bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neutrophil Elastase Inhibition by Sivelestat (ONO-5046) Attenuates AngII-Induced Abdominal Aortic Aneurysms in Apolipoprotein E-Deficient Mice
Authors: Hada Yoshiko , Uchida Haruhito A , Okamoto Shugo , Otaka Nozomu , Katayama Katsuyoshi , Subramanian Venkateswaran , Daugherty Alan , Wada Jun 
Published: November 2023

Abstract

BACKGROUND
Abdominal aortic aneurysm (AAA) is an arterial disease characterized by dilatation of the aortic wall. It has been suggested that neutrophil counts and neutrophil elastase activity are associated with AAA. We investigated whether a neutrophil elastase (NE) inhibitor, sivelestat (Siv), had a protective effect against angiotensin II (AngII)-induced AAAs.

METHODS
Male apolipoprotein E-deficient mice were assigned into three groups: Vehicle + saline, AngII + saline, and AngII + Siv. All mice were administered intraperitoneally with either Siv or vehicle twice daily after AngII infusion.

RESULTS
In the 4-week AngII infusion study, plasma NE concentration (P = 0.041) and its activity (P = 0.011) were elevated by AngII. These increases were attenuated by Siv (concentration:P = 0.010, activity:P = 0.027). Further, plasma elastase activity was closely correlated with aortic width (R = 0.6976, P &lt; 0.001). In the 1-week AngII infusion study, plasma and tissue elastase activity increased by AngII (plasma:P = 0.034, tissue:P &lt; 0.001), but were reduced by Siv (plasma:P = 0.014, tissue:P = 0.024). AngII increased aortic width (P = 0.011) but was attenuated by co-administration of Siv (P = 0.022). Moreover, Siv decreased the incidence of AAAs (P = 0.009). Elastin fragmentation induced by AngII was reduced by Siv. Many inflammatory cells that were either CD68 or Gr-1 positive were observed in the AngII + saline group, whereas few inflammatory cells were accumulated in the AngII + Siv group. MMP-2 and MMP-9 were enhanced by AngII, but were reduced by Siv. In vitro, MMP-2 activity was induced by human NE (medium:P &lt; 0.001, cells:P = 0.001), which was attenuated by co-incubation of Siv in medium (P &lt; 0.001) and protein of human aortic smooth muscle cells (P = 0.001).

CONCLUSIONS
Siv attenuated AngII-induced AAA through the inhibition of NE.
Use of remote patient monitoring kits to reduce hospitalization and mortality rates for patients with heart failure
Authors: Ehringer Daniel S , Mughmaw Taylor E , Albers Ryan C 
Published: November 2023

Abstract

Purpose
Patients with heart failure (HF) are at an increased risk of volume overload, which can lead to hospital admission. Use of noninvasive remote patient monitoring (RPM) devices utilizing biometric sensors and weighing scales to track vital signs and body weight has uncertain benefits. At the Baptist Health Louisville (BHLOU) HF Clinic, high-risk patients were given RPM kits. The purpose of this study was to determine whether RPM led to reductions in HF hospitalizations and mortality.

Methods
This single-center, retrospective chart review evaluated adult patients presenting to the BHLOU HF Clinic after a recent hospitalization for HF or need for intravenous diuretics within the past 60 days. The study evaluated patients before and after implementation of RPM kits. The primary endpoints were differences in the rates of 30-day HF hospitalization and 30-day mortality. Secondary endpoints included differences in the number of interventions in 90 days, the 90-day rate of HF hospitalization, and the 90-day rate of mortality.

Results
The final analysis included 58 patients in the preimplementation group and 34 patients in the postimplementation group. The rate of 30-day HF hospitalization was 10.3% in the preimplementation group and 0% in the postimplementation group. The rate of 30-day mortality was 3.4% in the preimplementation group and 0% in the postimplementation group. For the secondary endpoints, the number of interventions in 90 days was 3 vs 4, the 90-day rate of HF hospitalization was 22.4% vs 11.8%, and the rate of 90-day mortality was 6.9% vs 5.9% in the preimplementation vs postimplementation group, respectively.

Conclusion
Implementation of RPM in patients with acutely decompensated HF led to numerically lower 30-day and 90-day rates of HF hospitalization.
Parenting Practices and Children’s Quality of Life in China: The Mediating Role of Self-Esteem
Authors: Sun Xiaoyue , He Xuesong 
Published: November 2023

Abstract
Drawing upon a sample of 1,482 primary school students and their parents in Shanghai, China, this study investigated the relationship between parenting practices, children’s self-esteem and children’s quality of life. The results from the correlation analysis and structural equation modelling showed that parenting practices were significantly associated with children’s quality of life. In addition, children’s self-esteem could mediate the relationship between parenting practices and children’s quality of life. Children’s self-esteem can promote the positive effects of positive parenting practices and alleviate the negative effects of negative parenting practices on their quality of life. Interventions could consider strengthening positive parenting skills and children’s self-esteem to improve children’s quality of life.
Regional homogeneity alterations in patients with functional constipation and their associations with gene expression profiles
Authors: Cai Wangli , Tian Hongliang , Sun Peiwen , Hua Ting , Gong Jian , Zhang Ruiling , Wan Lidi , Gu Guoqing , Zhang Haiying , Tang Guangyu , Chen Qiyi , Zhang Lin 
Published: November 2023

Abstract
Functional constipation, a highly prevalent functional gastrointestinal disorder, often accompanies by mental and psychological disorders. Previous neuroimaging studies have demonstrated brain functional and structural alterations in patients with functional constipation. However, little is known about whether and how regional homogeneity is altered in these patients. Moreover, the potential genetic mechanisms associated with these alterations remain largely unknown. The study included 73 patients with functional constipation and 68 healthy controls, and regional homogeneity comparison was conducted to identify the abnormal spontaneous brain activities in patients with functional constipation. Using Allen Human Brain Atlas, we further investigated gene expression profiles associated with regional homogeneity alterations in functional constipation patients with partial least squares regression analysis applied. Compared with healthy controls, functional constipation patients demonstrated significantly decreased regional homogeneity in both bilateral caudate nucleus, putamen, anterior insula, thalamus and right middle cingulate cortex, supplementary motor area, and increased regional homogeneity in the bilateral orbitofrontal cortex. Genes related to synaptic signaling, central nervous system development, fatty acid metabolism, and immunity were spatially correlated with abnormal regional homogeneity patterns. Our findings showed significant regional homogeneity alterations in functional constipation patients, and the changes may be caused by complex polygenetic and poly-pathway mechanisms, which provides a new perspective on functional constipation’s pathophysiology.
Stress, burnout, and the need for support: a survey of early career pharmacists
Authors: Bradley Fiona , Hammond Michael , Braund Rhiannon 
Published: November 2023

Abstract

Background
Burnout of health professionals is of concern internationally and the pharmacy profession is no exception. The period of transition from University to autonomous practitioner is recognized to be challenging and these Early Career Pharmacists (ECPs), may be at increased risk of stress and burnout.

Objectives
This study aimed to collect data on the current extent of self-identified stress and burnout, of ECPs, and to (i) identify contributing factors and (ii) identify strategies used to manage this stress.

Methods
This study was conducted in Aotearoa New Zealand and was based on a survey used previously in Australia. A national database was used to identify all pharmacists who had been registered for &lt;10 years. The survey was emailed to each pharmacist, and was further advertised through social media platforms.

Results
A total of 1418 ECPs were identified and invited to participate, and responses were received by 416 of these. The majority of respondents were female (73%) and community pharmacy based (79%). A vast majority (89%) indicated that a normal working day was at least moderately stressful with 79% indicating a level of burnout. These reflect a combination of “external” stressors, i.e. negative patient interactions, staff shortages, and “internal” stressors, i.e. fear of making a mistake, adjustment from University to working life.

Conclusions
Stress and burnout appear to be widespread in the ECPs, this study highlights areas of concern and potential support where efforts can be focussed to create a more sustainable working environment.
Antitrust under the popular economy: the birth of the antitrust law in Brazil
Authors: Medeiros José Augusto 
Published: November 2023

ABSTRACT
This article analyses the context of the first Brazilian antitrust law, between 1930 and 1945. Its goal is to clarify how the ‘popular economy’—a constitutional and legal concept of the time—functioned as a protective instrument for the internal market. The study explores the hypothesis that the legislation was directed at foreign economic power, already embedded in national economic structures at the time. The research demonstrates that the antitrust legislation arose not only to control prevailing economic power but also to provide meaning to it within the framework of the Estado Novo and its intent to reformulate the internal market. Furthermore, this article highlights the influence of constitutional and administrative doctrines in this movement, indicating how the antitrust system was modulated on liberal bases, assuming the curious figure of a strong State subsidiary to the private sector. The work demonstrates that, aside from the question of supply, a crisis in the insurance policy market throughout 1938 was crucial to drafting the first antitrust law.
Comparative study of the steady-state subcellular distribution of lysosome-associated membrane glycoprotein-2 (LAMP-2) isoforms with GYXXΦ-type tyrosine-based motifs that interact differently with four adaptor protein (AP) complexes
Authors: Yamaguchi Fumiaki , Sakane Hiroshi , Akasaki Kenji 
Published: November 2023

Abstract
Lysosome-associated membrane protein-1 and -2 (LAMP-1 and LAMP-2, respectively) are type I transmembrane proteins. LAMP-2 comprises three splice isoforms (LAMP-2A, -B and-C) with different cytoplasmic tails (CTs). These three CTs possess different tyrosine-based motifs (GYXXΦ, where Φ is a bulky hydrophobic amino acid) at their C-termini. Interactions between tyrosine-based motifs and μ-subunits of four tetrameric adaptor protein (AP) complexes are necessary for their vesicular transport to lysosomes. Little is known about how the interaction strengths of these tyrosine motifs with μ-subunits affect the localization of isoforms to lysosomes. The interactions were first investigated using a yeast two-hybrid system to address this question. LAMP-2A-CT interacted with all four μ-subunits (μ1, μ2, μ3A and μ4 of AP-1, AP-2, AP-3 and AP-4, respectively). The interaction with μ3A was more robust than that with other μ-subunits. LAMP-2B-CT interacted exclusively and moderately with μ3A. LAMP-2C-CT did not detectably interact with any of the four μ-subunits. Immunofluorescence microscopy showed that all isoforms were localized in late endosomes and lysosomes. LAMP-2C was present in the plasma membrane and early endosomes; however, LAMP-2A and -2B were barely detectable in these organelles. In cell fractionation, LAMP-2A was the most abundant in the dense lysosomes, whereas LAMP-2C was significantly present in the low-density fraction containing the plasma membrane and early endosomes, in addition to the dense lysosomes. LAMP-2B considerably existed in the low-density late endosomal fraction. These data strongly suggest that the LAMP-2 isoforms are distributed differently in endocytic organelles depending on their interaction strengths with AP-3.
Molecular Mechanism of Autophagy, Cytoplasmic Zoning by Lipid Membranes
Authors: Kotani Tetsuya , Yasuda Yuri , Nakatogawa Hitoshi 
Published: November 2023

Abstract
Autophagy is a highly conserved intracellular degradation mechanism. The most distinctive feature of autophagy is the formation of double-membrane structures called autophagosomes, which compartmentalize portions of the cytoplasm. The outer membrane of the autophagosome fuses with the vacuolar/lysosomal membrane, leading to the degradation of the contents of the autophagosome. Approximately 30 years have passed since the identification of autophagy-related (ATG) genes and Atg proteins essential for autophagosome formation, and the primary functions of these Atg proteins have been elucidated. These achievements have significantly advanced our understanding of the mechanism of autophagosome formation. This article summarizes our current knowledge on how the autophagosome precursor is generated, and how the membrane expands and seals to complete the autophagosome.
Clinical Outcomes of Human Rhinovirus Infections in Pediatric Hemopoietic Stem Cell Transplant Patients
Authors: Castejon-Ramirez Sandra , Chaisavaneeyajirn Sujittra , Ferrolino Jose A , Allison Kim J , Peterson Megan , Dallas Ronald H , Suliman Ali , Hayden Randall T , Maron Gabriela , Hijano Diego R 
Published: November 2023

Abstract

Background
Respiratory viral infections (RVIs) are common among pediatric transplant patients, with Human rhinovirus (HRV) being most frequently. In pediatric patients undergoing hematopoietic cell transplant (HCT), HRV infection prior to, or early post-transplant has been associated with progression to lower respiratory tract infection (LRTI) and adverse outcomes. The primary objective is to describe the clinical presentation and outcomes of HRV infections in patients undergoing HCT at St. Jude Children’s Research Hospital.

Methods
This is a single-center retrospective cohort study. HCT recipients who had a respiratory sample positive for HRV (HRV positive) or negative for any respiratory virus (virus negative) between October 1, 2014, and December 31, 2017, were included. Testing was performed using BioFire® Respiratory Panel. Primary outcomes were progression to LRTI, ICU admission, all-cause mortality rate, and respiratory event-related mortality rate.

Results
A total of 227 patients (166 allogeneic and 61 autologous transplants) were included in the analysis. Of these, 108 (47.5%) were HRV positive and 119 (52.4%) were virus negative. Of the HRV patients, 63.6% were diagnosed pretransplant. All samples were nasopharyngeal, except for 1 tracheal aspirate. There were no significant differences in sex, race, type of transplant, underlying malignancy, and conditioning regimen between patients with and without HRV infection. However, patients who had HRV were significantly younger compared with virus negative (Table 1). Cough and rhinorrhea were more frequently observed in patients with HRV (53.7% vs 19.8%, and 60.2% vs 22.8%, respectively). Almost 1 in 4 patients with HRV had LRTI. No significant association was found between the severity of respiratory disease and the type of conditioning regimen, type of transplant, or absolute lymphocyte count (ALC) within a week of infection. HRV positive patients were more likely to be tested due to symptoms, have URTI, and present with co-infections compared to the virus negative group. There were no differences in the proportion of abnormal radiological findings, and no differences in outcomes between groups (Table 1). Clearance of HRV infection was confirmed with a negative PCR in 45 patients. Of these, 60% remained positive by week 4.

Conclusion
HRV infection is frequently detected in symptomatic patients undergoing transplant. Despite presenting respiratory symptoms more frequently, there was not a significant association with progression to LRTI, need for intensive care unit, mechanical ventilation or mortality.
Hold your Horses! An Uncommon Cause of Bacteremia in HCT Recipients
Authors: Castejon-Ramirez Sandra , Hijano Diego R , Maron Gabriela 
Published: November 2023

Abstract

Background
Diagnosis and management of bloodstream infections due to uncommon microorganisms in immunocompromised hosts (ICH) are challenging. Removing central venous catheters (CVC) and combination antimicrobial therapy may be necessary.

Case
A 2-year-old female with Mucopolysaccharidosis type I on day +125 after matched unrelated donor allogenic transplant presented with 2 days of decreased activity. Two days prior, she had completed 4 weeks of ciprofloxacin and clarithromycin for treatment of Mycobacterium cosmeticum catheter-related bacteremia (CRBSI). The CVC was removed. The patient lived in a rural area but had no direct animal exposure, except for an indoor vaccinated dog. Household contacts were healthy and immunized.
The patient was febrile and tachycardic with no evidence of infection around CVL or G-tube. Laboratory results showed pancytopenia and elevated C-reactive protein Blood cultures grew diphtheroid gram-positive bacilli (GPB) and gram-positive cocci (GPC) in clusters, the later identified as S. epidermidis. The GPB could not be identified from the liquid media and was sent to an outside lab. The report was corrected to GPC after growing on solid medium culture.
The patient was started on meropenem and vancomycin and the CVC was removed. The GPB was identified as Rhodococcus equi. A chest CT showed new ground glass nodules in the left lower lobe. The patient defervesced and was discharged on a 10-day course of oral linezolid for S. epidermidis, clarithromycin and levofloxacin. She completed one month of clarithromycin and levofloxacin. Chest CT at end of treatment confirmed resolution.

Discussion and conclusions
Rhodococcus equi is a pleomorphic gram-positive bacteria that presents as cocci in solid media and as a diphtheroid gram-positive rod in liquid media. Horses are the primary hosts, but most herbivores are fecal carriers. Transmission occurs through inhalation of dust from contaminated soil. R.equi frequently presents as pulmonary infection with cavitated nodules. Over half of ICH develop secondary bacteremia. Extrapulmonary infection secondary to dissemination of pulmonary disease can occur but isolated extrapulmonary disease is rare. R.equi can be easily dismissed as a contaminant requiring a high level of suspicion and communication with lab personnel. When isolated from an extrapulmonary location, chest imagining is essential to guide treatment. Treatment should combine two antibiotics, at least one of them with intracellular activity, with fluoroquinolones and macrolides among the preferred options. For device-related infections, removal is recommended. Treatment duration for uncomplicated infections is 10 to 14 days, but cavitary lesions require longer treatment based on the resolution of lesions
MTDH enhances radiosensitivity of head and neck squamous cell carcinoma by promoting ferroptosis based on a prognostic signature
Authors: Cao Xiang , Ge Yizhi , Yan Zhenyu , Hu Xinyu , Peng Fanyu , Zhang Yujie , He Xia , Zong Dan 
Published: November 2023

Abstract
Ionizing radiation (IR) induces ferroptosis in head and neck squamous cell carcinoma (HNSCC). But, it remains unclear whether ferroptosis affects the prognosis of HNSCC patients after receiving radiotherapy. This study aims to develop a ferroptosis signature to predict the radiosensitivity and prognosis of HNSCC. Ferroptosis-related genes, clinical data and RNA expression profiles were obtained from the FerrDb database, The Cancer Genome Atlas and GEO database. Prognostic genes were identified by random survival forest, univariate Cox regression, Kaplan–Meier and ROC analyses. Principal component analysis, multivariate Cox regression, nomogram and DCA analyses were conducted to estimate its predictive ability. Functional enrichment and immune-related analyses were performed to explore potential biological mechanisms and tumor immune microenvironment. The effect of the hub gene on ferroptosis and radiosensitivity was verified using flow cytometry, quantitative real-time PCR and clonogenic survival assay. We constructed a ferroptosis-related signature, including IL6, NCF2, metadherin (MTDH) and CBS. We classified patients into high-risk (HRisk) and low-risk groups according to the risk scores. The risk score was confirmed to be an independent predictor for overall survival (OS). Combining the clinical stage with the risk score, we established a predictive nomogram for OS. Furthermore, pathways related to tumorigenesis and tumor immune suppression were mainly enriched in HRisk. MTDH was verified to have a potent effect on IR-induced ferroptosis and consequently promoted radiosensitivity. We constructed a ferroptosis-related signature to predict radiosensitivity and OS in HNSCC patients. MTDH was identified as a promising therapeutic target in radioresistant HNSCC patients.
The accretion history of the Milky Way – II. Internal kinematics of globular clusters and of dwarf galaxies
Authors: Hammer Francois , Wang Jianling , Mamon Gary A , Pawlowski Marcel S , Yang Yanbin , Jiao Yongjun , Li Hefan , Bonifacio Piercarlo , Caffau Elisabetta , Wang Haifeng 
Published: November 2023

ABSTRACT
We study how structural properties of globular clusters and dwarf galaxies are linked to their orbits in the Milky Way halo. From the inner to the outer halo, orbital energy increases and stellar-systems gradually move out of internal equilibrium: in the inner halo, high-surface brightness globular clusters are at pseudo-equilibrium, while further away, low-surface brightness clusters and dwarfs appear more tidally disturbed. Dwarf galaxies are the latest to arrive into the halo as indicated by their large orbital energies and pericentres, and have no time for more than one orbit. Their (gas-rich) progenitors likely lost their gas during their recent arrival in the Galactic halo. If dwarfs are at equilibrium with their dark matter (DM) content, the DM density should anticorrelate with pericentre. However, the transformation of DM dominated dwarfs from gas-rich rotation-supported into gas-poor dispersion-supported systems is unlikely accomplished during a single orbit. We suggest instead that the above anticorrelation is brought by the combination of ram-pressure stripping and of Galactic tidal shocks. Recent gas removal leads to an expansion of their stellar content caused by the associated gravity loss, making them sufficiently fragile to be transformed near pericentre passage. Out of equilibrium dwarfs would explain the observed anticorrelation of kinematics-based DM density with pericentre without invoking DM density itself, questioning its previous estimates. Ram-pressure stripping and tidal shocks may contribute to the dwarf velocity dispersion excess. It predicts the presence of numerous stars in their outskirts and a few young stars in their cores.