bluuebunny/crossref_metadata_2025_split huggingface dataset:
Imaging in the era of risk-adapted treatment in colon cancer
Authors: Lahaye Max J , Lambregts Doenja M J , Aalbers Arend G J , Snaebjornsson Petur , Beets-Tan Regina G H , Kok Niels F M 
Published: April 2024

Abstract
The treatment landscape for patients with colon cancer is continuously evolving. Risk-adapted treatment strategies, including neoadjuvant chemotherapy and immunotherapy, are slowly finding their way into clinical practice and guidelines. Radiologists are pivotal in guiding clinicians toward the most optimal treatment for each colon cancer patient. This review provides an overview of recent and upcoming advances in the diagnostic management of colon cancer and the radiologist’s role in the multidisciplinary approach to treating colon cancer.
Inhibition of cyclin-dependent kinase 7 mitigates doxorubicin cardiotoxicity and enhances anticancer efficacy
Authors: Chen Jingrui , Wei Jing , Xia Peng , Liu Yuening , Belew Mahder Dawit , Toohill Ryan , Wu Boyang Jason , Cheng Zhaokang 
Published: April 2024

Abstract

Aims
The anthracycline family of anticancer agents such as doxorubicin (DOX) can induce apoptotic death of cardiomyocytes and cause cardiotoxicity. We previously reported that DOX-induced apoptosis is accompanied by cardiomyocyte cell cycle re-entry. Cell cycle progression requires cyclin-dependent kinase 7 (CDK7)-mediated activation of downstream cell cycle CDKs. This study aims to determine whether CDK7 can be targeted for cardioprotection during anthracycline chemotherapy.

Methods and results
DOX exposure induced CDK7 activation in mouse heart and isolated cardiomyocytes. Cardiac-specific ablation of Cdk7 attenuated DOX-induced cardiac dysfunction and fibrosis. Treatment with the covalent CDK7 inhibitor THZ1 also protected against DOX-induced cardiomyopathy and apoptosis. DOX treatment induced activation of the proapoptotic CDK2–FOXO1–Bim axis in a CDK7-dependent manner. In response to DOX, endogenous CDK7 directly bound and phosphorylated CDK2 at Thr160 in cardiomyocytes, leading to full CDK2 kinase activation. Importantly, inhibition of CDK7 further suppressed tumour growth when used in combination with DOX in an immunocompetent mouse model of breast cancer.

Conclusion
Activation of CDK7 is necessary for DOX-induced cardiomyocyte apoptosis and cardiomyopathy. Our findings uncover a novel proapoptotic role for CDK7 in cardiomyocytes. Moreover, this study suggests that inhibition of CDK7 attenuates DOX-induced cardiotoxicity but augments the anticancer efficacy of DOX. Therefore, combined administration of CDK7 inhibitor and DOX may exhibit diminished cardiotoxicity but superior anticancer activity.
Aquaporins enriched in endothelial vacuole membrane regulate the diameters of microvasculature in hyperglycaemia
Authors: Chen Changsheng , Qin Yinyin , Xu Yidan , Wang Xiaoning , Lei Wei , Shen Xiaozhong , Chen Lixun , Wang Linnong , Gong Jie , Wang Yongming , Hu Shijun , Liu Dong 
Published: April 2024

Abstract

Aims
In patients with diabetic microvascular complications, decreased perfusion or vascular occlusion, caused by reduced vascular diameter, is a common characteristic that will lead to insufficient blood supply. Yet, the regulatory mechanism and effective treatment approach remain elusive.

Methods and results
Our initial findings revealed a notable decrease in the expression of human AQP1 in both diabetic human retina samples (49 healthy vs. 54 diabetic samples) and high-glucose-treated human retinal microvascular endothelial cells. Subsequently, our investigations unveiled a reduction in vascular diameter and compromised perfusion within zebrafish embryos subjected to high glucose treatment. Further analysis indicated a significant down-regulation of two aquaporins, aqp1a.1 and aqp8a.1, which are highly enriched in ECs and are notably responsive to hyperglycaemic conditions. Intriguingly, the loss of function of aqp1a.1 and/or aqp8a.1 resulted in a reduction of intersegmental vessel diameters, effectively mirroring the phenotype observed in the hyperglycaemic zebrafish model. The overexpression of aqp1a.1/aqp8a.1 in zebrafish ECs led to notable enlargement of microvascular diameters. Moreover, the reduced vessel diameters resulting from high-glucose treatment were effectively rescued by the overexpression of these aquaporins. Additionally, both aqp1a.1 and apq8a.1 were localized in the intracellular vacuoles in cultured ECs as well as the ECs of sprouting ISVs, and the loss of Aqps caused the reduction of those vacuoles, which was required for lumenization. Notably, while the loss of AQP1 did not impact EC differentiation from human stem cells, it significantly inhibited vascular formation in differentiated ECs.

Conclusion
EC-enriched aquaporins regulate the diameter of blood vessels through an intracellular vacuole-mediated process under hyperglycaemic conditions. These findings collectively suggest that aquaporins expressed in ECs hold significant promise as potential targets for gene therapy aimed at addressing vascular perfusion defects associated with diabetes.
Mechanisms of ischaemia-induced arrhythmias in hypertrophic cardiomyopathy: a large-scale computational study
Authors: Coleman James A , Doste Ruben , Ashkir Zakariye , Coppini Raffaele , Sachetto Rafael , Watkins Hugh , Raman Betty , Bueno-Orovio Alfonso 
Published: April 2024

Abstract

Aims
Lethal arrhythmias in hypertrophic cardiomyopathy (HCM) are widely attributed to myocardial ischaemia and fibrosis. How these factors modulate arrhythmic risk remains largely unknown, especially as invasive mapping protocols are not routinely used in these patients. By leveraging multiscale digital twin technologies, we aim to investigate ischaemic mechanisms of increased arrhythmic risk in HCM.

Methods and results
Computational models of human HCM cardiomyocytes, tissue, and ventricles were used to simulate outcomes of Phase 1A acute myocardial ischaemia. Cellular response predictions were validated with patch-clamp studies of human HCM cardiomyocytes (n = 12 cells, N = 5 patients). Ventricular simulations were informed by typical distributions of subendocardial/transmural ischaemia as analysed in perfusion scans (N = 28 patients). S1-S2 pacing protocols were used to quantify arrhythmic risk for scenarios in which regions of septal obstructive hypertrophy were affected by (i) ischaemia, (ii) ischaemia and impaired repolarization, and (iii) ischaemia, impaired repolarization, and diffuse fibrosis. HCM cardiomyocytes exhibited enhanced action potential and abnormal effective refractory period shortening to ischaemic insults. Analysis of ∼75 000 re-entry induction cases revealed that the abnormal HCM cellular response enabled establishment of arrhythmia at milder ischaemia than otherwise possible in healthy myocardium, due to larger refractoriness gradients that promoted conduction block. Arrhythmias were more easily sustained in transmural than subendocardial ischaemia. Mechanisms of ischaemia–fibrosis interaction were strongly electrophysiology dependent. Fibrosis enabled asymmetric re-entry patterns and break-up into sustained ventricular tachycardia.

Conclusion
HCM ventricles exhibited an increased risk to non-sustained and sustained re-entry, largely dominated by an impaired cellular response and deleterious interactions with the diffuse fibrotic substrate.
Work Productivity Impairment in Persons with Inflammatory Bowel Diseases: A Systematic Review and Meta-analysis
Authors: Youssef Michael , Hossein-Javaheri Nariman , Hoxha Tedi , Mallouk Christina , Tandon Parul 
Published: April 2024

Abstract

Background and Aims
The impact of inflammatory bowel disease [IBD] on work productivity remains unclear. In this systematic review and meta-analysis, we quantify work-related outcomes and employment data among persons with IBD.

Methods
A systematic literature search was conducted in MEDLINE, EMBASE, the Cochrane library, Scopus, ProQuest, and clinicaltrials.gov from inception to February 2023, to identify studies on work productivity in persons with IBD aged &gt; 18 years. Work productivity was defined primarily by the Work Productivity and Activity Impairment [WPAI] questionnaire which includes absenteeism, presenteeism, overall work impairment, and non-work activity impairment. In addition, we included data on employment, sick leaves, disability pensions, and indirect costs due to productivity loss. Pooled effect analysis was conducted using a random-effects model for pooled estimates of continuous and proportional data with 95% confidence intervals.

Results
Among all patients with IBD, the pooled estimates were 16.4% for absenteeism, 35.9% for presenteeism, 39.4% for overall work impairment, and 46.0% for non-work activity impairment. Indirect costs from overall work impairment were 5131.09 euros/patient/year. Only two-thirds of IBD patients were employed, and one in three lost their jobs due to IBD. Among those employed, 39.5% report sick days, 21.3% report work disability, and 12.3% receive disability pensions. Most studies demonstrate clinically meaningful improvements in work productivity with medical and/or surgical therapies.

Conclusion
Persons with IBD experience significant work impairment and associated indirect costs. This highlights the need for appropriate workplace accommodations and timely medical therapy to alleviate the burden of disease and improve work outcomes.
Bridge to transplant in single-ventricle anatomy: subpulmonary support with EXCOR ventricular assist device associated with pulmonary artery reconstruction
Authors: Domínguez del Castillo José Joaquín , Merino Cejas Carlos Manuel , Gómez Guzmán Elena , Frías Pérez Manuel Angel 
Published: April 2024

Abstract
Patients with a single ventricle circulation continue to be a challenge for a heart transplant. The patients in this cohort, often in poor clinical condition with frequent hepatic and renal impairment having undergone previous multiple surgical procedures, are often allosensitive and consequently have an increased risk of post-transplant complications. Although the most recently published series results are improved, this group of patients, with preserved ventricular function, continues to have a higher mortality rate. Moreover, the operation can be complicated by anatomical differences among the pulmonary arteries. This case report presents a child with tricuspid atresia and pulmonary vascular resistance contraindicating Fontan surgery, unfavourable anatomy of the central pulmonary arteries and in poor clinical condition. An EXCOR ventricular assist device (Berlin Heart) was used for sub- pulmonary mechanical circulatory support and pulmonary bifurcation reconstruction, as a bridge to a transplant.
First report from the European registry for anomalous aortic origin of coronary artery (EURO-AAOCA)
Authors: Gräni Christoph , Stark Anselm W , Lo Rito Mauro , Frigiola Alessandro , Siepe Matthias , Tchana Bertrand , Cipriani Alberto , Zorzi Alessandro , Pergola Valeria , Crea Domenico , Sarris George , Protopapas Elephterios , Sirico Domenico , Di Salvo Giovanni , Pegoraro Cinzia , Sarto Patrizio , Francois Katrien , Frigiola Alessandra , Cristofaletti Alessandra , Accord Ryan E , Gonzalez Rocafort Alvaro , Debeco Geoffroy , Padalino Massimo 
Published: April 2024

Abstract

OBJECTIVES
Anomalous aortic origin of a coronary artery (AAOCA) is a group of rare congenital heart defects with various clinical presentations. The lifetime-risk of an individual living with AAOCA is unknown, and data from multicentre registries are urgently needed to adapt current recommendations and guide optimal patient management. The European AAOCA Registry (EURO-AAOCA) aims to assess differences with regard to AAOCA management between centres.

METHODS
EURO-AAOCA is a prospective, multicentre registry including 13 European centres. Herein, we evaluated differences in clinical presentations and management, treatment decisions and surgical outcomes across centres from January 2019 to June 2023.

RESULTS
A total of 262 AAOCA patients were included, with a median age of 33 years (12–53) with a bimodal distribution. One hundred thirty-nine (53.1%) were symptomatic, whereas chest pain (n = 74, 53.2%) was the most common complaint, followed by syncope (n = 21, 15.1%). Seven (5%) patients presented with a myocardial infarction, 2 (1.4%) with aborted sudden cardiac death. Right-AAOCA was most frequent (150, 57.5%), followed by left-AAOCA in 51 (19.5%), and circumflex AAOCA in 20 (7.7%). There were significant differences regarding diagnostics between age groups and across centres. Seventy-four (28.2%) patients underwent surgery with no operative deaths; minor postoperative complications occurred in 10 (3.8%) cases.

CONCLUSIONS
Currently, no uniform agreement exists among European centres with regard to diagnostic protocols and clinical management for AAOCA variants. Although surgery is a safe procedure in AAOCA, future longitudinal outcome data will hopefully shed light on how to best decide towards optimal selection of patients undergoing revascularization versus conservative treatment.
An Introduction to the Complete Blood Count for Clinical Chemists: Red Blood Cells
Authors: Marin Maximo J , van Wijk Xander M R , Boothe Paul D , Harris Neil S , Winter William E 
Published: April 2024

Abstract

Background
The most frequently ordered laboratory test worldwide is the complete blood count (CBC).

Content
In this primer, the red blood cell test components of the CBC are introduced, followed by a discussion of the laboratory evaluation of anemia and polycythemia.

Summary
As clinical chemists are increasingly tasked to direct laboratories outside of the traditional clinical chemistry sections such as hematology, expertise must be developed. This review article is a dedication to that effort.
Exposure to imipenem at sub-minimum inhibitory concentration leads to altered expression of major outer membrane proteins in Acinetobacter baumannii
Authors: Nayak Srajana , Akshay Sadanand Dangari , Deekshit Vijaya Kumar , Raj Juliet Mohan , Maiti Biswajit 
Published: April 2024

Abstract

Aims
Acinetobacter baumannii is a nosocomial pathogen known to be multidrug-resistant (MDR), especially to drugs of the carbapenem class. Several factors contribute to resistance, including efflux pumps, β-lactamases, alteration of target sites, and permeability defects. In addition, outer membrane proteins (OMPs), like porins are involved in the passage of antibiotics, and their alteration could lead to resistance development. This study aimed to explore the possible involvement of porins and OMPs in developing carbapenem resistance due to differential expression.

Methods and results
The antibiotic-susceptible and MDR isolates of A. baumannii were first studied for differences in their transcriptional levels of OMP expression and OMP profiles. The antibiotic-susceptible isolates were further treated with imipenem, and it was found that the omp genes were differentially expressed. Six of the nine genes studied were upregulated at 1 h of exposure to imipenem. Their expression gradually decreased with time, further confirmed by their OMP profile and two-dimensional gel electrophoresis.

Conclusions
This study could identify OMPs that were differentially expressed on exposure to imipenem. Hence, this study provides insights into the role of specific OMPs in antibiotic resistance in A. baumannii.
Breakdown of hawking evaporation opens new mass window for primordial black holes as dark matter candidate
Authors: Thoss Valentin , Burkert Andreas , Kohri Kazunori 
Published: April 2024

ABSTRACT
The energy injection through Hawking evaporation has been used to put strong constraints on primordial black holes as a dark matter candidate at masses below 1017 g. However, Hawking’s semiclassical approximation breaks down at latest after half-decay. Beyond this point, the evaporation could be significantly suppressed, as was shown in recent work. In this study we review existing cosmological and astrophysical bounds on primordial black holes, taking this effect into account. We show that the constraints disappear completely for a reasonable range of parameters, which opens a new window below 1010 g for light primordial black holes as a dark matter candidate.
Cortical Network Disruption Is Minimal in Early Stages of Psychosis
Authors: Van Dyken Peter C , MacKinley Michael , Khan Ali R , Palaniyappan Lena 
Published: April 2024

Abstract

Background and Hypothesis
Schizophrenia is associated with white matter disruption and topological reorganization of cortical connectivity but the trajectory of these changes, from the first psychotic episode to established illness, is poorly understood. Current studies in first-episode psychosis (FEP) patients using diffusion magnetic resonance imaging (dMRI) suggest such disruption may be detectable at the onset of psychosis, but specific results vary widely, and few reports have contextualized their findings with direct comparison to young adults with established illness.

Study Design
Diffusion and T1-weighted 7T MR scans were obtained from N = 112 individuals (58 with untreated FEP, 17 with established schizophrenia, 37 healthy controls) recruited from London, Ontario. Voxel- and network-based analyses were used to detect changes in diffusion microstructural parameters. Graph theory metrics were used to probe changes in the cortical network hierarchy and to assess the vulnerability of hub regions to disruption. The analysis was replicated with N = 111 (57 patients, 54 controls) from the Human Connectome Project-Early Psychosis (HCP-EP) dataset.

Study Results
Widespread microstructural changes were found in people with established illness, but changes in FEP patients were minimal. Unlike the established illness group, no appreciable topological changes in the cortical network were observed in FEP patients. These results were replicated in the early psychosis patients of the HCP-EP datasets, which were indistinguishable from controls in most metrics.

Conclusions
The white matter structural changes observed in established schizophrenia are not a prominent feature in the early stages of this illness.
Work Experience and Mental Health from Adolescence to Mid-Life
Authors: Staff Jeremy , Mortimer Jeylan T 
Published: April 2024

Abstract
The etiology of psychological differences among those who pursue distinct lines of work have long been of scholarly interest. A prevalent early and continuing assumption is that experiences on the job influence psychological development; contemporary analysts focus on dimensions indicative of mental health. Still, such work-related psychological differences may instead be attributable to selection processes to the extent that individuals can choose, or be selected to, different lines of work, based on their prior characteristics. Whereas much attention has been directed to employment per se as a key determinant of mental health, we consider work status (employed or not) and hours of work, as well as work quality, including both intrinsic and extrinsic dimensions among those who are employed. We also investigate differences in the effects of work experiences on mental health in distinct phases of the work career. Drawing on eleven waves of longitudinal data obtained from a cohort of ninth grade students followed prospectively to age 45–46 (54% female; 73% white), we examine whether key psychological dimensions indicative of mental health (mastery, depressive affect, and self-esteem) change in response to employment and to particular experiences on the job. The findings, based on a fixed-effects modeling strategy, indicate that observed psychological differences related to employment and work quality are not attributable to stable individual proclivities. Evidence suggests that mental health is responsive to changing experiences at work from mid-adolescence to mid-life.
The Soil Microbiomes of American Ginseng (Panax quinquefolius) Cultivated in North America Differ by Location but Not Always by Disease Status
Authors: Maggard Isabella J. , Deel Kayla B. , Gao Ying , Cahoon A. Bruce 
Published: April 2024

One of the greatest challenges faced by ginseng producers is control of fungal pathogens that adversely affect harvest yields and are a contributing factor to replant failure syndrome. The goal of this project was to survey the soil microbiome of healthy versus diseased American ginseng grown in North America. Soils associated with healthy and diseased plants were collected from commercial farms in Garett County, Maryland, and Marathon County, Wisconsin. Environmental DNA metabarcoding was used to compare the bacterial and fungal microbiomes of healthy versus diseased plants from both locations. The most common bacteria occurred within the phylum Proteobacteria, Firmicutes, and Bacteroidota and the most common fungi occurred within Ascomycota, Basidiomycota, Mortierellomycota, and Glomeromycota. Overall, alpha- and beta-diversities were statistically significant between the two locations. Community analyses (beta-diversity) of the Maryland site revealed a significant difference in the bacterial composition of soils associated with healthy versus diseased plants but not in the fungi. Conversely, there was a significantly different assemblage of fungi in healthy versus diseased associated soils from the Wisconsin site, but not for bacteria. Our results, when compared to previous metabarcoding studies, suggest that there is little congruence between the soil microbiomes associated with cultivated ginseng and that we are still in the early stages of ginseng soil rhizosphere exploration. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Repair and regeneration of the alveolar epithelium in lung injury
Authors: Wang Yaxuan , Wang Lan , Ma Shuaichen , Cheng Lianhui , Yu Guoying 
Published: April 2024

AbstractConsiderable progress has been made in understanding the function of alveolar epithelial cells in a quiescent state and regeneration mechanism after lung injury. Lung injury occurs commonly from severe viral and bacterial infections, inhalation lung injury, and indirect injury sepsis. A series of pathological mechanisms caused by excessive injury, such as apoptosis, autophagy, senescence, and ferroptosis, have been studied. Recovery from lung injury requires the integrity of the alveolar epithelial cell barrier and the realization of gas exchange function. Regeneration mechanisms include the participation of epithelial progenitor cells and various niche cells involving several signaling pathways and proteins. While alveoli are damaged, alveolar type II (AT2) cells proliferate and differentiate into alveolar type I (AT1) cells to repair the damaged alveolar epithelial layer. Alveolar epithelial cells are surrounded by various cells, such as fibroblasts, endothelial cells, and various immune cells, which affect the proliferation and differentiation of AT2 cells through paracrine during alveolar regeneration. Besides, airway epithelial cells also contribute to the repair and regeneration process of alveolar epithelium. In this review, we mainly discuss the participation of epithelial progenitor cells and various niche cells involving several signaling pathways and transcription factors.