bluuebunny/crossref_metadata_2025 huggingface dataset:
The anti‐obesity and anti‐diabetic effects of the edible seaweed Gloiopeltis furcata (Postels et Ruprecht) J. Agardh in mice fed a high‐fat diet
Authors: Murakami Shigeru , Hirazawa Chihiro , Mizutani Toshiki , Yoshikawa Rina , Ohya Takuma , Ma Ning , Owaki Yutaka , Owaki Toyohiro , Ito Takashi , Matsuzaki Chiaki
Published: October 2022

Obesity and diabetes are serious, chronic medical conditions associated with a wide range of life‐threatening conditions. The aim of this study was to investigate the effects of the edible red seaweed Gloiopeltis furcata (Postels et Ruprecht) J. Agardh (G. furcata) on the development of obesity, diabetes and related metabolic diseases in mice. Male C57BL/6J mice were fed a high‐fat (HF) diet (60% energy as fat), or an HF diet containing 2% (w/w) or 6% powdered G. furcata for 13 weeks. Polysaccharides of G. furcata were isolated and their anti‐inflammatory effects were evaluated in lipopolysaccharide‐stimulated RAW264.7 cells. The HF diet group showed greater weight gain, lipid accumulation in the body and liver, and increased serum levels of glucose and cholesterol in comparison to the normal group fed a normal diet (10% energy as fat). The treatment of HF diet mice with G. furcata reduced these changes and stimulated the fecal excretion of fat. In addition, G. furcata suppressed the HF diet‐induced elevation of inflammation and oxidative stress markers in the serum and liver. The isolated sulfated polysaccharide from G. furcata inhibited pancreatic lipase activity and decreased the production of nitric oxide and TNF‐α in the murine macrophage cell line RAW264.7. These results show that G. furcata treatment can attenuate obesity, diabetes, hepatic steatosis, and dyslipidemia in mice fed an HF diet, which is associated with inhibited intestinal fat absorption and reduced inflammation and oxidative stress by a sulfated polysaccharide.
Information‐based multivariate decoding reveals imprecise neural encoding in children with attention deficit hyperactivity disorder during visual selective attention
Authors: Li Dongwei , Luo Xiangsheng , Guo Jialiang , Kong Yuanjun , Hu Yiqing , Chen Yanbo , Zhu Yu , Wang Yufeng , Sun Li , Song Yan
Published: October 2022

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in school‐age children. Attentional orientation is a potential clinical diagnostic marker to aid in the early diagnosis of ADHD. However, the underlying pathophysiological substrates of impaired attentional orienting in childhood ADHD remain unclear. Electroencephalography (EEG) was measured in 135 school‐age children (70 with childhood ADHD and 65 matched typically developing children) to directly investigate target localization during spatial selective attention through univariate ERP analysis and information‐based multivariate pattern machine learning analysis. Compared with children with typical development, a smaller N2pc was found in the ADHD group through univariate ERP analysis. Children with ADHD showed a lower parieto‐occipital multivariate decoding accuracy approximately 240–340 ms after visual search onset, which predicts a slower reaction time and larger standard deviation of reaction time. Furthermore, a significant correlation was found between N2pc and decoding accuracy in typically developing children but not in children with ADHD. These observations reveal that impaired attentional orienting in ADHD may be due to inefficient neural encoding responses. By using a personalized information‐based multivariate machine learning approach, we have advanced the understanding of cognitive deficits in neurodevelopmental disorders. Our study provides potential research directions for the early diagnosis and optimization of personalized intervention in children with ADHD.
“It Was Rough”: The experiences of first‐generation collegians transitioning into higher education amid COVID‐19
Authors: Santa‐Ramirez Stephen , Block Sarah , Vargas Anthony , Muralidhar Kavitha , Ikegwuonu Chukwu(emeka)
Published: October 2022

During the global health pandemic caused by COVID‐19, most collegians and higher education agents abruptly transitioned to online learning and virtual interactions. Although online education is not a new phenomenon, this was an unforeseen transition for most students in higher education. This study investigated what first‐generation collegians in their 1st year and 1st‐year transfers experienced at a public university in the northeast United States during the 2020–2021 academic year. Findings include increased isolation and mental health issues, connection‐building, a lack of faculty and peer connections, and belongingness via in‐person and virtual community spaces. Recommendations are provided for how higher education agents can best serve these collegians in virtual courses, programming initiatives, and beyond.
Variation in the infant health effects of the women, infants, and children program by predicted risk using novel machine learning methods
Authors: Peet Evan D. , Schultz Dana , Lovejoy Susan , Tsui Fuchiang (Rich)
Published: October 2022

The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) has an extensive literature documenting positive effects on infant health outcomes, specifically preterm birth, low birthweight, small size for gestational age, and infant mortality. However, existing studies focus on average effects for these relatively infrequent outcomes, thus providing no evidence for how WIC affects those at greatest risk of negative infant health outcomes. Our study focuses on documenting how WIC's infant health effects vary by level of risk. In doing so, we leverage a uniquely rich database describing maternal and infant outcomes and risk factors. Additionally, we use high dimensional data to generate predictions of risk and combine these predictions with the novel double machine learning method to stratify the effects of WIC by predicted risk. Our estimates of WIC's average treatment effects align with those in the existing literature. More importantly, we document significant variation in the effects of WIC on infant health by predicted risk level. Our results show that WIC is most beneficial among those at greatest risk of poor outcomes.
Microelectrodes and radiofrequency for transoral horizontal supraglottic laryngectomy in T3 tumors
Authors: Basterra Jorge , Oishi Natsuki , Alba José Ramón , Zapater Enrique
Published: October 2022

The aim of this manuscript is to show the surgical technique for horizontal supraglottic laryngectomy in T3 carcinomas by a transoral approach using microelectrodes and radiofrequency. From 2009 to 2020, 11 selected cases of T3 laryngeal supraglottic carcinomas invading the pre‐epiglottic space, with preserved vocal cords mobility underwent surgery. The technique is described step by step. Average time duration of the larynx surgery was 95 min. Nine percent of the patients presented a profuse hemorrhage 7 days postoperative; in 73% of patients the nasogastric feeding tube was withdrew 10 days after surgery. We emphasize a remarkable short surgical time and high hemostatic effectiveness. The ME tips allow to perform cuts at angles and contribute with a sense of touch. The low cost of the equipment and its easy handling and maintenance is a remarkable advantage over other technologies for transoral surgery.
Alpha‐2‐Heremans‐Schmid‐glycoprotein (AHSG) a potential biomarker associated with prognosis of chromophobe renal cell carcinoma: The PROPOLIS study
Authors: Li Xin , Ma Cuiyan
Published: October 2022

Background and Aims

Chromophobe renal cell carcinoma (chRCC) is the third common pathological subtype in renal cancers. However, the underlying mechanisms of specific genetic characteristics of chRCC are currently unclear. In this study, protein expression profiles, gene ontology (GO), and survival plots were provided by integrated bioinformatics analysis to investigate key genes associated with the mechanism of tumorigenesis and prognosis of chRCC.

Methods

The chRCC data set of gene expression profiles and clinical data were obtained from the gdc‐client (https://portal.gdc.cancer.gov) deposited on The Cancer Genome Atlas (TCGA) data portal. Differentially expressed genes (DEGs) in chRCC, compared with normal samples, were analyzed by R packages “DESeq2,” “edgeR,” and “limma.” Heat maps, volcano plots, and principal component analysis (PCA) were performed for integrated analyses. GUniGO, mutant analysis, and survival plots were performed by R packages. A protein–protein interaction (PPI) network was generated and analyzed by R packages, online String software, and Cytoscape software. Survival analysis and gene expressing comparison in tumor and normal samples were used to detect the core genes of chRCC. Furthermore, the top interacting proteins were reanalyzed.

Results

A total of 306 upregulated genes and 678 downregulated genes were identified by a Venn diagram. Ten hub genes were extracted from PPI network. Furthermore, Alpha‐2‐Heremans‐Schmid‐glycoprotein (AHSG), one of 10 hub genes, was found to be associated with chRCC, and had a big difference in expression between survival and dead events. AHSG could predict potential prognostic and may be a diagnostic biomarker in chRCC.

Conclusion

This study illustrated that AHSG may be a potential therapeutic target and prognostic genetic marker for chRCC.
Assessment of mental health problems among adolescents in Sri Lanka: Findings from the cross‐sectional Global School‐based Health Survey
Authors: Rasalingam Gajarishiyan , Rajalingam Arrosan , Chandradasa Miyuru , Nath Mintu
Published: October 2022

Background and Aims

Mental health condition among adolescents is a leading cause of health‐related disability in Sri Lanka. The study aims to estimate the prevalence and evaluate the associated risk factors in three major mental health domains—loneliness, anxiety and suicidal ideation—among Sri Lankan adolescents.

Methods

We conducted a secondary analysis of cross‐sectional data of 3262 adolescents from the Global School‐based Health Survey (GSHS) conducted by the WHO in 2016. We modeled the binary outcome variables using multivariable logistic regression models with exposures representing demography, food habits, personal hygiene, behavior, substance abuse, parental and social engagement of the respondents.

Results

We estimated the prevalence of loneliness, anxiety and suicidal ideation as 30.8% (95% CI: 29.3, 32.5), 20.2% (95% CI: 18.8, 21.6) and 3.7% (95% CI: 3.1, 4.4), respectively, and the overall prevalence as 40.3% (95% CI: 38.6, 42.0). Mental health problems were more prevalent among females than males. Engagement with parents and close friends, adequate nutritional intake and physically active lifestyles reduced the risk of common mental health problems. Exposure variables like food insecurity, truancy, second‐hand smoking, physical fight, and being bullied increased adolescents’ risk of reported psychological problems.

Conclusions

We conclude that the prevalence of mental health problems in the Sri Lankan adolescent population was higher than the global average. Results suggest that future policy decisions to mitigate mental health problems among Sri Lankan adolescents should incorporate an integrated approach involving the individual, family and community to promote positive home and school environments combined with an active and healthy lifestyle.
Performance analysis of induced draft cooling tower integrated with rotary silica gel mesh
Authors: Sanjay  , Mishra Sanjay , Alam Tabish
Published: October 2022

A humid environment decreases the performance of induced draft counter flow cooling towers (IDCFCT) normally used in power plants and process industries. The primary objective of this study is to experimentally analyze the effect of using rotary silica gel mesh (RSGM) on the performance of IDCFCT. Experimental setups of IDCFCT with and without RSGM have been designed and fabricated to perform the comparative analysis. The performance of both cooling towers (CTs) in terms of output temperature, relative humidity of air, range, approach, and effectiveness at different air velocities has been investigated. The results indicate that the outlet air temperature of IDCFCT integrated with the RSGM wheel is 0.5–1.5°C higher than the IDCFCT without the RSGM wheel. IDCFCT with RSGM wheel shows maximum effectiveness of 0.67 at an air velocity of 1.5 m/s and inlet water temperature of 55°C; whereas, for IDCFCT without RSGM wheel, it is only 0.54. In terms of efficiency, RSGM wheel integrated IDCFCT shows an improvement of 24% compared to IDCFCT without RSGM wheel. It has been observed that RSGM‐integrated IDCFCT also helps to save water up to 431.7 kg/h at an air velocity of 1 m/s with a water inlet temperature of 35°C. Moreover, the advantage of integrating the RSGM wheel with IDCFCT has been further corroborated in terms of the reduction in the height of the CT obtained with the help of a thermodynamic model.
Effect of CuO‐, SiO2‐, and Al2O3‐based nanofluids on automotive cooling systems from laminar to turbulent flow regime—A CFD study
Authors: Ijaz Hamdoon , Raza Hassan , Gohar Ghulam Abbas , Ullah Sana
Published: October 2022

In recent studies, much attention has been given to nanofluids suggesting that adding nanoparticles in base fluids offers a higher heat transfer rate compared with conventional fluids. This study is based on the numerical investigation of different types of nanofluids, consisting of CuO (50 nm), SiO2 (40 nm), and Al2O3 (15 nm) nanoparticles at different volume concentrations. Several simulations were performed from low to high Reynolds numbers, corresponding to laminar and turbulent flow regimes using ANSYS‐Fluent CFD solver. Results suggest that under a laminar flow regime with the same Reynolds number of 2000, CuO‐based nanofluids perform better as compared with SiO2 and Al2O3‐based nanofluids with Nusselt number (Nu) having percentage increase of 90% and 60% comparing with SiO2‐ and Al2O3‐based nanofluids, respectively. However, at higher Reynolds numbers when the flow is turbulent, Al2O3‐based nanofluids demonstrate better performance having a percentage increase in Nusselt numbers equal to 40% and 23% as compared with CuO and SiO2‐based nanofluids respectively under the same Reynolds number of 15,000. This implies that turbulence has a significant effect on heat transfer rate, and is not only related to thermal conductivity. This study will help in designing more compact cooling systems for engines and the internal environment of motor vehicles.
Systematic reviews of the acute effects of amphetamine on working memory and other cognitive performances in healthy individuals, with a focus on the potential influence of personality traits
Authors: Kassim Faiz M.
Published: October 2022

Objectives

This research aimed to systematically review the acute effects of amphetamine (AMP), a dopamine‐releasing agent, on working memory (WM) and other cognitive performances. The investigation also aimed to review the impact of personality traits on the subjective and objective effects of AMP and possible links between personality traits and effects of AMP.

Methods

Previous double‐blind controlled studies assessing the main effects of AMP on WM and other cognitive performances in healthy volunteers were systematically reviewed. An electronic search was performed in the PUBMED and SCOPUS databases. Narrative reviews of the influence of personality traits on the subjective and objective effects of AMP were included.

Results

Nineteen WM studies were included in the current review. Seven studies found effects of AMP on spatial WM, but only one study found the effect of AMP on verbal WM. Thirty‐seven independent studies on other aspects of cognitive performance were identified. Twenty‐two reported effects of AMP on cognitive functions. Studies also showed that personality traits are associated with the subjective effects of AMP. However, few studies reported the impacts of personality traits on the objective (such as WM) effects of AMP.

Conclusion

Overall, findings indicate that AMP has mixed‐effects on spatial WM and other cognitive functions, but it lacks effects on verbal WM. Although there are insufficient studies on objective measures, studies also indicated that the subjective effects of AMP administration are linked to between‐person variations in personality traits.
Can we predict non‐response in developmental tasks? Assessing the longitudinal relation between toddlers' non‐response and early academic skills
Authors: Spit Sybren , Mulder Hanna , van Houdt Carolien , Verhagen Josje
Published: October 2022

To date, virtually no studies have examined toddlers' non‐response in developmental tasks. This study investigates data from 3667 toddlers to address (1) whether two aspects of non‐response (completion and engagement) are separable, (2) how stable these aspects are from ages two to three, (3) how non‐response relates to background characteristics, and (4) whether non‐response at ages two and three predicts early academic skills at age six. Structural equation modelling shows that completion and engagement are separable constructs, relatively stable across age, and related to several background characteristics. Especially engagement predicts later academic performance. Results show that non‐response in behavioural tasks in toddlers is not random, increasing the likelihood of sampling bias and lack of generalizability in developmental studies.
CXCR4 expression is associated with proneural‐to‐mesenchymal transition in glioblastoma
Authors: Khan A. Basit , Lee Sungho , Harmanci Akdes Serin , Patel Rajan , Latha Khatri , Yang Yuhui , Marisetty Anantha , Lee Hyun‐Kyoung , Heimberger Amy B. , Fuller Gregory N. , Deneen Benjamin , Rao Ganesh
Published: October 2022

Glioblastoma (GBM) is the most common primary intracranial malignant tumor and consists of three molecular subtypes: proneural (PN), mesenchymal (MES) and classical (CL). Transition between PN to MES subtypes (PMT) is the glioma analog of the epithelial‐mesenchymal transition (EMT) in carcinomas and is associated with resistance to therapy. CXCR4 signaling increases the expression of MES genes in glioma cell lines and promotes EMT in other cancers. RNA sequencing (RNAseq) data of PN GBMs in The Cancer Genome Atlas (TCGA) and secondary high‐grade gliomas (HGGs) from an internal cohort were examined for correlation between CXCR4 expression and survival as well as expression of MES markers. Publicly available single‐cell RNA sequencing (scRNAseq) data was analyzed for cell type specific CXCR4 expression. These results were validated in a genetic mouse model of PN GBM. Higher CXCR4 expression was associated with significantly reduced survival and increased expression of MES markers in TCGA and internal cohorts. CXCR4 was expressed in immune and tumor cells based on scRNAseq analysis. Higher CXCR4 expression within tumor cells on scRNAseq was associated with increased MES phenotype, suggesting a cell‐autonomous effect. In a genetically engineered mouse model, tumors induced with CXCR4 exhibited a mesenchymal phenotype and shortened survival. These results suggest that CXCR4 signaling promotes PMT and shortens survival in GBM and highlights its inhibition as a potential therapeutic strategy.
Revisiting positionality through intersectional identities: A retrospective of parent and child research
Authors: Kabuto Bobbie
Published: October 2022

Parent and child research has made important contributions to literacy research and advanced research methodologies in studying linguistically diverse families. Positionality has been a cornerstone concept in ethnographic research and often referenced in parent and child studies. In this article, I present a review of the literature on parent and child research published between 2010 and 2021 to explore matters of positionality. The data consist of 24 articles in peer‐reviewed journals, which were analyzed through a content analysis to investigate the diverse ways that parents and children were co‐positioned within a research context through the lens of intersectional identities. Findings specifically focus on nine of the 24 studies that address linguistic diversity in language and literacy learning. This article will conclude with recommendations for addressing positionality within parent and child research processes.
Development of workplace‐based assessment tools to support postgraduate training of provisionally registered pharmacists in Australia
Authors: Maundu Josephine , Galbraith Kirsten , Croft Hayley , Clark Bronwyn , Kirsa Sue , Wilkinson Glenys , Abeyaratne Carmen
Published: October 2022

The Australian Pharmacy Council (APC) is the national accreditation authority for pharmacy education and training in Australia. In 2020, APC published revised Accreditation Standards and a new Performance Outcomes Framework (POF). The POF details expected performance for pharmacy students at the point of graduation and for pharmacy graduates on completion of postgraduate training. The APC and the pharmacist regulator, the Pharmacy Board of Australia collaborated on a project to develop workplace‐based assessment (WBA) tools for use in assessing performance of pharmacy graduates in the postgraduate training period. The objectives of the project were to; identify and develop an initial suite of WBA tools; develop accompanying guidance and supporting documentation; seek feedback from stakeholders; and pilot the WBA tools in community and hospital settings. The WBA tools were developed through consultative process overseen by a group of education experts (a Technical Working Group) and a governance group. The latter comprising members from the Pharmacy Board and APC. The Technical Working Group agreed on the tools to develop based on an available Intern Year Assessment Blueprint and the tools were then drafted by a consultant. APC held consultative forums and a pilot study to gather feedback from intern pharmacists and preceptors. The project resulted in development of a suite of three types of WBA tools; Entrustable Professional Activities (EPAs), Case Based Discussions (CbD), and In Training Assessment (ITA) activities covering six areas of focus. All types of tools that were initially agreed upon were made available for use. The WBA tools address 15 performance outcomes in the POF. Future direction will involve further evaluation of the tools in diverse practice settings and expansion of the current suite of tools to cover additional performance outcomes.
Longitudinal associations between adolescent out‐of‐school time and adult substance use
Authors: Hsieh Ta‐yang , Simpkins Sandra D. , Vandell Deborah Lowe
Published: October 2022

Introduction

Based on Bronfenbrenner's bioecological theory and Bornstein's specificity principle, the purpose of this study was to examine adolescents' time in out‐of‐school settings as a precursor of three types of problematic substance use in adulthood (i.e., binge drinking, regular marijuana use, and use of illicit drugs).

Method

Adolescents (N = 978) reported the time they spent in four common out‐of‐school settings at ages 15 and 18: unsupervised time with peers, organized sports, other organized activities, and paid employment. At age 26, participants reported binge drinking, marijuana use, and illicit drug use.

Results and Conclusions

Adolescents' time in out‐of‐school settings during high school predicted age 26 substance use over and above family and adolescent factors, including adolescents' substance use during high school. Adolescents' unsupervised time with peers increased the odds and frequency of binge drinking and regular marijuana use at age 26. Time in high school organized sports increased the odds of binge drinking at age 26, but not marijuana or illicit drug use. Time spent in other organized activities, such as community service and the arts, lowered the odds of illicit drug use whereas paid employment in high school was not related to age 26 substance use. Aligned with Bornstein's specificity principle, time spent in specific out‐of‐school settings during adolescence were differentially related to substance use problems in early adulthood, with some activities serving as a risk factor and other activities serving as a protective factor for young adults.
Development of chitosan‐polygalacturonic acid polyelectrolyte complex fibrous scaffolds using the hydrothermal treatment for bone tissue engineering
Authors: Wasupalli Geeta Kumari , Verma Devendra
Published: October 2022

An ideal bone regeneration scaffold system needs to meet the high compressive properties of the bone. The stiffness of the scaffold extracellular matrix determines the cell's fate via cell adhesion migration and differentiation in‐vitro and in‐vivo. This study aims to investigate the effect of hydrothermal treatment on polyelectrolyte complex (PEC) fibrous biomaterials and its effect on scaffold morphology, cell viability, and function in‐vitro. FTIR analysis revealed the ability of the thermal treatment to set the interaction of HAp with polymeric PEC fibers. FESEM analysis showed that with an increase in temperature, the interconnectivity and pore size increased (control—82.38 ± 12.92 μm; at 120°C—335.48 ± 85.10 μm). Mechanical tests showed that the scaffolds heated at 90°C showed the highest stiffness in both dry and wet states (dry state: 1.82 ± 0.07 MPa, wet state: 122 ± 1.78 kPa). Additionally, the hydrothermal treatment also improved the aqueous stability as well as swelling capacity. According to the experimental findings, hydrothermal treatment is a useful technique for crosslinker‐free gelation with improved mechanical strength and nanofibrous structure. Furthermore, the cell adhesion, proliferation, and osteogenic differentiation of the MG63 cells on the hydrogel scaffolds in‐vitro were evaluated by MTT assay, confocal imaging, alkaline phosphatase assay, and collagen estimation. The in‐vitro study showed that scaffolds fabricated at 90°C promoted better MG63 cell attachment, proliferation, and differentiation. These results suggest the potential use of hydrothermal treated chitosan‐polygalacturonic acid (PgA) fibrous scaffolds in bone tissue engineering.
Effect of Osteoblast‐Specific Deletion of the Proton Receptor OGR1
Authors: Krieger Nancy S , Chen Luojing , Becker Jennifer , Chan Michaela , Bushinsky David A
Published: October 2022

Metabolic acidosis (MET) stimulates bone resorption through inhibition of osteoblast (OB) bone formation and stimulation of osteoclast (OC) bone resorption. We found that OGR1, a G protein‐coupled proton (H+)‐sensing receptor, was critical for initial H+ signaling in the OB. In mice with a global deletion of OGR1, we demonstrated that loss of OGR1 impairs H+‐induced bone resorption, leading to increased bone density through effects on both the OB and OC. Using an OC‐specific deletion of OGR1, we found that MET directly activates OGR1 in the OC. To determine if the response of OGR1 to MET in the OB is independent of a response in OCs and to characterize direct activation of OGR1 in the OB, we studied female mice with an OB‐specific deletion of OGR1 (OB‐cKO) and differentiated osteoblasts derived from marrow of OB‐cKO and wild‐type (WT) mice. In OB‐cKO mice, we found increased bone area in both tibial and femoral cortical bone. Specific loss of OB OGR1 increased in vitro mineralization, alkaline phosphatase activity, and expression of osteoblast‐specific genes compared with WT with no alteration in OC activity. MET stimulation of OB cox2 and fgf23 gene expression was inhibited in OB‐cKO OB. These results indicate that MET activation of OGR1 in the OB is independent of the response in the OC and that OGR1 in both cell types is required for a complete response to MET. Characterization of the role of OGR1 in MET‐induced bone resorption will improve our understanding of bone loss associated with metabolic acidosis in patients with chronic kidney disease. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
The abnormal level and prognostic potency of multiple inflammatory cytokines in PCI‐treated STEMI patients
Authors: Zhang Jing , Xu Huichuan , Yao Mingyan , Jia Hongdan , Cong Hongliang
Published: October 2022

Objective

Inflammatory cytokines modulate atherogenesis and plaque rupture to involve in ST‐segment elevation myocardial infarction (STEMI) progression. The present study determined eight inflammatory cytokine levels in 212 percutaneous coronary intervention (PCI)‐treated STEMI patients, aiming to comprehensively investigate their potency in estimating major adverse cardiac event (MACE) risk.

Methods

Serum tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, IL‐6, IL‐8, IL‐10, IL‐17A, vascular cell adhesion molecule‐1 (VCAM‐1), and intercellular adhesion molecule‐1 (ICAM‐1) of 212 PCI‐treated STEMI patients and 30 angina pectoris patients were determined using enzyme‐linked immunosorbent assay.

Results

TNF‐α (52.5 (43.9–62.6) pg/ml versus 46.4 (39.0–59.1) pg/ml, p = 0.031), IL‐8 (61.6 (49.6–81.7) pg/ml versus 46.7 (32.5–63.1) pg/ml, p = 0.001), IL‐17A (57.4 (45.7–77.3) pg/ml versus 43.2 (34.2–64.6) pg/ml, p = 0.001), and VCAM‐1 (593.6 (503.4–811.4) ng/ml versus 493.8 (390.3–653.7) ng/ml, p = 0.004) levels were elevated in STEMI patients compared to angina pectoris patients, while IL‐1β (p = 0.069), IL‐6 (p = 0.110), IL‐10 (p = 0.052), and ICAM‐1 (p = 0.069) were of no difference. Moreover, both IL‐17A high (vs. low) (p = 0.026) and VCAM‐1 high (vs. low) (p = 0.012) were linked with increased cumulative MACE rate. The multivariable Cox's analysis exhibited that IL‐17A high (vs. low) (p = 0.034) and VCAM‐1 high (vs. low) (p = 0.014) were independently associated with increased cumulative MACE risk. Additionally, age, diabetes mellitus, C‐reactive protein, multivessel disease, stent length, and stent type were also independent factors for cumulative MACE risk.

Conclusion

IL‐17A and VCAM‐1 high level independently correlate with elevated MACE risk in STEMI patients, implying its potency in identifying patients with poor prognoses.
ATM‐ and ATR‐induced primary ciliogenesis promotes cisplatin resistance in pancreatic ductal adenocarcinoma
Authors: Chao Yu‐Ying , Huang Bu‐Miin , Peng I‐Chen , Lee Pei‐Rong , Lai Yi‐Shyun , Chiu Wen‐Tai , Lin Yi‐Syuan , Lin Shih‐Chieh , Chang Jung‐Hsuan , Chen Pai‐Sheng , Tsai Shaw‐Jenq , Wang Chia‐Yih
Published: October 2022

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers because of its late diagnosis and chemoresistance. Primary cilia, the cellular antennae, are observed in most human cells to maintain development and differentiation. Primary cilia are gradually lost during the progression of pancreatic cancer and are eventually absent in PDAC. Here, we showed that cisplatin‐resistant PDAC regrew primary cilia. Additionally, genetic or pharmacological disruption of primary cilia sensitized PDAC to cisplatin treatment. Mechanistically, ataxia telangiectasia mutated (ATM) and ATM and RAD3‐related (ATR), tumor suppressors that initiate DNA damage responses, promoted the excessive formation of centriolar satellites (EFoCS) and autophagy activation. Disruption of EFoCS and autophagy inhibited primary ciliogenesis, sensitizing PDAC cells to cisplatin treatment. Collectively, our findings revealed an unexpected interplay among the DNA damage response, primary cilia, and chemoresistance in PDAC and deciphered the molecular mechanism by which ATM/ATR‐mediated EFoCS and autophagy cooperatively regulate primary ciliogenesis.
CD133‐Src‐TAZ signaling stimulates ductal fibrosis following DDC diet‐induced liver injury
Authors: Oh Ho Taek , Heo Woong , Yoo Gi Don , Kim Kyung Min , Hwang Jun‐Ha , Hwang Eun Sook , Ko Jesang , Ko Young‐Gyu , Hong Jeong‐Ho
Published: October 2022

Chronic liver injury follows inflammation and liver fibrosis; however, the molecular mechanism underlying fibrosis has not been fully elucidated. In this study, the role of ductal WW domain‐containing transcription regulator 1 (WWTR1)/transcriptional coactivator with PDZ‐binding motif (TAZ) was investigated after liver injury. Ductal TAZ‐knockout (DKO) mice showed decreased liver fibrosis following a Diethyl 1,4‐dihydro‐2,4,6‐trimethyl‐3,5‐pyridinedicarboxylate (DDC) diet compared to wild‐type (WT) mice, as evidenced by decreased expression levels of fibrosis inducers, including connective tissue growth factor (Ctgf)/cellular communication network factor 2 (CCN2), cysteine‐rich angiogenic inducer 61 (Cyr61/CCN1), and transforming growth factor beta 1 (Tgfb1), in DKO mice. Similarly, TAZ‐knockout (KO) cholangiocyte organoids showed decreased expression of fibrosis inducers. Additionally, the culture supernatant of TAZ‐KO cholangiocyte organoids decreased the fibrogenic gene expression in liver stellate cells. Further studies revealed that prominin 1 (PROM1/CD133) stimulated TAZ for fibrosis. After the administration of DDC diet, fibrosis was decreased in CD133‐KO (CD133‐KO) mice compared to that in WT mice. Similarly, CD133‐KO cholangiocyte organoids showed decreased Ctgf, Cyr61, and Tgfb1 expression levels compared to WT cholangiocyte organoids. Mechanistically, CD133 stabilized TAZ via Src activation. Inhibition of Src decreased TAZ levels. Similarly, CD133‐knockdown HCT116 cells showed decreased TAZ levels, but reintroduction of active Src recovered the TAZ levels. Taken together, our results suggest that TAZ facilitates liver fibrosis after a DDC diet via the CD133‐Src‐TAZ axis.
Circadian clock‐mediated nuclear receptors in cancer
Authors: Niu Ya , Tang Shuang
Published: October 2022

Circadian system coordinates the daily periodicity of physiological and biochemical functions to adapt to environmental changes. Circadian disruption has been identified to increase the risk of cancer and promote cancer progression, but the underlying mechanism remains unclear. And further mechanistic understanding of the crosstalk between clock components and cancer is urgent to achieve clinical anticancer benefits from chronochemotherapy. Recent studies discover that several nuclear receptors regulating circadian clock, also play crucial roles in mediating multiple cancer processes. In this review, we aim to summarize the latest developments of clock‐related nuclear receptors in cancer biology and dissect mechanistic insights into how nuclear receptors coordinate with circadian clock to regulate tumorigenesis and cancer treatment. A better understanding of circadian clock‐related nuclear receptors in cancer could help prevent tumorigenesis and improve anticancer efficacy.
Metabolic labeling of cardiomyocyte‐derived small extracellular‐vesicle (sEV) miRNAs identifies miR‐208a in cardiac regulation of lung gene expression
Authors: Han Chaoshan , Yang Junjie , Zhang Eric , Jiang Ying , Qiao Aijun , Du Yipeng , Zhang Qinkun , An Junqing , Sun Jiacheng , Wang Meimei , Nguyen Thanh , Lal Hind , Krishnamurthy Prasanna , Zhang Jianyi , Qin Gangjian
Published: October 2022

Toxoplasma gondii uracil phosphoribosyltransferase (UPRT) converts 4‐thiouracil (4TUc) into 4‐thiouridine (4TUd), which is incorporated into nascent RNAs and can be biotinylated, then labelled with streptavidin conjugates or isolated via streptavidin‐affinity methods. Here, we generated mice that expressed T. gondii UPRT only in cardiomyocytes (CMUPRT mice) and tested our hypothesis that CM‐derived miRNAs (CMmiRs) are transferred into remote organs after myocardial infarction (MI) by small extracellular vesicles (sEV) that are released from the heart into the peripheral blood (PBsEV). We found that 4TUd was incorporated with high specificity and sensitivity into RNAs isolated from the hearts and PBsEV of CMUPRT mice 6 h after 4TUc injection. In PBsEV, 4TUd was incorporated into CM‐specific/enriched miRs including miR‐208a, but not into miRs with other organ or tissue‐type specificities. 4TUd‐labelled miR208a was also present in lung tissues, especially lung endothelial cells (ECs), and CM‐derived miR‐208a (CMmiR‐208a) levels peaked 12 h after experimentally induced MI in PBsEV and 24 h after MI in the lung. Notably, miR‐208a is expressed from intron 29 of α myosin heavy chain (αMHC), but αMHC transcripts were nearly undetectable in the lung. When PBsEV from mice that underwent MI (MI‐PBsEV) or sham surgery (Sham‐PBsEV) were injected into intact mice, the expression of Tmbim6 and NLK, which are suppressed by miR‐208a and cooperatively regulate inflammation via the NF‐κB pathway, was lower in the lungs of MI‐PBsEV–treated animals than the lungs of animals treated with Sham‐PBsEV or saline. In MI mice, Tmbim6 and NLK were downregulated, whereas endothelial adhesion molecules and pro‐inflammatory cells were upregulated in the lung; these changes were significantly attenuated when the mice were treated with miR‐208a antagomirs prior to MI surgery. Thus, CMUPRT mice enables us to track PBsEV‐mediated transport of CMmiRs and identify an miR‐208a‐mediated mechanism by which myocardial injury alters the expression of genes and inflammatory response in the lung.
Summary of the experiences, knowledge, medical management, and family communication of monoallelic MUTYH carriers
Authors: McKenna Danielle B. , Sanchez Pauleen , Powers Jacquelyn , Brower Jamie , Wang Louise , Mueller Rebecca , Symecko Heather , Hamilton Jada G. , Wildman Temima , Domchek Susan M. , Couch Fergus J. , Garber Judy E. , Offit Kenneth , Robson Mark E. , Katona Bryson W.
Published: October 2022

Germline genetic testing for inherited cancer risk is increasingly being performed with multigene panel testing with MUTYH often included on colorectal cancer‐ and polyposis‐focused panels, as well as on broader pan‐cancer panels. With up to 1%–2% of the general population being monoallelic MUTYH carriers, pathogenic/likely pathogenic (P/LP) variants in MUTYH are one of the most common findings on multigene cancer panels. However, little is known about patient experience and understanding of monoallelic MUTYH P/LP variants, nor whether such findings influence medical management recommendations and familial communication, which this study aims to better understand. Monoallelic P/LP MUTYH carriers were recruited from the Prospective Registry of Multiplex Testing (PROMPT) and completed a cross‐sectional self‐report survey on sociodemographic characteristics, medical and family history, experiences with MUTYH genetic testing, genetics and MUTYH knowledge, perceived cancer risk, and familial communication. Of 115 eligible PROMPT participants, 49 (43%) completed the survey who were primarily female (94%), white (96%), had a history of cancer (61%), and a median age of 51.4 years. Most participants (61%) reported satisfaction with how their healthcare provider managed their genetic test result and care, and 65% of survey participants reported their provider recommended colonoscopy based on their genetic test results. Participants' responses also reflected variable levels of knowledge regarding cancer risks and screening recommendations for MUTYH carriers. The majority (98%) of participants shared their genetic test results with at least some of their relatives; however, only 13% of eligible relatives reportedly underwent cascade testing. Taken together, this study provides needed insight into the overall experiences of monoallelic MUTYH carriers and highlights numerous areas for improvement in clinician education, communication, and management of these individuals.
Patient and provider perceptions of a community‐based accompaniment intervention for adolescents transitioning to adult HIV care in urban Peru: a qualitative analysis
Authors: Galea Jerome T. , Wong Milagros , Ninesling Brennan , Ramos Alicia , Senador Liz , Sanchez Hugo , Kolevic Lenka , Matos Eduardo , Sanchez Eduardo , Errea Renato A. , Lindeborg Andrew , Benites Carlos , Lecca Leonid , Shin Sonya , Franke Molly F.
Published: October 2022

Introduction

Adolescents living with HIV (ALWH) experience higher mortality rates compared to other age groups, exacerbated by the suboptimal transition from paediatric to adult HIV care, during which decreased adherence to antiretroviral therapy (ART) and unsuppressed viremia are frequent. Care transition—a process lasting months or years—ideally prepares ALWH for adult care and can be improved by interventions that are youth‐friendly and address psychosocial issues affecting ART adherence; however, such interventions are infrequently operationalized. Community‐based accompaniment (CBA), in which laypeople provide individualized support and health system navigation, can improve health outcomes among adults with HIV. Here, we describe patient and provider perceptions of a novel HIV CBA intervention called “PASEO” for ALWH in Lima, Peru.

Methods

PASEO consisted of six core elements designed to support ALWH during and after the transition to adult HIV care. During 2019–2021, community‐based health workers provided tailored accompaniment for ALWH aged 15–21 years over 9 months, after which adolescent participants were invited to provide feedback in a focus group or in‐depth interview. HIV care personnel were also interviewed to understand their perspectives on PASEO. A semi‐structured interview guide probing known acceptability constructs was used. Qualitative data were analysed using a framework analysis approach and emergent themes were summarized with illustrative quotes.

Results

We conducted five focus groups and 11 in‐depth interviews amongN= 26 ALWH and nine key‐informant interviews with HIV care personnel. ALWH participants included males, females and one transgender female, and those with both early childhood and recent HIV infection. ALWH praised PASEO, attributing increased ART adherence to the project. Improved mental health, independence, self‐acceptance and knowledge on how to manage their HIV were frequently cited. HIV professionals similarly voiced strong support for PASEO. Both ALWH and HIV professionals expressed hope that PASEO would be scaled. HIV professionals voiced concerns regarding financing PASEO in the future.

Conclusions

A multicomponent CBA intervention to increase ART adherence among ALWH in Peru was highly acceptable by ALWH and HIV programme personnel. Future research should determine the efficacy and economic impact of the intervention.
Assessment of Prognostic Factors and Molecular Subtypes of Breast Cancer With a Continuous‐Time Random‐Walk MR Diffusion Model: Using Whole Tumor Histogram Analysis
Authors: Qin Yanjin , Tang Caili , Hu Qilan , Yi Jingru , Yin Ting , Ai Tao
Published: October 2022

Background

The continuous‐time random‐walk (CTRW) diffusion model to evaluate breast cancer prognosis is rarely reported.

Purpose

To investigate the correlations between apparent diffusion coefficient (ADC) and CTRW‐specific parameters with prognostic factors and molecular subtypes of breast cancer.

Study Type

Retrospective.

Population

One hundred fifty‐seven women (median age, 50 years; range, 26–81 years) with histopathology‐confirmed breast cancer.

Field Strength/Sequence

Simultaneous multi‐slice readout‐segmented echo‐planar imaging at 3.0T.

Assessment

The histogram metrics of ADC, anomalous diffusion coefficient (D), temporal diffusion heterogeneity (α), and spatial diffusion heterogeneity (β) were calculated for whole‐tumor volume. Associations between histogram metrics and prognostic factors (estrogen receptor [ER], progesterone receptor [PR], human epidermal growth factor receptor 2 [HER2], and Ki‐67 proliferation index), axillary lymph node metastasis (ALNM), and tumor grade were assessed. The performance of histogram metrics, both alone and in combination, for differentiating molecular subtypes (HER2‐positive, Luminal or triple negative) was also assessed.

Statistical Tests

Comparisons were made using Mann–Whitney test between different prognostic factor statuses and molecular subtypes. Receiver operating characteristic curve analysis was used to assess the performance of mean and median histogram metrics in differentiating the molecular subtypes. A P value <0.05 was considered statistically significant.

Results

The histogram metrics of ADC, D, and α differed significantly between ER‐positive and ER‐negative status, and between PR‐positive and PR‐negative status. The histogram metrics of ADC, D, α, and β were also significantly different between the HER2‐positive and HER2‐negative subgroups, and between ALNM‐positive and ALNM‐negative subgroups. The histogram metrics of α and β significantly differed between high and low Ki‐67 proliferation subgroups, and between histological grade subgroups. The combination of αmean and βmean achieved the highest performance (AUC = 0.702) to discriminate the Luminal and HER2‐positive subtypes.

Data Conclusion

Whole‐tumor histogram analysis of the CTRW model has potential to provide additional information on the prognosis and intrinsic subtyping classification of breast cancer.

Evidence Level

4

Technical Efficacy

Stage 2
Comparison of nucleocapsid and spike antibody ELISAs for determining SARS‐CoV‐2 seropositivity in Kenyan women and infants
Authors: Fish Carolyn S. , Owiti Prestone , Begnel Emily R. , Itell Hannah L. , Ojee Ednah , Adhiambo Judith , Ogweno Vincent , Holland LaRinda A. , Richardson Barbra A. , Khan Adam K. , Maqsood Rabia , Gantt Soren , Lim Efrem S. , Slyker Jennifer , Kinuthia John , Overbaugh Julie , Wamalwa Dalton , Lehman Dara A. , Chohan Bhavna H.
Published: October 2022

A multitude of enzyme‐linked immunosorbent assays (ELISAs) has been developed to detect severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) antibodies since the coronavirus disease 2019 pandemic started in late 2019. Assessing the reliability of these assays in diverse global populations is critical. This study compares the use of the commercially available Platelia Total Ab Assay (Bio‐Rad) nucleocapsid ELISA to the widely used Mount Sinai spike IgG ELISA in a Kenyan population seroprevalence study. Using longitudinal plasma specimens collected from a mother–infant cohort living in Nairobi, Kenya between May 2019 and December 2020, this study demonstrates that the two assays have a high qualitative agreement (92.7%) and strong correlation of antibody levels (R2 = 0.973) in repeated measures. Within this cohort, seroprevalence detected by either ELISA closely resembled previously published seroprevalence estimates for Kenya during the sampling period and no significant difference in the incidence of SARS‐CoV‐2 antibody detection by either assay was observed. Assay comparability was not affected by HIV exposure status. These data support the use of the Platelia SARS‐CoV‐2 Total Ab ELISA as a suitable high‐throughput method for seroprevalence studies in Kenya.
Small molecule RAF265 as an antiviral therapy acts against HSV‐1 by regulating cytoskeleton rearrangement and cellular translation machinery
Authors: Li Cui‐Cui , Chi Xiao‐Jing , Wang Jing , Potter Alexandra L , Wang Xiao‐Jia , Yang Chi‐Fu Jeffrey
Published: October 2022

Host‐targeting antivirals (HTAs) have received increasing attention for their potential as broad‐spectrum antivirals that pose relatively low risk of developing drug resistance. The repurposing of pharmaceutical drugs for use as antivirals is emerging as a cost‐ and time‐ efficient approach to developing HTAs for the treatment of a variety of viral infections. In this study, we used a virus titer method to screen 30 small molecules for antiviral activity against Herpes simplex virus‐1 (HSV‐1). We found that the small molecule RAF265, an anticancer drug that has been shown to be a potent inhibitor of B‐RAF V600E, reduced viral loads of HSV‐1 by 4 orders of magnitude in Vero cells and reduced virus proliferation in vivo. RAF265 mediated cytoskeleton rearrangement and targeted the host cell's translation machinery, which suggests that the antiviral activity of RAF265 may be attributed to a dual inhibition strategy. This study offers a starting point for further advances toward clinical development of antivirals against HSV‐1.