized as a reducing and stabilizing agent in the synthesis of gold (AuNPs) and copper (CuNPs) nanoparticles. Results: UV-Vis spectra of the AuNPs and CuNPs showed peaks at the wavelengths of 530 nm and 440 nm, respectively. Transmission electron microscopy showed that nanoparticles exhibited a mainly spherical form, with a distribution range of 100 to 113 nm in diameter for AuNPs and of 130 to 135 nm in diameter for CuNPs. While energy-dispersive X-ray spectroscopy was able to confirm the existence of AuNPs and CuNPs. The alcoholic extract of the fruit SP was analyzed by GC-MS in order to identify whether or not it contained any active phytochemicals. Fourier-transform infrared spectra confirmed the presence capping functional biomolecules of SP on the surface of nanoparticles that acts as stabilizers. Analysis of the zeta potential revealed that NPs with high degree of stability, as demonstrated by a strong negative potential value in the range of 25.2 to 28.7 mV. Results showed that both green AuNPs and CuNPs have potential antimicrobial activity against human pathogens such gram-negative bacteria and gram-positive bacteria, with CuNPs having antimicrobial activity higher than AuNPs. In addition, AuNPs and CuNPs have promising antioxidant and anticancer properties when applied to MCF-7 and MDA-MB-231 breast cancer cells. Studies of molecular docking of SP bioactive compounds were conducted against methenyl tetrahydrofolate synthetase. Among all of them, Beta - Sitosterol was the most prominent. Conclusion: These AuNPs and CuNPs are particularly appealing in a variety of applications in the pharmaceutical and medicinal industries due to their economical and environmentally friendly production.

Cryptococcal chest wall mass and rib osteomyelitis associated with the use of fingolimod: A case report and literature review.

Being introduced in 2010, fingolimod was among the first oral therapies for relapsing multiple sclerosis (MS). Since that time, postmarketing surveillance has noted several case reports of various cryptococcal infections associated with fingolimod use. To date, approximately 15 such case reports have been published. We present the first and unique case of cryptococcal chest wall mass and rib osteomyelitis associated with fingolimod use. The patient presented with left-side chest pain and was found to have a lower left chest wall mass. Computerized tomography (CT) showed chest wall mass with the destruction of left 7th rib. Aspirate from the mass grew Cryptococcus neoformans. The isolate was serotype A. Fingolimod was stopped. The patient received liposomal amphotericin B for 2 weeks and started on fluconazole with a plan to continue for 6-12 months. The follow-up CT in 6 weeks showed a marked decrease in the size of the chest wall mass. In conclusion, our case highlights the atypical and aggressive form of cryptococcal infection possibly related to immunosuppression from fingolimod use.

Salvadora persica attenuates DMBA-induced mammary cancer through downregulation oxidative stress, estrogen receptor expression and proliferation and augmenting apoptosis.

Naturally occurring phytochemicals especially polyphenolic compounds have received increasing attention as chemopreventive agents. The chemopreventive potential of the ethanolic extract of Salvadora persica L. fruits SP, (the arak tree or miswak) on 7,12-dimethylbenz (a) anthracene (DMBA)-induced mammary carcinogenesis in female albino rats was investigated in this work. Ethanolic extract of SP fruits was supplemented to the experimental groups at a concentration of 500 mg/kg body weight for 22 weeks. Administration of SP extract suppressed DMBA-induced mammary carcinogenesis as revealed by incidence of tumors in histological investigation. There was a significant reduction in cell proliferation and an increase in apoptosis with downregulation of estrogen receptor expression in the mammary tissue of SP-treated animals. Additionally, SP extract prevented the oxidative damage induced in breast tissues of DMBA-treated rats. SP treatment also decreased the viability of MCF-7 breast cancer cells and induced early and late apoptosis and induced S cell cycle arrest. The chemo-preventive properties and anticancer effects of SP could be attributed to its anti-oxidative and a high percentage of phenolic compounds and esters which were detected here in the SP fruit extract.

Multi-criteria text mining model for COVID-19 testing reasons and symptoms and temporal predictive model for COVID-19 test results in rural communities.

This study is conducted to build a multi-criteria text mining model for COVID-19 testing reasons and symptoms. The model is integrated with a temporal predictive classification model for COVID-19 test results in rural underserved areas. A dataset of 6895 testing appointments and 14 features is used in this study. The text mining model classifies the notes related to the testing reasons and reported symptoms into one or more categories using look-up wordlists and a multi-criteria mapping process. The model converts an unstructured feature to a categorical feature that is used in building the temporal predictive classification model for COVID-19 test results and conducting some population analytics. The classification model is a temporal model (ordered and indexed by testing date) that uses machine learning classifiers to predict test results that are either positive or negative. Two types of classifiers and performance measures that include balanced and regular methods are used: (1) balanced random forest and (2) balanced bagged decision tree. The balanced or weighted methods are used to address and account for the biased and imbalanced dataset and to ensure correct detection of patients with COVID-19 (minority class). The model is tested in two stages using validation and testing sets to ensure robustness and reliability. The balanced classifiers outperformed regular classifiers using the balanced performance measures (balanced accuracy and G-score), which means the balanced classifiers are better at detecting patients with positive COVID-19 results. The balanced random forest achieved the best average balanced accuracy (86.1%) and G-score (86.1%) using the validation set. The balanced bagged decision tree achieved the best average balanced accuracy (83.0%) and G-score (82.8%) using the testing set. Also, it was found that the patient history, age, testing reasons, and time are the key features to classify the testing results.

Outcomes of balloon-expandable versus self-expandable stent graft for endovascular repair of iliac aneurysms using iliac branch endoprosthesis.

PURPOSE: The purpose of this study was to compare outcomes of internal iliac artery (IIA) stenting using balloon-expandable (BESG) or self-expandable stent grafts (SESG) during endovascular repair of aortoiliac aneurysms with iliac branch endoprosthesis (IBE; W. L. Gore, Flagstaff, Ariz). METHODS: We retrospectively reviewed all consecutive patients treated for aortoiliac aneurysms using IBE between 2014 and 2020. IIA stenting was performed using either the IIA side branch SESG or a Gore VBX BESG (W. L. Gore). Indications for use of BESGs were "up-and-over" IBE technique for type IB endoleak after prior endovascular aortic aneurysm repair (EVAR), short IIA length, and need for IIA extension into divisional branches (outside instructions for use). End points included technical success, freedom from buttock claudication, primary IIA patency, and freedom from IIA branch instability (eg, branch-related death or rupture, occlusion, disconnection, or reintervention for stenosis, kink, or endoleak), freedom from type IC/IIIC endoleak, and freedom from secondary interventions. RESULTS: There were 90 patients (86 males and 4 females) with a mean age of 74 ± 7 years treated by EVAR with 108 IBEs. Choice of stent was BESG in 43 and SESG in 65 targeted IIAs. BESGs were used more frequently in patients with prior EVAR (22% vs 2%; P = .003,), isolated IBEs (31% vs 2%; P < .001), and in patients with IIA aneurysms requiring stenting into divisional branches (36% vs 5%; P < .001). Technical success was similar for BESGs and SESGs (97% vs 100%; P = .40), respectively. The mean follow-up was 25 ± 16 months (range, 11-34 months). At 2 years, freedom from buttock claudication was 100% for BESG and 95 ± 3% for SESG (Log-rank 0.26), with no difference in primary patency (BESG, 100% vs SESG, 94 ± 4%; Log-rank 0.94). There were four (9%) IIA-related endoleaks in the BESG group and one (2%) in the SESG group (P = .08). Freedom from IIA branch instability was 87 ± 6% for BESG and 96 ± 3% for SESG at 2 years (Log-rank 0.043). Freedom from type IC/IIIC endoleak was 87 ± 7% for BESG and 98 ± 2% for SESG at the same interval (Log-rank 0.06). There was no difference in freedom from reinterventions for BESG and SESG (92 ± 6% vs 98 ± 2%; Log-rank 0.34), respectively. CONCLUSIONS: BESGs were used more frequently during IBE procedures indicated for failed EVAR, isolated common iliac aneurysms, and IIA aneurysms requiring extension into divisional branches. Despite these differences and BESG being used outside instructions for use, both stent types had similar primary patency, freedom from buttock claudication, and freedom from reinterventions. However, BESGs were associated with higher rates of IIA-related branch instability.

Rules of incidental operation risk propagation in metro networks under fully automatic operations mode.

The frequent interruptions of network operation due to any incident suggest the necessity to study the rules of operational risk propagation in metro networks, especially under fully automatic operations mode. In this study, risk indicator computation models were developed by analyzing risk propagation processes within transfer stations and metro networks. Moreover, indicator variance rules for a transfer station and different structural networks were discussed and verified through simulation. After reviewing the simulation results, it was concluded that under the impacts of both sudden incident and peak passenger flow, the more the passengers coming from platform inlets, the longer the non-incidental line platform total train operation delay and the higher the crowding degree. However, train headway has little influence on non-incidental line platform risk development. With respect to incident risk propagation in a metro network, the propagation speed varies with network structure, wherein an annular-radial network is the fastest, a radial is moderately fast, and a grid-type network is the slowest. The conclusions are supposed to be supports for metro operation safety planning and network design.

A Systematic Review of Parkinson's Disease Cluster Analysis Research.

One way to understand the Parkinson's disease (PD) population is to investigate the similarities and differences among patients through cluster analysis, which may lead to defined, patient subgroups for diagnosis, progression tracking and treatment planning. This paper provides a systematic review of PD patient clustering research, evaluating the variables included in clustering, the cluster methods applied, the resulting patient subgroups, and evaluation metrics. A search was conducted from 1999 to 2021 on the PubMed database, using various search terms including: Parkinson's disease, cluster, and analysis. The majority of studies included a variety of clinical scale scores for clustering, of which many provide a numerical, but ordinal, categorical value. Even though the scale scores are ordinal, these were treated as numerical values with numerical and continuous values being the focus of the clustering, with limited attention to categorical variables, such as gender and family history, which may also provide useful insights into disease diagnosis, progression, and treatment. The results pointed to two to five patient clusters, with similarities among the age of onset and disease duration. The studies lacked the use of existing clustering evaluation metrics which points to a need for a thorough, analysis framework, and consensus on the appropriate variables to include in cluster analysis. Accurate cluster analysis may assist with determining if PD patients' symptoms can be treated based on a subgroup of features, if personalized care is required, or if a mix of individualized and group-based care is the best approach.

A New Tool for Safety Evaluation and a Combination of Measures for Efficacy Assessment of Cotransplanting Human Allogenic Neuronal Stem Cells and Mesenchymal Stem Cells for the Treatment of Parkinson Disease: Protocol for an Interventional Study.

BACKGROUND: Parkinson disease (PD) is a neurodegenerative disorder associated with a broad spectrum of motor and nonmotor symptoms. Any proposed cure needs to address the many aspects of the disease. Stem cell therapy may have potential in this regard as indicated in recent preclinical and clinical studies. OBJECTIVE: This protocol aims to examine the safety and therapeutic benefit of human Wharton jelly-derived mesenchymal stem cells (WJ-MScs) and their derivatives, neuronal stem cells (NSCs) in PD. METHODS: This clinical trial is a double-arm, single-blinded, phase I-II interventional study. Participants have been allocated to 1 of 2 groups: one receiving allogeneic WJ-MSCs alone, the other receiving NSCs and WJ-MScs. Participants are being followed-up and assessed over a period of 6 months. To assess safety, an incidence of treatment-emergent adverse events (TEAEs) tool tailored for PD is being used immediately and up to 6 months after treatment. For efficacy assessment, a number of factors are being used, including the gold standard severity test and the Unified Parkinson Disease Rating Scale. In addition, the following standardized assessments for different common symptoms in PD are being included: motor (both subjectively and objectively assessed with wearable sensors), sensory, quality of life and psychological well-being, cognition, and sleep quality. Furthermore, immune-modulatory cytokines and neuronal damage versus regeneration markers in PD, including the neuronal protein linked to PD, α-synuclein, are being monitored. RESULTS: Ten patients have been enrolled in this study and thus participant recruitment has been completed. The study status is active and beyond the recruiting stage. Study chart implementation, data collection, and analysis are ongoing. CONCLUSIONS: The combination of NSCs and MSCs in PD may be useful for harnessing the best of the immunomodulation and neural repair characteristics of these cell types. The tailored comprehensive and scaled TEAEs and the variety of evaluation tools used enables a comprehensive assessment of this cellular therapy treatment protocol. A consideration of this expanded tool set is important in the design of future clinical studies for PD. TRIAL REGISTRATION: ClinicalTrials.gov NCT03684122; https://clinicaltrials.gov/ct2/show/NCT03684122. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/29695.

Predictors of aortic clamp time duration and intensive care unit length of stay in elective adult cardiac surgery.

BACKGROUND: Aortic cross-clamp utilized during cardiac surgery facilitates motionless and bloodless surgical field. However, the duration of clamp time has an inverse effect on early post-operative recovery period. In this study, we sought to examine the predictors of aortic clamp duration and intensive care unit length of stay. RESULTS: Six hundred and nine adult patients presented for elective cardiac surgery between December 2019 and December 2020 were enrolled. The age of patients ranged from 18 to 82 years (mean 55.62 years, SD ± 12.3 years). Male/female ratio is 4.6:1. Most patients (87.2%) were planned for coronary artery bypass grafting (CABG) and 78 patients (12.8%) for single heart valve procedure. Operative time (OT) ranged from 120 to 402 min and averaged 259.4 min (SD ± 45.9 min). ACC time ranged from 15 to 159 min and averaged 50.56 min (SD ± 19.4 min). Factors associated with significantly longer ACCT were: smoking (OR = 1.89 (95% CI 1.3-2.74), p value = 0.01), respiratory disease (OR = 0.48 (95% CI 0.24-0.96), p value = 0.039), obesity (OR = 1.76 (95% CI 1.18-2.63), p value = 0.005) and AVR (OR = 2.11 (95% CI 1.17-3.83), p value = 0.013). Low cardiac output syndrome (LCOS) was observed in 19.2% of patients. Longer than average ACCT was associated with increased use of inotropes (p value < 0.001), intra-aortic balloon pump (p value < 0.001) and first 24 h post-operative blood loss (p value < 0.001). The average intensive care unit length of stay (ICULOS) was 1.64 days (SD ± 1.1 days). Patients' ACCT converged positively and significantly on ICULOS (Beta coefficient = 1.013 (95% CI 1.01-1.015), p value < 0.001). CONCLUSION: Aortic cross-clamping is a crucial method in cardiac surgery to achieve motionless field; however, prolongation of this method had an incremental risks for the development of low cardiac output syndrome, increased first 24 h post-operative blood loss and longer stay in the intensive care unit.

Cluster Analysis of Categorical Variables of Parkinson's Disease Patients.

Parkinson's disease (PD) is a chronic disease. No treatment stops its progression, and it presents symptoms in multiple areas. One way to understand the PD population is to investigate the clustering of patients by demographic and clinical similarities. Previous PD cluster studies included scores from clinical surveys, which provide a numerical but ordinal, non-linear value. In addition, these studies did not include categorical variables, as the clustering method utilized was not applicable to categorical variables. It was discovered that the numerical values of patient age and disease duration were similar among past cluster results, pointing to the need to exclude these values. This paper proposes a novel and automatic discovery method to cluster PD patients by incorporating categorical variables. No estimate of the number of clusters is required as input, whereas the previous cluster methods require a guess from the end user in order for the method to be initiated. Using a patient dataset from the Parkinson's Progression Markers Initiative (PPMI) website to demonstrate the new clustering technique, our results showed that this method provided an accurate separation of the patients. In addition, this method provides an explainable process and an easy way to interpret clusters and describe patient subtypes.