bluuebunny/crossref_metadata_2025 huggingface dataset:
The public–private partnerships in healthcare sector in China
Authors: Liu Bo , Shi Leiyu , Min Hanyi , Liang Hailun , Dong Jiahong
Published: August 2023

This manuscript is a narrative review on experience in the healthcare public–private partnerships (PPP) field project in China. The PPP model allows healthcare officials to share the risk of building new facilities with the private sector. The objective of this study is to evaluate and to review the PPP of healthcare sector in China, and to investigate the critical success factors and best practice of PPP. We adapted the PPP evaluation framework of the World Bank Independent Evaluation Group as our conceptual framework to summarize the literatures. The current study systematically reviewed the evolution and current status of public and private hospitals development in China, and to investigate factors related to the successful and less successful deployment and performance of PPP in the healthcare sector of China, and to develop best practice models of PPP among hospitals of China. We found that the PPP organizations providing finance and political risk coverage, thus enabling specific PPP transactions to reach financial closure—potentially setting demonstration effects. Such PPPs may then contribute to improving access to infrastructure and social services, which drives economic growth and other optimal outcomes.
Effect of Copper Oxide Nanoparticles on the Performance of Polyvinyl Chloride Membranes
Authors: Khezraqa Homayun , Samiei Arian , Etemadi Habib , Salami-Kalajahi Mehdi
Published: August 2023

Polyvinyl chloride (PVC)/copper oxide (CuO) nanocomposite membranes were fabricated at different CuO nanoparticles loading levels using the phase inversion method. The fabricated membranes were tested through two filtration cycles in a submerged membrane system to remove bovine serum albumin (BSA) from water. Results showed that the hydrophilicity and porosity of the nanocomposite membranes were enhanced with an increase of CuO nanoparticles loading. The field emission electron microscopy images from the membrane surface demonstrated that the number and size of pores increased with addition of CuO nanoparticles. The atomic force microscopy test displayed that all nanocomposite membranes showed lower surface roughness in comparison to neat PVC membranes. The obtained results from membrane performance indicated that the irreversible fouling ratio for neat PVC membranes in the first and second cycles of filtration decreased for PVC/CuO‐1.5 membranes. Compared with the neat PVC membrane, the membrane containing CuO exhibited better capabilities such as the enhanced permeation flux, higher BSA rejection rate, and better antifouling properties.
Comparative Life Cycle Assessment and Exergy Analysis of Coal‐ and Natural Gas‐Based Ammonia Production
Authors: Çetinkaya Afşın Yusuf , Bilgili Levent , Kuzu S. Levent , Yılmaz Fatih
Published: August 2023

A comprehensive life cycle assessment (LCA) analysis of ammonia production is presented, focusing on the comparison between natural gas‐based and coal‐based processes. Ammonia production is associated with high energy consumption and significant carbon dioxide (CO2) emissions. The objective of this research is to identify key processes and parameters within the ammonia synthesis industry and provide recommendations for cleaner and more sustainable development. Exergy analysis is performed to assess the efficiency of ammonia production technologies and determine optimal operating conditions. Natural gas‐based ammonia production has lower environmental impacts compared to coal‐based production in most categories, except for ionizing radiation. Natural gas, being a cleaner‐burning fossil fuel, produces fewer greenhouse gas emissions and other air pollutants. However, it is essential to address the issue of ionizing radiation in natural gas‐based processes. The potential for more efficient technologies and the importance of removing sulfur and other impurities during the production process to optimize catalyst performance are highlighted.
Challenges and opportunities in lymph node FNA: Insights from the DELYCYUS study
Authors: Ruiz‐Cordero Roberto
Published: August 2023

The DELYCYUS study represents a significant step forward in the field of lymph node cytology, providing evidence that digital cytopathology, when applied using the Sydney system, yields reliable and reproducible results.
A Practical Nanoplasmonic SERS Substrate for Differential Diagnosis of Lung Normal and Cancer Cells through Multivariate Statistical Analysis
Authors: Abraham Bini , Emmanuel Neethu , Ajikumar Nandu , Pulassery Sanoop , Varghese Liya Elsa , Murali Vishnu Priya , Munnilath Arun , Maiti Kasutabh Kumar , Yoosaf Karuvath
Published: August 2023

Lung cancer ranks first for cancer‐related mortalities primarily due to late diagnosis. Though Surface‐Enhanced Raman spectroscopy (SERS) is a popular bioanalytical technique, its direct application to diagnosis is impeded by low data reproducibility. Colloidal nanoparticles suffer from SERS intensity fluctuations due to unavoidable aggregation, and Brownian and diffusion motions in biological samples. The processes for solid‐state SERS substrates are either sophisticated or difficult to reproduce. Herein, we revisit the well‐established thermal evaporation process for the easy and reproducible preparation of silver nanoparticles loaded SERS glass substrates. The static mode of thermal evaporation yielded closely packed and uniformly distributed silver nanoparticles. The properties of these nanoparticles are tuned for the best performance by controlling the thermal evaporation process. And SERS substrate exhibited a reasonably good enhancement factor of ~105 with uniformity and reproducibility <6 % RSD over a large area. It was utilized for label‐free SERS fingerprinting of lung adenocarcinoma cells A549 and normal lung fibroblast cells, WI‐38. The obtained data shows a slight distinction of Raman fingerprints in terms of certain biomolecules like nucleic acids, proteins, and lipids. Further multivariate statistical tools have been utilized which ensures a clear divergence between the cancerous cells and normal cells.
Safety, Tolerability, and Pharmacokinetics of Valemetostat Tablets and the Effect of Food on Valemetostat Pharmacokinetics in Healthy Subjects: Two Phase 1 Studies
Authors: Tachibana Masaya , Matsuki Shunji , Toyama Kaoru , Maekawa Yutaro , Fukae Masato , Shimizu Takako , Tsutsumi Junko , Shinohara Sayaka , Ishizuka Hitoshi
Published: August 2023

Valemetostat is an oral, selective inhibitor of enhancer of zeste homolog‐2 (EZH2) and EZH1. In a first‐in‐human phase‐1 trial, valemetostat capsules were well tolerated and clinically active in patients with relapsed/refractory non‐Hodgkin lymphoma. Subsequently, a film‐coated tablet formulation was developed for future clinical trials and commercialization. We report outcomes from 2 phase 1 trials in healthy Japanese participants, assessing the safety, tolerability, and pharmacokinetics (PK) of valemetostat tablets at single ascending doses (50, 100, and 200‐mg), the relative bioavailability between capsules and tablets, and the effect of food (high‐fat or low‐fat meals) on the PK of valemetostat tablets. In the ascending‐dose study, valemetostat maximum plasma concentration (Cmax) and area under the concentration–time curve (AUC) increased dose‐proportionally. Valemetostat plasma PK parameters were similar between the capsule and tablet formulations following a single 200‐mg dose. Administration of valemetostat, 200 mg after a meal, was associated with 50%‐60% lower Cmax, 30%‐50% lower AUC, and a median Tmax delay of 2.5‐3 hours relative to fasted administration. Valemetostat was well tolerated in healthy subjects; treatment‐emergent adverse events were mild (grade 1) in severity. Based on these trials, the tablet formulation of valemetostat is suitable for use in subsequent clinical trials and should be administered under fasted conditions to avoid a negative food effect.
Safety, Pharmacokinetics, and Pharmacodynamics of Subcutaneous Sibeprenlimab in Healthy Participants
Authors: Zhang Xiaoyan , Wang Yanlin , Yarbrough Jill , Mathur Mohit , Andrews Lee , Pereira Brian , Sloan Susan E. , Schachter Asher D.
Published: August 2023

Sibeprenlimab blocks the cytokine “A Proliferation‐Inducing Ligand” (APRIL), which may play a key role in immunoglobulin A nephropathy pathogenesis. A phase 1 study of subcutaneous (SC) sibeprenlimab evaluated preliminary safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy participants. This was an open‐label, single‐ascending‐dose study. Twelve participants in each of 4 sequential dosing cohorts received 1 SC dose of sibeprenlimab (200 mg [1×1 mL injection], 400 mg [2×1 mL injections], 400 mg [1×2 mL injection], or 600 mg [1 mL+2 mL injections]) and underwent 16‐week follow‐up for adverse events, pharmacokinetics, and pharmacodynamics (serum APRIL, immunoglobulin [Ig] levels). Sibeprenlimab in single SC doses of 200‐600 mg was slowly absorbed into the systemic circulation, with a median time to maximum serum concentration of approximately 6‐10.5 days, and a mean elimination half‐life of approximately 8‐10 days. Serum APRIL, IgA, IgM, and, to a lesser extent, IgG decreased in a dose‐dependent and reversible manner. Maximal reduction in serum IgA was approximately 60% at the 400‐ and 600‐mg doses and 40% at 200 mg. Serum APRIL rapidly decreased to near the lower limit of quantification, and duration of suppression was dose‐dependent, with near complete suppression until weeks 4‐6 at the 400‐mg dose and week 8 at the 600‐mg dose. Adverse events occurred in 30/48 (62.5%) participants; none were serious or led to study discontinuation. Sibeprenlimab rapidly and sustainably reduced target APRIL and Ig biomarkers in a dose‐dependent and reversible manner, with acceptable preliminary safety and pharmacokinetics.
Insight into the Structure of MOF‐Containing Hybrid Polymeric Microspheres
Authors: Goliszek Marta , Kochaniec Maria , Podkościelna B. Beata
Published: August 2023

Polymer science exploited metal organic frameworks (MOFs) for various purposes, which is due to the fact that these materials are ideal platforms for identifying design features for advanced functional materials. The mechanism of polymerization using MOFs, is still largely unexplored and the detailed characterization of both materials in essential to understand the important interactions between the components. In this work modern advanced research methods were used to investigate the properties of MOF‐containing hybrid polymeric microspheres. Hydrothermal conversion of CFA‐derived iron particles was used to obtain MOF nanostructures, which were then introduced to the structure of hybrid polymer microspheres based on ethylene glycol dimethylacrylate (EGDMA) and triethoxyvinylsilane (TEVS). Chemical structures were confirmed by ATR‐FTIR method. To provide information about the elemental composition of the tested materials and for the determination of chemical bonds present in the tested samples XPS method was applied. Morphology was studied using SEM microscopy, whereas porosity was investigated using ASAP technique. Swellability coefficients were determined using typical organic solvents and distilled water. Moreover, the ecological aspect concerning the use of fly ashes deserves to be emphasized.
Peri‐urban systems alter trophic niche size and overlap in sympatric coastal bird species
Authors: Lato Kimberly A. , Fuirst Matthew , Veit Richard R. , Thorne Lesley H.
Published: August 2023

Urban habitats can create empty trophic niche space by providing abundant alternative dietary resources, allowing some generalist species to either shift or expand their trophic niches. Resulting changes to trophic niche size may consequently affect interspecific interactions and competition, although trophic impacts are less clear in peri‐urban systems, where both natural and urban resources are readily accessible to highly mobile species. We combined stable isotope (δ13C, δ15N, δ34S) data with GPS tracking of two sympatric coastal bird species (Larus argentatus, L. marinus) across four study sites on the east coast of the United States, ranging from a study site in New York City (the most populous city in the United States) to less‐urban sites off Massachusetts. We quantified the trophic niche size and trophic niche overlap in three‐dimensional isotopic space and assessed spatial overlap in foraging habitat between species at both peri‐urban and less‐urban study sites. We found that for both species, birds at peri‐urban study sites had significantly larger trophic niches than birds from the less‐urban sites. Furthermore, for study sites where both species occurred, we found that overlap in trophic niche space and foraging habitats between species was lower at the peri‐urban study site than at the less‐urban site. These results suggest that peri‐urban environments may facilitate trophic niche expansion and decrease niche overlap in mobile generalist species, contrasting with previous studies showing increased trophic niche overlap in more isolated urban populations. Following further analysis, we found that trophic niche expansion was facilitated by both within‐ and between‐individual differences in foraging strategies. We posit that peri‐urban environments, particularly along coastal areas, can reduce interspecific competition between sympatric species by providing access to a variety of natural and anthropogenic diet items, especially for highly mobile generalist consumers that can access both natural and urban foraging areas. Research assessing how and at what scale peri‐urban systems influence wildlife is key to understanding how further global urbanization will shape ecosystem structures.
Epigenetic profiling of the D4Z4 locus: Optimization of the protocol for studying DNA methylation at single CpG site level
Authors: Megalizzi Domenica , Trastulli Giulia , Caputo Valerio , Colantoni Luca , Caltagirone Carlo , Strafella Claudia , Cascella Raffaella , Giardina Emiliano
Published: August 2023

The alteration of epigenetic modifications, including DNA methylation, can contribute to the etiopathogenesis and progression of many diseases. Among them, facioscapulohumeral dystrophy (FSHD) is a muscular disorder characterized by the loss of repressive epigenetic features affecting the D4Z4 locus (4q35). As a consequence, these alterations are responsible for DNA hypomethylation and a transcriptional‐active chromatin conformation change that, in turn, lead to the aberrant expression of DUX4 in muscle cells. In the present study, methylation levels of 29 CpG sites of the DR1 region (within each repeat unit of the D4Z4 macrosatellite) were assessed on 335 subjects by employing primers designed for enhancing the performance of the assay. First, the DR1 original primers were optimized by adding M13 oligonucleotide tails. Moreover, the DR1 reverse primer was replaced with a degenerate one. As a result, the protocol optimization allowed a better sequencing resolution and a more accurate evaluation of DR1 methylation levels. Moreover, the assessment of the repeatability of measurements proved the reliability and robustness of the assay. The optimized protocol emerges as an excellent method to detect methylation levels compatible with FSHD.
Epilepsy classification using artificial intelligence: A web‐based application
Authors: Asadi‐Pooya Ali A. , Fattahi Davood , Abolpour Nahid , Boostani Reza , Farazdaghi Mohsen , Sharifi Mehrdad
Published: August 2023

Objective

The purpose of the current endeavor was to evaluate the feasibility of using easily accessible and applicable clinical information (based on history taking and physical examination) in order to make a reliable differentiation between idiopathic generalized epilepsy (IGE) versus focal epilepsy using machine learning (ML) methods.

Methods

The first phase of the study was a retrospective study of a prospectively developed and maintained database. All patients with an electro‐clinical diagnosis of IGE or focal epilepsy, at the outpatient epilepsy clinic at Shiraz University of Medical Sciences, Shiraz, Iran, from 2008 until 2022, were included. The first author selected a set of clinical features. Using the stratified random portioning method, the dataset was divided into the train (70%) and test (30%) subsets. Different types of classifiers were assessed and the final classification was made based on their best results using the stacking method.

Results

A total number of 1445 patients were studied; 964 with focal epilepsy and 481 with IGE. The stacking classifier led to better results than the base classifiers in general. This algorithm has the following characteristics: precision: 0.81, sensitivity: 0.81, and specificity: 0.77.

Significance

We developed a pragmatic algorithm aimed at facilitating epilepsy classification for individuals whose epilepsy begins at age 10 years and older. Also, in order to enable and facilitate future external validation studies by other peers and professionals, the developed and trained ML model was implemented and published via an online web‐based application that is freely available at http://www.epiclass.ir/f‐ige.
Predictors of malignant transformation in oral leukoplakia and proliferative verrucous leukoplakia: An observational prospective study including the DNA ploidy status
Authors: Pentenero Monica , Castagnola Patrizio , Castillo Faride Victoria , Isaevska Elena , Sutera Samuele , Gandolfo Sergio
Published: August 2023

Background

This prospective observational study investigated the determinants of malignant transformation (MT) in localized oral leukoplakia (OL) and proliferative verrucous leukoplakia (PVL).

Methods

Demographic, clinical, histological, and DNA ploidy status data were collected at enrolment. Survival analysis was performed (MT being the event of interest).

Results

One‐hundred and thirty‐three patients with OL and 20 patients with PVL entered the study over 6 years (mean follow‐up 7.8 years). The presence of OED, DNA ploidy, clinical presentation, and lesion site were associated with MT in patients with OL in a univariate analysis. In a multivariate model, OED was the strongest predictor of MT in patients with OL. Adding DNA ploidy increased the model's predictive power. None of the assessed predictors was associated with MT in patients with PVL.

Conclusions

DNA ploidy might identify a subset OL with low risk or minimal risk of MT, but it does not seem to be a reliable predictor in patients with PVL.
Prevalence and associated factors of depression, anxiety, and stress among pregnant women in Herat, Afghanistan: A cross‐sectional study
Authors: Niazi Aziz‐ur‐Rahman , Alekozay Mina , Osmani Khadejah , Najm Abdul Fattah
Published: August 2023

Background and Aims

Pregnancy is an important and natural event in a woman's life. It represents a time of substantial social and bio‐psychological challenges for a pregnant woman that may increase vulnerability to emotional disturbances such as depression, anxiety, and stress (DAS). This study aims to assess the prevalence and associated factors of DAS among pregnant women in Herat city of Afghanistan.

Methods

This hospital‐based cross‐sectional study was conducted between July and November 2019, on 691 Dari‐speaking pregnant women aged 15‐49 years, who attended the antenatal clinic of Herat Razaei Maternity Hospital. The interview process involved the use of a structured questionnaire that collected data on sociodemographic characteristics of participants, as well as the validated Dari‐translated version of DASS‐42 questionnaire. A χ2 test was used to test for association between categorical data. Forward likelihood ratio was used to assess the strength of association between sociodemographic variables and DAS; independently. The significance level was set to 0.05 and the confidence interval to 95% in all statistical analyses. Statistical analyses were performed in IBM SPSS Statistics (version 27).

Results

The mean age of participants was 26.17 ± 6.06. The overall prevalence of DAS among study participants were 42.8%, 40.0%, and 59.5%, respectively. Planning of current pregnancy, women's health, husband's health, women's nutrition, family support, husband's support, women's education, women's employment, and family economy were significantly associated with DAS, while gestational age was not significantly associated with DAS.

Conclusion

The prevalence of DAS among pregnant women in Herat city of Afghanistan is very high. Considering scientific evidence on high prevalence and associated factors of DAS among pregnant women, policymakers, public health authorities, and medical practitioners must devote significant attention in reducing the magnitude of these mental disorders and/or reducing their impact on women, their families, and the society.
Corporate risk disclosure and firm value: UK evidence
Authors: Ibrahim Awad Elsayed Awad , Aboud Ahmed
Published: August 2023

This study examines the influence of risk disclosure (RD) in the annual reports on Firm Value (FV) in the UK context. Furthermore, it addresses the moderating role of the analyst information environment in shaping this relation. Our study distinguishes between favourable and unfavourable information and examines whether the different nature of risk information could affect the FV differently. Our study contributes to the existing literature by providing empirical evidence on the value relevance of the narrative risk information. In particular, using a sample of UK listed firms, we find a positive relation between risk information and FV. We also contribute to the dilemma of risk disclosure measurement by using four different RD proxies. Our study has important implications for academics, standard setters, investors and managers.
Circ_LDLR promotes the progression of papillary thyroid carcinoma by regulating miR‐1294/HMGB3 axis
Authors: Chen Guo , Han Pengli , Zhang Qingsong , Li Mingchuang , Song Ting , Chen Zheng , Zhao Yatong , Yin Detao , Lv Jing
Published: August 2023

Circular RNAs (circRNAs) have been found to be associated with the development and progression of cancers including papillary thyroid carcinoma (PTC). Circ_LDLR has been reported to be highly expressed in PTC, but its underlying mechanism of action has not been fully elucidated. This study aimed to investigate the role of circ_LDLR in PTC. The expression of circ_LDLR, miR‐1294 and high mobility group box (HMGB) 3 was detected by quantitative real‐time polymerase chain reaction (qRT‐PCR). CCK‐8 assay and transwell assays were employed to value cell viability, invasion and migration abilities. Western blot assay was to detect HMGB3 protein expression. Luciferase reporter gene and pull down assay were used to validate the interaction between miR‐1294 and HMGB3 or circ_LDLR. Circ_LDLR showed high expression levels in PTC tissues and cells and knockdown of it inhibited the growth, invasion, and migration of PTC cells. In addition, miR‐1294 was considered as a downstream target of circ_LDLR, and inhibition of miR‐1294 partially reversed the inhibitory effects of circ_LDLR knockdown on PTC cells growth, invasion, and migration. More importantly, HMGB3 was identified as a downstream target of miR‐1294. Our findings suggest circ_LDLR may plays a promoting role in PTC by downregulating miR‐1294 and upregulating HMGB3 expression. Therefore, circ_LDLR may serve as a valuable prognostic biomarker and therapeutic target for PTC.
TMEM175 downregulation participates in impairment of the autophagy related lysosomal dynamics following neonatal hypoxic‐ischemic brain injury
Authors: Zhang Huiyi , Tian Ye , Yu Weiwei , Tong Dongyi , Ji Yichen , Qu Xinrui , Deng Tianjiao , Li Xinsheng , Xu Ying
Published: August 2023

The mechanism underlying long‐term cognitive impairment caused by neonatal hypoxic‐ischemic brain injury (HIBI) remains unclear. Autophagy is a closely related mechanism and may play a role in this process. We aimed to investigate the role of lysosomal transmembrane protein 175 (TMEM175) in the autophagy‐lysosome pathway in neonatal rats with HIBI. A neonatal rat model of HIBI was established, hypoxia was induced, followed by left common carotid artery ligation. Expression levels of TMEM175 and the corresponding proteins involved in autophagy flux and the endolysosomal system fusion process were measured. Rats were administered TMEM175 plasmid via intracerebroventricular injection to induce overexpression. Brain damage and cognitive function were then assessed. TMEM175 was downregulated in the hippocampal tissue, and the autophagy‐lysosome pathway was impaired following HIBI in neonatal rats. Overexpression of TMEM175 significantly mitigated neuronal injury and improved long‐term cognitive and memory function in neonatal rats with HIBI. We found that improvement in the autophagy‐lysosome pathway and endolysosomal system homeostasis, which are TMEM175 related, occurred via regulation of lysosomal membrane dynamic fusion. TMEM175 plays a critical role in maintaining the autophagy‐lysosome pathway and endolysosomal homeostasis, contributing to the amelioration of neuronal injury and impaired long‐term cognitive function following neonatal HIBI.
Evaluation of Safety and Efficacy of Add‐on Alpha‐Lipoic Acid on Migraine Prophylaxis in an Adolescent Population: A Randomized Controlled Trial
Authors: Puliappadamb Haridas Mundot , Satpathy Amit Kumar , Mishra Biswa Ranjan , Maiti Rituparna , Jena Monalisa
Published: August 2023

Nutraceuticals like alpha‐lipoic acid (ALA) may have potential benefits as prophylactic agents for adolescent migraine, with fewer adverse events than existing medications. The present study was conducted to evaluate the safety and efficacy of add‐on ALA for prophylaxis in adolescent migraine. A randomized, open‐label, add‐on clinical trial was conducted with 60 adolescent migraineurs, who were randomized to receive flunarizine or flunarizine with an add‐on ALA. A clinical evaluation of the frequency and severity of migraine, responder rate, Pediatric Migraine Disability Assessment (PedMIDAS) scoring, serum thiol, and serum calcitonin gene‐related peptide (CGRP) was performed both at baseline and following 12 weeks of treatment. The frequency of acute attacks of migraine decreased significantly (P = .001) in the test group compared with the control group. The responder rate was found to be significantly higher (80%) in the test group than in the control group (33.3%) (P = .001). The mean monthly migraine headache days in the test group showed a significant reduction (−7.7 days, 95%CI −9.1 to −6.3 days; P = .010). The severity of acute migraine attacks (mild, moderate, severe) also showed a significant reduction in the test group (P = .001). PedMIDAS scores showed significant improvement in the test group (P = .021), in comparison with the control group. Serum thiol levels were significantly increased in the test group (18 mmol/L, 95%CI 13.5 to 36.1 mmol/L; P = .001). Serum CGRP levels showed a significant reduction with adjunctive ALA therapy (−122.4 pg/mL, 95%CI −142.3 to −89.0 pg/mL; P = .006). Add‐on ALA with flunarizine as a prophylactic agent for migraine in adolescents can improve clinical outcomes by improving clinical and biochemical parameters.
Correlations of PCSK9 and LDLR Gene Polymorphisms and Serum PCSK9 Levels With Atherosclerosis and Lipid Metabolism in Patients on Maintenance Hemodialysis
Authors: Cui Jun , Qiu Yuxiang , Kang Ningsu , Lu Jianxun , Zheng Lu
Published: August 2023

This study is aimed at investigating the correlations of PCSK9 and LDLR gene polymorphisms as well as serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels with atherosclerosis and lipid metabolism in patients on maintenance hemodialysis (HD). A single nucleotide polymorphism at the E670G locus of the PCSK9 gene and the rs688 locus of the LDLR gene was analyzed by polymerase chain reaction–restriction fragment length polymorphism. All study subjects’ blood lipid (triglyceride [TG], total cholesterol [TC], high‐density lipoprotein cholesterol [HDL‐C], and low‐density lipoprotein cholesterol [LDL‐C]) concentrations and lipoprotein(a) and PCSK9 levels were measured. The differences in blood lipid levels between different genotypes of the E670G locus of the PCSK9 gene and the rs688 locus of the LDLR gene in patients on maintenance HD with atherosclerosis were compared. Patients on maintenance HD with atherosclerosis at the E670G locus of the PCSK9 gene AG + GG genotype had higher levels of TG, TC, LDL‐C, and lipoprotein(a) than the AA genotype, and lower levels of HDL‐C than the AA genotype. Patients on maintenance HD with atherosclerosis at the rs688 locus of the LDLR gene CT + TT genotype had higher levels of TG, TC, LDL‐C, and lipoprotein(a) than the CC genotype, and lower levels of HDL‐C than the CC genotype. Serum PCSK9 contents in patients on maintenance HD with atherosclerosis were positively correlated with lipid indices (TG, TC, LDL‐C, and lipoprotein(a)) and carotid ultrasound indices (intima‐media thickness and resistance index), and negatively correlated with HDL‐C, maximum systolic blood flow velocity, and minimum diastolic blood flow velocity (all P < .05).
Longitudinal studies of child mental disorders in the general population: A systematic review of study characteristics
Authors: Bogdan Theodora , Xie Weiyi , Talaat Habeba , Mir Hafsa , Venkataraman Bhargavi , Banfield Laura E. , Georgiades Katholiki , Duncan Laura
Published: August 2023

Introduction

Longitudinal studies of child mental disorders in the general population (herein study) investigate trends in prevalence, incidence, risk/protective factors, and sequelae for disorders. They are time and resource intensive but offer life‐course perspectives and examination of causal mechanisms. Comprehensive syntheses of the methods of existing studies will provide an understanding of studies conducted to date, inventory studies, and inform the planning of new longitudinal studies.

Methods

A systematic review of the research literature in MEDLINE, EMBASE, and PsycINFO was conducted in December 2022 for longitudinal studies of child mental disorders in the general population. Records were grouped by study and assessed for eligibility. Data were extracted from one of four sources: a record reporting study methodology, a record documenting child mental disorder prevalence, study websites, or user guides. Narrative and tabular syntheses of the scope and design features of studies were generated.

Results

There were 18,133 unique records for 487 studies—159 of these were eligible for inclusion. Studies occurred from 1934 to 2019 worldwide, with data collection across 1 to 68 time points, with 70% of studies ongoing. Baseline sample sizes ranged fromn = 151 to 64,136. Studies were most frequently conducted in the United States and at the city/town level. Internalizing disorders and disruptive, impulse control, and conduct disorders were the most frequently assessed mental disorders. Of studies reporting methods of disorder assessment, almost all used measurement scales. Individual, familial and environmental risk and protective factors and sequelae were examined.

Conclusions

These results summarize characteristics of existing longitudinal studies of child mental disorders in the general population, provide an understanding of studies conducted to date, encourage comprehensive and consistent reporting of study methodology to facilitate meta‐analytic syntheses of longitudinal evidence, and offer recommendations and suggestions for the design of future studies. Registration DOI: 10.17605/OSF.IO/73HSW.
Tumour extracellular vesicles induce neutrophil extracellular traps to promote lymph node metastasis
Authors: Su Xin , Brassard Ariane , Bartolomucci Alexandra , Dhoparee‐Doomah Iqraa , Qiu Qian , Tsering Thupten , Rohanizadeh Ramin , Koufos Olivia , Giannias Betty , Bourdeau France , Feng Lixuan , Messina‐Pacheco Julia , Leo Sabrina , Sangwan Veena , Quail Daniela , Tankel James , Spicer Jonathan , Burnier Julia Valdemarin , Bailey Swneke Donovan , Ferri Lorenzo , Cools‐Lartigue Jonathan
Published: August 2023

Lymph nodes (LNs) are frequently the first sites of metastasis. Currently, the only prognostic LN assessment is determining metastatic status. However, there is evidence suggesting that LN metastasis is facilitated by the formation of a pre‐metastatic niche induced by tumour derived extracellular vehicles (EVs). Therefore, it is important to detect and modify the LN environmental changes. Earlier work has demonstrated that neutrophil extracellular traps (NETs) can sequester and promote distant metastasis. Here, we first confirmed that LN NETs are associated with reduced patient survival. Next, we demonstrated that NETs deposition precedes LN metastasis and NETs inhibition diminishes LN metastases in animal models. Furthermore, we discovered that EVs are essential to the formation of LN NETs. Finally, we showed that lymphatic endothelial cells secrete CXCL8/2 in response to EVs inducing NETs formation and the promotion of LN metastasis. Our findings reveal the role of EV‐induced NETs in LN metastasis and provide potential immunotherapeutic vulnerabilities that may occur early in the metastatic cascade.
Comprehensive characterization of human brain‐derived extracellular vesicles using multiple isolation methods: Implications for diagnostic and therapeutic applications
Authors: Zhang Zhengrong , Yu Kaiwen , You Yang , Jiang Peizhou , Wu Zhiping , DeTure Michael A. , Dickson Dennis W. , Ikezu Seiko , Peng Junmin , Ikezu Tsuneya
Published: August 2023

Extracellular vesicles (EVs) have emerged as critical mediators of intercellular communication and promising biomarkers and therapeutics in the central nervous system (CNS). Human brain‐derived EVs (BDEVs) provide a comprehensive snapshot of physiological changes in the brain's environment, however, the isolation of BDEVs and the comparison of different methods for this purpose have not been fully investigated. In this study, we compared the yield, morphology, subtypes and protein cargo composition of EVs isolated from the temporal cortex of aged human brains using three established separation methods: size‐exclusion chromatography (SEC), phosphatidylserine affinity capture (MagE) and sucrose gradient ultracentrifugation (SG‐UC). Our results showed that SG‐UC method provided the highest yield and collected larger EVs compared to SEC and MagE methods as assessed by transmission electron microscopy and nanoparticle tracking analysis (NTA). Quantitative tandem mass‐tag (TMT) mass spectrometry analysis of EV samples from three different isolation methods identified a total of 1158 proteins, with SG‐UC showing the best enrichment of common EV proteins with less contamination of non‐EV proteins. In addition, SG‐UC samples were enriched in proteins associated with ATP activity and CNS maintenance, and were abundant in neuronal and oligodendrocytic molecules. In contrast, MagE samples were more enriched in molecules related to lipoproteins, cell‐substrate junction and microglia, whereas SEC samples were highly enriched in molecules related to extracellular matrix, Alzheimer's disease and astrocytes. Finally, we validated the proteomic results by performing single‐particle analysis using the super‐resolution microscopy and flow cytometry. Overall, our findings demonstrate the differences in yield, size, enrichment of EV cargo molecules and single EV assay by different isolation methods, suggesting that the choice of isolation method will have significant impact on the downstream analysis and protein discovery.
Clinical and haematological characteristics of 38 individuals with Hb G‐Makassar in Malaysia
Authors: Esa Ezalia , Mohamad Ahmad Sabry , Hamzah Roszymah , Hamid Faidatul Syazlin Abdul , Aziz Nur Aisyah , Sevaratnam Veena , Sathar Jameela , Chen Guo , Yasin Norafiza Mohd
Published: August 2023

Haemoglobin (Hb) G‐Makassar is a rare Hb variant. It presents a diagnostic challenge as it imitates sickle Hb (Hb S) in standard electrophoresis and high‐performance liquid chromatography assays requiring DNA analysis to confirm diagnosis. Both have point mutations in codon 6, exon 1 in the β‐globin (HBB) gene with different pathogenicities. This study describes the clinical phenotype, haematology and genotype of Hb G‐Makassar. Clinical and laboratory data of 38 cases of Hb G‐Makassar over 8 years were analysed. Hb G‐Makassar was confirmed by a direct sequencing of HBB gene and co‐inheritance of α‐thalassaemia determined through multiplex gap‐PCR and multiplex Amplification Refractory Mutation System polymerase chain reaction. All cases were Malays, predominantly from Terengganu (n = 20, 52.6%). There were 14 (36.8%) males and 24 (63.2%) females with median age of 25 years. Majority (n = 33, 86.8%) had features of thalassaemia trait with mean ± SD for Hb, mean cell volume (MCV) and mean cell haemoglobin (MCH) as 13.21 g/dL ± 1.69, 73.06 ± 4.48 fL and 24.71 ± 1.82 pg, respectively. None had evidence of haemolysis or thromboembolic complications. Six genotypes were identified; ßG‐Makassar/ß,αα/αα (n = 19, 50.0%), ßG‐Makassar/ßE,αα/αα (n = 4, 10.5%), ßG‐Makassar/ßNewYork,αα/αα (n = 1, 2.6%), ßG‐Makassar/ß,αα/‐α (n = 11, 28.9%), ßG‐Makassar/ß,αα/αAdanaα (n = 2, 5.3%) and ßG‐Makassar/ß,αα/–SEA (n = 1, 2.6%). The ßG‐Makassar/ß,αα/αα showed that features of thalassaemia trait with mean ± SD for Hb, MCV and MCH were 13.74 g/dL ± 2.40, 76.18 ± 6.02 fL and 25.79 ± 2.41 pg, respectively. This is the largest study reporting a significant number of Hb G‐Makassar in Malaysia. Although the mutation is similar to Hb S, the phenotype is benign.
Description of the neuroanatomy of the brachial plexus in South American lizards. Phylogenetic implications
Authors: Navarro Exequiel Alejandro , Quipildor Matias , Quinteros Sebastián
Published: August 2023

Few studies considered the anatomy of the nerve plexuses and musculature associated with them in ectothermic sauropsids. Based on differentiated Sudan Black B staining and conventional dissections, we describe the neuroanatomy of the brachial plexus, its main associated nerves, and muscles. For that, representatives of the genera Diplolaemus, Liolaemus, Phymaturus, and Tropidurus were selected. Based on this, potentially useful characters for phylogenetic analysis were described. Our results show that the brachial plexus can be formed by four, five, or six nerve branches. The brachial flexor trunk, circumflex, interosseous, median, radial, subscapulocoracoid, supracoracoid, and ulnar nerves were identified. Regarding the muscles innervated by the main nerves, the following muscles were identified: biceps brachii, deltoideus scapularis, latissimus dorsi, levator scapulae, pectoralis, serratus thoracis, trapezius, triceps longus caudalis, and triceps longus lateralis. Phylogenetic analyzes revealed 31 potential synapomorphies. There exists evidence that neuroanatomy studies in a phylogenetic context could provide useful information helping to elucidate the relationships between taxonomic groups.
Molecular and immune signatures, and pathological trajectories of fatal COVID‐19 lungs defined by in situ spatial single‐cell transcriptome analysis
Authors: Das Arun , Meng Wen , Liu Zhentao , Hasib Md Musaddaqul , Galloway Hugh , Ramos da Silva Suzane , Chen Luping , Sica Gabriel L. , Paniz‐Mondolfi Alberto , Bryce Clare , Grimes Zachary , Sordillo Emilia M. , Cordon‐Cardo Carlos , Rivera Karla Paniagua , Flores Mario , Chiu Yu‐Chiao , Huang Yufei , Gao Shou‐Jiang
Published: August 2023

Despite intensive studies during the last 3 years, the pathology and underlying molecular mechanism of coronavirus disease 2019 (COVID‐19) remain poorly defined. In this study, we investigated the spatial single‐cell molecular and cellular features of postmortem COVID‐19 lung tissues using in situ sequencing (ISS). We detected 10 414 863 transcripts of 221 genes in whole‐slide tissues and segmented them into 1 719 459 cells that were mapped to 18 major parenchymal and immune cell types, all of which were infected by SARS‐CoV‐2. Compared with the non‐COVID‐19 control, COVID‐19 lungs exhibited reduced alveolar cells (ACs) and increased innate and adaptive immune cells. We also identified 19 differentially expressed genes in both infected and uninfected cells across the tissues, which reflected the altered cellular compositions. Spatial analysis of local infection rates revealed regions with high infection rates that were correlated with high cell densities (HIHD). The HIHD regions expressed high levels of SARS‐CoV‐2 entry‐related factors including ACE2, FURIN, TMPRSS2 and NRP1, and co‐localized with organizing pneumonia (OP) and lymphocytic and immune infiltration, which exhibited increased ACs and fibroblasts but decreased vascular endothelial cells and epithelial cells, mirroring the tissue damage and wound healing processes. Sparse nonnegative matrix factorization (SNMF) analysis of niche features identified seven signatures that captured structure and immune niches in COVID‐19 tissues. Trajectory inference based on immune niche signatures defined two pathological routes. Trajectory A primarily progressed with increased NK cells and granulocytes, likely reflecting the complication of microbial infections. Trajectory B was marked by increased HIHD and OP, possibly accounting for the increased immune infiltration. The OP regions were marked by high numbers of fibroblasts expressing extremely high levels of COL1A1 and COL1A2. Examination of single‐cell RNA‐seq data (scRNA‐seq) from COVID‐19 lung tissues and idiopathic pulmonary fibrosis (IPF) identified similar cell populations consisting mainly of myofibroblasts. Immunofluorescence staining revealed the activation of IL6‐STAT3 and TGF‐β‐SMAD2/3 pathways in these cells, likely mediating the upregulation of COL1A1 and COL1A2 and excessive fibrosis in the lung tissues. Together, this study provides a spatial single‐cell atlas of cellular and molecular signatures of fatal COVID‐19 lungs, which reveals the complex spatial cellular heterogeneity, organization, and interactions that characterized the COVID‐19 lung pathology.
Drought metrics and temperature extremes over the Okavango River basin, southern Africa, and links with the Botswana high
Authors: Moses Oliver , Blamey Ross C. , Reason Chris J. C.
Published: August 2023

The Okavango River Basin (ORB), including the World Heritage site Okavango Delta, is a region of high biodiversity projected to suffer increased early summer drying under climate change. Little work has been done on drought over this sensitive region. Here, various drought metrics are analysed over the ORB. These include a cumulative drought intensity index, based on the product of maximum temperature anomaly and maximum duration of a dry spell, and the Standardized Precipitation‐Evapotranspiration Index. Strong gradients in dry spell and hot day frequencies shift south over the ORB from August to November as the tropical rain‐belt moves increasingly south of the equator, the Congo Air Boundary declines and the Botswana High strengthens and moves southwestwards. By December, the tropical gradient in dry spell frequencies has vanished while that across the Limpopo River and southern ORB region, where the Botswana High is centred, is prominent. sub‐seasonal analyses highlight October–November 2013–2021 as particularly dry and hot over the Okavango Delta region. This dry and hot epoch appears related to a stronger and southward shifted Botswana High and reduced low‐level moisture convergence. On interannual scales, strong relationships were found with the Botswana High and El Niño‐Southern Oscillation (ENSO). The early summer shows a strong drying‐warming trend, related to a significant strengthening of the Botswana High. These trends, together with the Coupled Model Intercomparison Project Phase 6 projected early summer drying over southern Africa, may impact severely on the sensitive ecosystems of the ORB and on agriculture, with important implications for the management of agricultural activities, water resources and biodiversity.
Gender and Artistic Creativity: The Perspectives and Experiences of Eminent Female Visual Artists
Authors: Ginis Katrina , Stewart Sandra Elizabeth , Kronborg Leonie
Published: August 2023

The historically male‐dominated discourse encompassing artistic creativity has often failed to acknowledge the voices and contributions of women. Female artists continue to face barriers in terms of accessing opportunities, attaining positions of prominence, and earning potential, in comparison with their male counterparts. This inequality is deleterious to female artists and society. Therefore, it is important to understand the relationship between artistic creativity and gender, with a particular emphasis on elite female artistic exemplars. The present qualitative study utilized in‐depth semi‐structured interviews, in accordance with the methodology of Interpretive Phenomenological Analysis, to explore the role of gender in relation to artistic creativity among 10 eminent Australian female visual artists. Findings indicated that participants were affected detrimentally by gender‐based inequality on personal, professional, and sociocultural levels. Their experiences as women, however, also inspired and informed their artistic creativity aesthetically and conceptually. The findings challenge patriarchal conceptualizations of the “male artistic genius” by presenting a female‐focused counternarrative. Implications for educating, supporting, and empowering current and emerging female artists to excel are discussed.
Effect of microwave‐vacuum drying on the physicochemical properties of a functional tomato snack bar
Authors: Gul Muhammed Rasim , Ince Alev Emine , Ozel Baris , Uslu Aymelek Kubra , Çetin Melis , Mentes Duygu , Sumnu Servet Gulum , Oztop Mecit Halil
Published: August 2023

BACKGROUND

Tomato is an indispensable ingredient of the Mediterranean diet. Reformulation of traditional Mediterranean products to increase the adherence of consumers is becoming popular. In this study, a tomato snack bar enriched with olive powder and pea protein was developed by using microwave‐vacuum drying. Formulations also included tomato powder (TP) and low‐methoxylated pectin (LMP) as a structuring agent.

RESULTS

The moisture content of microwave‐vacuum‐dried samples varied in the range 13.6–19.8% and water activity (aw) values were ~0.6. LMP and TP concentrations affected the color of microwave‐vacuum‐dried samples. However, the color mainly changed in conventionally dried samples due to browning. In microwave‐vacuum‐dried samples, lycopene content decreased with increasing LMP, but increased with increasing TP. Textural properties of microwave‐vacuum‐dried snack bars increased with increasing LMP and TP.

CONCLUSION

Both texture and Fourier transform infrared spectroscopy results indicated that there was a network formation due to the contribution of protein and pectin; however, the type of interaction was highly dependent on the drying mechanism. Nuclear magnetic resonance relaxometry data showed that microwave‐vacuum‐dried samples had a more uniform water distribution. Besides its time and energy efficiency, microwave‐vacuum drying improved the color and textural properties of tomato snack bars compared to conventionally dried ones. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.