bluuebunny/crossref_metadata_2025 huggingface dataset:
Group Gender Composition and Perceptions of Legitimacy
Authors: Shalaby Marwa , kao kristen , Weiss Chagai , Lust Ellen
Published: October 2022

How does the gender composition of deliberative committees affect citizens’ evaluations of decision-making processes? Do citizens perceive decisions made by gender-balanced, legislative bodies as more legitimate than those made by all-male bodies? Extant work on the link between women’s descriptive representation and perceptions of democratic legitimacy in advanced democracies finds the equal presence of women legitimizes decision-making processes. However, this relationship has not been tested in more patriarchal, less democratic settings. We employ survey experiments in Jordan, Morocco and Tunisia to investigate how citizens respond to gender representation in committees. We find that women’s presence promotes citizens’ perceptions of the legitimacy of committee processes and outcomes, and moreover, that pro-women decisions are associated with higher levels of perceived legitimacy. Thus, this study demonstrates remarkable robustness of findings from theWest regarding gender representation and contributes to the burgeoning literature on women’s descriptive representation, and women and politics in gender conservative settings
Authority and Participation: The Role of Leader Type, Shared Identity, and Community Influence on Campaign Participation in Zambia
Authors: Jöst Prisca , Lust Ellen
Published: October 2022

Why are some leaders more effective in mobilizing citizens than others? We draw on original survey data and a survey experiment conducted in the run-up to the 2021 Zambian elections to answer this question. The experiment varies the type of authority and the type of activity, as well as whether participation is monitored. The surveys also gathered information on the respondents’ shared identity traits with the leader and their perceptions of the leader’s social influence over (1) the scope of the individual’s life, and (2) the members of the community. This allows us to explore the extent to which it is the leader type or the nature of the relationships between leaders and citizens that drive compliance. We find that leader influence is associated with reported willingness to participate, and leader sanctioning and legitimacy are likely mechanisms. Leader type and identity have no influence on the respondents’ willingness to participate.
КОЛЛЕКЦИЯ ПОЧТОВЫХ ОТКРЫТОК ДОРЕВОЛЮЦИОННОЙ РОССИИ С ТЕКСТАМИ НА РЕЛИГИОЗНУЮ И ПАТРИОТИЧЕСКУЮ ТЕМЫ
Authors: Шляхтина Наталья Валерьевна
Published: October 2022

В статье анализируется коллекция почтовых открыток начала XX в. из архива Н. М. Добровой. Часть открыток использовалась как страницы дневника. На одних – выписки из духовной православной литературы с комментариями. На других – отрывки из публицистической литературы монархической, патриотической направленности. Работа с открытками Надежды Матвеевны Добровой дает возможность включиться в повседневную жизнь русской православной семьи начала XX в. Памятные записи в формате дневника раскрывают духовный мир многодетной женщины, представительницы старинного священнического рода, чувствующей тесную связь со своей страной и ее историей. Корреспонденция от детей Надежды Матвеевны позволяет сделать вывод о том, что семья жила общими интересами.
The article analyzes the collection of postcards from the beginning of the 20th century. from the archive of N. M. Dobrova. Some of the postcards were used as diary pages. On some – extracts from spiritual Orthodox literature with comments. On others – excerpts from publicistic literature of a monarchist and patriotic orientation. Working with postcards by Nadezhda Matveevna Dobrova makes it possible to get involved in the daily life of a Russian Orthodox family at the beginning of the 20th century. Commemorative entries in the format of a diary reveal the spiritual world of a woman with many children, who feels a close connection with her country and its history. Correspondence from the children of Nadezhda Matveevna allows us to conclude that the family lived by common interests.
«ЛЮБЛЮ ВСЕ РУССКОЕ!..»:
СОБИРАТЕЛЬНИЦА СЕВЕРНОРУССКОГО ФОЛЬКЛОРА
МАРИЯ ВАСИЛЬЕВНА ХВАЛЫНСКАЯ
Authors: Дурасов Геннадий Петрович
Published: October 2022

Очерк посвящен памяти М. В. Хвалынской – собирательнице севернорусского фольклора, с которой автора связывали долгие годы творческого общения. В текст включена биография народной собирательницы частушек, описан ее творческий путь, разобрана ее исследовательская лаборатория, мотивация ее действий, приведены примеры фольклорного материала, которые показались автору очерка важными и демонстративными. Также отмечается такая важная характеристика исследовательницы М. В. Хвалынской, как ее любовь к своему народу, русской народной культуре, народной фольклорной традиции; бережное и сознательное отношение к тому делу, которое она осуществляла не профессионально, но со всей тщательностью, настойчивостью и вниманием в течение длительного времени.
The essay is dedicated to the memory of M. V. Khvalynskaya, a collector of northern Russian folklore, with whom the author was associated for many years of creative communication. The text includes a biography of the folk collector of ditties, describes her creative path, examines her research laboratory, the motivation for her actions, provides examples of folklore material that seemed important and demonstrative to the author of the essay. Also noted is such an important characteristic of the researcher M.V. Khvalynskaya as her love for her people, Russian folk culture, folklore tradition; a careful and conscious attitude to the work that she carried out not professionally, but with all care, perseverance and attention for a long time.
Engineered biosynthesis of plant polyketides by type III polyketide synthases in microorganisms
Authors: Liu Chang , Li Sijin
Published: October 2022

Plant specialized metabolites occupy unique therapeutic niches in human medicine. A large family of plant specialized metabolites, namely plant polyketides, exhibit diverse and remarkable pharmaceutical properties and thereby great biomanufacturing potential. A growing body of studies has focused on plant polyketide synthesis using plant type III polyketide synthases (PKSs), such as flavonoids, stilbenes, benzalacetones, curcuminoids, chromones, acridones, xanthones, and pyrones. Microbial expression of plant type III PKSs and related biosynthetic pathways in workhorse microorganisms, such as Saccharomyces cerevisiae, Escherichia coli, and Yarrowia lipolytica, have led to the complete biosynthesis of multiple plant polyketides, such as flavonoids and stilbenes, from simple carbohydrates using different metabolic engineering approaches. Additionally, advanced biosynthesis techniques led to the biosynthesis of novel and complex plant polyketides synthesized by diversified type III PKSs. This review will summarize efforts in the past 10 years in type III PKS-catalyzed natural product biosynthesis in microorganisms, especially the complete biosynthesis strategies and achievements.
Material property alterations for phenotypes of heart failure with preserved ejection fraction: A numerical study of subject-specific porcine models
Authors: Weissmann Jonathan , Charles Christopher J. , Richards A. Mark , Yap Choon Hwai , Marom Gil
Published: October 2022

A substantial proportion of heart failure patients have a preserved left ventricular (LV) ejection fraction (HFpEF). This condition carries a high burden of morbidity and mortality and has limited therapeutic options. left ventricular pressure overload leads to an increase in myocardial collagen content, causing left ventricular stiffening that contributes to the development of heart failure patients have a preserved left ventricular ejection fraction. Although several heart failure patients have a preserved left ventricular ejection fraction models have been developed in recent years to aid the investigation of mechanical alterations, none has investigated different phenotypes of the disease and evaluated the alterations in material properties. In this study, two similar healthy swine were subjected to progressive and prolonged pressure overload to induce diastolic heart failure characteristics, providing a preclinical model of heart failure patients have a preserved left ventricular ejection fraction. Cardiac magnetic resonance imaging (cMRI) scans and intracardiac pressures were recorded before and after induction. In both healthy and disease states, a corresponding finite element (FE) cardiac model was developed via mesh morphing of the Living Heart Porcine model. The material properties were derived by calibrating to its passive and active behavior. The change in the passive behavior was predominantly isotropic when comparing the geometries before and after induction. Myocardial thickening allowed for a steady transition in the passive properties while maintaining tissue incompressibility. This study highlights the importance of hypertrophy as an initial compensatory response and might also pave the way for assessing disease severity.
c-Met-integrin cooperation: Mechanisms, tumorigenic effects, and therapeutic relevance
Authors: Stanislovas Justas , Kermorgant Stéphanie
Published: October 2022

c-Met is a receptor tyrosine kinase which upon activation by its ligand, the hepatocyte growth factor, mediates many important signalling pathways that regulate cellular functions such as survival, proliferation, and migration. Its oncogenic and tumorigenic signalling mechanisms, greatly contributing to cancer development and progression, are well documented. Integrins, heterogeneous adhesion receptors which facilitate cell-extracellular matrix interactions, are important in biomechanically sensitive cell adhesion and motility but also modulate diverse cell behaviour. Here we review the studies which reported cooperation between c-Met and several integrins, particularly β1 and β4, in various cell models including many tumour cell types. From the various experimental models and results analysed, we propose that c-Met-integrin cooperation occurs via inside-out or outside-in signalling. Thus, either c-Met activation triggers integrin activation and cell adhesion or integrin adhesion to its extracellular ligand triggers c-Met activation. These two modes of cooperation require the adhesive function of integrins and mostly lead to cell migration and invasion. In a third, less conventional, mode of cooperation, the integrin plays the role of a signalling adaptor for c-Met, independently from its adhesive property, leading to anchorage independent survival. Recent studies have revealed the influence of endocytic trafficking in c-Met-integrin cooperation including the adaptor function of integrin occurring on endomembranes, triggering an inside-in signalling, believed to promote survival of metastatic cells. We present the evidence of the cooperation in vivo and in human tissues and highlight its therapeutic relevance. A better understanding of the mechanisms regulating c-Met-integrin cooperation in cancer progression could lead to the design of new therapies targeting this cooperation, providing more effective therapeutic approaches than c-Met or integrin inhibitors as monotherapies used in the clinic.
Proteomic and metabolomic analyses reveal the novel targets of spermine for alleviating diabetic cardiomyopathy in type II diabetic mice
Authors: Sun Jian , Xu Jiyu , Liu Yong , Xu Xiaoyi , Zhang Shumin , Hao Yankun , Lin Yitong , Han Yue , Li Feiya , Yuan Hui
Published: October 2022

Diabetic cardiomyopathy (DCM) is one of the most serious complications of diabetes. Recent cardiology studies suggest that spermine has a cardioprotective effect. Here, we used proteomic and metabolomic analyses to reveal the underlying research targets in a type II diabetic (T2D) mouse model treated with spermine. Left ventricular tissues from nine mice (Control group, three; T2D group, three; T2D+SP group, three) were excised and analyzed. Quantitative analysis of the global proteome and metabolome was performed using the 4D label-free technique and untargeted metabolomics, respectively, and differentially expressed proteins (DEPs) and metabolites were used to perform bioinformatic analyses. A total of 169 DEPs were identified in T2D/Control group, including 115 upregulated and 54 downregulated proteins. Furthermore, 16 DEPs were identified in T2D+SP/T2D group, where these DEPs were found highly enriched in the cellular, metabolic processes, biological regulation, response to stimulus, and immune system process. The results of association analysis between proteomics and metabolomics showed that SP could affect the production of 51 metabolites by regulating the expression of 16 DEPs in the T2D+SP/T2D group. We also found that PRKG1 was closely related to the expressions of 10 overlapping metabolites between db/db and SP-treated mice. Our findings provide insights into the underlying mechanisms for DCM and suggest the potential applicability of utilizing spermine on protecting against DCM-associated cardiac function deterioration.
Deformation monitoring and influence factor analysis of expressway over strong saline soil based on an advanced multi-temporal InSAR technique
Authors: Wang Zhiheng , Li Shengfu , Jia Yang , Sun Xiaopeng , Wang Yi , Pu Huilong , Nan Ke , Li Peng
Published: October 2022

Saline soil harbors crystallized salt in the solid phase and salt solution in the liquid phase. By the natural environmental and human activity factors, migration and accumulation of the salt and crystallization process alternated with dissolving, which makes saline soil with significant seasonal differences appear in the deformation and regional scattering characteristic. These phenomena raise the limitation of conventional multi-temporal interferometric synthetic aperture radar (MT-InSAR) technique and consequently high-precision deformation monitoring of strong saline soil subgrade and pavement. To overcome the limitations, this study aimed to propose an advanced MT-InSAR method, which considers the seasonal interferometric coherences caused by precipitation and the temporal physical deformation evolution of the subgrade and pavement over strong saline soil. To present the better performance of the advanced method, a segment of the Qarhan–Golmud Expressway (QGE), which is the first expressway built in the strong saline soil area in China, was selected for this study. Two sets of SAR images acquired from January 2018 to January 2022 from Sentinel-1A ascending and descending orbits over the QGE were utilized, 774 and 928 seasonal filtered interferograms are optimized for deformation monitoring based on the deformation Poisson curve (PC) model. Compared with the method in the previous studies, the accuracy, efficiency, and reliability of the monitoring results increased dramatically. Subsequently, further discussions are conducted in detail on the regularity of expressway deformation over strong saline soil, especially from physical and chemical perspectives. Findings show that the ratio between Cl− and SO42- determines the deformation distribution and morphology. Also, the precipitation and temperature affect the seasonal characteristics. The contributions of this investigation might provide technical references for related expressway management and policy-making departments to ensure the long-term safe operation and stability of the QGE.
Sex differences in metabolically healthy and metabolically unhealthy obesity among Chinese children and adolescents
Authors: Cai Shan , Dang Jiajia , Zhong Panliang , Ma Ning , Liu Yunfei , Shi Di , Zou Zhiyong , Dong Yanhui , Ma Jun , Song Yi
Published: October 2022

Objectives

To analyze sex differences in the prevalence of obesity phenotypes and their risk factors among children and adolescents aged 7-18 years in China.

Methods

We enrolled 15,114 children and adolescents aged 7-18 years into the final analysis. Obesity phenotypes were classified by body mass index (BMI) and metabolic status as metabolically healthy or unhealthy obesity. In addition, we collected four possible influencing factors on obesity phenotypes through questionnaires, including demographic, parental, early life, and lifestyle indicators. Multinomial logistic regression analysis in a generalized linear mixed model (GLMM) was selected to estimate the odds ratio (OR) and 95% confidence interval (95% CI) for identifying risk factors and control the cluster effects of schools. More importantly, the interaction terms of sex and each indicator were established to demonstrate the sex differences.

Results

The prevalence of metabolically healthy obesity (MHO), metabolically unhealthy obesity (MUO), metabolically healthy overweight and obesity (MHOO), and metabolically unhealthy overweight and obesity (MUOO) were 3.5%, 5.6%, 11.1%, and 13.0% respectively, with higher prevalence in boys (5.3% vs. 1.6%, 7.9% vs. 3.1%, 14.3% vs. 7.7%, 15.6% vs. 10.1%). In addition, younger ages, single children, parental smoking, parental history of diseases (overweight, hypertension, diabetes), caesarean, premature, and delayed delivery time, high birth weight, insufficient sleep time, and excessive screen time were considered as important risk factors of MHO and MUO among children and adolescents (p < 0.05). More notably, boys were at higher risks of MUO when they were single children (boys: OR = 1.56, 95% CI: 1.24-1.96; girls: OR = 1.12, 95% CI: 0.82-1.54), while girls were more sensitive to MUO with parental smoking (girls: OR = 1.34, 95% CI: 1.02-1.76; boys: OR = 1.16, 95% CI: 0.97-1.39), premature delivery (girls: OR = 3.11, 95% CI: 1.59-6.07; boys: OR = 1.22, 95% CI: 0.67-2.22), high birth weight (girls: OR = 2.45, 95% CI: 1.63-3.69; boys: OR = 1.28, 95% CI: 0.96-1.70), and excessive screen time (girls: OR = 1.47, 95% CI: 1.06-2.04; boys: OR = 0.97, 95% CI: 0.79-1.20), with significant interaction term for sex difference (pinteraction < 0.05).

Conclusions

MHO and MUO are becoming prevalent among Chinese children and adolescents. Significant sex differences in the prevalence of obesity phenotypes as well as their environmental and genetic risk factors suggest it might be necessary to manage obesity phenotypes problems from a sex perspective.
Crop residual burning correlations with major air pollutants in mainland China
Authors: Wang Tianwei , Meng Ke , Fu Peihong , Huang Wei
Published: October 2022

Many studies have established the correlation between crop residual burning (CRB) and air pollutants such as particulate matter (PM) pollutants. However, few studies have compared CRB’s correlations with all major air pollutants, including PM with aerodynamic diameters less than 10µm (PM10) and 2.5 µm (PM2.5), sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3), and carbon monoxide (CO), during open-field CRB seasons. This study monitored daily CRB spots from 2015 to 2016 in China, together with daily concentrations of PM2.5, PM10, CO, SO2, NO2, and 8 h average O3 provided by the China National Environmental Monitoring Center. Temporal changes in air pollutant concentration at the provincial level and spatial contributions of CRB to air pollution at the monitoring-site level were analyzed. The results indicated that the decrease in CRB from 2015 to 2016 probably led to a decrease in the mean air pollutant concentration and maxima; it also probably led to more outliers at the provincial level in the CRB seasons, especially in Heilongjiang, Jilin, and Liaoning. Spatial contributions suggest that the Heilongjiang, Jilin, and Liaoning provinces experienced a regional increase in the concentrations of almost all major air pollutants during the CRB seasons. In Heilongjiang, Jilin, and Liaoning, 67.88%, 72.12%, 80.00%, 77.58%, and 69.09% of the monitoring sites recorded higher concentrations of PM2.5, PM10, NO2, O3 , and CO, respectively, in the winter CRB season of 2015 compared to other periods. In contrast, in other provinces with fewer and more widely distributed CRB spots, only the monitoring sites close to or on CRB spots experienced increases.
Financial development, foreign trade, regional economic development level and carbon emissions
Authors: Sun Yongchun
Published: October 2022

Drawing on balanced panel data of 30 Chinese provinces in 2000–2020, this paper uses the Panel Smooth Transformation Regression (PSTR) model to explore the impact of financial development and foreign trade on carbon emissions under different regional economic development levels. The empirical results show that: 1) Financial development and foreign trade have a non-linear impact on carbon emissions under different economic development levels; 2) As the level of economic development exceeds the threshold, the positive effect of financial development on carbon emissions will weaken, while the effect of foreign trade on carbon emissions will change from negative to positive; 3) The sub-sample estimates further found that the impact on carbon emissions in southern and northern regions are different. The threshold in the south is lower than that in the north, but all the conversion speed is faster.
Perinatal outcomes of pregestational hypertension according to blood pressure range at 11–14 week scan: Impact of the 2017 ACC/AHA guidelines
Authors: Sepúlveda-Martínez Alvaro , Conrads Tomas , Guiñez Rodolfo , Guiñez Javiera , Llancaqueo Marcelo , Parra-Cordero Mauro
Published: October 2022

Objective

The aim of this study was to evaluate the impact on perinatal outcomes related to placental insufficiency with the application of the new 2017 ACC/AHA guidelines to a group of chronic hypertensive pregnancies during their first-trimester assessment.

Study design

This retrospective cohort study included pregnancies with preconceptional hypertension and known perinatal outcomes. In the first trimester, a combined screening for preterm preeclampsia (p-PE) was performed, including blood pressure (BP), mean uterine artery Doppler, and maternal characteristics. Patients were divided, according to the 2017 ACC/AHA consensus, into the following groups: elevated or less, Stage 1, and Stage 2. For adverse perinatal outcome assessment, univariate and multivariate regression analyses were performed, considering the “elevated or less” group as a reference. Odds ratios (OR) were compared with linear trend analysis. The main outcomes measured were preterm PE and FGR < 3rd percentile.

Results

Of the 130 included patients, 59 (45.4%) were classified as elevated or less, 47 (36.2%) as Stage 1, and 24 (18.4%) as Stage 2. p-PE showed a significant increase according to BP range [7% (OR = 1.0), 19.6% (OR = 3.2), and 21.7% (OR = 3.7)]; trend p = 0.02, for elevated or less, Stage 1, and Stage 2, respectively. There was a non-significant increased trend of FGR < 3rd percentile according to the BP stage. The best multivariate predictive model for p-PE included a previous PE background (OR = 15) and mean arterial pressure in mmHg (OR = 1.1).

Conclusion

The use of the 2017 ACC/AHA consensus in pregnancies with chronic hypertension identifies an intermediate risk group for placental-mediated diseases.
Clinical characteristics and genotype-phenotype correlation analysis of familial Alzheimer’s disease patients with pathogenic/likely pathogenic amyloid protein precursor mutations
Authors: Liu Yingzi , Xiao Xuewen , Liu Hui , Liao Xinxin , Zhou Yafang , Weng Ling , Zhou Lu , Liu Xixi , Bi Xiang-yun , Xu Tianyan , Zhu Yuan , Yang Qijie , Zhang Sizhe , Hao Xiaoli , Zhang Weiwei , Wang Junling , Jiao Bin , Shen Lu
Published: October 2022

Alzheimer’s disease (AD) is a progressive neurodegenerative disease associated with aging, environmental, and genetic factors. Amyloid protein precursor (APP) is a known pathogenic gene for familial Alzheimer’s disease (FAD), and now more than 70 APP mutations have been reported, but the genotype-phenotype correlation remains unclear. In this study, we collected clinical data from patients carrying APP mutations defined as pathogenic/likely pathogenic according to the American college of medical genetics and genomics (ACMG) guidelines. Then, we reanalyzed the clinical characteristics and identified genotype-phenotype correlations in APP mutations. Our results indicated that the clinical phenotypes of APP mutations are generally consistent with typical AD despite the fact that they show more non-demented symptoms and neurological symptoms. We also performed genotype-phenotype analysis according to the difference in APP processing caused by the mutations, and we found that there were indeed differences in onset age, behavioral and psychological disorders of dementia (BPSD) and myoclonus.
Some sufficient conditions on hamilton graphs with toughness
Authors: Cai Gaixiang , Yu Tao , Xu Huan , Yu Guidong
Published: October 2022

Let G be a graph, and the number of components of G is denoted by c(G). Let t be a positive real number. A connected graph G is t-tough if tc(G − S) ≤ |S| for every vertex cut S of V(G). The toughness of G is the largest value of t for which G is t-tough, denoted by τ(G). We call a graph G Hamiltonian if it has a cycle that contains all vertices of G. Chvátal and other scholars investigate the relationship between toughness conditions and the existence of cyclic structures. In this paper, we establish some sufficient conditions that a graph with toughness is Hamiltonian based on the number of edges, spectral radius, and signless Laplacian spectral radius of the graph.

MR subject classifications: 05C50, 15A18.
Sleep medicine: Practice, challenges and new frontiers
Authors: Parrino Liborio , Halasz Peter , Szucs Anna , Thomas Robert J. , Azzi Nicoletta , Rausa Francesco , Pizzarotti Silvia , Zilioli Alessandro , Misirocchi Francesco , Mutti Carlotta
Published: October 2022

Sleep medicine is an ambitious cross-disciplinary challenge, requiring the mutual integration between complementary specialists in order to build a solid framework. Although knowledge in the sleep field is growing impressively thanks to technical and brain imaging support and through detailed clinic-epidemiologic observations, several topics are still dominated by outdated paradigms. In this review we explore the main novelties and gaps in the field of sleep medicine, assess the commonest sleep disturbances, provide advices for routine clinical practice and offer alternative insights and perspectives on the future of sleep research.
Association between vitamin D serum levels and insulin resistance assessed by HOMA-IR among non-diabetic adults in the United States: Results from NHANES 2007–2014
Authors: Yin Xin , Chen Jia-Yu , Huang Xiang-Jie , Lai Jia-Hong , Huang Chang , Yao Wang , Li Nan-Xi , Huang Wei-Chao , Guo Xu-Guang
Published: October 2022

Insulin resistance, a pathological response to insulin hormone in insulin-dependent cells, is characterized by the presence of high glucose and insulin concentrations. The homeostasis model of insulin resistance (HOMA-IR) is one of the most used indexes to estimate insulin resistance by assessing the fasting glucose and insulin levels. An association was observed between vitamin D levels and insulin resistance, which varied in different ethnic groups, and there is some evidence that vitamin D supplementation could contribute to the improvement of insulin resistance. This study assessed the association between 25-hydroxyvitamin D (25[OH]D) concentration and HOMA-IR in American adults aged 20 years and older, without diabetes and other chronic diseases that can influence insulin resistance. The data from the National Health and Nutrition Examination Survey (NHANES) 2007–2014 were used by exploiting the free and publicly-accessible web datasets. Linear regression models were performed to evaluate the association between serum 25(OH)D concentration and HOMA-IR, and a negative association was observed, which remained significant following the adjustment for age, gender, race/ethnicity, education, body mass index (BMI), physical activity, the season of examination, current smoking, hypertension, the use of drugs which can influence insulin resistance, serum bicarbonates, triglycerides, and calcium and phosphorus levels. Only in non-Hispanic Blacks was this inverse association between vitamin D and HOMA-IR not observed in the fully adjusted model. Further studies are needed to explain the mechanisms of the observed ethnic/racial differences in the association of vitamin D levels with HOMA-IR.
Defining pain-validation: The importance of validation in reducing the stresses of chronic pain
Authors: Nicola Melinda , Correia Helen , Ditchburn Graeme , Drummond Peter D.
Published: October 2022

Purpose

To validate an individual's feelings or behaviour is to sanction their thoughts or actions as worthy of social acceptance and support. In contrast, rejection of the individual's communicated experience indicates a denial of social acceptance, representing a potential survival threat. Pain-invalidation, though ill-defined, appears to be a fundamental component of psychosocial stress for people with chronic pain. As such, the aim of this paper was to define pain-validation and outline its importance for those with chronic pain.

Methods

The pain-validation construct was defined using themes inherent in the narratives of those with chronic pain, as identified in a previously published systematic search and thematic analysis, together with examination of additional literature on pain-validation in the clinical context.

Results

We present a construct definition, proposing that pain-validation must necessarily include: (i) belief that the pain experience is true for the individual, (ii) acceptability of the individual's expressions of pain, and (iii) communication of belief and acceptability to the individual experiencing pain. Further, we outline the importance of pain-validation as a protective factor and means of reducing many of the psychosocial stresses of chronic pain; for example, by indicating social support for pain-coping, buffering negative emotions, and re-enforcing unity and shared identity.

Implications

The role of pain-validation in the current era of pain management intervention is discussed. Adhering to interventions that involve cognitive and behavioural change is often difficult. Acknowledging and validating the acceptability of the patient's pain experience in the early stages of pain management may, therefore, be a key component of intervention that encourages compliance to the treatment plan and achieving therapeutic goals.
Caregiver distress: A mixed methods evaluation of the mental health burden of caring for children with bladder exstrophy
Authors: Spencer Katelyn A. , Ramji Jaishri , Unadkat Pooja , Nadeem Iqra , Lalakia Parth A. , Shah Jay , Reddy Pramod P. , Canning Douglas A. , Pippi-Salle Joao , Merguerian Paul , Kundu Anjana , Weiss Dana A. , Shukla Aseem R. , Joshi Rakesh , Frazier Jennifer R.
Published: October 2022

Introduction

Caring for children with bladder exstrophy-epispadias complex (BEEC) exacts a long-term emotional toll on caregivers. Previous studies leave a gap in understanding the impact that caring for a child with BEEC has on caregivers in low- and middle-income countries (LMIC). We hypothesize that families and caregivers experience psychological distress that has long gone unaddressed.

Materials and methods

From 2018 to 2020, researchers conducted a multi-method evaluation of caregiver distress with participants recruited as part of the annual International Bladder Exstrophy Collaboration based in Ahmedabad, Gujarat, India. In 2018, pilot data was collected through cognitive interviews. In 2019, researchers conducted structured interviews predicated on themes from the previous year, which subsequently prompted formal mental health screenings in 2020. Caregivers who reported suicidal thoughts were immediately referred for intervention.

Results

In 2018, caregivers described the primary source of stigma arose from their village (n = 9, 26.5%). Caregivers also identified long-term concerns (n = 18, 52.9%), including future fertility and marital prospects, as sources of anxiety. In 2019, caregivers substantiated preliminary findings with the primary source of anticipated (n = 9, 31%) and experienced (n = 19, 65.5%) stigma again stemming from their communities. Both cohorts identified the collaboration as a positive source of support (n = 23, 36.5%). In 2020, caregivers stated decreased emotional wellbeing as number of subsequent repairs increased (n = 54, 75%, p = 0.002). Caregivers of children who underwent initial surgery within 5 years of screening reported higher anxiety (n = 46, 63.8%) and this was exacerbated as the number of subsequent repairs increased (p = 0.043).

Conclusion

Complex, long-term course of care, including additional surgeries, significantly impacts caregiver distress in the LMIC setting. Screening for caregivers of children with complex congenital anomalies, like BEEC, should be an essential element of any comprehensive effort to alleviate the global burden of disease.
Predictors of advanced chronic kidney disease in infancy after definitive vesicoamniotic shunting for congenital lower urinary tract obstruction
Authors: Katsoufis Chryso Pefkaros , DeFreitas Marissa , Leuchter Jessica , Seeherunvong Wacharee , Chandar Jayanthi , Abitbol Carolyn
Published: October 2022

Background

Severe congenital lower urinary tract obstruction (cLUTO) is associated with poor postnatal outcomes, including chronic and end stage kidney disease, and high mortality. Studies of the impact of fetal intervention through vesicoamniotic shunting are marred by a device malfunction rate of up to 60%. In this study, we delineate the postnatal course and infant kidney function following definitive urinary diversion in utero.

Materials and Methods

This is a retrospective, single-center cohort study of 16 male infants who survived the fetal intervention to birth, from 2010 to 2014 at a single center. All had patent shunts in place at birth. Perinatal and biochemical characteristics were collected with patients followed for one year, or until demise, with serial measures of serum creatinine (SCr) and serum cystatin C (CysC).

Results

Of the 16 males, 81% were non-white (38% black, 43% Hispanic). Shunts were placed at a median of 20 weeks (IQR 19,23) gestation, with median fetal bladder volume of 39 cm3 (IQR 9.9,65). All neonates were born preterm [median 34 weeks (IQR 31,35)] and the majority with low birth weight [median 2340 grams (1,895, 2,600)]. 63% required positive pressure ventilation. Advanced chronic kidney disease stage 4–5 at 1 year of age was predicted by neonatal characteristics: peak SCr ≥2 mg/dl, time to peak SCr > 6 days, discharge SCr ≥1.0 mg/dl, CysC ≥2.5 mg/l, urine protein:creatinine ≥4.8 mg/mg, urine microalbumin:creatinine ≥2.2 mg/mg. In infancy, a nadir SCr ≥0.5 mg/dl occurring before 160 days (5.3 months) of age was also predictive of advanced chronic kidney disease stage 4–5 at 1 year. Three patients died in the neonatal period, with 1 receiving kidney replacement therapy (KRT). Three additional patients required KRT before 12 months of age.

Conclusions

Even with definitive vesicoamniotic shunting for cLUTO, postnatal morbidity and mortality remain high, emphasizing the role of renal dysplasia, in spite of urinary diversion, in postnatal kidney dysfunction. Neonatal and infant biochemical parameters exhibit distinct trends that offer families and physicians a better understanding of the prognosis of childhood kidney function.
Anti-prostate cancer metabolites from the soil-derived Aspergillus neoniveus
Authors: Fayek Menna , Ebrahim Hassan Y. , Elsayed Heba E. , Abdel-Aziz Mohamed S. , Kariuki Benson M. , Moharram Fatma A.
Published: October 2022

Prostate cancer (PCa) ranks as one of the most commonly diagnosed malignancies worldwide. Toxicity, lack of clinical efficacy, and development of resistance phenotypes are the main challenges in the control of prostate malignancies. Notably, castration-resistance prostate cancer (CRPCa) is a highly aggressive and metastatic phenotype of the disease with a poor prognosis and very limited therapeutic options. Herein, we report the isolation and genotypic identification of a soil-derived fungus Aspergillus neoniveus using the PCR-based internal transcribed spacer (ITS) region amplification approach. HPLC/MS investigation of the metabolic profile of the ethyl acetate extract from the fungal biomass revealed tentative identification of forty-five compounds belonging to various chemical classes including γ-butyrolactones, alkaloids, phenolics, and quinoids. Furthermore, the chromatographic purification of microbial extract enabled the identification of nervonic acid methyl ester (1) for the first time from endophytic fungi, as well as acetyl aszonalenin (2), and butyrolactone II (3) for the first time from A. neoniveus. The chemical frameworks of the isolated compounds were identified via extensive spectral analysis including 1 and 2D NMR and MS. The X-ray crystal structure and absolute configuration of acetyl aszonalenin (2) were also determined. Additionally, screening of in vitro anticancer activity of the fungal extract revealed its potential antiproliferative and anti-migratory activities against five different prostate cancer cells (PC3, PC-3M, DU-145, CWR-R1ca, and 22Rv1), including different cells with the castration-resistance phenotype. Moreover, the isolated metabolites significantly inhibited the proliferation, migration, and colonization of human prostate cancer cells at low micromolar levels, thus providing credence for future investigation of these metabolites in relevant anti-prostate cancer animal models. Furthermore, computational target prediction tools identified the cannabinoid G-protein coupled receptors type 1 (CB1) as a potential biological target mediating, at least in part, the anticancer effects of acetylaszonalenin (2). Moreover, molecular modeling and docking studies revealed a favorable binding pose at the CB1 receptor orthosteric ligand pocket aided by multiple polar and hydrophobic interactions with critical amino acids. In conclusion, the Aspergillus neoniveus-derived prenylated indole alkaloid acetylaszonalenin has promising anticancer activity and is amenable to further hit-to-lead optimization for the control of prostate malignancies via modulating CB1 receptors
The potential mechanism of huazhuojiedu decoction in the treatment of ulcerative colitis based on network pharmacology and experimental validation
Authors: Jia Xuemei , Li Ze , Guo Yuxi , Ma Hongyu , Wang Jie , Xue Yucong , Li Bolin , Cai Yanru , Yang Qian
Published: October 2022

Huazhuojiedu decoction (HZJDD), a traditional Chinese medicine prescription, has been clinically proven to be an effective treatment for ulcerative colitis (UC). However, the mechanism of HZJDD in the treatment of UC remains unclear. This study combined network pharmacology with experimental validation to explore the potential mechanism of HZJDD on UC. First, the relationship network diagrams between HZJDD and UC were established based on multiple databases. Then, the HZJDD-UC intersection genes target network was constructed and Gene Ontology-Biological processes (GO-BP) analysis was performed to discover the potential pharmacological mechanism. Finally, the results of GO-BP were verified in dextran sulfate sodium salt (DSS) induced UC rats. The network pharmacology results showed that 119 active components and 146 potential targets were screened for HZJDD, and six of the top 15 biological processes belonged to inflammatory response, cellular response to hypoxia, and cellular response to lipopolysaccharide (LPS). The GO-BP results indicated that the mechanism of HZJDD treatment of UC was related to inflammation, oxidative stress, and the regulation of LPS. Animal experiments showed that HZJDD could significantly reduce the disease activity index (DAI) score, improve colon length, and effectively repair the histomorphological and micromorphological changes in DSS-induced UC rats. Moreover, HZJDD reduced the expressions of CRP, TNF-α, IL-6, LPS, IL-1β, and IL-18; downregulated the activity of MDA; and upregulated the activities of CAT, GSH, and SOD in DSS-induced UC rats. Furthermore, HZJDD suppressed the expression of the NLRP3/caspase-1 signaling pathway at the gene and protein levels to inhibit pyroptosis. Network pharmacology and animal experiments showed that HZJDD exerted a therapeutic effect on DSS-induced UC rats by reducing inflammation, oxidative stress, and restraining the NLRP3/caspase-1 signaling pathway to inhibit pyroptosis.
Transcriptomic analysis of the anti-inflammatory effect of Cordyceps militaris extract on acute gouty arthritis
Authors: Jiao Chunwei , Liang Huijia , Liu Li , Li Shunxian , Chen Jiaming , Xie Yizhen
Published: October 2022

Background: Gouty arthritis (GA) is a common inflammatory disease that causes pain due to the deposition of monosodium urate (MSU) crystals into joints and surrounding tissues. Anti-inflammatory drugs have significant clinical anti-inflammatory and analgesic effects, but they have many side effects. Cordyceps militaris is an edible and medicinal fungus, and its extract (CME) has good anti-inflammatory and analgesic effects. This study aimed to investigate the anti-inflammatory effect of CME on GA and its underlying mechanism.

Methods: The effect of CME on the expression of related inflammatory factors and histopathological changes in the MSU-induced acute inflammatory gout model in rats was studied by ELISA and HE, and its anti-inflammatory mechanism was analyzed by transcriptome combined with RT-qPCR.

Results: CME significantly improved gait scores and joint swelling in GA rats, and reduced MSU-induced inflammatory cell infiltration. CME inhibited MSU-induced inflammatory responses by reducing the levels of pro-inflammatory factors TNF-α, IL-1β, IL-6, and Caspase-1 and increasing the anti-inflammatory factor IL-10. Transcriptome analysis showed that CME significantly altered inflammation-related cytokine pathways, and identified four major genes involved in regulation of inflammation, CCL7, CSF2RB, LIF, and IL-1β. In addition, RT-qPCR was performed to verify these differential genes.

Conclusion: CME significantly alleviated the inflammatory progression of GA and ameliorated the onset of GA. The underlying mechanism may be related to triggering the cytokine-cytokine receptor interaction signaling pathway to inhibit the activation of the inflammasome and regulate the immune system. And it regulates the inflammatory response induced by MSU crystals through the genes CCL7, CSF2RB, and IL-1β.
Using electronic admission data to monitor temporal trends in local medication use: Experience from an Australian tertiary teaching hospital
Authors: Woodman Richard J. , Horwood Chris , Kunnel Aline , Hakendorf Paul , Mangoni Arduino A.
Published: October 2022

Background and aims: Medication usage varies according to prescribing behavior, professional recommendations, and the introduction of new drugs. Local surveillance of medication usage may be useful for understanding and comparing prescribing practices by healthcare providers, particularly in countries such as Australia that are in the process of enhancing nationwide data linkage programs. We sought to investigate the utility of electronic hospital admission data to investigate local trends in medication use, to determine similarities and differences with other Australian studies, and to identify areas for targeted interventions.

Methods: We performed a retrospective longitudinal analysis using combined data from a hospital admissions administrative dataset from a large tertiary teaching hospital in Adelaide, South Australia and a hospital administrative database documenting medication usage matched for the same set of patients. All adult admissions over a 12-year period, between 1 January 2007 and 31st December 2018, were included in the study population. Medications were categorized into 21 pre-defined drug classes of interest according to the ATC code list 2021.

Results: Of the 692,522 total admissions, 300,498 (43.4%) had at least one recorded medication. The overall mean number of medications for patients that were medicated increased steadily from a mean (SD) of 5.93 (4.04) in 2007 to 7.21 (4.98) in 2018. Results varied considerably between age groups, with the older groups increasing more rapidly. Increased medication usage was partly due to increased case-complexity with the mean (SD) Charlson comorbidity index increasing from 0.97 (1.66) in 2007-to-2012 to 1.17 (1.72) in 2013-to-2018 for medicated patients. Of the 21 medication classes, 15 increased (p < 0.005), including antithrombotic agents; OR = 1.18 [1.16–1.21], proton pump inhibitors; OR = 1.14 [1.12–1.17], statins; OR = 1.12; [1.09–1.14], and renin-angiotensin system agents; OR = 1.06 [1.04–1.08], whilst 3 decreased (p < 0.005) including anti-inflammatory drugs (OR = 0.55; 99.5% CI = 0.53–0.58), cardiac glycosides (OR = 0.81; 99.5% CI = 0.78–0.86) and opioids (OR = 0.82; 99.5% CI = 0.79–0.83). The mean number of medications for all admissions increased between 2007 and 2011 and then declined until 2018 for each age group, except for the 18-to-35-year-olds.

Conclusion: Increased medication use occurred in most age groups between 2007 and 2011 before declining slightly even after accounting for increased comorbidity burden. The use of electronic hospital admission data can assist with monitoring local medication trends and the effects of initiatives to enhance the quality use of medicines in Australia.
The pathogenesis, diagnosis, prevention, and treatment of CAR-T cell therapy-related adverse reactions
Authors: Li Yanping , Ming Yue , Fu Ruoqiu , Li Chen , Wu Yuanlin , Jiang Tingting , Li Ziwei , Ni Rui , Li Li , Su Hui , Liu Yao
Published: October 2022

Chimeric antigen receptor (CAR)-T cell therapy is effective in the treatment of refractory/relapsed (r/r) hematological malignancies (r/r B-cell lymphoblastic leukemia, B-cell lymphoma, and multiple myeloma). In addition, it is being explored as a treatment option for solid tumors. As of 31 March 2022, seven CAR-T therapies for hematological malignancies have been approved worldwide. Although CAR-T therapy is an effective treatment for many malignancies, it also causes adverse effects. The incidence of cytokine release syndrome (CRS), the most common adverse reaction after infusion of CAR-T cells, is as high as 93%.CRS, is the leading risk factor of immune effector cell-associated neurotoxicity syndrome (ICANS), as well as cardiovascular, hematological, hepatorenal, skin, pulmonary, and gastrointestinal toxicity. Severe adverse reactions complicated by CRS severely impede the widespread application of CAR-T therapy. The CAR-T product was initially approved in 2017; however, only limited studies have investigated the adverse reactions owing to CAR-T therapy compared to that of clinically approved drugs. Thus, we aimed to elucidate the mechanisms, risk factors, diagnostic criteria, and treatment of toxicities concurrent with CRS, thereby providing a valuable reference for the safe, effective, and widespread application of CAR-T therapy.