bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of Phytosterols as an Alternative to Cholesterol in Practical Diets on Growth and Nonspecific Immunity of Litopenaeus vannamei
Authors: Chen Yongkang , Pan Zhongchao , Li Xiaoyue , Yao Xinzhou , He Guilun , Xie Shiwei 
Published: April 2023

This study is aimed at evaluating the effectiveness of phytosterols as an alternative to cholesterol in practical diets of Pacific white shrimp Litopenaeus vannamei from the perspective of growth and nonspecific immunity. Five diets were formulated to contain different sterol sources and levels. Two diets were supplemented with 1 g/kg cholesterol (LC (low cholesterol)) or phytosterol (LP (low phytosterol)). Other three experimental diets were supplemented with 2 g/kg cholesterol (HC (high cholesterol)), 2 g/kg phytosterol (HP (high phytosterol)), or mixed sterol source (CP,

1

g
/
kg

cholesterol
+
1

g
/
kg

phytosterol

), respectively. A total of 750 healthy and uniform-sized shrimp (

0.52
±
0.008

g

) were randomly distributed into 5 groups with 3 replicates and fed with the five experimental diets for 60 days. Results showed that the growth performance of shrimp was influenced by the sterol levels and supplementation with 2 g/kg sterol level facilitated the growth of shrimp. The inclusion of phytosterol has a cholesterol-lowering effect on shrimp, as evidenced by a reduction in hemolymph cholesterol and triglyceride contents in the HP group. Besides, supplementation with 2 g/kg phytosterol or mixed sterol sources had positive effects on the hemolymph superoxide dismutase, phenol oxidase, and lysozyme as well as hepatopancreas alkaline phosphatase activities, demonstrating that the nonspecific immunity and antioxidative capacity were improved. In conclusion, phytosterols could be an appropriate alternative to partially replace dietary cholesterol in shrimp feeds. This study preliminarily revealed the effects of different sterol sources and levels on the growth and nonspecific immunity of shrimp and provided a basis for further exploration of the mechanism of phytosterol.
Dimeric p53 Mutant Elicits Unique Tumor-Suppressive Activities through an Altered Metabolic Program
Authors: Gencel-Augusto Jovanka , Su Xiaoping , Qi Yuan , Whitley Elizabeth M. , Pant Vinod , Xiong Shunbin , Shah Vrutant , Lin Jerome , Perez Encarnacion , Fiorotto Marta L. , Mahmud Iqbal , Jain Abhinav K. , Lorenzi Philip L. , Navin Nicholas E. , Richie Ellen R. , Lozano Guillermina 
Published: April 2023

Abstract

Cancer-related alterations of the p53 tetramerization domain (TD) abrogate wild-type (WT) p53 function. They result in a protein that preferentially forms monomers or dimers, which are also normal p53 states under basal cellular conditions. However, their physiologic relevance is not well understood. We have established in vivo models for monomeric and dimeric p53, which model Li–Fraumeni syndrome patients with germline p53 TD alterations. p53 monomers are inactive forms of the protein. Unexpectedly, p53 dimers conferred some tumor suppression that is not mediated by canonical WT p53 activities. p53 dimers upregulate the PPAR pathway. These activities are associated with lower prevalence of thymic lymphomas and increased CD8+ T-cell differentiation. Lymphomas derived from dimeric p53 mice show cooperating alterations in the PPAR pathway, further implicating a role for these activities in tumor suppression. Our data reveal novel functions for p53 dimers and support the exploration of PPAR agonists as therapies.

Significance:
New mouse models with TP53R342P (monomer) or TP53A347D (dimer) mutations mimic Li–Fraumeni syndrome. Although p53 monomers lack function, p53 dimers conferred noncanonical tumor-suppressive activities. We describe novel activities for p53 dimers facilitated by PPARs and propose these are “basal” p53 activities.
See related commentary by Stieg et al., p. 1046.
See related article by Choe et al., p. 1250.
This article is highlighted in the In This Issue feature, p. 1027
Patient-Derived iPSCs Faithfully Represent the Genetic Diversity and Cellular Architecture of Human Acute Myeloid Leukemia
Authors: Kotini Andriana G. , Carcamo Saul , Cruz-Rodriguez Nataly , Olszewska Malgorzata , Wang Tiansu , Demircioglu Deniz , Chang Chan-Jung , Bernard Elsa , Chao Mark P. , Majeti Ravindra , Luo Hanzhi , Kharas Michael G. , Hasson Dan , Papapetrou Eirini P. 
Published: April 2023

Abstract

The reprogramming of human acute myeloid leukemia (AML) cells into induced pluripotent stem cell (iPSC) lines could provide new faithful genetic models of AML, but is currently hindered by low success rates and uncertainty about whether iPSC-derived cells resemble their primary counterparts. Here we developed a reprogramming method tailored to cancer cells, with which we generated iPSCs from 15 patients representing all major genetic groups of AML. These AML-iPSCs retain genetic fidelity and produce transplantable hematopoietic cells with hallmark phenotypic leukemic features. Critically, single-cell transcriptomics reveal that, upon xenotransplantation, iPSC-derived leukemias faithfully mimic the primary patient-matched xenografts. Transplantation of iPSC-derived leukemias capturing a clone and subclone from the same patient allowed us to isolate the contribution of a FLT3-ITD mutation to the AML phenotype. The results and resources reported here can transform basic and preclinical cancer research of AML and other human cancers.

Significance:
We report the generation of patient-derived iPSC models of all major genetic groups of human AML. These exhibit phenotypic hallmarks of AML in vitro and in vivo, inform the clonal hierarchy and clonal dynamics of human AML, and exhibit striking similarity to patient-matched primary leukemias upon xenotransplantation.
See related commentary by Doulatov, p. 252.
This article is highlighted in the In This Issue feature, p. 247
A judicialização da fosfoetalonamina sintética no Brasil
Authors: Pitanga Mayara Costa Freire Vasconcellos , Silva Janaína Lima Penalva da , Ramalho Pedro Ivo Sebba 
Published: April 2023

Este artigo analisou a judicialização da fosfoetanolamina sintética no Brasil, a partir de estudo exploratório das decisões judiciais da vara de fazenda pública da comarca de São Carlos, em São Paulo, após a interrupção do fornecimento da substância pela Universidade de São Paulo. O estudo catalogou os argumentos constantes da Ação Direta de Inconstitucionalidade 5.501/DF, que julgou inconstitucional a Lei n. 13.269/2016, que autorizou a produção e a prescrição da fosfoetanolamina sintética para quaisquer tipos de câncer (neoplasia maligna) enquanto os estudos clínicos não fossem concluídos. As sentenças de primeira instância concederam a fosfoetanolamina com base no testemunho dos pacientes sobre impactos positivos do uso da substância em sua saúde e pela ausência de registro de efeitos colaterais. Juízes que concederam acesso à fosfoetanolamina tinham ciência da carência de evidências científicas de segurança e eficácia, bem como do necessário registro da substância como medicamento no órgão regulador, nos termos da legislação sanitária. No Supremo Tribunal Federal, a ausência de evidências científicas e a utilização de legislação para criar exceção casuísta levaram à declaração de inconstitucionalidade da norma pela maioria dos votos. O estudo registra, todavia, certa indisposição do Poder Judiciário em incorporar no processo decisório a avaliação das autoridades de regulação e fiscalização em saúde como fonte da correta avaliação da segurança e eficácia de medicamentos. Em conclusão, o testemunho dos pacientes sobre as perspectivas de cura ou redução do sofrimento, somado à ausência de provas nos processos judiciais sobre os riscos do consumo da fosfoetanolamina, foram cruciais para tais decisões.
Association of Chronic Kidney Disease With Atrial Fibrillation in the General Adult Population: A Nationwide Population‐Based Study
Authors: Kim Seon‐Mi , Jeong Yujin , Kim Yae Lim , Kang Minjung , Kang Eunjeong , Ryu Hyunjin , Kim Yunmi , Han Seung Seok , Ahn Curie , Oh Kook‐Hwan 
Published: April 2023

Background
The incidences of atrial fibrillation (AF) and chronic kidney disease (CKD) are increasing, and AF is prevalent in patients with CKD. However, few studies have investigated the incidence or association of AF in a large CKD population from a longitudinal study.

Methods and Results
From a nationwide cohort, a total of 4 827 987 Korean individuals without prior AF, who received biennial health checkups provided by the National Health Insurance Service between 2009 and 2012 in Korea, were analyzed. Incidence of AF was ascertained through the end of 2018. During a median follow‐up of 8.1 years, the annual incidence rate of AF was 1.17 per 1000 person‐years among subjects without CKD, 1.55 for stage 1 CKD, 1.86 for stage 2 CKD, 2.1 for stage 3 CKD, and 4.33 for stage 4 CKD. In Fine‐Gray regression models, CKD was associated with an increased risk of AF; the adjusted hazard ratios and 95% CIs of AF occurrence were 1.77 (1.69–1.85), 1.85 (1.80–1.91), 1.99 (1.95–2.04), and 4.04 (3.07–5.33) in individuals with CKD stages 1, 2, 3, and 4, respectively, compared with non‐CKD. The association between CKD and incident AF remained statistically significant after adjustment for multiple confounding factors and was consistent across subgroups stratified by sex and age.

Conclusions
CKD is associated with an increased incidence of AF. Even mild CKD is associated with incident AF, and there was a stepwise increase in the risk of incident AF with a decrease in renal function.
Design and Rationale the SCAN‐MP (Screening for Cardiac Amyloidosis With Nuclear Imaging in Minority Populations) Study
Authors: Ruberg Frederick L. , Blaner William S. , Chiuzan Codruta , Connors Lawreen H. , Einstein Andrew J. , Fine Denise , Helmke Stephen , Kurian Damian , Pandey Shivda , Raiszadeh Farbod , Rodriguez Carlos , Sabogal Natalia , Teruya Sergio , Winburn Morgan , Chung Wendy K. , Cohn Elizabeth , Miller Edward J. , Kelly Jeffery W. , Maurer Mathew S. 
Published: April 2023

Background

Transthyretin amyloid cardiomyopathy (ATTR‐CM) is an important cause of heart failure in older individuals. Misfolding and deposition of transthyretin or prealbumin protein causes ATTR‐CM in the context of a normal (wild‐type) or variant
TTR
sequence. Variant ATTR‐CM is most commonly caused by the substitution of valine for isoleucine at position 122 in transthyretin (Val122Ile or pV142I, almost exclusively observed in individuals of West African ancestry), demonstrated in 3.4% of self‐identified Black individuals in the United States with an estimated 1.5 million carriers. Despite the large number of known pV142I carriers, the proportion of older Black patients with heart failure attributable to ATTR‐CM remains unknown.

Methods

To address this knowledge gap, the SCAN‐MP (Screening for Cardiac Amyloidosis with Nuclear Imaging in Minority Populations) study was funded by the National Institutes of Health/National Heart, Lung, and Blood Institute (R01HL139671) to enroll a targeted population of self‐identified, community‐dwelling Black or Caribbean Hispanic patients (many of whom are of West African ancestry) >60 years of age with heart failure and identify ATTR‐CM by noninvasive nuclear imaging. The principal objective of SCAN‐MP is to determine the prevalence of ATTR‐CM in this population. Secondary objectives will explore
TTR
genotype, demographics, progression of variant versus wild‐type ATTR‐CM, and biochemical mechanisms of transthyretin amyloid fibril formation.

Conclusions
The SCAN‐MP study is the largest, prospective study of cardiac amyloidosis in Black and Hispanic individuals. Both wild‐type and variant ATTR‐CM are now treatable with the US Food and Drug–approved drug tafamidis. The insights gained from SCAN‐MP are likely to improve those at risk for or afflicted with ATTR‐CM.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03812172.
Microvascular Dysfunction Is Associated With Impaired Myocardial Work in Obstructive and Nonobstructive Hypertrophic Cardiomyopathy: A Multimodality Study
Authors: Garcia Brás Pedro , Rosa Sílvia Aguiar , Cardoso Isabel , Branco Luísa Moura , Galrinho Ana , Gonçalves António Valentim , Thomas Boban , Viegas José Miguel , Fiarresga António , Branco Gonçalo , Pereira Ricardo , Selas Mafalda , Silva Filipa , Cruz Inês , Baquero Luís , Ferreira Rui Cruz , Lopes Luís Rocha 
Published: April 2023

Background
Two‐dimensional speckle tracking echocardiography has been shown to correlate with microvascular dysfunction, a hallmark of hypertrophic cardiomyopathy (HCM). We hypothesized that there is an association between myocardial work and left ventricular ischemia, with incremental value to global longitudinal strain, in patients with HCM.

Methods and Results

We performed a prospective assessment of patients with HCM, undergoing 2‐dimensional speckle tracking echocardiography and stress perfusion cardiac magnetic resonance. Results were stratified according to obstructive or nonobstructive HCM and the presence of significant replacement fibrosis (late gadolinium enhancement ≥15% of left ventricular mass). Seventy‐five patients with HCM (63% men, age 55±15 years) were evaluated, 28% with obstructive HCM (mean gradient 89±60 mm Hg). Perfusion defects were found in 90.7%, involving 22.5±16.9% of left ventricular mass, and 38.7% had late gadolinium enhancement ≥15%. In a multivariable analysis, a lower global work index (
r
=−0.519, β‐estimate −10.822;
P
=0.001), lower global work efficiency (
r
=−0.379, β‐estimate −0.123;
P
=0.041), and impaired global constructive work (
r
=−0.532, β‐estimate −13.788;
P
<0.001) significantly correlated with ischemia. A segmental analysis supported these findings, albeit with lower correlation coefficients. A global work index cutoff ≤1755 mm Hg% was associated with hypoperfusion with a sensitivity of 88% and a specificity of 71%, while the best cutoff for global longitudinal strain (>−15.5%) had a sensitivity of 64% and a specificity of 57%. The association between myocardial work and perfusion defects was significant independently of late gadolinium enhancement ≥15% and obstructive HCM.

Conclusions
Impaired myocardial work was significantly correlated with the extent of ischemia in cardiac magnetic resonance, independently of the degree of left ventricular hypertrophy or fibrosis, with a higher predictive power than global longitudinal strain.
An Increase in Precipitation Driven by Irrigation over the North China Plain Based on RegCM and WRF Simulations
Authors: Fan Yuwen , Im Eun-Soon , Lan Chia-Wei , Lo Min-Hui 
Published: April 2023

Abstract
Anthropogenic land-use change, irrigation, is considered to strongly modulate the hydroclimate at the regional scale by directly triggering evaporative cooling as the preliminary local effect. However, subsequent interactions with the background climate are highly nonlinear, which introduces diverse and unexpected consequences. The North China Plain (NCP) is one of the regions where irrigation has expanded the most rapidly since the twentieth century. The scarce rainfall in this region makes it necessary for irrigation to supplement the level of soil water for agricultural production. In this study, we quantify the effect of irrigation on the regional climate in China. Two regional climate models, WRF and RegCM, are used to mimic the large-scale practice of irrigation on the NCP. The results of our experiments show consistent cooling and moistening effects centered over the NCP across all experiments. Although the moisture budget and wind field pattern demonstrate that the vertical downdraft and low-level divergence could inhibit rainfall, the humidification dominates the climatic response in the dry April–June and increases the amount of precipitation significantly and consistently in the NCP region and the surrounding area in northern China. The enhanced CAPE increases sharply on some “calm days” when the vertical moisture advection is small, especially during the afternoon, triggering frequent light rains convectively by destabilizing the atmosphere. The consistent response to irrigation in two different models that employ structurally different land surface schemes could enhance the robustness of the physical mechanism behind the precipitation increase in the heavily irrigated region of NCP.
The Treatment of Adult Laryngeal Hemangiomas Located on the Arytenoids: Excision vs. Chemotherapy
Authors: Wu Xiufa , Ma Jingru , Zhang Jing , Wei Chunsheng 
Published: April 2023

Objective To evaluate and compare the results of the excision and bleomycin injection treatment methods for adult laryngeal hemangiomas (ALHs) located on the arytenoids. Methods Twenty-six ALH patients in 29 different cases were enrolled in the study at our department between June 2012 and March 2021. Some patients were treated more than once. Twenty-nine cases of ALH treated with either bleomycin injection or excision were studied to assess the efficacy of both treatments. A lumen constriction score (from 1 to 4) was used to evaluate the therapeutic effect three months later. Results The ALHs in the ALH excision group were resected successfully, and the ALHs did not recur. The mean lumen constriction score for the bleomycin injection group was 2.95. The lumen constriction score for the ALH excision group was higher than that of the bleomycin injection group. Conclusions Both bleomycin injection and excision are safe and effective treatments for ALHs located on the arytenoids. On the condition that the ALH is well exposed and can be completely removed, ALH excision surgery is the preferable method to treat ALHs located on the arytenoids.
Disparities in Radiologist Fee-For-Service Payments by Gender in Canada
Authors: McKee Hayley , Walsh Cynthia , Modares Mana , Yap Wan Wan , Gorelik Natalia , Brown Maura , Yong-Hing Charlotte J , Hanneman Kate 
Published: April 2023

Objective: To examine differences in fee-for-service (FFS) payments to men and women radiologists in Canada and evaluate potential contributors. Methods: Publicly available FFS radiology billing data was analyzed from British Columbia (BC), Ontario (ON), Prince-Edward Island (PEI) and Nova Scotia (NS) between 2017 and 2021. Data was analyzed by gender on a per-province and national level. Variables evaluated included year, province, procedure billings, and days worked (BC and ON only). The gender pay gap was expressed as the difference in mean billing payments between men and women divided by mean payments to men. Results: Data points from 8478 radiologist years were included (2474 [29%] women and 6004 [71%] men). The unadjusted difference in annual FFS billings between men and women was $126,657. Overall, payments to women were 81% of payments to men with a 19% gender pay gap. The difference in billings between men and women did not change significantly between 2017 and 2021 (range in gender pay gap, 17–21%) but did vary by province (highest gap NS). Compared to men, women worked fewer days per year (weighted mean 218 ± 29 vs 236 ± 25 days/year, P < .001, 8% difference). Conclusion: In an analysis of fee-for-service payments to radiologists in 4 Canadian provinces between 2017 and 2021, payments to women were 81% of payments to men with a 19% gender pay gap. Payments were lower to women across all years evaluated. Women worked 8% fewer days per year on average than men, which did not fully account for the difference in FFS billing payments between men and women. Summary Statement: In an analysis of fee-for-service payments to Canadian radiologists between 2017 and 2021, payments to women were 81% of payments to men with a 19% gender pay gap which is not fully accounted for by time spent working.
Rhubarb Anthraquinones Ameliorates Inflammatory Lung Injury by Enhancing Alveolar Epithelium Tight Junction Proteins through RhoA/ROCK1 Signalling
Authors: Liu Guiyuan , Bai Yinliang , Leng Guangxian , Ma Hanwei , Kong Yin , Guo Liuqing , Wu Fahong , Wei Fengxian , Pang Yi , Zhang Youcheng 
Published: April 2023

Background: Leakage of the alveolar epithelial barrier can lead to pulmonary oedema, leading to organ dysfunction. Objectives: Combination anthraquinone (CA) and free anthraquinone (FA) were extracted from Rhubarb, and the prevention and therapeutic effects of Rhubarb anthraquinones (RA) on lipopolysaccharide (LPS)-induced lung injury were investigated. Materials and Methods: The CA and FA were extracted from Rhubarb by water solvent extraction and ethanol solvent extraction. The extracted RA content was determined using spectrophotometry and high-performance liquid chromatography (HPLC). A mouse model of inflammatory lung injury was established by LPS induction to study the mechanism of RA activity. Inflammatory factors were measured using an enzyme-linked immunosorbent assay. Changes in alveolar epithelial leakage were assessed using a permeability assay. Changes in lung injury were evaluated by histopathological and ultrastructural observations. Tight junction (TJ) markers and Ras homolog gene family member A (RhoA)/Rho-associated protein kinase 1 (ROCK1) pathway-related proteins were measured using immunohistochemistry and Western blotting. As an agonist of RhoA/Rock signalling, U46619 was used to further verify whether RA acts through this pathway. Results: RA could inhibit pulmonary inflammation by decreasing the level of inflammatory factors. The alveolar epithelial permeability was reduced, and the pathological injury of the lung tissue was alleviated after administration with RA. Furthermore, the expression of TJ proteins was up regulated and RhoA/ROCK1 signalling was inhibited in the presence of RA. The effects of RA on TJ proteins were partially reversed by U46619. Conclusion: RA effectively protects mice against inflammatory lung injury by enhancing alveolar epithelial TJ via RhoA/ROCK1 signalling.
Dietary Diversity and Haemoglobin Level Associated With Under Nutrition Among Pregnant Women at Sidama Hawassa, Ethiopia: Facility Based Cross-Sectional Study
Authors: Alemu Tsegaye , Yakob Tigist , Solomon Tarekegn 
Published: April 2023

Background: Under nutrition among pregnant women is common public health problem in developing countries including Ethiopia. It leads to poor maternal and neonatal outcomes. Despite its consequences there is shortage of research evidence to support intervention in this regard in the southern part of the country. Therefore, the aim of the study was to assess the determinates of under nutrition among pregnant women visiting antenatal care clinics at selected health facilities in Hawassa town. Methods: Health facility based cross-sectional study was employed among 454 systematically selected study participants. Data were collected by using structured and pre-tested questionnaires with face to face interview. Data were entered into Epi info and then exported to SPSS version 26 statistical software for analysis. Data were analyzed with descriptive statistics; bivariate and multivariate binary logistic regression. Result: The over all of prevalence of under nutrition among pregnant women was 27.6% [95% CI (22.6, 30.8)]. In multivariate logistic regression model, lowest wealth quintile [AOR = 3.3, 95% CI (1.7, 7.0)], women with dietary diversity [AOR = 2.0, 95% CI (1.3, 4.0)], presence of anemia [AOR = 10.7, 95% CI (5.8,19.8)], lower pregnant women education level [AOR = 3.3, 95% CI (1.4, 7.9)], lower partner education level [AOR = 3.1, 95% CI (1.1, 8.5)], not ate flush/meat food [AOR = 2.8, 95% CI (1.7, 4.8)], and not ate other fruits [AOR = 1.8, 95% CI (1.1, 2.8)] had significant association with under nutrition. Conclusion: In this health facility based study, the burden of under nutrition was high. Lowest wealth quintiles, low dietary diversity scores, being anemic and low education of the pregnant women and her partner were associated with under nutrition. Therefore, counseling for dietary diversity during antenatal care, health promotion and education for pregnant women and empowering women on income generation activities are a key intervention to tackle under nutrition.