bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elevated level of serum human epididymis protein 4 (HE4) predicts disease severity and mortality in COVID-19 pneumonia
Authors: Sütő Renáta , Pócsi Marianna , Szabó Zsolt , Fejes Zsolt , Ivády Gergely , Kerekes György , Fagyas Miklós , Nagy Attila , Szentkereszty Zoltán , Kappelmayer János , Nagy Béla 
Published: December 2023

Abstract
Background
We retrospectively analyzed serum level of human epididymis protein 4 (HE4) as a pulmonary inflammatory biomarker in patients with COVID-19 pneumonia in association with disease severity and outcome.

Methods
Ninety-nine (40 critically ill, 40 severe and 19 mild) COVID-19 patients and as controls 25 age- and sex-matched non-COVID-19 bacterial sepsis subjects were included. Serum HE4 was measured by an immunoassay (Architect® i1000SR, Abbott) in the baseline samples of all study participants obtained at intensive care unit (ICU) admission or during outpatient clinic visit and follow-up sera were available in case of 30 COVID-19 subjects with life-threating conditions. Associations were studied between serum HE4, routinely available laboratory parameters, clinical characteristics, and disease progression.

Results
Baseline HE4 level was significantly higher (P < 0.0001) in critically ill (524.7 [300.1–1153.0] pmol/L) than severe COVID-19 subjects (157.4 [85.2-336.9] pmol/L) and in mild SARS-CoV-2 infection (46.7 [39.1–57.2] pmol/L). Similarly increased HE4 concentrations were found in bacterial sepsis (1118.0 [418.3–1953.0] pmol/L, P = 0.056) compared to critically ill COVID-19 individuals. Serum HE4 levels significantly correlated with age, SOFA-score, inflammation-dependent biomarkers, and the degree of lung manifestation evaluated by chest CT examination in ICU COVID-19 individuals. Based on ROC-AUC curve analysis, baseline HE4 independently indicated the severity of COVID-19 with an AUC value of 0.816 (95% CI [0.723–0.908]; P < 0.0001), while binary logistic regression test found HE4 as an independent prognostic parameter for death (OR: 10.618 [2.331–48.354]; P = 0.002). Furthermore, COVID-19 non-survivors showed much higher baseline HE4 levels without a substantial change under treatment vs. survivors (P < 0.0001). Finally, pre-treatment HE4 level of ≥ 331.7 pmol/L effectively predicted a larger risk for mortality (Log-Rank P < 0.0001) due to severe COVID-19 pneumonia.

Conclusion
Elevated serum HE4 level at ICU admission highly correlates with COVID-19 severity and predicts disease outcome.
Completeness of medication information in admission notes from emergency departments
Authors: Zahl-Holmstad Birgitte , Garcia Beate H. , Svendsen Kristian , Johnsgård Tine , Holis Renata V. , Ofstad Eirik H. , Risør Torsten , Lehnbom Elin C. , Wisløff Torbjørn , Chan Macty , Elenjord Renate 
Published: December 2023

Abstract
Background
Medication lists prepared in the emergency department (ED) form the basis for diagnosing and treating patients during hospitalization. Since incomplete medication information may lead to patient harm, it is crucial to obtain a correct and complete medication list at hospital admission. In this cross-sectional retrospective study we wanted to explore medication information completeness in admission notes from Norwegian EDs and investigate which factors were associated with level of completeness.

Methods
Medication information was assessed for completeness by applying five evaluation criteria; generic name, formulation, dose, frequency, and indication for use. A medication completeness score in percent was calculated per medication, per admission note and per criterion. Quantile regression analysis was applied to investigate which variables were associated with medication information completeness.

Results
Admission notes for patients admitted between October 2018 and September 2019 and using at least one medication were included. A total of 1,080 admission notes, containing 8,604 medication orders, were assessed. The individual medications had a mean medication completeness score of 88.1% (SD 16.4), while admission notes had a mean medication completeness score of 86.3% (SD 16.2). Over 90% of all individual medications had information about generic name, formulation, dose and frequency stated, while indication for use was only present in 60%. The use of an electronic tool to prepare medication information had a significantly strong positive association with completeness. Hospital visit within the last 30 days, the patient’s living situation, number of medications in use, and which hospital the patient was admitted to, were also associated with information completeness.

Conclusions
Medication information completeness in admission notes was high, but potential for improvement regarding documentation of indication for use was identified. Applying an electronic tool when preparing admission notes in EDs seems crucial to safeguard completeness of medication information.
Development of a web-based care networking system to support visiting healthcare professionals in the community
Authors: Lee Jakyung , Park Susan , Cho Mi-hee , Kang Ji-Won , Kim Minkyoung , Choi Suhyeon , Kim Seok-gyu , Choi Ji-hee , Han Keumhee , Kim Chang-O , Moon Il-Chul , Choi Moon , Jang Soong-nang 
Published: December 2023

Abstract
Background
The role of visiting health services has been proven to be effective in promoting the health of older populations. Hence, developing a web system for nurses may help improve the quality of visiting health services for community-dwelling frail older adults. This study was conducted to develop a web application that reflects the needs of visiting nurses.

Methods
Visiting nurses of public health centers and community centers in South Korea participated in the design and evaluation process. Six nurses took part in the focus group interviews, and 21 visiting nurses and community center managers participated in the satisfaction evaluation. Focus group interviews were conducted to identify the needs of visiting nurses with respect to system function. Based on the findings, a web application that can support the effective delivery of home visiting services in the community was developed. An artificial intelligence (AI) algorithm was also developed to recommend health and welfare services according to each patient’s health status. After development, a structured survey was conducted to evaluate user satisfaction with system features using Kano’s model.

Results
The new system can be used with mobile devices to increase the mobility of visiting nurses. The system includes 13 features that support the management of patient data and enhance the efficiency of visiting services (e.g., map, navigation, scheduler, protocol archives, professional advice, and online case conferencing). The user satisfaction survey revealed that nurses showed high satisfaction with the system. Among all features, the nurses were most satisfied with the care plan, which included AI-based recommendations for community referral.

Conclusions
The system developed from the study has attractive features for visiting nurses and supports their essential tasks. The system can help with effective case management for older adults requiring in-home care and reduce nurses' workload. It can also improve communication and networking between healthcare and long-term care institutions.
Oxidative stress, gene expression and histopathology of cultured gilthead sea bream (Sparus aurata) naturally co-infected with Ergasilus sieboldi and Vibrio alginolyticus
Authors: Abou-Okada Mahmoud , Rashad Maha M. , Ali Ghada E. , Abdel-Radi Shimaa , Hassan Azza 
Published: December 2023

Abstract
Background
Parasitic and bacterial co-infections have been associated with increasing fish mortalities and severe economic losses in aquaculture through the past three decades. The aim of this study was to evaluate the oxidative stress, histopathology, and immune gene expression profile of gilthead sea bream (Sparus aurata) co-infected with Ergasilus sieboldi and Vibrio alginolyticus.

Results
Vibrio alginolyticus and Ergasilus sieboldi were identified using 16 S rRNA and 28 S rRNA sequencing, respectively. The collagenase virulence gene was found in all Vibrio alginolyticus isolates, and the multiple antimicrobial resistance index ranged from 0.286 to 0.857. Oxidant-antioxidant parameters in the gills, skin, and muscles of naturally infected fish revealed increased lipid peroxidation levels and a decrease in catalase and glutathione antioxidant activities. Moreover, naturally co-infected gilthead sea bream exhibited substantial up-regulation of il-1β, tnf-α, and cyp1a1. Ergasilus sieboldi encircled gill lamellae with its second antennae, exhibited severe gill architectural deformation with extensive eosinophilic granular cell infiltration. Vibrio alginolyticus infection caused skin and muscle necrosis in gilthead sea bream.

Conclusion
This study described some details about the gill, skin and muscle tissue defense mechanisms of gilthead sea bream against Ergasilus sieboldi and Vibrio alginolyticus co-infections. The prevalence of co-infections was 100%, and no resistant fish were detected. These co-infections imbalance the health status of the fish by hampering the oxidant-antioxidant mechanisms and proinflammatory/inflammatory immune genes to a more detrimental side. Our results suggest that simultaneous screening for bacterial and parasitic pathogens should be considered.
Treatable traits and challenges in the clinical management of non-tuberculous mycobacteria lung disease in people with cystic fibrosis
Authors: Gramegna Andrea , Misuraca Sofia , Lombardi Andrea , Premuda Chiara , Barone Ivan , Ori Margherita , Amati Francesco , Retucci Mariangela , Nazzari Erica , Alicandro Gianfranco , Ferrarese Maurizio , Codecasa Luigi , Bandera Alessandra , Aliberti Stefano , Daccò Valeria , Blasi Francesco 
Published: December 2023

Abstract
Introduction
Over the last ten years an increasing prevalence and incidence of non-tuberculous mycobacteria (NTM) has been reported among patients with cystic fibrosis (CF) Viviani (J Cyst Fibros, 15(5):619–623, 2016). NTM pulmonary disease has been associated with negative clinical outcomes and often requires pharmacological treatment. Although specific guidelines help clinicians in the process of diagnosis and clinical management, the focus on the multidimensional assessment of concomitant problems is still scarce.

Main body
This review aims to identify the treatable traits of NTM pulmonary disease in people with CF and discuss the importance of a multidisciplinary approach in order to detect and manage all the clinical and behavioral aspects of the disease. The multidisciplinary complexity of NTM pulmonary disease in CF requires careful management of respiratory and extra-respiratory, including control of comorbidities, drug interactions and behavioral factors as adherence to therapies.

Conclusions
The treatable trait strategy can help to optimize clinical management through systematic assessment of all the aspects of the disease, providing a holistic treatment for such a multi-systemic and complex condition.
A supernumerary synthetic chromosome in Komagataella phaffii as a repository for extraneous genetic material
Authors: Abramczyk Dariusz , del Carmen Sanchez Olmos Maria , Rojas Adan Andres Ramirez , Schindler Daniel , Robertson Daniel , McColm Stephen , Marston Adele L. , Barlow Paul N. 
Published: December 2023

Abstract
Background
Komagataella phaffii (Pichia pastoris) is a methylotrophic commercially important non-conventional species of yeast that grows in a fermentor to exceptionally high densities on simple media and secretes recombinant proteins efficiently. Genetic engineering strategies are being explored in this organism to facilitate cost-effective biomanufacturing. Small, stable artificial chromosomes in K. phaffii could offer unique advantages by accommodating multiple integrations of extraneous genes and their promoters without accumulating perturbations of native chromosomes or exhausting the availability of selection markers.

Results
Here, we describe a linear “nano”chromosome (of 15–25 kb) that, according to whole-genome sequencing, persists in K. phaffii over many generations with a copy number per cell of one, provided non-homologous end joining is compromised (by KU70-knockout). The nanochromosome includes a copy of the centromere from K. phaffii chromosome 3, a K. phaffii-derived autonomously replicating sequence on either side of the centromere, and a pair of K. phaffii-like telomeres. It contains, within its q arm, a landing zone in which genes of interest alternate with long (approx. 1-kb) non-coding DNA chosen to facilitate homologous recombination and serve as spacers. The landing zone can be extended along the nanochromosome, in an inch-worming mode of sequential gene integrations, accompanied by recycling of just two antibiotic-resistance markers. The nanochromosome was used to express PDI, a gene encoding protein disulfide isomerase. Co-expression with PDI allowed the production, from a genomically integrated gene, of secreted murine complement factor H, a plasma protein containing 40 disulfide bonds. As further proof-of-principle, we co-expressed, from a nanochromosome, both PDI and a gene for GFP-tagged human complement factor H under the control of PAOX1 and demonstrated that the secreted protein was active as a regulator of the complement system.

Conclusions
We have added K. phaffii to the list of organisms that can produce human proteins from genes carried on a stable, linear, artificial chromosome. We envisage using nanochromosomes as repositories for numerous extraneous genes, allowing intensive engineering of K. phaffii without compromising its genome or weakening the resulting strain.
Loss of two-pore channel 2 function in melanoma-derived tumours reduces tumour growth in vivo but greatly increases tumour-related toxicity in the organism
Authors: Hanbashi Ali , Alotaibi Moureq , Sobeai Homood M. As , Binobaid Lama , Alhazzani Khalid , Jin Xuhui , Kamli Faroq , Alhoshani Ali , Parrington John 
Published: December 2023

Abstract
Background
Melanoma, a severe form of skin cancer, poses significant health risks due to its aggressive nature and potential for metastasis. The role of two-pore channel 2 (TPC2) in the development and progression of melanoma remains poorly understood. This study aims to investigate the impact of TPC2 knockout (KO) on melanoma-derived tumors, focusing on tumour growth and related toxicity in the organism.

Methods
The study utilized CHL-1 and B16 melanoma cell lines with TPC2 KO to assess the changes in proliferation dynamics. Methods included real-time monitoring of cell proliferation using the xCELLigence system, in vivo tumour growth assays in mice, histopathological analyses, inflammation marker assessment, and quantitative PCR (qPCR) for gene expression analysis

Results
TPC2 KO was found to significantly alter the proliferation dynamics of CHL-1 and B16 melanoma cells. The in vivo studies demonstrated reduced tumor growth in TPC2 KO cell-derived tumors. However, a notable increase in tumor-related toxicity in affected organs, such as the liver and spleen, was observed, indicating a complex role of TPC2 in melanoma pathology.

Conclusions
The loss of TPC2 function in melanoma cells leads to reduced tumour growth but exacerbates tumour-related toxicity in the organism. These findings highlight the dual role of TPC2 in melanoma progression and its potential as a therapeutic target. Further research is needed to fully understand the mechanisms underlying these effects and to explore TPC2 as a treatment target in melanoma.

Graphical Abstract
Helicobacter pylori-induced fibroblast-derived Serpin E1 promotes gastric cancer growth and peritoneal dissemination through p38 MAPK/VEGFA-mediated angiogenesis
Authors: Cheng Wei , Liao Yonghui , Xie Yuan , Wang Qinrong , Li Leilei , Chen Yuanjia , Zhao Yan , Zhou Jianjiang 
Published: December 2023

Abstract
Background
Fibroblasts, especially cancer-associated fibroblasts (CAFs), represent the predominant stromal cell population in the tumor microenvironment and have an important function in tumorigenesis by interacting with tumor cells. However, their interaction remains elusive in an inflammatory tumor microenvironment induced by Helicobacter pylori (H. pylori).

Methods
The expression of Serpin family E member 1 (Serpin E1) was measured in fibroblasts with or without H. pylori infection, and primary gastric cancer (GC) cells. Serpin E1 knockdown and overexpression fibroblasts were generated using Serpin E1 siRNA or lentivirus carrying Serpin E1. Co-culture models of fibroblasts and GC cells or human umbilical vein endothelial cells (HUVECs) were established with direct contact or the Transwell system. In vitro functional experiments and in vivo tumorigenesis assay were employed to study the malignant behaviors of GC cells interacting with fibroblasts. ELISA was used for quantifying the levels of Serpin E1 and VEGFA in the culture supernatant. The tube formation capacity of HUVECs was assessed using a tube formation assay. Recombinant human Serpin E1 (recSerpin E1), anti-Serpin E1 antibody, and a MAPK pathway inhibitor were utilized to treat HUVECs for elucidating the underlying molecular mechanisms.

Results
Serpin E1 was predominantly expressed in gastric CAFs. H. pylori infection significantly enhanced the expression and secretion of Serpin E1 by CAFs. Both fibroblast-derived Serpin E1 and recSerpin E1 enhanced the growth, invasion, and migration of GC cells, along with increased VEGFA expression and tube formation in HUVECs. Furthermore, the co-inoculation of GC cells and fibroblasts overexpressing Serpin E1 triggered the expression of Serpin E1 in cancer cells, which facilitated together xenograft tumor growth and peritoneal dissemination of GC cells in nude mice, with an increased expression of Ki67, Serpin E1, CD31 and/or VEGFA. These processes may be mediated by Serpin E1-induced migration and p38 MAPK/VEGFA-mediated angiogenesis of HUVECs.

Conclusion
H. pylori infection induces Serpin E1 expression in fibroblasts, subsequently triggering its expression in GC cells through their interaction. Serpin E1 derived from these cells promotes the migration and p38 MAPK/VEGFA-mediated angiogenesis of HUVECs, thereby facilitating GC growth and peritoneal metastasis. Targeting Serpin E1 signaling is a potential therapy strategy for H. pylori-induced GC.
PRRG4 regulates mitochondrial function and promotes migratory behaviors of breast cancer cells through the Src-STAT3-POLG axis
Authors: Wang Yang , Wang Jieyi , Chen Lan , Chen Zhuo , Wang Tong , Xiong Shuting , Zhou Tong , Wu Guang , He Licai , Cao Jiawei , Liu Min , Li Hongzhi , Gu Haihua 
Published: December 2023

Abstract
Background
Breast cancer is the leading cause of cancer death for women worldwide. Most of the breast cancer death are due to disease recurrence and metastasis. Increasingly accumulating evidence indicates that mitochondria play key roles in cancer progression and metastasis. Our recent study revealed that transmembrane protein PRRG4 promotes the metastasis of breast cancer. However, it is not clear whether PRRG4 can affect the migration and invasion of breast cancer cells through regulating mitochondria function.

Methods
RNA-seq analyses were performed on breast cancer cells expressing control and PRRG4 shRNAs. Quantitative PCR analysis and measurements of mitochondrial ATP content and oxygen consumption were carried out to explore the roles of PRRG4 in regulating mitochondrial function. Luciferase reporter plasmids containing different lengths of promoter fragments were constructed. Luciferase activities in breast cancer cells transiently transfected with these reporter plasmids were analyzed to examine the effects of PRRG4 overexpression on promoter activity. Transwell assays were performed to determine the effects of PRRG4-regulated pathway on migratory behaviors of breast cancer cells.

Results
Analysis of the RNA-seq data revealed that PRRG4 knockdown decreased the transcript levels of all the mitochondrial protein-encoding genes. Subsequently, studies with PRRG4 knockdown and overexpression showed that PRRG4 expression increased mitochondrial DNA (mtDNA) content. Mechanistically, PRRG4 via Src activated STAT3 in breast cancer cells. Activated STAT3 in turn promoted the transcription of mtDNA polymerase POLG through a STAT3 DNA binding site present in the POLG promoter region, and increased mtDNA content as well as mitochondrial ATP production and oxygen consumption. In addition, PRRG4-mediated activation of STAT3 also enhanced filopodia formation, migration, and invasion of breast cancer cells. Moreover, PRRG4 elevated migratory behaviors and mitochondrial function of breast cancer cells through POLG.

Conclusion
Our results indicate that PRRG4 via the Src-STAT3-POLG axis enhances mitochondrial function and promotes migratory behaviors of breast cancer cells.
Prevalence of depression among people living with HIV in rural hospitals in South-Western Nigeria-Association with clinico-demographic factors
Authors: Adedeji Waheed Adeola , Ma Qing , Raji Abiodun Muhammed , Cha Raymond , Rasaki Olaniran Mudasiru , Hutson Alan , Taiwo Babafemi O. , Charurat Man E. , Yusuf Oyindamola B. , Fehintola Fatai Adewale , Gureje Oye , Morse Gene D. 
Published: December 2023

AbstractMajor depression is the most common neuropsychiatric disorder among people living with HIV (PLWH) and is predictive of high morbidity and mortality among them. This study estimated the prevalence and explored factors associated with depression among PLWH in two rural secondary health facilities providing anti-retroviral therapy (ART) services in Southwestern Nigeria between September and December 2020. The Patient Health Questionnaire-9 (PHQ-9) was used to screen and identify PLWH aged 18 years or older with depression. Descriptive statistics, bivariate and multivariate analyses were performed with SPSS version 23. A total of 172 respondents were screened. The prevalence of depression was 16.3% (95% CI 11.1%, 22.7%). Mild, moderate, and moderately severe depression was identified in 17 (9.9%), 8(4.7%) and 3(1.7%) of the participants, respectively. One (0.6%) respondent had suicidal ideation. Of PLWH with any depression, 20/28(71.4%) were within the 40–59 years of age range. None of the participants was on antidepressants. The factor most associated with depression was hypertension, with adjusted odd ratios of 9.8(95% CI 3.5–27.3, p < 0.0001). The study highlights the importance of screening for the severity of depression among PLWH in rural hospitals providing ART services in Africa. PLWH with comorbid hypertension were more likely to suffer from some form of depression.