bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac fibrosis affects electrical conduction and arrhythmogenesis in a pacing-rate-dependent manner
Authors: Sacconi Leonardo , Giardini Francesco , Olianti Camilla , Marchal Gerrit Adam , Campos Fernando , Steyer Joshua , Madl Josef , Piersanti Roberto , Arecchi Giulia , Vanaja Induja Perumal , Biasci Valentina , Nesi Gabriella , Loew Leslie , Cerbai Elisabetta , Chelko Stephen , Regazzoni Francesco , Loewe Axel , Bishop Martin , Mongillo Marco , Kohl Peter , Zaglia Tania , Johnston Callum Michael 
Published: January 2025

Abstract

Cardiac fibrosis is a key factor in electrical conduction disturbances, yet its specific impact on conduction remains unclear, hindering predictive insight of cardiac electrophysiology and arrhythmogenesis. Among the different cardiac disorders, arrhythmogenic cardiomyopathy (ACM) is known to be associated with massive fibrotic remodelling of the myocardium, and it accounts for most cases of stress-related arrhythmic sudden death. To explore ACM further, we employed a Desmoglein-2-mutant mouse model and developed a correlative imaging approach to integrate macro-scale cardiac electrophysiology with 3D micro-scale reconstructions of the ventricles, to characterise the dynamics of conduction wavefronts and relate them to the underlying structural substrate. Our findings confirm that this ACM model shows localised replacement of cardiomyocytes with collagen and non-myocytes, contributing to electrical dysfunction. Moreover, we observed that conduction through fibrotic tissue areas shows a frequency-dependent behaviour, where conduction fails at high stimulation frequencies, promoting re-entrant arrhythmias, even in regions that were electrophysiologically inconspicuous at lower stimulation rates. Using a computational model, informed by high-resolution structural data, we found that frequency-dependent conduction through fibrotic tissue cannot be explained solely by collagen deposition or cardiomyocyte re-organisation. Indeed, fibrotic areas feature electrophysiological remodelling which acts as a low-pass filter for conduction, which can be quantitatively explained by electrotonic coupling of cardiomyocytes with non-myocytes. Collectively, our study provides a novel structure-function mapping pipeline and describes a previously unrecognised pro-arrhythmogenic mechanism in ACM, underscoring the need for dynamic assessment of functional conduction block in fibrotic myocardium using multiple diagnostic pacing protocols.
Polymerization-Induced Nano-Order, Ordered Melt, Chain Explosion and Meso-Superstructures of E-Polyethylene
Authors: maimaitiming Aizezi , Cui Kun , Tian Feng 
Published: January 2025

Abstract

During the past 70 years, it has been well established that melts of crystalline homopolymers adopt disordered random coil conformations and are densely packed in globules above the melting temperature (Tm). Flow-induced melt orientation promotes crystal nucleation and polymorphism upon cooling. Here, we present polymerization-induced nano-to-mesoscale condensed-ordering as well as order-to-order and order-to-disorder (O-D) melt transformations at TO-D in engineering polyethylene (E-PE). Moreover, we demonstrate fast chain explosion and re-entanglements at TO-D. Liquid-crystalline-like macroscale 2D-ordered nanofibrils and meso-ordered superstructures self-assemble from high-order condensed states and ordered melts via isothermal crystallization, respectively. Self-reinforced optical and shape memory sheets are made by preserving nascent meso-ordering. Eplastomers, which exhibit both elastomeric and soft‒plastic properties, are prepared by nano-fibrillation of non-crosslinked E-PE meso-particles in a polyolefin elastomer matrix and dynamic exchange of 1D-ordered nanofibrillar networks with disordered 3D meso-granules. These findings enable further development of ultrahigh-performance intelligent, photonic and sustainable polymeric materials.
Intensified treatment in patients with local operable but oligometastatic pancreatic cancer - multimodal surgical treatment versus chemotherapy alone: a randomized controlled trial (METAPANC)
Authors: Ghadimi Michael , Pelzer Uwe , Besselink Marc G. , Siveke Jens , Telgmann Ralph , Braren Rickmer , Wilmink Hanneke , Crede Marie , Koenig Alexander , Koenig Ute , Liffers Sven Thorsten , Antweiler Kai , Uijterwijk Bas , Seppanen Hanna , Nordin Arno , Puolakkainen Pauli , Dajani Olav F. , Labori Knut Jørgen , Johansson Mia , Bratlie Svein Olav , Friede Tim , Jo Peter 
Published: January 2025

Abstract

Background
Based on current guidelines, surgical treatment of hepatic oligometastases in patients with pancreatic ductal adenocarcinoma (PDAC) is not primarily recommended. Systematic chemotherapy is the therapy of choice for these patients. The relevance of subsequent surgical resection after chemotherapy remains unclear. This multicentre, randomized, controlled phase III trial is planned to evaluate whether resection of the primary tumor and liver metastases can improve overall survival in patients with PDAC with hepatic oligometastases in a multimodal treatment setting.
Methods
After an induction therapy with eight cyles of mFOLFIRINOX and a response assessment after four and eight cycles, patients will be randomized to either Arm 1 (perioperative mFOFIRINOX plus resection of the primary tumor with resection or ablation of all hepatic metastases) or Arm 2 (continuation of 4 cycles of the standard-of-care mFOLFIRINOX chemotherapy). This clinical trial will focus on a well-defined patient group with metastatic disease limited to the liver as the target organ, with a maximum of three metastases.
Discussion
METAPANC is the first international, randomized, controlled, open-label, multicentre, phase III clinical trial for curative intended surgical therapy of oligometastatic pancreatic cancer in Europe and America. The multimodal surgical treatment of patients with oligometastatic pancreatic cancer could significantly extend the overall survival of this patient group. A possible recommendation of this multimodal treatment regimen outside of clinical trials requires data from randomized controlled trials first. To identify patient subgroups that might benefit from multimodal surgical therapy, additional information on tumor genetics could supplement valid parameters.
Trial registration: EU Clinical Trials No. 2023-503558-10-00
The analysis of the ferroptosis metabolic regulatory network in patients with intrauterine adhesions (IUA) using a metabolomics approach
Authors: Zhang Fang , Yuan Aijuan , Bian Jia , Liu Minjie , Yan Chunhong , Hu Jie 
Published: January 2025

Abstract

Background: Recently, there has been a notable rise in the prevalence of intrauterine adhesions (IUA), exerting a substantial impact on female reproductive capacity. The phenomenon of ferroptosis is evident in IUA, yet the regulatory network associated with it remains unclear. Consequently, the objective of this study is to elucidate the metabolic regulatory network of ferroptosis in IUA through metabolomics, offering a fresh perspective for a more profound comprehension of the mechanisms underlying IUA. Concurrently, new active metabolites may emerge as potential targets for the prevention and treatment of IUA.
Methods and Results: Uterine endometrial samples were collected from both healthy individuals and patients with IUA, with each endometrium pathologically confirmed. Liquid chromatography-mass spectrometry (LC-MS) was employed for sample analysis. A total of 6250 differential metabolites were identified, of which 102 were screened (VIP>1 and P<0.05). Among these, 29 showed upregulation, while 73 were downregulated. KEGG pathway analysis identified biological processes and metabolic pathways. Differentially regulated metabolic pathways included glucose metabolism, amino acid degradation, fatty acid metabolism, etc. Notably associated were pathways like AMPK signaling pathway, unsaturated fatty acid biosynthesis, oxidative phosphorylation, fatty acid biosynthesis, and sphingolipid metabolism. Joint pathway analysis identified six metabolite pathways (Glutathione metabolism, Arachidonic acid metabolism, Citrate cycle (TCA cycle), Lysine degradation, Glycerolipid metabolism, Cysteine and methionine metabolism) from the differentially expressed metabolites (DEMs). These pathways collectively constitute the Ferroptosis metabolic regulatory network in intrauterine adhesions (IUA).
Conclusions: This study conducted a non-targeted metabolomics investigation on IUA . Taking the perspective of differential metabolites between normal and IUA, the study utilized metabolomics to reveal the metabolic regulatory network associated with iron death in IUA. ferroptosis in IUA is regulated by multiple metabolic pathways, including lipid metabolism, amino acid metabolism, and energy metabolism. These metabolic pathways, by modulating the activity of key enzymes such as lipid peroxidase and glutathione peroxidase, impact the occurrence and progression of ferroptosis. The metabolic regulatory network of iron death in IUA is closely related to the occurrence of intrauterine adhesions (IUA). ferroptosis plays a crucial role in the pathological process of intrauterine adhesions by regulating the metabolic pathways of adhesive tissues, potentially contributing to the prevention and treatment of IUA. This research not only aids in a deeper understanding of the pathological mechanisms of IUA but also provides new targets and strategies for preventing and treating diseases related to IUA.
Acute Appendicitis: Outcomes and Disparities based on Geographical Location and Race
Authors: Nonnemacher Cory , Glenn Joshua 
Published: January 2025

Abstract

Purpose
Studies have shown better outcomes in pediatric patients with appendicitis managed by pediatric surgeons. There has been an increase rate in hospital-to-hospital transfer to divert pediatric patients to pediatric facilities. We looked to assess how initial presenting facility was associated with patient outcomes and assess how race impacts outcomes.
Methods
Pediatric patients managed at our Children’s Hospital from 2015-2021 with appendicitis were assessed. Retrospective analysis assessing rates of perforation, ionizing radiation use and readmission and hospital LOS were assessed and evaluated based on distance from the hospital and race.
Results
240 patients transferred and 132 direct presentations were identified. We identified higher rates of perforation, 40.8% versus 27.2%, LOS of 3.56 versus 2.11 days, and higher rates of readmission, 7.3% versus 2.2% in those transferred versus direct presentation (p<0.05). Minorities that transferred had a higher LOS, 4.38 versus 2.57 days (p<0.05), compared to minorities who presented directly.
Conclusions
There are higher rates of perforation, readmission and LOS in those transferred than direct presentations. Transferring showed disproportionally worse outcomes in minority patients. This suggests distance from specialized pediatric care as well as patient race leads to worse outcomes and these variables have the potential to compound into poorer overall outcomes in minorities requiring transfer.
Estimating the size of aedes mosquitoes’ population involved in outbreaks of dengue and chikungunya and its relationship with climatic factors
Authors: Coutinho Francisco Antônio Bezerra , Amaku Marcos , Boulos Fernanda Castro , Moreira José Alfredo Sousa , Barros Eliana Nogueira Castro , Kallas Esper Jorge , Massad Eduardo 
Published: January 2025

Abstract

Background
Aedes aegypti continues to cause large number of cases of dengue, chikungunya and zika fever in the affected areas of the tropical world. After being eradicated from Brazil in the decades if 1940 and 1950, Aedes aegipti returned with full force in the early 1970s. Knowing the total number of mosquitoes transmitting aedes-borne infections in crucial to quantifying the intensity of transmission of these infections.
Methods
In this paper, we propose a model to estimate the distribution of aedes mosquitoes’ population during an outbreak of either dengue or chikungunya. The model assumes that the mosquitoes’ distribution follows a Gaussian Mesa Function, which has five parameters and allows for a variable asymmetry. These five parameters are adjusted so that it fits indirectly, from a modified Ross-Macdonald model, the incidence of dengue or chikungunya infections (see main text).
Results
We illustrate the model with data of dengue and chikungunya from five cities from the State of Minas Gerais in the Southeastern region of Brazil for the 2023-2024 transmission season. In addition, we show that the calculated mosquitoes’ distribution correlates with climatic variables in the five cities studied.
Conclusions
The model shows that it is possible to estimate the size of the mosquitoes’ population from incidence data, circumventing the logistic hurdles involved in the actual counting of mosquitoes, and that the mosquitoes’ distribution correlates well with rain patterns in the studied cities, but not with temperature.
Dietary Sources of Sodium in Nigerian Adults From 3 Geographic Regions: A Population-Based Cross-Sectional Study
Authors: George Aniekeme , Ojji Dike , Orji Anthony , Adurosakin Felix 
Published: January 2025

Abstract

Background
To address the growing burden of hypertension and related diseases, Nigeria seeks to reduce excess dietary sodium through policymaking. The current study aims to describe the levels and sources of dietary sodium intake among Nigerian adults to inform targeted policies for reducing sodium intake.
Methods
From June 2023 to July 2023, adults aged 18 to 70 years old were recruited from the Federal Capital Territory, Kano States, and Ogun States to participate in a population-based, cross-sectional non-communicable diseases survey. Data were also collected to assess levels and dietary sources of sodium through four 24-hour dietary recalls by trained study personnel with 90.7% response rate. Concurrent 24-hour urine sodium data were collected. The primary analyses included the distribution of sodium intake and sources of sodium, overall and by sex and state. Results were adjusted to the Nigerian population. Multivariate regression models evaluated associations between baseline sociodemographic factors and sodium intake.
Results
Among 537 participants, 365 (68.0%) were female, and median (Interquartile range) age was 38 (27, 48) years. Adjusted median (IQR) daily sodium intake according to 24-hour dietary recalls was 3,803 (2,663, 5,085) mg per day with higher intake reported among males (males: 3,878 [2,663, 5,032] mg/dl; females: 3,415 [2,373, 4,689], p<.0001). Two-thirds (67.0%) of the sodium intake was from home-cooked meals. Nearly half (48.7%) of sodium came from discretionary sources, including 21.4% from bouillon. Salt and yaji spice added at the table accounted for 9.1% of sodium intake and was highest among females (18.8%) and males (13.7%) in Kano. On the other hand, sodium from street food was highest in males (35.9%) and females (34.2%) in Ogun. After adjustment, older participants and those with higher education had lower daily sodium intake compared to younger participants and those with less education, respectively. Results were similar when excluding individuals with cardiovascular disease or hypertension.
Conclusions
Adults in the Federal Capital Territory, Kano, and Ogun consume nearly twice the recommended level of dietary sodium. Most dietary sodium intake came from home cooked foods, nearly half of which came from discretionary sources, which has important policy implications for SHAKE package implementation.
Registration number: NCT04765865
Bushen Daozhuo Granules Alleviate Chronic Non-Bacterial Prostatitis in Rats through p38 MAPK and Akt Signaling Pathways Based on Tandem
Mass Tag-Based Quantitative Proteomics and Network Pharmacology Analyses
Authors: Sun Dalin , Liu Yuanyuan , Xing Dong , Wang Dandan , Cai Bin , Tang Zhian , Hu Qinglin , Ma Wenjun , Jin Baofang 
Published: January 2025

Introduction:
The traditional Chinese medicine formula, Bushen Daozhuo Granules
(BSDZG), is used to treat chronic non-bacterial prostatitis (CNP) clinically. However, its mechanism
of action is unclear. The aim of our study was to determine the effect of BSDZG on CNP
and its underlying mechanisms.

Methods:
Male Wistar rats were randomly assigned to control, CNP, and BSDZG groups. CNP
was induced using purified prostaglandin solution and Freund's complete adjuvant, after which
the BSDZG group received 1.54 g/kg/d of BSDZG for 30 days. Prostate tissues were used to determine
apoptosis and inflammatory cytokines. The herb-composition-target network and functional
signaling pathways were built using a network pharmacology approach, which was also
confirmed in vivo.

Results:
Treatment with BSDZG significantly alleviated the histopathological lesions, inflammation,
and apoptosis in the prostate of CNP rats. The herb-composition-target network comprising
42 active compounds and 32 targets of 11 herbs was illustrated, and KEGG pathways analysis
identified the Akt and MAPK pathways as related to the effects of BSDZG. Phosphorylation of
p38 MAPK, NF-кB, and Bax expression was significantly enhanced and phosphorylated Akt and
Bcl-2 levels were decreased in CNP rats, which could be reversed by BSDZG.

Conclusion:
This study presented for the first time that BSDZG effectively alleviated CNP
symptoms in rats and elucidated the underlying mechanisms mediated by the Akt and MAPK
pathways, providing the theoretical basis for the clinical use and promotion of BSDZG.
Morphine-Induced Elevation of Reactive Oxygen Species
Attenuates Chemotherapy Efficacy in Diverse Cancer Cell Types
Authors: Chen Gong , Zeng Si , Wang Bin , Wang Daguo , Ding Jie , Feng Tao 
Published: January 2025

Background:
Morphine, a mu-opioid receptor (MOR) agonist commonly
utilized in clinical settings alongside chemotherapy to manage chronic pain in cancer
patients, has exhibited contradictory effects on cancer, displaying specificity toward
certain cancer types and doses.

Objective:
The aim of this study was to conduct a systematic assessment and
comparison of the impacts of morphine on three distinct cancer models in a preclinical
setting.

Methods:
Viability and apoptosis assays were conducted on a panel of cancer cell
lines following treatment with morphine, chemotherapy drugs alone, or their
combination. Oxidative stress levels, along with the activities of superoxide dismutase
and catalase, were measured. Rescue studies were also carried out using antioxidant
reagents.

Results:
Morphine induces resistance to conventional chemotherapeutic agents. It
was observed that while morphine affected cell viability differently among ovarian
cancer, anaplastic thyroid cancer, and oral squamous cell carcinoma, at
concentrations that did not directly impact cancer cell viability, it significantly mitigated
the inhibitory effects of chemotherapeutic agents across all tested cancer cells. This
phenomenon persisted irrespective of the chemotherapeutic agent used, including
cisplatin, doxorubicin, and 5-FU. It remained unaffected by adding naloxone, the MOR
receptor antagonist, indicating that morphine's mechanism is independent of the μ-
opioid receptor. Moreover, it was demonstrated that morphine heightened cellular
reactive oxygen species (ROS) levels and suppressed the activities of superoxide
dismutase and catalase. Rescue studies revealed that the addition of antioxidant
reversed the protective impact of morphine on cancer cells against chemotherapy.

Conclusion:
These findings hold promise in potentially guiding the clinical application
of morphine for cancer patients undergoing chemotherapy.
Value of Label-Free Ubiquitin-Proteomic Analysis on Defining the Protective Mechanism of Valsartan against Doxorubicin-Induced Heart Failure
Authors: Zhang Liyuan , Zhang Yujing , Chen Di , Shao Shujuan , Yu Qin 
Published: January 2025

Introduction:
The cardiotoxicity and subsequent Heart Failure (HF) induced by Doxorubicin (DOX) limit the clinical application of DOX. Valsartan (Val) is an angiotensin II receptor blocker that could attenuate the HF induced by DOX. However, the underlying mechanism of Val in this process is not fully understood.

Methods:
In this study, we explored the cardio-protective mechanism of Val against DOX-induced cardiotoxicity using label-free ubiquitin-proteomic analysis.

Results:
Results showed that 27 lysine-ubiquitination sites in 25 proteins were differentially expressed between DOX and DOX+Val treated groups. In addition, the levels of ubiquitin modification of the myosin family and Ankrd1 were upregulated post-Val. Val also in-creased ATP production and activated the Akt/mTOR pathway by regulating the sarcoplas-mic/endoplasmic reticulum calcium ATPase (SERCA2a) and cardiomyocyte calcium hemo-stasis.

Conclusion:
The results highlight the value of label-free ubiquitin-proteomic analysis in de-fining the molecular mechanism of Val against HF and may be helpful in the development of new therapeutic agents for HF via targeting molecules defined in this research.
Colorimetric Determination of Ascorbic Acid Using Peroxidase Activity of Allium Sativum (Garlic) Extract
Authors: saadat maryam , Hallajzadeh Jamal , Nikkhah Elhameh , Seidi Sadegh 
Published: January 2025

Background:
Detection and determination of ascorbic acid (AA) or vitamin C as a potent
antioxidant substrate in commercial samples have an emerging significance. In relation to the colorimetry
of ascorbic acid, the use of organometallic networks as enzyme peroxidase mimics has been
reported many times, which is not cost-effective for commercialization. Therefore, this research, for
the first time, examined the peroxidase behavior using garlic extract without additional extraction
and purification steps. Peroxidase behavior was examined to measure ascorbic acid.

Methods:
In this research work, firstly, allium sativum (AS) extract was prepared simply by crushing,
stirring, and sonicating garlic bulbs in water. It exhibited peroxidase activity, which enabled the
oxidation of 3, 30, 5, and 50-tetramethylbenzidine (TMB) in the presence of H2O2 to generate bluecolored
oxidized TMB (ox-TMB) with a sharp absorption peak at 6526 nm. In continuation, the ox-
TMB could be reduced by the addition of AA to the TMB+H2O2 system, leading to a decrease in
absorbance and the fading of the blue color. Determination performance was accomplished after
optimization of several factors, such as pH, time, TMB, and AS concentration.

Results:
The results showed that the decrease in absorbance (ΔA) after AA addition was in a good
linear relationship with AA concentration in the range of 9.46-155.24 μM, with a low detection limit
of 0.0223 μM. The feasibility of this approach was also assayed in commercial orange drinks and
effervescent tablets of vitamin C with a 97.70 %-110.17 % recovery.

Conclusion:
Finally, a sensitive and simple colorimetric sensor for the detection of AA using AS
extract as a biocatalyst was developed.