A ternary system of meloxicam with matching hydrophilic polymer and cyclodextrin for improved stability in liquid preprations.

The purpose of the study is to investigate the effect of ternary systems consisting of meloxicam with cyclodextrins (HP-ß-CD or SBE-ß-CD) and different polymers (HA, HPMC and PVP) on the stability of meloxicam. The t 0.9 values of meloxicam were determined within all the aforementioned systems and the influence of various polymers on the alteration in meloxicam's stability was evaluated. All three polymers altered the stability of meloxicam to varying degrees, with the extent of the effect being related to hydrophilicity, concentration of components, and the interaction of the newly formed ternary system. Among them, meloxicam demonstrated its highest degree of stabilization within the ternary system formed by SBE-ß-CD&HPMC and HP-ß-CD&HA. We characterized the ternary system of meloxicam using differential scanning calorimetry (DSC), X-ray diffraction, and scanning electron microscopy analysis, which determined the presence of ternary system inclusions. In addition, we investigated the optimized prescription of eye drops of meloxicam using the ternary system and further determined that the ternary system improved the stability of the drug in liquid formulations.

Poland Syndrome and Multimorbidity in a 79-Year-Old Male.

This case study highlights a 79-year-old man with chronic low back pain attributed to severe lumbar scoliosis. Physical examination revealed the unilateral absence of pectoral muscles and ipsilateral hand anomalies, indicative of Poland syndrome (PS). The patient also experienced depression due to chronic pain and PS-related anomalies. A multi-disciplinary approach proved effective in alleviating both pain and depression.

A Case Report of an Elderly Patient With Cushing's Disease and Multiple Chronic Conditions.

Cushing's disease (CD) is a rare and serious condition characterized by a persistent increase in cortisol levels, resulting in various complications across multiple bodily systems. Elderly individuals often face a multitude of chronic illnesses and geriatric syndromes, which can complicate the diagnosis and treatment of CD in this demographic. This case study details the presentation of an elderly patient with adrenocorticotropic hormone (ACTH)-dependent CD, who initially presented with an acute exacerbation of chronic obstructive pulmonary disease. The article delves into the unique onset characteristics and treatment strategies for CD in the elderly, providing valuable insights for the comprehensive management of similar clinical cases.

Peracetic Acid Activation by Modified Hematite for Water Purification: Performance, Degradation Pathways, and Mechanism.

Natural mineral-based advanced oxidation processes (AOPs) are now receiving increasing attention for the efficient degradation of pollutants. In this work, we used a common reducing agent (NaBH4) to treat natural Hematite to obtain modified Hematite (Hematite-(R)) and applied it to activate peracetic acid (PAA) for efficient degradation of cefazolin (CFZ). Compared with Hematite, the Hematite-(R)/PAA system increased the degradation rate of CFZ by 21.7% within 80 min under neutral conditions. Scavenging experiments and electron paramagnetic resonance (EPR) technology were introduced to identify the principal roles of 1O2, CH3C(O)OO•, and •OH for CFZ removal over the Hematite-(R)/PAA process. The outstanding capability of Hematite-(R) could be mainly due to the higher percentage of Fe(II) (52%) on the surface of catalysts. Furthermore, the possible degradation pathways of CFZ were explored. Moreover, the Hematite-(R)/PAA process showed a superior CFZ removal efficiency with a wide initial pH scope of 1.0-9.0. The degradation efficiency of CFZ showed a negligible effect in the presence of Cl-, SO42-, and NO3-, while significant inhibition was recorded after the addition of H2PO4- and CO32-. The inhibition of humic acid (HA) on CFZ degradation via the Hematite-(R)/PAA process showed an obvious concentration dependence. This work could provide strong support for the use of natural Hematite in water purification.

Acquisition of molecular rolling lubrication by self-curling of graphite nanosheet at cryogenic temperature.

Friction as a fundamental physical phenomenon dominates nature and human civilization, among which the achievement of molecular rolling lubrication is desired to bring another breakthrough, like the macroscale design of wheel. Herein, an edge self-curling nanodeformation phenomenon of graphite nanosheets (GNSs) at cryogenic temperature is found, which is then used to promote the formation of graphite nanorollers in friction process towards molecular rolling lubrication. The observation of parallel nanorollers at the friction interface give the experimental evidence for the occurrence of molecular rolling lubrication, and the graphite exhibits abnormal lubrication performance in vacuum with ultra-low friction and wear at macroscale. The molecular rolling lubrication mechanism is elucidated from the electronic interaction perspective. Experiments and theoretical simulations indicate that the driving force of the self-curling is the uneven atomic shrinkage induced stress, and then the shear force promotes the intact nanoroller formation, while the constraint of atomic vibration decreases the dissipation of driving stress and favors the nanoroller formation therein. It will open up a new pathway for controlling friction at microscale and nanostructural manipulation.

Data Flow Construction and Quality Evaluation of Electronic Source Data in Clinical Trials: Pilot Study Based on Hospital Electronic Medical Records in China.

Background: The traditional clinical trial data collection process requires a clinical research coordinator who is authorized by the investigators to read from the hospital's electronic medical record. Using electronic source data opens a new path to extract patients' data from electronic health records (EHRs) and transfer them directly to an electronic data capture (EDC) system; this method is often referred to as eSource. eSource technology in a clinical trial data flow can improve data quality without compromising timeliness. At the same time, improved data collection efficiency reduces clinical trial costs. Objective: This study aims to explore how to extract clinical trial-related data from hospital EHR systems, transform the data into a format required by the EDC system, and transfer it into sponsors' environments, and to evaluate the transferred data sets to validate the availability, completeness, and accuracy of building an eSource dataflow. Methods: A prospective clinical trial study registered on the Drug Clinical Trial Registration and Information Disclosure Platform was selected, and the following data modules were extracted from the structured data of 4 case report forms: demographics, vital signs, local laboratory data, and concomitant medications. The extracted data was mapped and transformed, deidentified, and transferred to the sponsor's environment. Data validation was performed based on availability, completeness, and accuracy. Results: In a secure and controlled data environment, clinical trial data was successfully transferred from a hospital EHR to the sponsor's environment with 100% transcriptional accuracy, but the availability and completeness of the data could be improved. Conclusions: Data availability was low due to some required fields in the EDC system not being available directly in the EHR. Some data is also still in an unstructured or paper-based format. The top-level design of the eSource technology and the construction of hospital electronic data standards should help lay a foundation for a full electronic data flow from EHRs to EDC systems in the future.

Associations of glymphatic function with structural network and cognition in self-limited epilepsy with centrotemporal spikes.

PURPOSE: To investigate glymphatic function by Virchow-Robin space (VRS) counts and volume in patients with newly diagnosed self-limited epilepsy with centrotemporal spikes (SeLECTS) and evaluate its relationship with structural connectivity and cognitive impairment. METHODS: Thirty-two children with SeLECTS and thirty-two age- and sex-matched typically developing (TD) children were enrolled in this study. VRS counts and volume were quantified. Structural networks were constructed and the topological metrics were analyzed. Wechsler Intelligence Scale (WISC) was used to assess cognitive function in all participants. Correlation analysis assessed the association between VRS counts and volume, network connectivity, and cognitive impairment. Mediation effects of topological metrics of the structural networks on the relationship between glymphatic function and cognitive impairment were explored. RESULTS: Patients with SeLECTS showed a higher VRS counts, VRS volume, and global shortest path length (Lp); they also showed a lower global efficiency (Eg). VRS counts and volume were significantly correlated with full-scale intelligence quotient (FIQ) (r_VRS counts = -0.520, r_VRS volume = -0.639), performance intelligence quotient (PIQ) (r_VRS counts = -0.693, r_VRS volume = -0.597), verbal intelligence quotient (VIQ) (r_VRS counts = -0.713, r_VRS volume = -0.699), Eg (r_VRS counts = -0.499, r_VRS volume = -0.490), and Lp (r_VRS volume = 0.671) in patients with SeLECTS. Eg mediated 24.59% of the effects for the relationship between VRS volume and FIQ. CONCLUSION: Glymphatic function may be impaired in SeLECTS reflected by VRS counts and volume. Glymphatic dysfunction may result in cognitive impairment by disrupting structural connectivity in SeLECTS.

A smartphone-enabled visual platform for detecting aflatoxins in peanut oil using colorimetric analysis coupled with magnetic imprinted solid-phase extraction.

The study aimed to develop a rapid and sensitive colorimetric platform based on the Emerson reaction to visualize and determine total aflatoxins (AFs) in peanut oil. This method offers the advantage of fast screening for AFs (AFB1, AFB2, AFG1, and AFG2), eliminating the need for specific antibodies. The proposed approach combined colorimetric detection with magnetic dummy imprinted solid-phase extraction and purification, enhancing sensitivity and selectivity. The oxidizer aided the colorless AFs in reacting with 4-aminoantipyrine, producing green condensates. Thus, a dual-mode approach was developed for AFs detection, employing both UV-vis colorimetric and smartphone-based colorimetry. Both methods showed a good linear relationship with the concentration of AFs. Notably, the smartphone-based method demonstrated a detection range of 0.5-57 µg/kg, with a detection limit as low as 0.21 µg/kg. The suggested colorimetric methods present a promising potential for onsite detection and fast screening of AFs in actual samples.

Prospects for the Protective Mechanisms and Compounds of Bufei Huoxue Capsule against COVID-19 Convalescence: Evaluation of Integrating UHPLC-HRMS Analysis and Network Pharmacology Strategy.

INTRODUCTION: Most COVID-19 survivors are troubled with chronic persistent symptoms, which have currently no definitive treatments. Bufei Huoxue (BFHX) capsule exerts clinical benefit, while the material basis and molecular mechanism remain unclear. AIM: The study aimed to elucidate the protective mechanisms of BFHX capsules against COVID-19 convalescence. UHPLC-HRMS and various databases were employed to explore potential compounds and targets. PPI, MCODE, transcription factor (TF), and miRNA analyses were conducted to receive hub targets and corresponding upstream regulators. METHOD: Molecular docking was applied to verify the binding activity of compound and target. Further, GO, KEGG, WIKI, and Reactome analyses were performed, and compound-targetsymptom and gene-disease networks were constructed. A total of 127 compounds and 313 targets were acquired. A sum of 10 hub targets were screened and showed good binding affinities with critical compounds. RESULT: MLLT1, CBFB, and EZH2 were identified as key TFs, and hsa-mir-146a-5p, hsa-mir- 26b-5p, and hsa-mir-24-3p were predicted to be important miRNAs. BFHX capsule may alleviate the symptoms by targeting TNF, IL-6, IFNG, and TGF-ß1. Besides, BFHX capsule may exert a therapeutic effect on respiratory disease (especially pulmonary fibrosis and lung infection) and multi-system damage during COVID-19 convalescence by regulating cytokine-cytokine receptor interaction, as well as TGF-ß, TNF, and Toll-like receptor signaling pathways. CONCLUSION: In summary, BFHX capsule may exert a therapeutic effect on multi-system damages during COVID-19 convalescence through multiple compounds (such as albiflorin, isopsoralen, and neobavaisoflavone), multiple targets (such as TNF, IL-6, and EGF) and multiple pathways (TGF-ß, TNF, and Toll-like receptor signaling pathways).

A bacterial ghost vaccine against Aeromonas salmonicida infection in turbot (Scophthalmus maximus).

Aeromonas salmonicida is one of the most prevalent pathogens that causes huge economic losses to aquaculture. Effective vaccination is the first choice for preventing infection. Bacterial ghost (BG), an empty bacterial shell devoid of cytoplasm, is a promising vaccine antigen with distinct advantages. Herein, we established strategies for producing a substantial yield of A. salmonicida ghost (ASG) and investigated the immune-protective properties of it. As a result, 2.84 mg/ml NaOH was discovered to be capable of inducing considerable amounts of ASG. Furthermore, the ASG vaccine elicited adaptive immunity in turbots after rapid activation of innate immunity. Even though formalin-killed cells (FKC) produced a few more antibodies than ASG, ASG ultimately provided a much stronger immune protection effect because it strengthened cellular immunity, with a relative percentage survival (RPS) of 50.1 % compared to FKC. These findings demonstrated that ASG effectively activated cell-mediated immunity, which helped get rid of microorganisms inside cells. Therefore, this study presented novel perspectives for future research on furunculosis vaccine products based on ASG as an antigen.

Integrating Multiple Database Resources to Elucidate the Gene Flow in Southeast Asian Pig Populations.

The domestic pig (Sus scrofa) and its subfamilies have experienced long-term and extensive gene flow, particularly in Southeast Asia. Here, we analyzed 236 pigs, focusing on Yunnan indigenous, European commercial, East Asian, and Southeast Asian breeds, using the Pig Genomics Reference Panel (PGRP v1) of Pig Genotype-Tissue Expression (PigGTEx) to investigate gene flow and associated complex traits by integrating multiple database resources. In this study, we discovered evidence of admixtures from European pigs into the genome of Yunnan indigenous pigs. Additionally, we hypothesized that a potential conceptual gene flow route that may have contributed to the genetic composition of the Diannan small-ear pig is a gene exchange from the Vietnamese pig. Based on the most stringent gene introgression scan using the fd statistic, we identified three specific loci on chromosome 8, ranging from 51.65 to 52.45 Mb, which exhibited strong signatures of selection and harbored the NAF1, NPY1R, and NPY5R genes. These genes are associated with complex traits, such as fat mass, immunity, and litter weight, in pigs, as supported by multiple bio-functionalization databases. We utilized multiple databases to explore the potential dynamics of genetic exchange in Southeast Asian pig populations and elucidated specific gene functionalities.

Curcumin suppresses colorectal cancer by induction of ferroptosis via regulation of p53 and solute carrier family 7 member 11/glutathione/glutathione peroxidase 4 signaling axis.

Driven by iron-dependent lipid peroxidation, ferroptosis is regulated by p53 and solute carrier family 7 member 11 (SLC7A11)/glutathione/glutathione peroxidase 4 (GPX4) axis in colorectal cancer (CRC). This study aimed to investigate the influence of curcumin (CUR) on ferroptosis in CRC. The efficacies of CUR on the malignant phenotype of CRC cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, wound healing, and clonogenic assays. The effects of CUR on ferroptosis of CRC cells were evaluated by transmission electron microscopy, lactate dehydrogenase release assay, Fe2+ staining, and analyses of reactive oxygen species, lipid peroxide, malondialdehyde, and glutathione levels. CUR's targets in ferroptosis were predicted by network pharmacological study and molecular docking. With SW620 xenograft tumors, the efficacy of CUR on CRC was investigated, and the effects of CUR on ferroptosis were assessed by detection of Fe2+, malondialdehyde, and glutathione levels. The effects of CUR on expressions of p53, SLC7A11, and GPX4 in CRC cells and tumors were analyzed by quantitative reverse transcription-polymerase chain reaction, western blotting, and immunohistochemistry. CUR suppressed the proliferation, migration, and clonogenesis of CRC cells and xenograft tumor growth by causing ferroptosis, with enhanced lactate dehydrogenase release and Fe2+, reactive oxygen species, lipid peroxide, and malondialdehyde levels, but attenuated glutathione level in CRC. In silico study indicated that CUR may bind p53, SLC7A11, and GPX4, consolidated by that CUR heightened p53 but attenuated SLC7A11 and GPX4 mRNA and protein levels in CRC. CUR may exert an inhibitory effect on CRC by inducing ferroptosis via regulation of p53 and SLC7A11/glutathione/GPX4 axis.

Architecting O3/P2 layered oxides by gradient Mn doping for sodium-ion batteries.

O3 phase layered oxides are highly attractive cathode materials for sodium-ion batteries because of their high capacity and decent initial Coulombic efficiency. However, their rate capability and long cycling life are unsatisfactory due to the narrow Na+ transfer channel and irreversible phase transitions of O3 phase during sodiation/desodiation process. Constructing O3/P2 multiphase structures has been proven to be an effective strategy to overcome these challenges. In this study, we synthesized bi-phasic structured O3/P2 Na(Ni2/9Fe1/3Cu1/9Mn1/3)1-xMnxO2 (x = 0.01, 0.02, 0.03, 0.04, 0.05) materials through Mn doping during sodiation process. Benefiting from surface P2 phase layer with the enhanced Na+ transfer dynamics and high structural stability, the Na(Ni2/9Fe1/3Cu1/9Mn1/3)0.98Mn0.02O2 (NFCM-M2) cathode delivers a reversible capacity of 139.1 mA h g-1 at 0.1 C, and retains 71.4 % of its original capacity after 300 cycles at 1 C. Our work provides useful guidance for designing multiphase cathodes and offers new insights into the structure-performance correlation for sodium-ion cathode materials.

Association between anxiety, depression, and symptom burden in patients with advanced colorectal cancer: A multicenter cross-sectional study.

OBJECTIVES: Patients with advanced colorectal cancer (CRC) have multiple concurrent physical and psychological symptoms. This study aimed to explore the relationship between anxiety, depression, and symptom burden in advanced CRC. METHODS: A multicenter cross-sectional study was conducted in 10 cancer centers from geographically and economically diverse sites in China. A total of 454 patients with advanced CRC completed the Hospital Anxiety and Depression Scale and the MD Anderson Symptom Inventory. Multiple regression analysis was applied to explore the relationship between anxiety, depression and symptom burden. RESULTS: About one-third of the patients showed symptoms of anxiety or depression. Patients with anxiety or depression reported significantly higher symptom burden than those without (p < 0.001). Patients with anxiety or depression reported a higher proportion of moderate-to-severe (MS) symptom number than those without (p < 0.001). About 52% of the patients with anxiety or depression reported at least three MS symptoms. The prevalence of MS symptoms was ranging from 7.3% (shortness of breath) to 22% (disturbed sleep), and in patients with anxiety or depression was 2-10 times higher than in those without (p < 0.001). Disease stage (ß = -2.55, p = 0.003), anxiety (ß = 15.33, p < 0.001), and depression (ß = 13.63, p < 0.001) were associated with higher symptom burden. CONCLUSIONS: Anxiety and depression in patients with advanced cancer correlated with higher symptom burden. Findings may lead oncology professionals to pay more attention to unrecognized and untreated psychological symptoms in symptom management for advanced cancer patients.

Development of a prediction model for suicidal ideation in patients with advanced cancer: A multicenter, real-world, pan-cancer study in China.

BACKGROUND: Patients diagnosed with advanced stage cancer face an elevated risk of suicide. We aimed to develop a suicidal ideation (SI) risk prediction model in patients with advanced cancer for early warning of their SI and facilitate suicide prevention in this population. PATIENTS AND METHODS: We consecutively enrolled patients with multiple types of advanced cancers from 10 cancer institutes in China from August 2019 to December 2020. Demographic characteristics, clinicopathological data, and clinical treatment history were extracted from medical records. Symptom burden, psychological status, and SI were assessed using the MD Anderson Symptom Inventory (MDASI), Hospital Anxiety and Depression Scale (HADS), and Patient Health Questionnaire-9 (PHQ-9), respectively. A multivariable logistic regression model was employed to establish the model structure. RESULTS: In total, 2814 participants were included in the final analysis. Nine predictors including age, sex, number of household members, history of previous chemotherapy, history of previous surgery, MDASI score, HADS-A score, HADS-D score, and life satisfaction were retained in the final SI prediction model. The model achieved an area under the curve (AUC) of 0.85 (95% confidential interval: 0.82-0.87), with AUCs ranging from 0.75 to 0.95 across 10 hospitals and higher than 0.83 for all cancer types. CONCLUSION: This study built an easy-to-use, good-performance predictive model for SI. Implementation of this model could facilitate the incorporation of psychosocial support for suicide prevention into the standard care of patients with advanced cancer.

Niraparib, Dostarlimab, and Bevacizumab as Combination Therapy in Pretreated, Advanced Platinum-Resistant Ovarian Cancer: Findings From Cohort A of the OPAL Phase II Trial.

PURPOSE: To report the results of OPAL (ClinicalTrials.gov identifier: NCT03574779) cohort A, a single-arm substudy of niraparib plus dostarlimab and bevacizumab for the treatment of advanced, platinum-resistant ovarian cancer (PROC). METHODS: Participants with PROC who received 1-2 previous lines of therapy were treated with niraparib (200 or 300 mg once daily), dostarlimab (500 mg once every 3 weeks for four 21-day cycles, followed by 1,000 mg once every 6 weeks), and bevacizumab (15 mg/kg once every 3 weeks). The primary end point was investigator-assessed objective response rate (ORR) per RECIST v1.1. Safety was also assessed. Exploratory biomarker end points included evaluation of changes in the tumor molecular profile and microenvironment using baseline and on-treatment tumor samples. RESULTS: Of 41 enrolled participants (median age, 66.0 years [range, 37-83 years]), 9.8% had tumors that were BRCA-mutated, 19.5% were homologous recombination (HR)-deficient, and 17.1% were HR repair (HRR)-mutated. As of the cutoff date, all participants discontinued treatment. The ORR was 17.1% (80% CI, 9.8 to 27.0), including one complete response (2.4%); the disease control rate was 73.2% (80% CI, 62.3 to 82.2). Two participants withdrew before first postbaseline scan because of adverse events (AEs). Grade ≥3 treatment-emergent AEs were reported in 92.7% of participants, with the most common being hypertension (26.8%). Response was not correlated with BRCA, HRR, HR deficiency (HRD), or PD-L1 status. Changes suggesting immune activation were observed in on-treatment samples after triplet therapy. CONCLUSION: Results demonstrated modest activity of niraparib, dostarlimab, and bevacizumab in participants with PROC, many of whom had prognostic factors for poor treatment response. Most participants with response were bevacizumab-naïve. No association was found with HRD, BRCA, or PD-L1 status. AEs were consistent with previous monotherapy reports, except that hypertension was reported more frequently.

A case study on soil slope landslide failure and parameter analysis of influencing factors for safety factor based on strength reduction method and orthogonal experimental design.

In civil engineering, stability analysis of slope is one of the main content of design. By using the finite element limit analysis software OptumG2, a landslide geological model is established to simulate the failure process of the landslide in Huadu District, Guangzhou City, China. The analysis focused on the deformation and failure characteristics, as well as the mechanical mechanism of landslide; the landslide mode of homogeneous soil is circular sliding. Additionally, investigating the influencing factors affecting slope stability is crucial in engineering implementation; in which the five influencing factors are considered as follow: slope height, slope gradient, soil cohesion, soil internal friction angle, and soil unit weight, respectively. A stability calculation model for a soil slope is established under 25 working conditions based on strength reduction method and orthogonal experimental design, in which the relationship between the safety factor and slope height, slope gradient, soil cohesion, soil internal friction angle, and soil unit weight is obtained. As the slope height increases from 5m to 45m, the safety factor of soil slope gradually decreases from 2.21 to 0.94; As the slope gradient increases from 20° to 60°, the safety factor of soil slope decreases approximately linearly from 1.80 to 0.95; As the cohesion of soil increases from 10kpa to 30kpa, the safety factor of soil slope increases approximately linearly from 1.04 to 1.60; As the internal friction angle of soil increases from 10° to 30°, the safety factor of soil slope increases approximately linearly from 1.00 to 1.81; As the unit weight of soil increases from 13kN/m3 to 21kN/m3, the safety factor of soil slope decreases approximately linearly from 1.50 to 1.21. The influencing factors affecting the safety factor of soil slope in descending order are slope height, slope angle, soil internal friction angle, soil cohesion, and soil unit weight. The research has reference significance for studying the stability and failure laws of soil slopes and conducting landslide control on soil slopes.

Mapping Knowledge Landscapes and Emerging Trends of the Links Between Frailty and Heart Failure: A Bibliometric Analysis From 2000 to 2023.

Background Frailty, within the context of heart failure (HF), is strongly linked to poor patient outcomes. Investigating the vulnerable condition of individuals with HF is crucial, not only for medical reasons but also as a significant public health challenge, especially among the elderly population where both HF and frailty are common. Therefore, it is essential to prioritize HF patients with frailty over those without such symptoms. To begin, promptly assessing the impact of academic research in this area is crucial, considering factors such as geographical regions, authors, journals, and institutions. Additionally, it is important to explore current topics and identify potential areas that could inspire future researchers to conduct further studies to advance public health. Methodology We conducted a search in the Web of Science Core Collection database to identify articles and reviews in the English language focusing on frailty and HF which were published from January 1, 2000, to December 31, 2023. To perform bibliometric analysis, VOSviewer (v.1.6.18) and CiteSpace (v.6.1.R2) were utilized. Results A total of 1,381 original English-language articles were gathered, comprising 1,162 articles and 219 reviews. The quantity of research publications in this area has experienced significant growth since 2013. Among all countries, the United States has contributed the largest number of publications, accounting for 409 articles (29.62% of the total). Additionally, the United States has received the highest number of citations, being cited a total of 13,329 times, as well as boasting the greatest total link strength. Duke University stands out as the institution with the highest number of research papers, having published 40 articles (2.90% of the total). It has also received the most citations, with a total of 2,455 times, and possesses the highest total link strength, which amounts to 212. Within the realm of prolific authors, Kentaro Kamiya from Kitasato University emerges as the most productive, having authored 28 articles (2.03% of the total). When considering scholarly journals, "Esc Heart Failure" contains the highest number of articles pertaining to frailty and HF, publishing a noteworthy 36 articles (2.61% of the total). Noteworthy keywords within this field encompass frailty, heart failure, elderly, mortality, and cardiovascular disease. Over the past five years, the most popular keywords have centered around "frailty syndrome," "sarcopenia," and "therapeutic interventions." Conclusions Research on frailty and HF at a global scale has experienced substantial growth between 2000 and 2023, demonstrating a prospective field for further exploration with potential advantages from ongoing progress. Prospective studies could prioritize the enhancement of cardiac rehabilitation for patients coping with HF and frailty while ensuring the preservation of their overall quality of life.

Optimal exposure of mycophenolic acid for induction therapy of childhood lupus nephritis patients: an observational cohort study.

OBJECTIVES: Mycophenolic acid (MPA) is recommended for lupus nephritis (LN) treatment, but with large inter-individual variability in pharmacokinetics (PK). The aim of this study is to reveal the relationship between MPA exposure and disease response and adverse drug reactions in pediatric LN patients. METHOD: This was a population-based observational cohort study. A total of 86 pediatric LN patients treated with mycophenolate mofetil (MMF) for induction therapy were enrolled. The area-under the concentration-time curve (AUC) was calculated using MPA concentrations according to a limited sampling strategy. Receiver operating characteristic analysis was performed to assess the MPA-AUC threshold values. The cumulative incidence of renal remission and inactive SLE over time was evaluated by Kaplan-Meier's analysis. RESULTS: MPA-AUC was identified as an independent factor associated with renal remission and lupus activity at 6 and 12 months after MMF treatment, and the improved renal remission rates was correlated with higher MPA-AUC, with thresholds of 29.81 and 30.63 µg·h·mL - 1 at 6 and 12 months, respectively. Furthermore, the thresholds for maintaining the hypoactive state of LN were 30.96 and 31.19 µg·h·mL - 1at 6 months and 12 months, respectively. Patients reaching target thresholds for MPA-AUC achieved renal response or stable disease earlier. In addition, the MPA-AUC threshold for decreasing MMF-related adverse reactions was 50.80 µg·h·mL - 1. CONCLUSION: The initial and long-term treatments of pediatric LN patients with MMF should be individualized according to the MPA-AUC, and the recommended MPA exposure is 31.19-50.80 µg·h·mL - 1.