bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interplay of oxidative stress, cellular communication and signaling pathways in cancer
Authors: Iqbal Muhammad Javed , Kabeer Ayesha , Abbas Zaighum , Siddiqui Hamid Anees , Calina Daniela , Sharifi-Rad Javad , Cho William C. 
Published: January 2024

AbstractCancer remains a significant global public health concern, with increasing incidence and mortality rates worldwide. Oxidative stress, characterized by the production of reactive oxygen species (ROS) within cells, plays a critical role in the development of cancer by affecting genomic stability and signaling pathways within the cellular microenvironment. Elevated levels of ROS disrupt cellular homeostasis and contribute to the loss of normal cellular functions, which are associated with the initiation and progression of various types of cancer. In this review, we have focused on elucidating the downstream signaling pathways that are influenced by oxidative stress and contribute to carcinogenesis. These pathways include p53, Keap1-NRF2, RB1, p21, APC, tumor suppressor genes, and cell type transitions. Dysregulation of these pathways can lead to uncontrolled cell growth, impaired DNA repair mechanisms, and evasion of cell death, all of which are hallmark features of cancer development. Therapeutic strategies aimed at targeting oxidative stress have emerged as a critical area of investigation for molecular biologists. The objective is to limit the response time of various types of cancer, including liver, breast, prostate, ovarian, and lung cancers. By modulating the redox balance and restoring cellular homeostasis, it may be possible to mitigate the damaging effects of oxidative stress and enhance the efficacy of cancer treatments. The development of targeted therapies and interventions that specifically address the impact of oxidative stress on cancer initiation and progression holds great promise in improving patient outcomes. These approaches may include antioxidant-based treatments, redox-modulating agents, and interventions that restore normal cellular function and signaling pathways affected by oxidative stress. In summary, understanding the role of oxidative stress in carcinogenesis and targeting this process through therapeutic interventions are of utmost importance in combating various types of cancer. Further research is needed to unravel the complex mechanisms underlying oxidative stress-related pathways and to develop effective strategies that can be translated into clinical applications for the management and treatment of cancer.
Predictors of fibrogenesis in children with JIA: a single-center pilot study
Authors: Pavlova Olga , Shevchenko Natalia , Pavlov Sergey , Holovko Tetiana , Bogmat Liudmyla 
Published: January 2024

Abstract
Background
Patients with rheumatological diseases are at high risk of developing irreversible fibrotic changes, both articular and extra-articular, as a result of tissue damage caused by the chronic phase of persistent inflammation. Thus, our purpose was to study early markers of fibrosis formation in children with juvenile idiopathic arthritis (JIA).

Methods
Seventy patients with juvenile idiopathic arthritis, namely, polyarthritis (64.29%) and oligoarthritis (35.71%) variant JIA (mean age 13.3 years, 64.29% girls, 35.71% boys), were included in this 4-year prospective study. Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) levels were determined by ELISA kits.

Results
We evaluated bFGF (mean: 7478.21 pg/ml; min: 4171.56 pg/ml; max: 18,011.25 pg/ml) and VEGF (mean: 342.47 pg/ml; min: 23.68 pg/ml; max: 2158.91 pg/ml) levels in children with JIA. Children with JIA had a higher VEGF level when JIA onset occurred after 15 years of age and they had a high disease activity; additionally, a higher bFGF level was observed in children older than 14 years and in those with a JIA onset after 15 years of age, the oligoarticular variant, a moderate disease activity and regardless of MTX administration but more often when MTX was administered at a dosage from 10 to 12.5 mg/m2/week.

Conclusions
Laboratory screening of fibrosis formation predictors could help identify patients who may be at greater risk of adverse outcomes. Children with JIA had higher bFGF and VEGF levels when JIA onset occurred after 15 years of age, depending on disease activity.
Methotrexate inhibits BMP4 and abrogates the hypertrophic chondrocyte phenotype of synovial fibroblasts in juvenile idiopathic arthritis
Authors: Simonds Megan M. , Freer Samuel T. , Brescia Anne Marie C. 
Published: January 2024

Abstract
Background
Juvenile Idiopathic Arthritis (JIA) induces growth disturbances in affected joints. Fibroblast-like synoviocytes (FLS) play a crucial role in JIA pathogenesis. FLS overexpress bone morphogenetic protein 4 (BMP4) and have a chondrocyte-like phenotype. FLS contribute directly to joint growth disturbances through endochondral bone formation. We investigated the ability of methotrexate to inhibit BMP4 expression and alter the hypertrophic chondrocyte-like phenotype of JIA FLS.

Methods
We selected primary cells from three subjects with persistent oligoarticular JIA, three subjects who eventually extended to a polyarticular disease course, which we termed extended-to-be (ETB), and three subjects who had polyarticular arthritis at time of diagnosis. We treated cells with methotrexate and two BMP4 inhibitors: noggin and chordin. We measured protein concentration from three chondrocyte cell markers: collagen II, aggrecan, and collagen X as well as BMP4.

Results
ColX, marker of chondrocyte hypertrophy, was significantly increased in polyarticular FLS when compared to both persistent FLS and ETB FLS, making polyarticular FLS the most like hypertrophic chondrocytes. Methotrexate caused significant decreases in BMP4 and ColX expression in persistent, ETB, and polyarticular FLS when compared to respective untreated cells. Ligand-binding BMP4 antagonists, noggin and chordin, caused significant decreases in ColX expression in FLS from all three disease courses and significant increases in collagen II protein, an early chondrocyte marker, when compared to respective untreated cells.

Conclusions
Methotrexate, the first-line therapy in the treatment of JIA, mimics BMP4 antagonists by effectively lowering BMP4 and ColX expression in FLS. Inhibiting FLS from undergoing hypertrophy could prevent these cells from contributing to joint growth disturbances via endochondral bone formation.
A rare case of coronary artery complication in a child with systemic juvenile idiopathic arthritis and macrophage activation syndrome: case report and literature review
Authors: Zhang Lian , Wei Yanwen , Zeng Ningjing , Wang Lianyu , Chen Xinying , Yang Jinghua , Xiao Xiaolan 
Published: January 2024

AbstractA rare case of coronary artery involvement in a child with Systemic Juvenile Idiopathic Arthritis (sJIA) complicated by Macrophage Activation Syndrome (MAS) is reported. The patient initially received an inaccurate diagnosis of Kawasaki Disease, sepsis, and mycoplasma infection and showed no improvement after Intravenous Immune Globulin (IVIG) treatment. Upon admission, symptoms included diffuse red rash, swelling of the limbs, lymph node enlargement, and hepatosplenomegaly. Post investigations, a diagnosis of sJIA and MAS was confirmed, and treatment involved a combination of hormones (methylprednisolone) and immunosuppressive drugs (methotrexate). The revealed widened coronary artery diameter was managed with a disease-specific treatment plan and prophylactic plus low-dose aspirin anti-coagulation therapy. Under this management, MAS was well controlled, and follow-ups showed normalization of the child’s coronary artery structure and function. This case and the associated literature review underscore the importance of early recognition, diagnosis, treatment, and long-term monitoring for children presenting with sJIA and MAS complicated by coronary artery involvement.
Effect of probiotic supplementation on lipoprotein-associated phospholipase A2 in type 2 diabetic patients: a randomized double blind clinical controlled trial
Authors: Jaff Salman , Gubari Mohammed , Shab-Bidar Sakineh , Djafarian Kurosh 
Published: January 2024

Abstract
Background
It has been recently reported that lipoprotein-associated phospholipase A2 (Lp-PLA2) may predict the risk of cardiovascular disease. The effect of multi-strain probiotics on Lp-PLA2 in patients with type 2 diabetes is still not clear.

Aims
This study aimed to determine the effect of multi-strain probiotic supplementation on lipoprotein-associated phospholipase A2, and glycemic status, lipid profile, and body composition in patients with type 2 diabetes.

Methods
In this randomized double-blind placebo-controlled clinical trial, 68 participants with type 2 diabetes, in the age group of 50–65 years, were recruited and randomly allocated to take either probiotic (n = 34) or placebo (n = 34) for 12 weeks. The primary outcome was lipoprotein-associated phospholipase A2, and secondary outcomes were glycemic parameters, lipid profile, anthropometric characters, and body composition (fat mass and fat-free mass).

Results
There was a significant reduction in serum lipoprotein-associated phospholipase A2, in the probiotic group, it dropped by 6.4 units at the end of the study (p < 0.001) compared to the placebo group. Probiotic supplementation also resulted in a significant improvement in the hemoglobin A1c and high-density lipoprotein cholesterol 1.5% (p < 0.001) and 6 mg/dl (p 0.005), respectively. There were no significant changes in other outcomes.

Conclusion
Probiotic supplementation was beneficial for reducing Lp-PLA2 and hemoglobin-A1c and improving high-density lipoprotein cholesterol, which may suggest an improvement in the prognosis in patients with type 2 diabetes.
HIV/AIDS, SARS, and COVID-19: the trajectory of China’s pandemic responses and its changing politics in a contested world
Authors: Zhou Yanqiu Rachel 
Published: January 2024

AbstractThe COVID-19 pandemic has revealed the contested politics of global health governance, though we still don’t know enough about the dynamics of domestic pandemic responses, or about the relationship between the politics of those responses and the politics of global health governance, both of which have changed significantly in recent decades. Focusing on three cases (HIV/AIDS, SARS, and COVID-19) of cross-border infectious diseases, this article explores the trajectory of China’s pandemic responses in the context of globalization. Attending to changing politics at domestic, international, and global levels, I argue that those responses have been a complex combination of China’s domestic politics (e.g., priorities, institutions, leadership, and timing), its international relations (especially with the US), and its engagements with global health governance. It is concluded that the increasing divergence of pandemic responses in a time of ubiquitous global health crisis demands urgent attention to the connections (including contestations) between domestic pandemic responses and the evolvement of global health governance from a broader perspective that considers changes in geopolitics.
Cluster-randomized implementation trial of two facilitation strategies to implement a novel information and communications technology at the Veterans Health Administration
Authors: Leonard Chelsea , Carey Evan , Holstein Ariel , Ho P. Michael , Heckman Jeffrey T. 
Published: January 2024

AbstractBackgroundInformation and communication technologies (ICTs) improve quality and efficiency of healthcare, but effective practices for implementing new ICTs are unknown. From 2019 to 2021, the Veterans Health Administration (VHA) implemented FLOW3, an ICT that facilitates prosthetic limb care. The goal of this study was to compare the impact of two facilitation strategies on FLOW3 adoption, implementation, and sustainment.MethodsFLOW3 is a computerized workflow management system comprised of three applications that facilitate the three steps for prosthesis authorization. During VHA’s implementation of FLOW3, we randomized 60 VHA sites to basic or enhanced facilitation groups. Basic facilitation included a manualized training toolkit and office hours. Enhanced facilitation included basic facilitation plus monthly learning collaboratives and site-specific performance reports. Outcomes included time to adoption of FLOW3 and complete FLOW3 utilization rates during implementation and sustainment periods. We compared outcomes between sites assigned to basic versus enhanced facilitation groups. Results were calculated using both intent-to-treat (ITT) and dose–response analyses. The dose–response analysis used a per-protocol approach and required sites in the enhanced facilitation group to join two of six learning collaboratives; sites that attended fewer were reassigned to the basic group.ResultsRandomization assigned 30 sites to enhanced facilitation and 30 to basic. Eighteen of 30 randomized sites were included in the enhanced facilitation group for dose–response analysis. During the implementation period, enhanced facilitation sites were significantly more likely to completely utilize FLOW3 than basic facilitation sites (HR: 0.17; 95%CI: 1.18, 4.53,p = 0.02) based on ITT analysis. In the dose–response analysis, the enhanced group was 2.32 (95%CI: 1.18, 4.53) times more likely to adopt FLOW3 than basic group (p = 0.014).ConclusionsEnhanced facilitation including a learning collaborative and customized feedback demonstrated greater likelihood for sites to complete a prosthetics consult using FLOW3 throughout our study. We identified statistically significant differences in likelihood of adoption using the dose–response analysis and complete utilization rate using ITT analysis during the implementation period. All sites that implemented FLOW3 demonstrated improvement in completion rate during the sustainment period, but the difference between facilitation groups was not statistically significant. Further study to understand sustainability is warranted.
Protocol for a hybrid type 3 effectiveness-implementation trial of a pragmatic individual-level implementation strategy for supporting school-based prevention programming
Authors: Lyon Aaron R. , Cook Clayton R. , Larson Madeline , Hugh Maria L. , Dopp Alex , Hamlin Corinne , Reinke Peter , Bose Mahasweta , Law Amy , Goosey Roger , Goerdt Annie , Morrell Nicole , Wackerle-Hollman Alisha , Pullmann Michael D. 
Published: January 2024

AbstractBackgroundFor approximately one in five children who have social, emotional, and behavioral (SEB) challenges, accessible evidence-based prevention practices (EBPPs) are critical. In the USA, schools are the primary setting for children’s SEB service delivery. Still, EBPPs are rarely adopted and implemented by front-line educators (e.g., teachers) with sufficient fidelity to see effects. Given that individual behavior change is ultimately required for successful implementation, focusing on individual-level processes holds promise as a parsimonious approach to enhance impact. Beliefs and Attitudes for Successful Implementation in Schools for Teachers (BASIS-T) is a pragmatic, multifaceted pre-implementation strategy targeting volitional and motivational mechanisms of educators’ behavior change to enhance implementation and student SEB outcomes. This study protocol describes a hybrid type 3 effectiveness-implementation trial designed to evaluate the main effects, mediators, and moderators of the BASIS-T implementation strategy as applied to Positive Greetings at the Door, a universal school-based EBPP previously demonstrated to reduce student disruptive behavior and increase academic engagement.MethodsThis project uses a blocked randomized cohort design with an active comparison control (ACC) condition. We will recruit and include approximately 276 teachers from 46 schools randomly assigned to BASIS-T or ACC conditions. Aim 1 will evaluate the main effects of BASIS-T on proximal implementation mechanisms (attitudes, subjective norms, self-efficacy, intentions to implement, and maintenance self-efficacy), implementation outcomes (adoption, reach, fidelity, and sustainment), and child outcomes (SEB, attendance, discipline, achievement). Aim 2 will examine how, for whom, under what conditions, and how efficiently BASIS-T works, specifically by testing whether the effects of BASIS-T on child outcomes are (a) mediated via its putative mechanisms of behavior change, (b) moderated by teacher factors or school contextual factors, and (c) cost-effective.DiscussionThis study will provide a rigorous test of BASIS-T—a pragmatic, theory-driven, and generalizable implementation strategy designed to target theoretically-derived motivational mechanisms—to increase the yield of standard EBPP training and support strategies.Trial registrationClinicalTrials.gov ID: NCT05989568. Registered on May 30, 2023.
Effectiveness of pleurodesis for postoperative air leaks after lung resection
Authors: Tsubokawa Norifumi , Mimae Takahiro , Ito Risa , Sasai Ryuma , Hirano Kouichi , Kamigaichi Atsushi , Kawamoto Nobutaka , Miyata Yoshihiro , Okada Morihito 
Published: January 2024

Abstract
Background
Pleurodesis is often performed for air leaks; however, the ideal materials and timing of the procedure remain controversial. We investigated the efficacy of pleurodesis using different materials and timing.

Methods
We retrospectively reviewed 913 consecutive patients who underwent segmentectomy or lobectomy for non-small cell lung cancer between 2014 and 2021. Pleurodesis efficacy was assessed on the day of chest tube removal.

Results
Eighty-six patients (9%) underwent pleurodesis for postoperative air leaks. Pleurodesis was performed on a median of postoperative day (POD) 5. Talc was the most frequently used material (n = 52, 60%), followed by autologous blood patches (n = 20, 23%), OK-432 (n = 12, 14%), and others (n = 2, 2%). No difference existed in the number of days from initial pleurodesis to chest tube removal among the three groups (talc, 3 days; autologous blood patch, 3 days; OK-432, 2 days; P = 0.55). No difference in patient background, except for sex, was observed between patients who underwent pleurodesis within 4 PODs and those who underwent pleurodesis on POD 5 or later. Drainage time was significantly shorter in patients who underwent pleurodesis within 4 PODs (median, 7 vs. 9 days; P = 0.004).

Conclusions
The efficacies of autologous blood patch, talc, and OK-432 would be considered comparable and early postoperative pleurodesis could shorten drainage time. Prospective studies are required.
Machine learning integration of multi-modal analytical data for distinguishing abnormal botanical drugs and its application in Guhong injection
Authors: Han Zhu , Zhao Jiandong , Tang Yu , Wang Yi 
Published: January 2024

Abstract
Background
Determination of batch-to-batch consistency of botanical drugs (BDs) has long been the bottleneck in quality evaluation primarily due to the chemical diversity inherent in BDs. This diversity presents an obstacle to achieving comprehensive standardization for BDs. Basically, a single detection mode likely leads to substandard analysis results as different classes of structures always possess distinct physicochemical properties. Whereas representing a workaround for multi-target standardization using multi-modal data, data processing for information from diverse sources is of great importance for the accuracy of classification.

Methods
In this research, multi-modal data of 78 batches of Guhong injections (GHIs) consisting of 52 normal and 26 abnormal samples were acquired by employing HPLC-UV, -ELSD, and quantitative 1H NMR (q1HNMR), of which data obtained was then individually used for Pearson correlation coefficient (PCC) calculation and partial least square-discriminant analysis (PLS-DA). Then, a mid-level data fusion method with data containing qualitative and quantitative information to establish a support vector machine (SVM) model for evaluating the batch-to-batch consistency of GHIs.

Results
The resulting outcomes showed that datasets from one detection mode (e.g., data from UV detectors only) are inadequate for accurately assessing the product's quality. The mid-level data fusion strategy for the quality evaluation enabled the classification of normal and abnormal batches of GHIs at 100% accuracy.

Conclusions
A quality assessment strategy was successfully developed by leveraging a mid-level data fusion method for the batch-to-batch consistency evaluation of GHIs. This study highlights the promising utility of data from different detection modes for the quality evaluation of BDs. It also reminds manufacturers and researchers about the advantages of involving data fusion to handle multi-modal data. Especially when done jointly, this strategy can significantly increase the accuracy of product classification and serve as a capable tool for studies of other BDs.
Father-to-daughter transmission in late-onset OTC deficiency: an underestimated mechanism of inheritance of an X-linked disease
Authors: Siri Barbara , Olivieri Giorgia , Lepri Francesca Romana , Poms Martin , Goffredo Bianca Maria , Commone Anna , Novelli Antonio , Häberle Johannes , Dionisi-Vici Carlo 
Published: January 2024

Abstract
Background
Ornithine Transcarbamylase Deficiency (OTCD) is an X-linked urea cycle disorder characterized by acute hyperammonemic episodes. Hemizygous males are usually affected by a severe/fatal neonatal-onset form or, less frequently, by a late-onset form with milder disease course, depending on the residual enzymatic activity. Hyperammonemia can occur any time during life and patients could remain non- or mis-diagnosed due to unspecific symptoms. In heterozygous females, clinical presentation varies based on the extent of X chromosome inactivation. Maternal transmission in X-linked disease is the rule, but in late-onset OTCD, due to the milder phenotype of affected males, paternal transmission to the females is possible. So far, father-to-daughter transmission of OTCD has been reported only in 4 Japanese families.

Results
We identified in 2 Caucasian families, paternal transmission of late-onset OTCD with severe/fatal outcome in affected males and 1 heterozygous female. Furthermore, we have reassessed the pedigrees of other published reports in 7 additional families with evidence of father-to-daughter inheritance of OTCD, identifying and listing the family members for which this transmission occurred.

Conclusions
Our study highlights how the diagnosis and pedigree analysis of late-onset OTCD may represent a real challenge for clinicians. Therefore, the occurrence of paternal transmission in OTCD should not be underestimated, due to the relevant implications for disease inheritance and risk of recurrence.