bluuebunny/crossref_metadata_2025 huggingface dataset:
Salivary Metabolomics of Well and Poorly Controlled Type 1 and Type 2 Diabetes
Authors: Bencharit Sompop , Carlson James , Byrd Warren C. , Howard-Williams Escher L. , Seagroves Jackson T. , McRitchie Susan , Buse John B. , Sumner Susan
Published: August 2022

Objective. The concentrations of endogenous metabolites in saliva can be altered based on the systemic condition of the hosts and may, in theory, serve as a reflection of systemic disease progression. Hemoglobin A1C is used clinically to measure long-term average glycemic control. The aim of the study was to demonstrate if there were differences in the salivary metabolic profiles between well and poorly controlled type 1 and type 2 subjects with diabetes. Subjects and Methods. Subjects with type 1 and type 2 diabetes were enrolled (n = 40). The subjects were assigned to phenotypic groups based on their current level of A1C: <7 = well-controlled and >7 = poorly controlled. Demographic data, age, gender, and ethnicity, were used to match the two phenotypic groups. Whole saliva samples were collected and immediately stored at −80°C. Samples were spiked using an isotopically labeled internal standard and analyzed by UPLC-TOF-MS using a Waters SYNAPT G2-Si mass spectrometer. Results. Unsupervised principal components analysis (PCA) and orthogonal partial least squares regression discrimination analysis (OPLS-DA) were used to define unique metabolomic profiles associated with well and poorly controlled diabetes based on A1C levels. Conclusion. OPLS-DA demonstrates good separation of well and poorly controlled in both type 1 and type 2 diabetes. This provides evidence for developing saliva-based monitoring tools for diabetes.
GPX8 as a Novel Prognostic Factor and Potential Therapeutic Target in Primary Glioma
Authors: Yang Zhao-shou , Yang Qin , Sun Xiao-xiao , Xiong Kui , Zhu Xiao-ting , Wang Yi-chen , Ren Qian-yao , Wu Guo-hui , Wang Shi-min , Cao Xu-qin , Yang Xiao-rong , Jiang Wen-gong
Published: August 2022

One of the most prevalent malignant primary brain tumors is primary glioma. Although glutathione peroxidase 8 (GPX8) is intimately associated with carcinogenesis, its function in primary gliomas has not yet been thoroughly understood. Here, we leveraged Chinese Glioma Genome Atlas (CGGA), The Cancer Genome Atlas (TCGA), and Genotype-Tissue Expression (GTEx) database to investigate the association between GPX8 and overall survival (OS) of patients with primary gliomas, and our results showed that GPX8 expression was negatively correlated with OS. Moreover, the expression of GPX8 is significantly lower in normal tissue when compared to glioma tissue. According to results of univariate and multivariate analysis from CGGA using R studio, GPX8 is a valuable primary glioma prognostic indicator. Interestingly, high GPX8 expression is correlated positively with the hedgehog and kras signaling pathways and negatively with G2 checkpoint, apoptosis, reactive oxygen species (ROS) pathway, and interferon gamma pathway, which could be beneficial for the proliferation of glioma cells. Furthermore, GPX8 knockdown caused G1 cell cycle arrest, increased cell death, and reduced colony formation in U87MG and U118MG cells. In conclusion, GPX8 is a promising therapeutic target and meaningful prognostic biomarker of primary glioma.
Exploring the Relationship between Allergic Rhinitis and Constitution Based on the “Traditional Chinese Medicine Constitution Theory”
Authors: Zhang Yueyu , Fu Jie , Zhou Zhongyu , Zhang Yangpu , Chen Yingying , Song Aiqun
Published: August 2022

Allergic rhinitis (AR) is a prevalent allergic disease affecting individuals of all ages, especially children and adolescents. Patients with AR develop a specific immunoglobulin E antibody response to allergens, including pollen, mold, dust mites, and animal dander. The main symptoms of AR patients include nasal congestion, rhinorrhea, sneezing, and nasal itching. Symptoms such as these can interfere with the patient’s sleep and quality of life when they become severe. Moreover, AR contributes too many complications, can exacerbate asthma, and has a negative impact on productivity and social costs. Therefore, the current review focuses on how to treat AR effectively. This review discusses the correlation between AR and constitution from the perspective of the Traditional Chinese Medicine (TCM) Constitution Theory in light of increasing research on AR in TCM. The constitution is adjustable, and adjusting the patient’s biased constitution can improve the diagnosis, treatment, and prognosis of the disease. TCM constitution is critical in AR pathogenesis, and both are closely linked. TCM constitution theory can be applied to treat AR with positive effects, which merits popularization and application, and provides a new approach to the treatment of AR.
A Blockchain-Based Normalized Searchable Encryption System for Medical Data
Authors: Liu Qin , Liu Yun Lian , Luo Min , Peng Cong , Xiao Xuan
Published: August 2022

As COVID-19 continues to spread around the world, the healthcare industry has accelerated the transformation to digital healthcare services. In the era of big data, many hospitals prefer to use remote cloud servers to store and manage massive electronic medical data. However, cloud-assisted medical data systems cannot guarantee the confidentiality, integrity, and availability of data. Searchable encryption can effectively address the above challenges by enabling data search on the ciphertext, which achieves the availability of medical data while ensuring data security and privacy. However, the search server may return mismatched search results due to economic interests or single points of failure. Blockchain is a decentralized computing paradigm with public verifiability, which provides an efficient solution to this problem. However, the existing blockchain-based searchable encryption solutions do not consider the flexible search function of multiple users and the restriction of encrypted data for medical scenarios. Therefore, we propose a blockchain-based multiuser normalized searchable encryption (BNSE) scheme and design a blockchain-based normalized searchable encryption system for medical data (BNSEM) based on the scheme. To verify the practicality of the system, we evaluate the performance from both theoretical and experimental aspects.
[Retracted] Related Factors and Economic Burden Evaluation of Nosocomial Infection in Patients with Chronic Kidney Disease
Authors: Wang Jinxian , Zhang Ling , Yang Zhaoxia , Liu Ju , Guo Wei
Published: August 2022

Kidney disease in China has the characteristics of “three highs and one low“, namely high incidence, high disability rate, high treatment cost and low awareness. The main outcome is a progressive deterioration of renal function that is not easily corrected, and patients are often hospitalized repeatedly due to factors such as infection, fatigue, lack of medication, water and electrolyte imbalances. It not only accelerates the deterioration of renal function, but also easily causes psychological problems and seriously affects the quality of life of patients. Kidney is an organ with dual functions of endocrine and material metabolism in the human body, and plays an important role in both physiological and pathological processes. Its main functions include urine generation, renal tubular reabsorption, regulation of water and electrolyte metabolism, and endocrine functions. Chronic kidney disease is defined by an unexplained decrease in GFR over three months. At present, clinicians usually take drug corrective measures only when CKD patients have intermediate and advanced PEM with abnormal index examinations (such as decreased plasma albumin, anemia, etc.), and the clinical efficacy is not stable. At present, there are few studies on the related factors and economic burden of nosocomial infection in patients with chronic kidney disease. This study understands the nutrient intake of patients in each disease process, and makes individualized nutritional dietary guidance programs more targeted. Starting from the second day of the patient's hospitalization, the food eaten by the patient was weighed by professionals using the weighing method for 3 consecutive days. By recording and entering into the analysis system, it performs the calculation and analysis of food composition and nutrient intake, and analyzes it using statistical methods. The experimental results showed that patients aged 31‐60 years had a higher risk of preoperative infection.
Cross-Border E-Commerce Business Model Based on Big Data and Blockchain
Authors: Hu Jinjuan , Xu Ling
Published: August 2022

In the context of the rapid development of Internet technology, the integration of the world economy has been strengthened. The continuous innovation of technology and foreign trade business forms has promoted the rapid development of cross-border e-commerce (CBE). Based on the research on the development status of CBE, this paper analyzes the reasons for the above problems in the development of CBE and discusses the innovation of CBE business models based on blockchain. Its purpose is to study the CBE business model based on big data and blockchain. This paper proposes to build a CBE framework system based on blockchain. It also uses blockchain technology (BT) to provide solutions to the problems of trust, customs supervision, cross-border payment, cross-border logistics, and cross-border data flow encountered in CBE. According to experimental statistics, China’s CBE exports were 7.29 trillion yuan, an increase of 40.1%, and imports were 3.76 trillion yuan, an increase of 16.5%.
Modular Smart Molecules for PSMA-Targeted Chemotherapy
Authors: Olatunji Feyisola P. , Pun Michael , Herman Jacob W. , Romero Oscar , Maniatopoulos Mitchell , Latoche Joseph D. , Parise Robert A. , Guo Jianxia , Beumer Jan H. , Anderson Carolyn J. , Berkman Clifford E.
Published: August 2022

New targeted chemotherapeutics are urgently needed to minimize off-target toxicity and reduce the high-mortality rate associated with metastatic prostate cancer. Herein, we report on the modular synthesis, pharmacokinetics, and efficacy of two small-molecule–drug conjugates (SMDC) targeted to prostate-specific membrane antigen (PSMA) incorporating either: (i) a cathepsin-B–cleavable valine–citrulline (Val–Cit), or (ii) an acid-cleavable phosphoramidate linker. Crucial components used in the design of the conjugates include: (i) CTT1298, a nanomolar affinity ligand that binds irreversibly to PSMA and has proven in past studies to rapidly internalize and shuttle payloads into PSMA-expressing prostate cancer cells, (ii) MMAE, a known potent cytotoxic payload, and (iii) an albumin-binder, proven to improve residence time of drug conjugates. At dose of 0.8 mg/kg (∼250 nmol/kg), the two SMDCs showed significant efficacy in a PSMA(+) PC3-PIP mouse model of human prostate cancer compared with controls, without inducing systemic toxicity. Though localization of the SMDCs was observed in tissues apart from the tumor, release of MMAE was observed predominantly in tumor tissue, at levels that were 2–3 orders of magnitude higher than non-target tissues. Furthermore, SMDC2, which incorporated a novel pH-responsive phosporamidate linker, demonstrated significantly improved efficacy over SMDC1 that has a Val–Cit linker, with a 100% survival over 90 days and 4 out of 8 mice showing complete tumor growth inhibition after 6 weekly doses of 0.8 mg/kg (244 nmol/kg). Our findings demonstrate the potential of irreversible PSMA inhibitors combined with pH-responsive linkers as a way to specifically deliver chemotherapeutic drugs to prostate cancer tumors with minimal toxicity.
A Retrospective Chart Review of 809 Patients with Physician-Diagnosed Essential Thrombocythemia Receiving Cytoreductive Therapy in US Community Oncology Practices
Authors: Yu Jingbo , Paranagama Dilan , Hanna Becky , Tang Jackson , Chojecki Aleksander
Published: August 2022

Introduction: This analysis reports demographic and clinical characteristics of patients with physician-diagnosed essential thrombocythemia (ET) receiving cytoreductive therapy in US community clinical practice. Methods: Patient characteristics, medical history, diagnostic test results, signs/symptoms, treatment patterns, and physician practice settings were extracted from medical charts for patients with physician-diagnosed ET receiving cytoreductive therapy. Results: Among 809 patients (51.1% female; 75.4% White; median age, 69 years) from 50 community practices, 64.5% had physician-reported diagnosis per World Health Organization criteria. Only 48.8% underwent diagnostic bone marrow biopsies; 87.5% had JAK2 mutation testing. Among those tested, 512/708 (72.3%), 57/213 (26.8%), and 37/213 (17.4%) had JAK2, CALR, and MPLmutations, respectively. Of physician-assigned risk assessments, 41.8% were misclassifications based on data-derived risk assessment. Most patients (93.3%) received first-line hydroxyurea (HU) cytoreductive therapy. Discontinuations were primarily for intolerance (35.4%) and resistance (23.8%). Of those who discontinued, 65.9% received no subsequent therapy and had higher ET symptom rates at last visit versus patients continuing HU (48.8% vs. 25.0%). Conclusion: This study shows notable gaps in ET diagnosis and management. Half of patients were diagnosed without bone marrow biopsy, many received incorrect risk assignment, and the majority who discontinued HU received no subsequent therapy despite continued need.
Effects of Intranasal Insulin Administration on Cerebral Blood Flow and Cognitive Performance in Adults: A Systematic Review of Randomized, Placebo-Controlled Intervention Studies
Authors: Nijssen Kevin M.R. , Mensink Ronald P. , Joris Peter J.
Published: August 2022

Introduction: Brain insulin resistance is an important hallmark of age-related conditions, including type 2 diabetes (T2D) and dementia. This systematic review summarized effects of cerebral blood flow (CBF) responses to intranasal insulin to assess brain insulin sensitivity in healthy and diseased populations. We also explored relationships between changes in brain insulin sensitivity and cognitive performance. Methods: A systemic literature search (PROSPERO: CRD42022309770) identified 58 randomized, placebo-controlled trials (RCTs) that investigated effects of intranasal insulin on (regional) CBF, cognitive performance, and systemic spill-over in adults. Results: Acute intranasal insulin did not affect whole-brain CBF in healthy adults, but increased regional CBF of the inferior frontal gyrus, dorsal striatum, and insular cortex, and reduced CBF around the middle frontal gyrus and hypothalamus. Obese adults showed increased CBF responses following internasal insulin for the middle frontal gyrus but decreased CBF for hypothalamic and cortico-limbic regions. Furthermore, increased CBF responses were reported for the insular cortex in T2D patients and for occipital and thalamic regions in older adults. The spray also improved memory and executive function, but a causal relation with regional CBF still needs to be established. Finally, intranasal insulin resulted in only a small amount of systemic spill-over, which is unlikely to have an impact on the observed findings. Conclusions: Region-specific changes in CBF after intranasal insulin administration were affected by obesity, T2D, and normal aging, indicating altered brain insulin sensitivity. Future RCTs should investigate longer-term effects of intranasal insulin and explore potential associations between effects on CBF and cognitive performance.
Cinema, memória e neoliberalismo: a representação da Argentina contemporânea no filme “Los Muertos” (2004)
Authors: Rodrigues Lucas Lourenço
Published: August 2022

O presente trabalho tem como objetivo analisar o modo como o filme "Los Muertos" (2004), de Lisandro Alonso, se insere no processo de construção de uma memória coletiva acerca da crise argentina na virada do século XXI provocada pelas transformações neoliberais durante o governo de Carlos Menem entre 1989 e 1999. Para isso, pretende-se traçar uma reconstituição histórica do período neoliberal na Argentina nos anos 1990, onde se deu uma renovação cinematográfica promovida pelo Novo Cinema Argentino - na qual se encontra o filme de Alonso -, responsável por retratar nas telas as consequências sociais trazidas pelo neoliberalismo.
“Educar é Higienizar”: as diretrizes do ensino de Higiene nas Escolas Normais paulistas e o papel do professor no livro de Biologia Educacional
Authors: Martins Samira
Published: August 2022

Este artigo tem como objetivo discorrer sobre as diretrizes de Educação Higiênica e o papel da professora primária na veiculação da mensagem de higiene nas escolas paulistas para a conformação de cidadãos saudáveis e eficientes ao Estado durante a Era Vargas. Para isto, analisamos o livro Biologia Educacional: noções fundamentais (1969) de Antônio de Almeida Junior. Essa obra foi utilizada como livro didático nas Escolas Normais paulistas, a partir de 1938 e sua última edição foi publicada em 1969. As diretrizes sobre higiene contidas no livro visavam instruir a futura professora a seguir seu papel de missionária da mensagem de higiene, para regenerar seus alunos através da educação.  A partir da perspectiva foucaultiana, operamos com o conceito de disciplina e biopoder como ferramenta de análise objetivando conhecer a rede de enunciados, da medicina, higiene e da educação escolar. A metodologia adotada para esta discussão volta-se para a pesquisa qualitativa de caráter bibliográfico e análise documental. Um das conclusões que este estudo levantou é que os enunciados veiculados no livro funcionaram como estratégias de disciplinamento de condutas e corpos, objetivando o saneamento dos problemas econômicos do país, tendo a futura professora primária e os alunos como ferramenta e alvos da transformação econômica e social.
O Ensino remoto e seu impacto na educação: um olhar sobre a disciplina de história
Authors: Reis Ana Clara Sousa , Conceição Graziela Feitosa , Feitosa Mayza Jorge
Published: August 2022

A pandemia do novo coronavírus, que chega ao Brasil em de março de 2020, mudou completamente o cotidiano das mais variadas instituições, inclusive a escola, que precisou se reinventar diante da nova realidade. Houve a necessidade de substituir o modelo presencial pelo remoto, como forma de dar continuidade às atividades diante do isolamento social posto em prática no país. A modalidade adotada impactou a realidade de milhões de jovens brasileiros e consequentemente as metodologias de ensino. Em função disso, o presente trabalho tem como intuito compreender as consequências da implementação do ensino remoto sobre a educação, bem como suas interferências na disciplina de história, tendo em vista os desafios futuros deixados por esse modelo.
Leksikon YU Mitologije: memória e nostalgia nos territórios da antiga Iugoslávia
Authors: Loureiro Mariana Hebling Alen
Published: August 2022

Considerando a ampla diversidade cultural e narrativa que atravessa os processos de independência e de construção de memória no território da antiga República Socialista Federativa Iugoslávia – atualmente dividido em seis repúblicas independentes e um espaço cuja autonomia ainda está em disputa –, se busca estabelecer um panorama das imagens mais presentes na memória coletiva, compartilhadas em toda a extensão do território, quando se fala no fenômeno recente da iugonostalgia. Para isso, se propõe um balanço dos grupos temáticos que aparecem com maior frequência no documento Leksikon YU mitologije, um compilado narrativo que conta com contribuições de inúmeros autores, relatando suas memórias pessoais na medida em que se misturam com imagens e símbolos da vida na ex-república socialista. Assim, através dos resultados obtidos pelo balanço quantitativo, que classifica em categorias todo o corpo do documento, se observa em que medida o sentimento nostálgico se reporta a um passado mistificado, em que há a confluência de elementos de natureza pessoal e coletiva e, principalmente, o que essas imagens nos revelam acerca das contradições do tempo presente.
Raymond Williams: sobre o materialismo cultural no processo histórico.
Authors: Nery Thaís
Published: August 2022

Raymond Williams (1921-1988) foi um dos pensadores mais originais e influentes de seu tempo, tendo contribuído de forma inestimável para a teoria cultural contemporânea. Intelectual engajado de convicções socialistas, Williams renovou profundamente o pensamento marxista sobre a cultura, por meio de estudos de sociologia e crítica cultural, produção literária e influência na cultura da mídia por uma análise profunda da vida em sociedade. Com base em seus estudos, o pensador britânico pode enfim pensar em uma definição de um dos conceitos mais complexos dentro das humanidades: a ideia de cultura, sobretudo na sociedade contemporânea Ocidental. O presente artigo tem como objetivo apresentar de forma simples, porém didática, a obra de Raymond William e sua reflexão sobre a teoria da cultura, materialismo cultural, o modo como ele se desenvolveu em importantes obras teóricas de diferentes momentos de sua trajetória intelectual a partir da interpretação do materialismo histórico e a importância da história cultural nesse processo.
ADAR1 Prevents Autoinflammatory Processes in the Heart Mediated by IRF7
Authors: Garcia-Gonzalez Claudia , Dieterich Christoph , Maroli Giovanni , Wiesnet Marion , Wietelmann Astrid , Li Xiang , Yuan Xuejun , Graumann Johannes , Stellos Konstantinos , Kubin Thomas , Schneider Andre , Braun Thomas
Published: August 2022

Background:

ADAR1 (adenosine deaminase acting on RNA-1)-mediated adenosine to inosine (A-to-I) RNA editing plays an essential role for distinguishing endogenous from exogenous RNAs, preventing autoinflammatory ADAR1 also regulates cellular processes by recoding specific mRNAs, thereby altering protein functions, but may also act in an editing-independent manner. The specific role of ADAR1 in cardiomyocytes and its mode of action in the heart is not fully understood. To determine the role of ADAR1 in the heart, we used different mutant mouse strains, which allows to distinguish immunogenic, editing-dependent, and editing-independent functions of ADAR1.

Methods:

Different
Adar1
-mutant mouse strains were employed for gene deletion or specific inactivation of ADAR1 enzymatic activity in cardiomyocytes, either alone or in combination with
Ifih1
(interferon induced with helicase C domain 1) or
Irf7
(interferon regulatory factor 7) gene inactivation. Mutant mice were investigated by immunofluorescence, Western blot, RNAseq, proteomics, and functional MRI analysis.

Results:

Inactivation of
Adar1
in cardiomyocytes resulted in late-onset autoinflammatory myocarditis progressing into dilated cardiomyopathy and heart failure at 6 months of age.
Adar1
depletion activated interferon signaling genes but not NFκB (nuclear factor kappa B) signaling or apoptosis and reduced cardiac hypertrophy during pressure overload via induction of
Irf7
. Additional inactivation of the cytosolic RNA sensor MDA5 (melanoma differentiation-associated gene 5; encoded by the
Ifih1
gene) in
Adar1
mutant mice prevented activation of interferon signaling gene and delayed heart failure but did not prevent lethality after 8.5 months. In contrast, compound mutants only expressing catalytically inactive ADAR1 in an
Ifih1
-mutant background were completely normal. Inactivation of
Irf7
attenuated the phenotype of
Adar1
-deficient cardiomyocytes to a similar extent as
Ifih1
depletion, identifying IRF7 as the main mediator of autoinflammatory responses caused by the absence of ADAR1 in cardiomyocytes.

Conclusions:

Enzymatically active ADAR1 prevents IRF7-mediated autoinflammatory reactions in the heart triggered by endogenous nonedited RNAs. In addition to RNA editing, ADAR1 also serves editing-independent roles in the heart required for long-term cardiac function and survival.
Inflammatory Role of Milk Fat Globule–Epidermal Growth Factor VIII in Age‐Associated Arterial Remodeling
Authors: Ni Leng , Liu Lijuan , Zhu Wanqu , Telljohann Richard , Zhang Jing , Monticone Robert E. , McGraw Kimberly R. , Liu Changwei , Morrell Christopher H. , Garrido‐Gil Pablo , Labandeira‐Garcia Jose Luis , Lakatta Edward G. , Wang Mingyi
Published: August 2022

Background

Age‐associated aortic remodeling includes a marked increase in intimal medial thickness (IMT), associated with signs of inflammation. Although aortic wall milk fat globule–epidermal growth factor VIII (MFG‐E8) increases with age, and is associated with aortic inflammation, it is not known whether MFG‐E8 is
required
for the age‐associated increase in aortic IMT. Here, we tested whether MFG‐E8 is
required
for the age‐associated increase in aortic IMT.

Methods and Results

To determine the role of MFG‐E8 in the age‐associated increase of IMT, we compared aortic remodeling in adult (20‐week) and aged (96‐week) MFG‐E8 (−/−) knockout and age matched wild‐type (WT) littermate mice. The average aortic IMT increased with age in the WT from 50±10 to 70±20 μm (
P
<0.0001) but did not significantly increase with age in MFG‐E8 knockout mice. Because angiotensin II signaling is implicated as a driver of age‐associated increase in IMT, we infused 30‐week‐old MFG‐E8 knockout and age‐matched littermate WT mice with angiotensin II or saline via osmotic mini‐pumps to determine whether MFG‐E8 is required for angiotensin II–induced aortic remodeling. (1) In WT mice, angiotensin II infusion substantially increased IMT, elastic lamina degradation, collagen deposition, and the proliferation of vascular smooth muscle cells; in contrast, these effects were significantly reduced in MFG‐E8 KO mice; (2) On a molecular level, angiotensin II treatment significantly increased the activation and expression of matrix metalloproteinase type 2, transforming growth factor beta 1, and its downstream signaling molecule phosphorylated mother against decapentaplegic homolog 2, and collagen type I production in WT mice; however, in the MFG‐E8 knockout mice, these molecular effects were significantly reduced; and (3) in WT mice, angiotensin II increased levels of aortic inflammatory markers phosphorylated nuclear factor‐kappa beta p65, monocyte chemoattractant protein 1, tumor necrosis factor alpha, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 molecular expression, while in contrast, these inflammatory markers did not change in knockout mice.

Conclusions

Thus, MFG‐E8 is required for both age‐associated proinflammatory aortic remodeling and also for the angiotensin II–dependent induction in younger mice of an aortic inflammatory phenotype observed in advanced age. Targeting MFG‐E8 would be a novel molecular approach to curb adverse arterial remodeling.
microRNA Expression Levels Change in Neonatal Patients During and After Exposure to Cardiopulmonary Bypass
Authors: Hsieh Lance , Tu Lan N. , Paquette Alison , Sheng Quanhu , Zhao Shilin , Bittel Douglas , O’Brien James , Vickers Kasey , Pastuszko Peter , Nigam Vishal
Published: August 2022

Background

The systemic inflammation that occurs after exposure to cardiopulmonary bypass (CPB), which is especially severe in neonatal patients, is associated with poorer outcomes and is not well understood. In order to gain deeper insight into how exposure to bypass activates inflammatory responses in circulating leukocytes, we studied changes in microRNA (miRNA) expression during and after exposure to bypass. miRNAs are small noncoding RNAs that have important roles in modulating protein levels and function of cells.

Methods and Results

We performed miRNA‐sequencing on leukocytes isolated from neonatal patients with CPB (n=5) at 7 time points during the process of CPB, including before the initiation of bypass, during bypass, and at 3 time points during the first 24 hours after weaning from bypass. We identified significant differentially expressed miRNAs using generalized linear regression models, and miRNAs were defined as statistically significant using a false discovery rate–adjusted
P
<0.05. We identified gene targets of these miRNAs using the TargetScan database and identified significantly enriched biological pathways for these gene targets. We identified 54 miRNAs with differential expression during and after CPB. These miRNAs clustered into 3 groups, including miRNAs that were increased during and after CPB (3 miRNAs), miRNAs that decreased during and after CPB (10 miRNAs), and miRNAs that decreased during CPB but then increased 8 to 24 hours after CPB. A total of 38.9% of the target genes of these miRNAs were significantly differentially expressed in our previous study. miRNAs with altered expression levels are predicted to significantly modulate pathways related to inflammation and signal transduction.

Conclusions

The unbiased profiling of the miRNA changes that occur in the circulating leukocytes of patients with bypass provides deeper insight into the mechanisms that underpin the systemic inflammatory response that occurs in patients after exposure to CPB. These data will help the development of novel treatments and biomarkers for bypass‐associated inflammation.
Renin‐Angiotensin System Inhibitors in Patients With COVID‐19: A Meta‐Analysis of Randomized Controlled Trials Led by the International Society of Hypertension
Authors: Gnanenthiran Sonali R. , Borghi Claudio , Burger Dylan , Caramelli Bruno , Charchar Fadi , Chirinos Julio A. , Cohen Jordana B. , Cremer Antoine , Di Tanna Gian Luca , Duvignaud Alexandre , Freilich Daniel , Gommans D. H. Frank , Gracia‐Ramos Abraham E. , Murray Thomas A. , Pelorosso Facundo , Poulter Neil R. , Puskarich Michael A. , Rizas Konstantinos D. , Rothlin Rodolfo , Schlaich Markus P. , Schreinlecher Michael , Steckelings Ulrike Muscha , Sharma Abhinav , Stergiou George S. , Tignanelli Christopher J. , Tomaszewski Maciej , Unger Thomas , van Kimmenade Roland R. J. , Wainford Richard D. , Williams Bryan , Rodgers Anthony , Schutte Aletta E. ,   the COVID‐METARASI Consortium
Published: August 2022

Background

Published randomized controlled trials are underpowered for binary clinical end points to assess the safety and efficacy of renin‐angiotensin system inhibitors (RASi) in adults with COVID‐19. We therefore performed a meta‐analysis to assess the safety and efficacy of RASi in adults with COVID‐19.

Methods and Results

MEDLINE, EMBASE,
ClinicalTrials.gov
, and the Cochrane Controlled Trial Register were searched for randomized controlled trials that randomly assigned patients with COVID‐19 to RASi continuation/commencement versus no RASi therapy. The primary outcome was all‐cause mortality at ≤30 days. A total of 14 randomized controlled trials met the inclusion criteria and enrolled 1838 participants (aged 59 years, 58% men, mean follow‐up 26 days). Of the trials, 11 contributed data. We found no effect of RASi versus control on all‐cause mortality (7.2% versus 7.5%; relative risk [RR], 0.95; [95% CI, 0.69–1.30]) either overall or in subgroups defined by COVID‐19 severity or trial type. Network meta‐analysis identified no difference between angiotensin‐converting enzyme inhibitors versus angiotensin II receptor blockers. RASi users had a nonsignificant reduction in acute myocardial infarction (2.1% versus 3.6%; RR, 0.59; [95% CI, 0.33–1.06]), but increased risk of acute kidney injury (7.0% versus 3.6%; RR, 1.82; [95% CI, 1.05–3.16]), in trials that initiated and continued RASi. There was no increase in need for dialysis or differences in congestive cardiac failure, cerebrovascular events, venous thromboembolism, hospitalization, intensive care admission, inotropes, or mechanical ventilation.

Conclusions

This meta‐analysis of randomized controlled trials evaluating angiotensin‐converting enzyme inhibitors/angiotensin II receptor blockers versus control in patients with COVID‐19 found no difference in all‐cause mortality, a borderline decrease in myocardial infarction, and an increased risk of acute kidney injury with RASi. Our findings provide strong evidence that RASi can be used safely in patients with COVID‐19.
Inequalities by Income in the Prevalence of Cardiovascular Disease and Its Risk Factors in the Adult Population of Catalonia
Authors: Mullachery Pricila H. , Vela Emili , Cleries Montse , Comin‐Colet Josep , Nasir Khurram , Diez Roux Ana V. , Cainzos‐Achirica Miguel , Mauri Josepa , Bilal Usama
Published: August 2022

Background

Understanding the magnitude of cardiovascular disease (CVD) inequalities is the first step toward addressing them. The linkage of socioeconomic and clinical data in universal health care settings provides critical information to characterize CVD inequalities.

Methods and Results

We employed a prospective cohort design using electronic health records data from all residents of Catalonia aged 18+ between January and December of 2019 (N=6 332 228). We calculated age‐adjusted sex‐specific prevalence of 5 CVD risk factors (diabetes, hypertension, hyperlipidemia, obesity, and smoking), and 4 CVDs (coronary heart disease, cerebrovascular disease, atrial fibrillation, and heart failure). We categorized income into high, moderate, low, and very low according to individual income (tied to prescription copayments) and receipt of welfare support. We found large inequalities in CVD and CVD risk factors among men and women. CVD risk factors with the largest inequalities were diabetes, smoking, and obesity, with prevalence rates 2‐ or 3‐fold higher for those with very low (versus high) income. CVDs with the largest inequalities were cerebrovascular disease and heart failure, with prevalence rates 2 to 4 times higher for men and women with very low (versus high) income. Inequalities varied by age, peaking at midlife (30–50 years) for most diseases, while decreasing gradually with age for smoking.

Conclusions

We found wide and heterogeneous inequalities by income in 5 CVD risk factors and 4 CVD. Our findings in a region with a high‐quality public health care system and universal coverage stress that strong equity‐promoting policies are necessary to reduce disparities in CVD.
Reconsidering ‘Art’ and ‘Life’
Authors: Routledge Laura
Published: August 2022

The categories of ‘art’ and ‘life’ play a central role in the critical reception of Allan Kaprow’s Happenings, which have predominantly been read as a generalized, “blithely affirmative” and even “faintly embarrassing” attempt to fuse the two. This paper attempts to rethink the definition and relation of these two categories in Kaprow’s work. Rather than an uncritical attempt to fuse art and life, I suggest, Kaprow’s Happenings developed an increasingly complex, branching and networked structure, capable of staging a plurality of different modes of interaction between work and world. This paper explores both the modes and the contexts of these interactions in three of Kaprow’s Happenings of the 1960s.
Early childhood developmental vulnerability associated with parental mental disorder comorbidity
Authors: Watkeys Oliver J , O’Hare Kirstie , Dean Kimberlie , Laurens Kristin R , Harris Felicity , Carr Vaughan J , Green Melissa J
Published: August 2022

Objectives:

Parental mental health has a profound influence on the mental health and well-being of their offspring. With comorbid mental disorders generally the rule rather than the exception, increased knowledge of the impact of parental mental disorder comorbidity on early child development may facilitate improved targeting and delivery of early intervention for vulnerable offspring.

Methods:

Participants were 66,154 children and their parents in the New South Wales Child Development Study – a prospective, longitudinal, record-linkage study of a population cohort of children born in NSW between 2002 and 2004. Early childhood developmental vulnerability was assessed at age ~5 years using the Australian Early Development Census, and information on parental mental disorders was obtained from administrative health records. Binomial and multinomial logistic regression were used to assess the relationship between parental mental disorders and early childhood developmental vulnerability on emotional and behavioural domains, as well as membership of latent developmental risk classes reflecting particular classes of vulnerability.

Results:

Multiple diagnoses of mental disorders in mothers and fathers were associated with an increased likelihood of early childhood emotional and behavioural developmental vulnerability in offspring, relative to parents without mental disorder. The likelihood of offspring vulnerability increased with the number of parental comorbidities, particularly maternal comorbidities.

Conclusion:

Early childhood developmental vulnerability was strongly associated with parental mental ill-health, with the strength of associations increasing in line with a greater number of mental disorder diagnoses among mothers and fathers. New and expectant parents diagnosed with multiple mental disorders should be prioritised for intervention, including attention to the developmental well-being of their offspring.
Production and Perception Evidence of a Merger: [l] and [n] in Fuzhou Min
Authors: Cheng Ruoqian , Jongman Allard , Sereno Joan A.
Published: August 2022

The current study investigated the merger-in-progress between word-initial nasal and lateral consonants in Fuzhou Min, examining the linguistic and social factors that modulate the merger. First, the acoustic cues to the l-n distinction were examined in Fuzhou Min. Acoustic analyses suggested a collapse of phonemic contrast between prescriptive L and N (phonemes in the unmerged system), with none of the six acoustic cues showing any difference across L and N. Linear discriminant analysis did identify acoustically distinct [l] and [n] tokens, although the mapping onto the phonetic space of prescriptive L and N substantially overlapped. Speakers of all ages and both genders tended to produce [l], and low vowels correlated with more [n]-like classification. In perception, AX discrimination data showed Fuzhou Min listeners confused both prescriptive L and N and acoustic [l] and [n]. Greater sensitivity to the acoustic differences occurred in the context of low vowels and a nasal coda, supported by the acoustics of the stimuli, and younger listeners were more sensitive to the difference between [l] and [n] than older listeners. In two-alternative forced choice (2AFC) identification, Fuzhou Min listeners also identified the merged form as L more frequently than N, with more L responses elicited in the context of low vowels and in the absence of nasal codas. Overall, although Fuzhou Min speakers produced some acoustically distinct [l] and [n] tokens in the context of a sound merger, these productions did not map onto prescriptive L and N. In addition, younger listeners were more sensitive to the acoustic distinction than older listeners, suggesting an emerging acoustic contrast possibly arising due to contact with Mandarin.
Investigation of Mandarin Word Production in Children and Adults: Evidence from Phonological Priming with Non-words
Authors: Chang Chih-Chao , Yang Hui-Chun
Published: August 2022

Using a cross-modal picture-word interference (PWI) task, we examined phonological representations and encoding in Mandarin-speaking children and adults. Pictures of monosyllabic words were presented visually, with auditory primes presented before, concurrent with, or after the picture’s appearance (SOA -200, -100, 0, +150). Primes were related to the targets in terms of Onset, Rhyme, Tone, Onset and Tone, Rhyme and Tone, or were unrelated. The rhymes of target words were counterbalanced between simple and complex structures to examine effects of rhyme complexity. Twenty Mandarin-speaking adults (aged 20;3 to 23;10), 20 school-age children (aged 9;1 to 10;11) and 20 preschoolers (aged 5;0 to 5;11) were asked to name the pictures as quickly as possible while ignoring the primes played over a headset. The results showed that adults exhibited consistent Onset and Onset-Tone priming effects across later SOAs, while the older children (9- to 10-year-olds) exhibited Onset, Rhyme, Onset-Tone and Rhyme-Tone priming effects across later SOAs. The younger children (5-year-olds), in contrast, exhibited Rhyme and Rhyme-Tone priming effects at the earliest SOA. For both groups of children, Rhyme and Rhyme-Tone priming effects were complexity-dependent. Our findings suggest that the phonological representations of Mandarin speakers develop from holistic units into those with an onset-based structure. Moreover, an incremental processing pattern at the sub-syllabic level is gradually developed around the age of 9 or 10, though susceptibility to holistic phonological similarity is retained to some degree.
Long-lasting leukocytosis in patients with schizophrenia treated with clozapine after electroconvulsive therapy
Authors: Sugita Kotaro , Mori Yasuhiro , Kanemoto Kousuke , Sugita Sotaro
Published: August 2022

Introduction

The present study was conducted to investigate the possible hematologic impact of long-term electroconvulsive therapy (ECT) in patients with drug-resistant schizophrenia and receiving clozapine therapy.

Subjects and Methods

In this retrospective study, clinical charts of 57 hospitalized patients with schizophrenia who required clozapine therapy because of active psychotic symptoms resistant to other antipsychotics were examined. For 18 who underwent ECT, the first assessment was conducted at the end of that therapy (average two months after start, 7.68 sessions) and the second two months later. As for the 39 patients who did not undergo ECT, the first and second assessment points were at two and four months, respectively, after a randomly chosen time point.

Results

Multiple regression analysis revealed that modified ECT (m-ECT) (ß = 0.346, p = 0.005), gender (males showed greater increase) (ß = 0.273, p = 0.023), and disease duration (longer associated with greater increase) (ß = 0.258, p = 0.033) were correlated with a change in white blood cell (WBC) count (ΔR2 = 0.277, p < 0.001) at the first assessment point. At the second assessment point, multiple regression analysis showed that m-ECT (ß = 0.262, p = 0.039), gender (males showed greater increase) (ß = 0.264, p = 0.036), and disease duration (longer associated with greater increase) (ß = 0.234, p = 0.068) were again correlated with changed WBC count (ΔR2 = 0.203, p < 0.007).

Discussion

An increase in leukocytes may have a protective influence against the adverse myelosuppressive effects of clozapine. However, a simple mobilization of leukocytes from bone marrow to peripheral circulation may not enhance the immune system, leading to only a masking of the effects of a potential immuno-insufficient state in the treated patient. In either case, should leukocytosis be induced and then remain for an extended period, hematologists, as well as psychiatrists involved in electroconvulsive intervention for clozapine-treated patients, must keep this factor in mind.
The conversion of a missionary: A missiological study of Acts 10
Authors: Whiteman Darrell L.
Published: August 2022

This missiological study of the interaction between the Apostle Peter and the Roman Centurion Cornelius in Acts 10 demonstrates that missionaries need two conversions. The first conversion is a spiritual conversion to Christ to combat our egocentrism. The second conversion is to cross-cultural understanding and awareness to cleanse us of our ethnocentrism. Peter had to undergo a cross-cultural conversion to combat his ethnocentrism against Gentiles before he was able to lead Cornelius and his entire household to faith in Christ.
Burning up on Reentry: The Effect of Entrepreneurial Exit in the Hiring Context
Authors: Waddingham Jacob A. , Zachary Miles A. , Walker H. Jack
Published: August 2022

A great deal of research on entrepreneurial exit focuses on the potential challenges entrepreneurs may face when launching a new venture, but very little is known about those who choose to re-enter the traditional workforce. It is commonly assumed that an entrepreneur can always “go back to work,” however, it is unclear how recruiters evaluate entrepreneurial experience early in the selection process. Drawing from screening theory, attribution theory, and the person-organization fit perspective, we designed three studies to begin answering questions about the challenges former entrepreneurs may face when attempting to find more traditional employment. Study 1 revealed that recruiters evaluate former entrepreneurs more negatively than job applicants with more traditional work experience, and this relationship is stronger when former entrepreneurs close—versus sell—their venture. Study 2 employed a qualitative, inductive approach to examine why recruiters may be biased against former entrepreneurs and found that there are often assumptions of rapid turnover, insubordinate behavior, and organizational misfit. Finally, the Study 3 results suggested that the negative evaluation of former entrepreneurs may not be universal and depends on important contextual factors such as job characteristics, length of entrepreneurial experience, and details about entrepreneurial exit.
Relationship between change in social evaluation learning and mood in early antidepressant treatment: A prospective cohort study in primary care
Authors: Hobbs Catherine , Beck Milly , Denham Faye , Pettitt Laura , Faraway Julian , Munafò Marcus R , Sui Jie , Kessler David , Button Katherine S
Published: August 2022

Background:

Antidepressants are proposed to work by increasing sensitivity to positive versus negative information. Increasing positive affective learning within social contexts may help remediate negative self-schema. We investigated the association between change in biased learning of social evaluations about the self and others, and mood during early antidepressant treatment.

Method:

Prospective cohort assessing patients recruited from primary care in South West England at four timepoints over the first 8 weeks of antidepressant treatment ( n = 29). At each timepoint, participants completed self-report measures of depression (Beck Depression Inventory II (BDI-II) and Patient Health Questionnaire 9 (PHQ-9)), anxiety (Generalised Anxiety Disorder Questionnaire 7 (GAD-7)), and a computerised task measuring learning of social evaluations about the self, a friend and a stranger.

Results:

We did not find evidence that learning about the self was associated with a reduction in PHQ-9 ( b = 0.08, 95% CI: −0.05, 0.20, p = 0.239) or BDI-II scores ( b = 0.10, 95% CI: −0.18, 0.38, p = 0.469). We found some weak evidence that increased positive learning about the friend was associated with a reduction in BDI-II scores ( b = 0.30, 95% CI: −0.02, 0.62, p = 0.069). However, exploratory analyses indicated stronger evidence that increased positive learning about the self ( b = 0.18, 95% CI: 0.07, 0.28, p = 0.002) and a friend ( b = 0.22, 95% CI: 0.10, 0.35, p = 0.001) was associated with reductions in anxiety.

Conclusions:

Change in social evaluation learning was associated with a reduction in anxiety but not depression. Antidepressants may treat anxiety symptoms by remediating negative affective biases towards socially threatening information directed towards the self and close others. However, our findings are based on exploratory analyses within a small sample without a control group and are therefore at risk of type 1 errors and order effects. Further research with larger samples is required.