Data-driven nexus between malaria incidence and World Bank indicators in the Mekong River during 2000-2022.

The increase in hydro dams in the Mekong River amidst the prevalence of multidrug-resistant malaria in Cambodia has raised concerns about global public health. Political conflicts during Covid-19 pandemic led cross-border movements of malaria cases from Myanmar and caused health care burden in Thailand. While previous publications used climatic indicators for predicting mosquito-borne diseases, this research used globally recognizable World Bank indicators to find the most impactful indicators related with malaria and shed light on the predictability of mosquito-borne diseases. The World Bank datasets of the World Development Indicators and Climate Change Knowledge Portal contain 1494 time series indicators. They were stepwise screened by Pearson and Distance correlation. The sets of five and four contain respectively 19 and 149 indicators highly correlated with malaria incidence which were found similarly among five and four GMS countries. Living areas, ages, career, income, technology accessibility, infrastructural facilities, unclean fuel use, tobacco smoking, and health care deficiency have affected malaria incidence. Tonle Sap Lake, the largest freshwater lake in Southeast Asia, could contribute to the larval habitat. Seven groups of indicator topics containing 92 indicators with not-null datapoints were analyzed by regression models, including Multiple Linear, Ridge, Lasso, and Elastic Net models to choose 7 crucial features for malaria prediction via Long Short Time Memory network. The indicator of people using at least basic sanitation services and people practicing open defecation were health factors had most impacts on regression models. Malaria incidence could be predicted by one indicator to reach the optimal mean absolute error which was lower than 10 malaria cases (per 1,000 population at risk) in the Long Short Time Memory model. However, public health crises caused by political problems should be analyzed by political indexes for more precise predictions.

Serial measurements of SIRS and SEP scores to identify unique phenotypes of sepsis.

Using scoring systems in discreet microbiologic cohorts in a serial fashion to identify unique phenotypes of sepsis remains unknown. Single-center, retrospective study that screened adults who triggered the hospital's SIRS (systemic inflammatory response syndrome) based sepsis alert into culture positive (Cx +) and culture negative (Cx-) groups. Subgroups were based on the location where the SIRS alert fired. SIRS scores and a novel score called SEP were calculated at t = 0 and at 3, 6, 12, and 24 h before and after t = 0. Primary outcome was a difference in SIRS/SEP scores in Cx + or Cx- groups over time. Secondary outcomes were differences in total SIRS/SEP scores and the components constituting SIRS/SEP scores at various locations over time. The study contained 7955 patients who met inclusion criteria. Cx + and Cx- groups had increases in SIRS/SEP scores and at similar rates starting 6 hours before t = 0. Both culture groups had decreasing SIRS/SEP scores, at varying gradients compared to the change in SIRS/SEP scores seen prior to t = 0. This pattern in SIRS/SEP scores before and after t = 0 was consistent in all location subgroups. Statistically significant differences were seen in the overall SIRS/SEP scores for Cx + and Cx- groups at hours 6, 12, and 24 after t = 0, in the ED group at t = 24 h after t = 0, the floor group at t = 0 h, and in the step-down group at t = 3 h after t = 0 h. Microbiological cohorting and serial assessments may be an effective tool to identify homogenous phenotypes of sepsis.

Inflammatory mediators drive neuroinflammation in autism spectrum disorder and cerebral palsy.

Inflammation conditions are associated with autism spectrum disorder (ASD) and cerebral palsy (CP), primarily observed in the peripheral immune system. However, the extent of neuro-inflammation and neuro-immune dysregulation remains poorly studied. In this study, we analyzed the composition of cerebrospinal fluid (CSF) to uncover the inflammatory mediators driving the neuro-immune system in ASD and CP patients. Our findings revealed that ASD patients had elevated levels of four inflammatory cytokines (TNF-α, IL-4, IL-21, and BAFF) compared to controls, while CP patients exhibited increased levels of eight inflammatory cytokines (IFN-γ, GM-CSF, TNF-α, IL-2, IL-4, IL-6, IL-17A and IL-12), one anti-inflammatory cytokine (IL-10), and five growth factors (GFs) (NGF-ß, EGF, GDF-15, G-CSF and BMP-9) compared to both controls and ASD patients. Additionally, intrathecal infusion of autologous bone marrow mononuclear cells (BMMNCs) led to a slight decrease in TGF-ß and GDF-15 levels in the CSF of ASD and CP patients, respectively. Our study provides new insights into the molecular composition of CSF in ASD and CP patients, with the potential to develop more effective diagnosis methods and improved treatment for these diseases.Clinical trial registration CSF samples used in this study are from clinical trials NCT03225651, NCT05307536, NCT02569775, NCT03123562, NCT02574923, NCT05472428 and previous reports [7, 9, 17-19].

Multivalvular involvement associated with Libman-Sacks endocarditis detected by multimodality imaging: A case report.

Libman-Sacks endocarditis accounts for 6-11 percent of systemic lupus erythematosus patients and is associated with varying degrees of valvular dysfunction, increased risk for stroke and transient ischemic attacks, and increased mortality. In previous studies, left-sided valvular Libman-Sacks vegetations were more frequently detected than right sided vegetations; reported cases of bilateral involvement is very rare. A comprehensive clinical assessment and the multimodality imaging is of utmost importance in the management of systemic lupus erythematosus. In this case report, we describe a 31-year-old female patient with uncontrolled systemic lupus erythematosus initially presented with gastrointestinal symptoms but eventually had a vegetation-like structure on the posterior leaflet of the mitral valve which was revealed during routine echocardiography. Two-dimensional/three-dimensional transthoracic and transesophageal echocardiography, cardiac magnetic resonance, and cardiac computed tomography further characterized the mitral valve vegetation and revealed an additional vegetation of the pulmonary valve. Echocardiography remains the cornerstone for the detection of Libman-Sacks vegetations. Cardiac MRI and cardiac CT are useful in characterizing lesion size and effects and may prove particularly helpful in the assessment of right-sided or multivalvular endocarditis. The presence of focal brain lesions on brain MRI prompted antithrombotic therapy.

Advances in Drug Delivery Systems Based on Red Blood Cells and Their Membrane-Derived Nanoparticles.

Red blood cells (RBCs) and RBC membrane-derived nanoparticles have been historically developed as bioinspired drug delivery systems to combat the issues of premature clearance, toxicity, and immunogenicity of synthetic nanocarriers. RBC-based delivery systems possess characteristics including biocompatibility, biodegradability, and long circulation time, which make them suited for systemic administration. Therefore, they have been employed in designing optimal drug formulations in various preclinical models and clinical trials to treat a wide range of diseases. In this review, we provide an overview of the biology, synthesis, and characterization of drug delivery systems based on RBCs and their membrane including whole RBCs, RBC membrane-camouflaged nanoparticles, RBC-derived extracellular vesicles, and RBC hitchhiking. We also highlight conventional and latest engineering strategies, along with various therapeutic modalities, for enhanced precision and effectiveness of drug delivery. Additionally, we focus on the current state of RBC-based therapeutic applications and their clinical translation as drug carriers, as well as discussing opportunities and challenges associated with these systems.

Endosomal escape of nucleic acids from extracellular vesicles mediates functional therapeutic delivery.

Extracellular vesicles hold great promise as a drug delivery platform for RNA-based therapeutics. However, there is a lack of experimental evidence for the intracellular trafficking of nucleic acid cargos, specifically, whether they are capable of escaping from the endolysosomal confinement in the recipient cells to be released into the cytosol and hence, interact with their cytoplasmic targets. Here, we demonstrated how red blood cell-derived extracellular vesicles (RBCEVs) release their therapeutic RNA/DNA cargos at specific intracellular compartments characteristic of late endosomes and lysosomes. The released cargos were functional and capable of knocking down genes of interest in recipient cells, resulting in tumor suppression in vitro and in an acute myeloid leukemia murine model without causing significant toxicity. Notably, surface functionalization of RBCEVs with an anti-human CXCR4 antibody facilitated their specific uptake by CXCR4+ leukemic cells, leading to enhanced gene silencing efficiency. Our results provide insights into the cellular uptake mechanisms and endosomal escape routes of nucleic acid cargos delivered by RBCEVs which have important implications for further improvements of the RBCEV-based delivery system.

Fe2O3/diatomite materials as efficient photo-Fenton catalysts for ciprofloxacin removal.

In this study, we used Fe2O3/diatomite material system toward ciprofloxacin (CIP) photo-Fenton removal in water under visible light (vis) excitation. The characterization of Fe2O3/diatomite catalysts was determined by X-ray diffraction patterns, Fourier-transform infrared analysis, inductively coupled plasma mass spectrometry, and scanning electron microscopy. The photo-Fenton catalytic activity of the Fe2O3/diatomite was appraised by the removal efficiency of the CIP throughout the effect of the H2O2 with various parameters such as initial pH, catalyst amount, and H2O2 amount. The results indicate that 0.2 gL-1 Fe2O3/diatomite catalysts achieved the highest performance at approximately 90.03% with a 50 µL H2O2 concentration. Furthermore, the Fe2O3/diatomite catalysts have high stability, with over 80% CIP removed after five cycles. This study is inspired to develop a potential material for photo-Fenton degradation of antibiotics in wastewater.

Dynamics of Amyloid Formation from Simplified Representation to Atomistic Simulations.

Amyloid fibril formation is an intrinsic property of short peptides, non-disease proteins, and proteins associated with neurodegenerative diseases. Aggregates of the Aß and tau proteins, the α-synuclein protein, and the prion protein are observed in the brain of Alzheimer's, Parkinson's, and prion disease patients, respectively. Due to the transient short-range and long-range interactions of all species and their high aggregation propensities, the conformational ensemble of these devastating proteins, the exception being for the monomeric prion protein, remains elusive by standard structural biology methods in bulk solution and in lipid membranes. To overcome these limitations, an increasing number of simulations using different sampling methods and protein models have been performed. In this chapter, we first review our main contributions to the field of amyloid protein simulations aimed at understanding the early aggregation steps of short linear amyloid peptides, the conformational ensemble of the Aß40/42 dimers in bulk solution, and the stability of Aß aggregates in lipid membrane models. Then we focus on our studies on the interactions of amyloid peptides/inhibitors to prevent aggregation, and long amyloid sequences, including new results on a monomeric tau construct.

Photoelectrochemical water oxidation over TiO2 nanotubes modified with MoS2 and g-C3N4.

TiO2 nanotube arrays (TNAs) have been studied for photoelectrochemical (PEC) water splitting. However, there are two major barriers of TNAs, including a low photo-response and the fast charge carrier recombination in TNAs, leading to poor photocatalytic efficiency. Through a comparison of MoS2/TNAs and g-C3N4/TNAs, it was found that TNAs modified with MoS2 and g-C3N4 exhibited a current density of, respectively, 210.6 and 139.6 µA·cm-2 at an overpotential of 1.23 V vs RHE, which is 18.2 and 12 times higher than that of pure TNAs under the same conditions. The stability of the MoS2/TNAs heterojunction is higher than that of g-C3N4/TNAs.