bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic factors and overall survival of breast cancer in Benin: a hospital-based study
Authors: Gnangnon Freddy Houéhanou Rodrigue , Parenté Alexis , Aboubakar Moufalilou , Kiki-migan Yannick , Totah Terence , Gbessi Dansou Gaspard , Tonato-Bagnan Josiane Angéline , Laleye Anatole , Preux Pierre-Marie , Denakpo Justin Lewis , Blanquet Véronique , Houinato Dismand Stephan 
Published: May 2024

Abstract
Background
In Benin, a country in West Africa, breast cancer is the leading cancer in women, both in terms of incidence and mortality. However, evidence on the mortality of breast cancer and its associated factors is lacking in this country. Our aim was to describe and analyze the clinical, histopathological, and prognostic aspects of breast cancer in Benin.

Methods
A descriptive and analytical study was carried out at the CNHU-HKM and the CHU-MEL, two major tertiary referral hospitals for breast cancer management located in Cotonou, the capital city of Benin. All breast cancer medical records with histological evidence and immunohistochemistry studies were retrospectively collected between January 1, 2014, and September 30, 2020, in these two tertiary referral hospitals and analyzed in the current study.

Results
Finally, 319 medical records were included. The mean age at diagnosis was 48.74 years. The tumors were most frequently classified as T4 (47.6%) with lymph node involvement N2 (34.5%), and metastases were clinically noted in 21.9% of cases. Stage was reported in the medical records of 284 patients. Tumors were diagnosed at very late AJCC stages: stage III (47.5%) and stage IV (24.7%). Grades SBR 2 (49.2%) and SBR 3 (32.6%) were the most frequent grades. Triple-negative breast cancer (31.3%) was the most common molecular type. The overall 5-year survival was 48.49%. In multivariable analysis, the poor prognostic factors were lymph node invasion (HR = 2.63; p = 0.026; CI: [1.12, 6.17]), the presence of metastasis (HR = 3.64; p < 0.001); CI: [2.36, 5.62] and the immunohistochemical profile (HR = 1.29; p < 0.001; CI: [1.13, 1.48]).

Conclusions
Breast cancer in Beninese is predominant in young adults and is often diagnosed at a late stage. The survival of breast cancer patients in Benin can be improved by enhancing early diagnosis and multidisciplinary management.
YAP/TAZ activation mediates PQ-induced lung fibrosis by sustaining senescent pulmonary epithelial cells
Authors: Yu Youjia , Chu Chunyan , Wang Kang , Li Yan , Mao Zhengsheng , Hu Li , Wang Jie , Yu Yanfang , Sun Hao , Chen Feng 
Published: May 2024

AbstractParaquat (PQ) is a widely used herbicide and a common cause of poisoning that leads to pulmonary fibrosis with a high mortality rate. However, the underlying mechanisms of PQ-induced pulmonary fibrosis and whether pulmonary epithelial cell senescence is involved in the process remain elusive. In this study, PQ-induced pulmonary epithelial cell senescence and Hippo-YAP/TAZ activation were observed in both C57BL/6 mice and human epithelial cells. PQ-induced senescent pulmonary epithelial cells promoted lung fibroblast transformation through secreting senescence-associated secretory phenotype (SASP) factors. Yap/Taz knockdown in mice lungs significantly decreased the expression of downstream profibrotic protein Ctgf and senescent markers p16 and p21, and alleviated PQ-induced pulmonary fibrosis. Interfering YAP/TAZ in senescent human pulmonary epithelial cells resulted in decreased expression of the anti-apoptosis protein survivin and elevated level of apoptosis. In conclusion, our findings reveal a novel mechanism by which the involvement of Hippo-YAP/TAZ activation in pulmonary epithelial cell senescence mediates the pathogenesis of PQ-induced pulmonary fibrosis, thereby offering novel insights and potential targets for the clinical management of PQ poisoning as well as providing the mechanistic insight of the involvement of Yap/Taz activation in cell senescence in pulmonary fibrosis and its related pulmonary disorders. The YIN YANG balance between cell senescence and apoptosis is important to maintain the homeostasis of the lung, the disruption of which will lead to disease.
Comparative microbiome analysis in cystic fibrosis and non-cystic fibrosis bronchiectasis.
Authors: Motta Heryk , Reuwsaat Júlia Catarina Vieira , Lopes Fernanda Cortez , Viezzer Graciele , Volpato Fabiana Caroline Zempulski , Barth Afonso Luís , de Tarso Roth Dalcin Paulo , Staats Charley Christian , Vainstein Marilene Henning , Kmetzsch Lívia 
Published: May 2024

Abstract
Background
Bronchiectasis is a condition characterized by abnormal and irreversible bronchial dilation resulting from lung tissue damage and can be categorized into two main groups: cystic fibrosis (CF) and non-CF bronchiectasis (NCFB). Both diseases are marked by recurrent infections, inflammatory exacerbations, and lung damage. Given that infections are the primary drivers of disease progression, characterization of the respiratory microbiome can shed light on compositional alterations and susceptibility to antimicrobial drugs in these cases compared to healthy individuals.

Methods
To assess the microbiota in the two studied diseases, 35 subjects were recruited, comprising 10 NCFB and 13 CF patients and 12 healthy individuals. Nasopharyngeal swabs and induced sputum were collected, and total DNA was extracted. The DNA was then sequenced by the shotgun method and evaluated using the SqueezeMeta pipeline and R.

Results
We observed reduced species diversity in both disease cohorts, along with distinct microbial compositions and profiles of antimicrobial resistance genes, compared to healthy individuals. The nasopharynx exhibited a consistent microbiota composition across all cohorts. Enrichment of members of the Burkholderiaceae family and an increased Firmicutes/Bacteroidetes ratio in the CF cohort emerged as key distinguishing factors compared to NCFB group. Staphylococcus aureus and Prevotella shahii also presented differential abundance in the CF and NCFB cohorts, respectively, in the lower respiratory tract. Considering antimicrobial resistance, a high number of genes related to antibiotic efflux were detected in both disease groups, which correlated with the patient’s clinical data.

Conclusions
Bronchiectasis is associated with reduced microbial diversity and a shift in microbial and resistome composition compared to healthy subjects. Despite some similarities, CF and NCFB present significant differences in microbiome composition and antimicrobial resistance profiles, suggesting the need for customized management strategies for each disease.
Circulating total and H-specific GDF15 levels are elevated in subjects with MASLD but not in hyperlipidemic but otherwise metabolically healthy subjects with obesity
Authors: Boutari Chrysoula , Stefanakis Konstantinos , Simati Stamatia , Guatibonza-García Valentina , Valenzuela-Vallejo Laura , Anastasiou Ioanna A. , Connelly Margery A. , Kokkinos Alexander , Mantzoros Christos S. 
Published: May 2024

Abstract
Background
Growth differentiation factor 15 (GDF15) is a mitokine, the role of which, total or H-specific, in modulating energy metabolism and homeostasis in obesity-related diseases, such as metabolic dysfunction associated steatotic liver disease (MASLD), has not been fully elucidated in adult humans. We aimed to investigate the fasting and stimulated levels of GDF15, total and H-specific, glucose-dependent insulinotropic polypeptide (GIP) and C-peptide, in two physiology interventional studies: one focusing on obesity, and the other on MASLD.

Methods
Study 1 investigated individuals with normal weight or with obesity, undergoing a 3-h mixed meal test (MMT); and study 2, examined adults with MASLD and controls undergoing a 120-min oral glucose tolerance test (OGTT). Exploratory correlations of total and H-specific GDF15 with clinical, hormonal and metabolomic/lipidomic parameters were also performed.

Results
In study 1, 15 individuals were included per weight group. Fasting and postprandial total and H-specific GDF15 were similar between groups, whereas GIP was markedly higher in leaner individuals and was upregulated following a MMT. Baseline and postprandial C-peptide were markedly elevated in people with obesity compared with lean subjects. GIP was higher in leaner individuals and was upregulated after a MMT, while C-peptide and its overall AUC after a MMT was markedly elevated in people with obesity compared with lean subjects. In study 2, 27 individuals were evaluated. Fasting total GDF15 was similar, but postprandial total GDF15 levels were significantly higher in MASLD patients compared to controls. GIP and C-peptide remained unaffected. The postprandial course of GDF15 was clustered among those of triglycerides and molecules of the alanine cycle, was robustly elevated under MASLD, and constituted the most notable differentiating molecule between healthy and MASLD status. We also present robust positive correlations of the incremental area under the curve of total and H-specific GDF15 with a plethora of lipid subspecies, which remained significant after adjusting for confounders.

Conclusion
Serum GDF15 levels do not differ in relation to weight status in hyperlipidemic but otherwise metabolically healthy individuals. In contrast, GDF15 levels are significantly increased in MASLD patients at baseline and they remain significantly higher compared to healthy participants during OGTT, pointing to a role for GDF15 as a mitokine with important roles in the pathophysiology and possibly therapeutics of MASLD.
Trial registration ClinicalTrials.gov NCT03986684, NCT04430946.
Acute kidney injury after out-of-hospital cardiac arrest
Authors: Jeppesen Karoline Korsholm , Rasmussen Sebastian Buhl , Kjaergaard Jesper , Schmidt Henrik , Mølstrøm Simon , Beske Rasmus Paulin , Grand Johannes , Ravn Hanne Berg , Winther-Jensen Matilde , Meyer Martin Abild Stengaard , Hassager Christian , Møller Jacob Eifer 
Published: May 2024

Abstract
Background
Acute kidney injury (AKI) is a significant risk factor associated with reduced survival following out-of-hospital cardiac arrest (OHCA). Whether the severity of AKI simply serves as a surrogate measure of worse peri-arrest conditions, or represents an additional risk to long-term survival remains unclear.

Methods
This is a sub-study derived from a randomized trial in which 789 comatose adult OHCA patients with presumed cardiac cause and sustained return of spontaneous circulation (ROSC) were enrolled. Patients without prior dialysis dependent kidney disease and surviving at least 48 h were included (N = 759). AKI was defined by the kidney disease: improving global outcome (KDIGO) classification, and patients were divided into groups based on the development of AKI and the need for continuous kidney replacement therapy (CKRT), thus establishing three groups of patients—No AKI, AKI no CKRT, and AKI CKRT. Primary outcome was overall survival within 365 days after OHCA according to AKI group. Adjusted Cox proportional hazard models were used to assess overall survival within 365 days according to the three groups.

Results
In the whole population, median age was 64 (54–73) years, 80% male, 90% of patients presented with shockable rhythm, and time to ROSC was median 18 (12–26) min. A total of 254 (33.5%) patients developed AKI according to the KDIGO definition, with 77 requiring CKRT and 177 without need for CKRT. AKI CKRT patients had longer time-to-ROSC and worse metabolic derangement at hospital admission. Overall survival within 365 days from OHCA decreased with the severity of kidney injury. Adjusted Cox regression analysis found that AKI, both with and without CKRT, was significantly associated with reduced overall survival up until 365 days, with comparable hazard ratios relative to no AKI (HR 1.75, 95% CI 1.13–2.70 vs. HR 1.76, 95% CI 1.30–2.39).

Conclusions
In comatose patients who had been resuscitated after OHCA, patients developing AKI, with or without initiation of CKRT, had a worse 1-year overall survival compared to non-AKI patients. This association remains statistically significant after adjusting for other peri-arrest risk factors.
Trial registration: The BOX trial is registered at ClinicalTrials.gov: NCT03141099.
Reference intervals for knee functions specific to outpatients with knee osteoarthritis: a cross-sectional study
Authors: Ito Hideyuki , Amano Tetsuya , Ichihara Kiyoshi 
Published: May 2024

Abstract
Background
Reference values (RVs) for knee function tests have been reported in perioperative patients with knee osteoarthritis (KOA); however, such values for practical use in outpatient setting has yet to be determined. Therefore, we aimed to establish the reference intervals (RIs) for outpatients with mild to moderate KOA.

Methods
This cross-sectional study enrolled 202 outpatients with KOA from 8 Japanese orthopedic clinics and measured knee extensor/flexor muscle strength (MS) and knee extension/flexion range of motion (ROM). We used multiple regression analysis to evaluate the sources of variation, including sex, age, body mass index, Kellgren–Lawrence (K-L) classification, bilateral KOA, and exercise habits. Magnitude of between-subgroup differences is expressed as standard deviation ratio (SDR) based on a three-level nested analysis of variance, with SDR ≥ 0.4 as the threshold for requiring RIs specific for subgroups. RIs were calculated parametrically using two-parameter Box-Cox formula if Gaussian transformation of RVs was successful, otherwise calculated nonparametrically.

Results
Partitioning was required by sex for extensor and flexor MS (SDR = 0.65, 0.57, respectively) and by K-L classification for flexion ROM (SDR = 0.54). RIs were determined parametrically for extensor MS as 0.27–2.09 (male) and 0.27–1.54 (female) Nm/kg and for flexor MS 0.18–1.20 (male) and 0.13–0.79 (female) Nm/kg. On the other hand, RIs for extension and flexion ROM were determined nonparametrically due to discrete nature of their RVs. The RIs determined for extension ROM were -15°–0° and for flexion ROM were 105°–150° (for K-L grade I/II) and 95°–140° (for K-L grade III/IV).

Conclusions
The ranges of RIs determined specifically for patients with mild to moderate KOA were in-between those of age-matched healthy controls and pre-surgical KOA patients, both of which we had reported for use in physiotherapeutic management of KOA patients undergone total knee arthroplasty. The newly derived RIs will provide an objective benchmark for physiotherapy targeting outpatients with mild to moderate KOA.
Blood biomarkers of neurodegeneration associate differently with amyloid deposition, medial temporal atrophy, and cerebrovascular changes in APOE ε4-enriched cognitively unimpaired elderly
Authors: Koivumäki Mikko , Ekblad Laura , Lantero-Rodriguez Juan , Ashton Nicholas J. , Karikari Thomas K. , Helin Semi , Parkkola Riitta , Lötjönen Jyrki , Zetterberg Henrik , Blennow Kaj , Rinne Juha O. , Snellman Anniina 
Published: May 2024

Abstract
Background
Alzheimer’s disease (AD) is characterized by the accumulation of amyloid-β (Aβ) plaques, neurofibrillary tau tangles, and neurodegeneration in the brain parenchyma. Here, we aimed to (i) assess differences in blood and imaging biomarkers used to evaluate neurodegeneration among cognitively unimpaired APOE ε4 homozygotes, heterozygotes, and non-carriers with varying risk for sporadic AD, and (ii) to determine how different cerebral pathologies (i.e., Aβ deposition, medial temporal atrophy, and cerebrovascular pathology) contribute to blood biomarker concentrations in this sample.

Methods
Sixty APOE ε4 homozygotes (n = 19), heterozygotes (n = 21), and non-carriers (n = 20) ranging from 60 to 75 years, were recruited in collaboration with Auria biobank (Turku, Finland). Participants underwent Aβ-PET ([11C]PiB), structural brain MRI including T1-weighted and T2-FLAIR sequences, and blood sampling for measuring serum neurofilament light chain (NfL), plasma total tau (t-tau), plasma N-terminal tau fragments (NTA-tau) and plasma glial fibrillary acidic protein (GFAP). [11C]PiB standardized uptake value ratio was calculated for regions typical for Aβ accumulation in AD. MRI images were analysed for regional volumes, atrophy scores, and volumes of white matter hyperintensities. Differences in biomarker levels and associations between blood and imaging biomarkers were tested using uni- and multivariable linear models (unadjusted and adjusted for age and sex).

Results
Serum NfL concentration was increased in APOE ε4 homozygotes compared with non-carriers (mean 21.4 pg/ml (SD 9.5) vs. 15.5 pg/ml (3.8), p = 0.013), whereas other blood biomarkers did not differ between the groups (p > 0.077 for all). From imaging biomarkers, hippocampal volume was significantly decreased in APOE ε4 homozygotes compared with non-carriers (6.71 ml (0.86) vs. 7.2 ml (0.7), p = 0.029). In the whole sample, blood biomarker levels were differently predicted by the three measured cerebral pathologies; serum NfL concentration was associated with cerebrovascular pathology and medial temporal atrophy, while plasma NTA-tau associated with medial temporal atrophy. Plasma GFAP showed significant association with both medial temporal atrophy and Aβ pathology. Plasma t-tau concentration did not associate with any of the measured pathologies.

Conclusions
Only increased serum NfL concentrations and decreased hippocampal volume was observed in cognitively unimpaired APOEε4 homozygotes compared to non-carriers. In the whole population the concentrations of blood biomarkers were affected in distinct ways by different pathologies.
Copper nanoparticles biosynthesis by Stevia rebaudiana extract: biocompatibility and antimicrobial application
Authors: Abdelhai Mostafa Fathi , Shabaan Romisaa H. , Kamal Noha M. , Elemary Esraa A. , Abd-Elhalim Basma T. , Hassan Enas A. 
Published: May 2024

AbstractThe growth of material science and technology places a high importance on the creation of better processes for the synthesis of copper nanoparticles. So that, an easy, ecological, and benign process for producing copper nanoparticles (CuNPs) has been developed using candy leaf (Stevia rebaudiana) leaves aqueous extract for the first time. UV-visible spectroscopy, dynamic light scattering (DLS), X-ray diffraction (XRD), high-resolution transmission electron microscope (HR-TEM), Fourier transmission infrared (FTIR), and zeta potential were applied to demonstrate strong characterization for the biosynthesized stevia-CuNPs. The UV-visible absorbance at 575 nm of surface plasmon resonance (SPR) was 1.2. The particle size mean diameter was recorded as 362.3 nm with − 10.8 mV zeta potential. The HR-TEM scanning revealed 51.46–53.17 nm and spherical-shaped stevia-CuNPs surrounded by coat-shell proteins. The cytotoxicity and cytocompatibility activity assay revealed that stevia-CuNPs was safe in lower concentrations and had a significant cell viability reduction in higher concentrations. The produced stevia-CuNPs were applied as antimicrobial agents against eight pathogenic bacteria and five fungi strains. The inhibitory action of the stevia-CuNPs was more pronounced in bacteria than in fungi, and they likewise demonstrated further inhibition zones in Staphylococcus aureus (50.0 mm) than in Aspergillus flavus (55.0 mm). With inhibition zone sizes of 50.0 mm and 47.0 mm and 50 µg/ml minimum inhibitory concentration, S. aureus and A. flavus were the most inhibited pathogens. The minimum lethal effect (MLC) estimate for S. aureus was 50 µg/ml, whereas 75 µg/ml for A. flavus. The stevia-CuNPs mode of action was characterized as bactericidal/fungicidal as the ratio of MIC to MLC was estimated to be equal to or less than 2. After all, stevia-CuNPs could be used as an alternative to commercial antibiotics to solve the problem of multidrug-resistant (MDR) microorganisms.
Disposal of spent oil into soils around auto parts markets impacts heavy metal concentrations and poses a potential ecological risk
Authors: Okebalama Chinyere Blessing , Onwurah Chioma Lucy , Jidere Chika Mike , Okolo Chukwuebuka Christopher 
Published: May 2024

AbstractNigeria is facing the problem of soil degradation as a result of continuous deposition of spent oil in the soil. The physiochemical properties, including heavy metals concentrations, of spent oil contaminated soils and adjacent control soils were investigated at 0–15 and 15–30 cm depths at Ladipo and Berger auto-mobile Markets in Lagos, southwest Nigeria. The soils were collected in triplicate and analyzed in a 2 (location) * 2 (study site) * 2 (soil depth) factorial experiment. The results showed a uniform soil texture in both study sites and at both soil depths, with loamy sand at Ladipo and sandy loam at Berger. Bulk density was significantly decreased, while the total porosity (46.44%), organic C (21.79 g kg− 1), available P (16.48 mg kg− 1), Na+ (0.72 cmolc kg− 1) and K+ (0.81 cmolc kg− 1) increased in the contaminated site compared to the control site. Soil pH was higher at Ladipo (8.4) than at Berger (7.4). However, the soil pH and available P concentration decreased in the contaminated soil compared to the control at both locations, resulting in a decrease in available P concentration of more than 300% and 100% at Ladipo and Berger, respectively. At the Ladipo location, the concentration of Ca2+ was higher in the control than in the contaminated counterpart, while the opposite was true at the Berger location. The concentrations of the heavy metals Pb and Zn in the contaminated soils were low, while the Cu concentration was high. Although the concentrations of these heavy metals were below the standards for potential environmental risks, the high Cu concentration at both locations poses a potential ecological risk and may affect soil and human health as Cu accumulates in critical levels in the soil due to the continued irresponsible disposal of spent oil on the ground.
Secondary cardiac lymphoma presenting with cardiac tamponade and cardiac mass: a case report
Authors: Lim Wei Juan , Kaisbain Neerusha , Bakar Rafidah Abu , Hadi Hafidz Abd , Mohamed Yusof Ahmad Khairuddin 
Published: May 2024

Abstract
Background
Cardiac tamponade as the presenting manifestation of systemic lymphoma is relatively uncommon. Pericardium is the commonest site of involvement in secondary malignancies with systemic lymphoma involving the heart in 20% of the cases.

Case presentation
We describe a case of a 78-year-old gentleman, who presented with symptoms of new onset cardiac failure, and hemodynamic compromise. An echocardiography revealed cardiac tamponade, necessitating an emergency pericardiocentesis. With the aid of multimodality imaging, he was found to have a right atrioventricular groove mass, widespread lymph node enlargement with bone and peritoneal involvement. Ultimately, a histopathological evaluation revealed a diagnosis of Diffuse Large B Cell Lymphoma (DLBCL).

Conclusions
Our case illustrates that a patient with DLBCL may present with cardiac tamponade as a result of metastasis. This diagnosis, although rare, is likely to be missed, which can cause fatal complications, such as cardiac tamponade, fatal arrhythmias or sudden cardiac death.
Complex decision making in a patient with lung cancer with incidentally found fast-growing atrial mass
Authors: Otchere Prince , Pak Stella , Ulloa-Rodriguez Juan , Fierro Maria , Sharma Aditi , Poku Tevonne , Kofi-Obeng Brandon , Yang Eric , Thallapureddy Keerthi 
Published: May 2024

AbstractAtrial myxomas are typically found in the left atrium and are the most common among overall rare cardiac tumors. Herein, we describe the clinical course of a 72-year-old female with non-small cell lung adenocarcinoma found to have an atrial mass during an imaging for evaluation for lung cancer progression. Differentiating between distinct types of masses can pose a challenge to the treatment team especially in the setting of exiting malignancy. This case demonstrates the complex decision making involved in the diagnosis, and timing of intervention to remove atrial mass in patients with frailty and a fast-growing cardiac mass.