bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aa-Z2 triggers ROS-induced apoptosis of osteosarcoma by targeting PDK-1
Authors: Liu Yixin , She Wenyan , Li Yi , Wang Miao , Liu Yin , Ning Biao , Xu Tianzi , Huang Tianhe , Wei Yongchang 
Published: January 2023

Abstract
Background
Osteosarcoma (OS) is the most frequent cancer derived from bone, and the prognosis of OS is poor. Metabolic alterations have been previously reported to contribute to the development of OS, and arsenic compounds have been suggested to exhibit strong anti-OS effects. However, few studies have described the therapeutic efficiency of arsenic compounds by targeting metabolism in OS.

Methods
Here, we presented a novel organo-arsenic compound, Aa-Z2, and its antitumour efficacy against OS both in vitro and in vivo.

Results
Aa-Z2 induced OS cell apoptosis, G2/M phase arrest, and autophagy through the accumulation of reactive oxygen species (ROS). Elevated ROS functioned by promoting the mitochondrial-dependent caspase cascade and attenuating the PI3K/Akt/mTOR signalling pathway. N-acetylcysteine (NAC), a kind of ROS scavenger, could reverse the effects of Aa-Z2 treatment on 143B and HOS cells. Specifically, by targeting pyruvate dehydrogenase kinase 1 (PDK-1), Aa-Z2 induced changes in mitochondrial membrane potential and alterations in glucose metabolism to accumulate ROS. Overexpression of PDK-1 could partially desensitize OS cells to Aa-Z2 treatment. Importantly, Aa-Z2 suppressed tumour growth in our xenograft osteosarcoma model.

Conclusion
The study provides new insights into the mechanism of Aa-Z2-related metabolic alterations in OS inhibition, as well as pharmacologic evidence supporting the development of metabolism-targeting therapeutics.
A proposal for systematic monitoring of the commercial determinants of health: a pilot study assessing the feasibility of monitoring lobbying and political donations in Australia
Authors: Lacy-Nichols Jennifer , Cullerton Katherine 
Published: January 2023

Abstract
Background
The commercial determinants of health include a range of practices to promote business interests, often at the expense of public health. Corporate political practices, such as lobbying and campaign donations, are used to influence policy makers and foster a political and regulatory environment conducive to business interests. Despite recognition of their public health importance, thus far there are relatively few efforts to systematically monitor commercial political practices.

Methods
A pilot study was conducted to explore the feasibility of systematically monitoring two political practices – lobbying and political contributions – for ‘harmful industries’ (alcohol, gambling, ultra-processed food and tobacco industries) in Australia. Potential data sources were reviewed to compare data availability and detail. Two publicly available datasets were selected for the pilot: ministerial diaries for New South Wales and annual donor filings from the Australian Electoral Commission. Google Data Studio was used to analyse and visualise findings.

Results
The pilot study resulted in the creation of several interactive charts and dashboards that supported analysis and interrogation of the data. These charts helped to easily convey the volume of lobbying and political donations, as well as changes over time. For example, we found that between July 2014 and December 2020, NSW ministers had 20,607 meetings, of which 634 meetings were with harmful industries. And between 1998 and 2020, a total of $576,519,472 disclosed donations were made to political parties and other entities, of which $35,823,937 were from harmful industries.

Conclusions
Opportunities to develop a program to monitor commercial political practices face several challenges including access barriers arising from poor availability and detail of data, technical barriers arising from the format of data disclosures and coding challenges arising from the diverse nature of the commercial sector. Despite these challenges, our pilot study demonstrates the potential to implement a monitoring program and to expand its scope to other commercial determinants of health.
Safety and efficacy of two-port thoracoscopic aortic valve replacement
Authors: Tan Tong , Wei Peijian , Liu Yanjun , Huang Huanlei , Zhuang Jian , Chen Jimei , Liu Jian , Guo Huiming 
Published: January 2023

Abstract
Background
Pure aortic valve disease is common and has been treated with sternotomy aortic valve replacement for decades. Minimally invasive cardiac surgery has been widely used in atrioventricular valve lesions, but totally thoracoscopic aortic valve replacement has rarely been reported.

Method
The profiles of 9 patients who were diagnosed with severe aortic valve diseases and treated with two-port thoracoscopic aortic valve replacement between February 2021 and February 2022 were retrospectively reviewed. The clinical data, including baseline characteristics, operative data, postoperative complications, and short-term outcomes, were reported.

Results
All nine patients successfully underwent two-port thoracoscopic aortic valve replacement, with a cardiopulmonary bypass time of 137.56 ± 27.99 min and an aortic cross-clamp time of 95.33 ± 17.96 min. Seven (77.78%) patients underwent mechanical valve replacement, and two (22.22%) patients underwent bioprosthetic valve replacement. Two (22.22%) patients underwent a concomitant aortic root enlargement procedure. There were no intraoperative or postoperative deaths. The incidence of procedural complications was 0%, while the results of ventilation time, intensive care unit stay length, blood transfusion, chest tube drainage, and kidney function were satisfactory.

Conclusion
Two-port thoracoscopic aortic valve replacement is a safe and effective surgical treatment option for carefully selected patients with pure aortic valve diseases.
Genome-wide association study of brain biochemical phenotypes reveals distinct genetic architecture of Alzheimer’s disease related proteins
Authors: Oatman Stephanie R. , Reddy Joseph S. , Quicksall Zachary , Carrasquillo Minerva M. , Wang Xue , Liu Chia-Chen , Yamazaki Yu , Nguyen Thuy T. , Malphrus Kimberly , Heckman Michael , Biswas Kristi , Nho Kwangsik , Baker Matthew , Martens Yuka A. , Zhao Na , Kim Jun Pyo , Risacher Shannon L. , Rademakers Rosa , Saykin Andrew J. , DeTure Michael , Murray Melissa E. , Kanekiyo Takahisa ,   for the Alzheimer’s Disease Neuroimaging Initiative, Dickson Dennis W. , Bu Guojun , Allen Mariet , Ertekin-Taner Nilüfer 
Published: January 2023

Abstract
Background
Alzheimer’s disease (AD) is neuropathologically characterized by amyloid-beta (Aβ) plaques and neurofibrillary tangles. The main protein components of these hallmarks include Aβ40, Aβ42, tau, phosphor-tau, and APOE. We hypothesize that genetic variants influence the levels and solubility of these AD-related proteins in the brain; identifying these may provide key insights into disease pathogenesis.

Methods
Genome-wide genotypes were collected from 441 AD cases, imputed to the haplotype reference consortium (HRC) panel, and filtered for quality and frequency. Temporal cortex levels of five AD-related proteins from three fractions, buffer-soluble (TBS), detergent-soluble (Triton-X = TX), and insoluble (Formic acid = FA), were available for these same individuals. Variants were tested for association with each quantitative biochemical measure using linear regression, and GSA-SNP2 was used to identify enriched Gene Ontology (GO) terms. Implicated variants and genes were further assessed for association with other relevant variables.

Results
We identified genome-wide significant associations at seven novel loci and the APOE locus. Genes and variants at these loci also associate with multiple AD-related measures, regulate gene expression, have cell-type specific enrichment, and roles in brain health and other neuropsychiatric diseases. Pathway analysis identified significant enrichment of shared and distinct biological pathways.

Conclusions
Although all biochemical measures tested reflect proteins core to AD pathology, our results strongly suggest that each have unique genetic architecture and biological pathways that influence their specific biochemical states in the brain. Our novel approach of deep brain biochemical endophenotype GWAS has implications for pathophysiology of proteostasis in AD that can guide therapeutic discovery efforts focused on these proteins.
Evaluation of thiol disulfide balance in adolescents with vitamin B12 deficiency
Authors: Demirtas Mehmet Semih , Erdal Huseyin 
Published: January 2023

Abstract
Background
Vitamin B12 is an important vitamin for metabolism and affects many mechanisms in the body including neuronal migration, DNA synthesis, neurotransmitter synthesis, brain and cognitive development. Increased oxidative stress in the body leads to the damage of the child development, but also plays a crucial role in the pathogenesis of many diseases encountered in the childhood period. Our aim is to investigate whether or not B12 deficiency is associated with dynamic thiol/disulfide homeostasis in adolescent patients.

Methods
This is a case-controlled observational study consisting of 45 adolescent patients with vitamin b12 deficiency and a control group consisting of 45 healthy adolescent. Patients between 11 and 18 ages who applied to the outpatient clinic for the first time with one of the complaints of headache were selected due to their decreased school performance, dizziness, and fatigue. Hemogram, vitamin B12, homocysteine levels and oxidative stress parameters such as native and total thiol disulfide levels and ratios of disulfide/native thiol, disulfide/total thiol, and native thiol/total thiol were measured from the patients.

Results
Vitamin B12 level was found to be significantly lower in vitamin B12 deficiency group (p < 0.001). The serum disulfide level was found to be 27.5 ± 8.38 in the case group and 20.5 ± 8.36 in the control group (p < 0.001). In the multiple linear regression analysis, it was determined that the independent variables of native thiol, homocysteine and disulfide levels effected of vitamin B12 levels (p < 0.001, p < 0.001, p < 0.005 respectively; R2 = 0.62).

Conclusion
The results obtained in terms of the effect of vitamin B12 deficiency on oxidative stress in adolescents are remarkable. The increase in oxidative stress parameters in the patient group may also suggest that oxidative stress plays a vital role in vitamin B12 deficiency in adolescence.
Implementation of an evidence-based management algorithm for patients with chronic pancreatitis (COMBO trial): study protocol for a stepped-wedge cluster-randomized controlled trial
Authors: de Rijk Florence E. M. , van Veldhuisen Charlotte L. , Besselink Marc G. , van Hooft Jeanin E. , van Santvoort Hjalmar C. , van Geenen Erwin J. M. , van Werkhoven Cornelis H. , de Jonge Pieter Jan F. , Bruno Marco J. , Verdonk Robert C. ,   for the Dutch Pancreatitis Study Group
Published: January 2023

Abstract
Background
Chronic pancreatitis (CP) is an inflammatory disease that may be complicated by abdominal pain, pancreatic dysfunction, nutritional deficiencies, and diminished bone density. Importantly, it is also associated with a substantially impaired quality of life and reduced life expectancy. This may partly be explained by suboptimal treatment, in particular the long-term management of this chronic condition, despite several national and international guidelines. Standardization of care through a structured implementation of guideline recommendations may improve the level of care and lower the complication rate of these patients. Therefore, the aim of the present study is to evaluate to what extent patient education and standardization of care, through the implementation of an evidence-based integrated management algorithm, improve quality of life and reduce pain severity in patients with CP.

Methods
The COMBO trial is a nationwide stepped-wedge cluster-randomized controlled trial. In a stepwise manner, 26 centers, clustered in 6 health regions, cross-over from current practice to care according to an evidence-based integrated management algorithm. During the current practice phase, study participants are recruited and followed longitudinally through questionnaires. Individual patients contribute data to both study periods. Co-primary study endpoints consist of quality of life (assessed by the PANQOLI score) and level of pain (assessed by the Izbicki questionnaire). Secondary outcomes include process measure outcomes, clinical outcomes (e.g., pancreatic function, nutritional status, bone health, interventions, medication use), utilization of healthcare resources, (in) direct costs, and the level of social participation. Standard follow-up is 35 months from the start of the trial.

Discussion
This is the first stepped-wedge cluster-randomized controlled trial to investigate whether an evidence-based integrated therapeutic approach improves quality of life and pain severity in patients with CP as compared with current practice.

Trial registration
ISRCTN, ISRCTN13042622. Registered on 5 September 2020.
TRansfusion strategies in Acute brain INjured patients (TRAIN): a prospective multicenter randomized interventional trial protocol
Authors: Taccone Fabio Silvio , Badenes Rafael , Rynkowski Carla Bittencourt , Bouzat Pierre , Caricato Anselmo , Kurtz Pedro , Moller Kirsten , Diaz Manuel Quintana , Van Der Jagt Mathieu , Videtta Walter , Vincent Jean-Louis 
Published: January 2023

Abstract
Background
Although blood transfusions can be lifesaving in severe hemorrhage, they can also have potential complications. As anemia has also been associated with poor outcomes in critically ill patients, determining an optimal transfusion trigger is a real challenge for clinicians. This is even more important in patients with acute brain injury who were not specifically evaluated in previous large randomized clinical trials. Neurological patients may be particularly sensitive to anemic brain hypoxia because of the exhausted cerebrovascular reserve, which adjusts cerebral blood flow to tissue oxygen demand.

Methods
We described herein the methodology of a prospective, multicenter, randomized, pragmatic trial comparing two different strategies for red blood cell transfusion in patients with acute brain injury: a “liberal” strategy in which the aim is to maintain hemoglobin (Hb) concentrations greater than 9 g/dL and a “restrictive” approach in which the aim is to maintain Hb concentrations greater than 7 g/dL. The target population is patients suffering from traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), or intracerebral hemorrhage (ICH). The primary outcome is the unfavorable neurological outcome, evaluated using the extended Glasgow Outcome Scale (eGOS) of 1–5 at 180 days after the initial injury. Secondary outcomes include, among others, 28-day survival, intensive care unit (ICU) and hospital lengths of stay, the occurrence of extra-cerebral organ dysfunction/failure, and the development of any infection or thromboembolic events. The estimated sample size is 794 patients to demonstrate a reduction in the primary outcome from 50 to 39% between groups (397 patients in each arm). The study was initiated in 2016 in several ICUs and will be completed in December 2022.

Discussion
This trial will assess the impact of a liberal versus conservative strategy of blood transfusion in a large cohort of critically ill patients with a primary acute brain injury. The results of this trial will help to improve blood product and transfusion use in this specific patient population and will provide additional data in some subgroups of patients at high risk of brain ischemia, such as those with intracranial hypertension or cerebral vasospasm.

Trial registration
ClinicalTrials.gov NCT02968654.
Integrative metabolomics of plasma and PBMCs identifies distinctive metabolic signatures in Behçet’s disease
Authors: Park Soo Jin , Park Mi Jin , Park Sun , Lee Eun-So , Lee Do Yup 
Published: January 2023

Abstract
Background
Behçet’s disease (BD) is a systemic inflammatory disease that involves various organs. The clinical manifestation-based diagnosis of BD is a time-consuming process, which makes it difficult to distinguish from patients with similar symptoms. Moreover, an authentic biomarker has not been developed for accurate diagnosis yet. Our current study investigated the unique metabolic signatures of BD and explored biomarkers for precise diagnosis based on an untargeted metabolomic approach.

Methods
Integrative metabolomic and lipidomic profiling was performed on plasma samples of BD patients (n = 40), healthy controls (HCs, n = 18), and disease controls (DCs, n = 17) using GC-TOF MS and LC-Orbitrap MS. Additionally, the lipid profiles of 66 peripheral blood mononuclear cells (PBMCs) were analyzed from 29 BD patients, 18 HCs, and 19 DCs.

Results
Plasma metabolic dysfunction in BD was determined in carbohydrate, hydroxy fatty acid, and polyunsaturated fatty acid metabolisms. A plasma biomarker panel with 13 compounds was constructed, which simultaneously distinguished BD from HC and DC (AUCs ranged from 0.810 to 0.966). Dysregulated PBMC metabolome was signatured by a significant elevation in lysophosphatidylcholines (LPCs) and ether-linked lysophosphatidylethanolamines (EtherLPEs). Ten PBMC-derived lipid composites showed good discrimination power (AUCs ranged from 0.900 to 0.973). Correlation analysis revealed a potential association between disease activity and the metabolites of plasma and PBMC, including sphingosine-1 phosphate and EtherLPE 18:2.

Conclusions
We identified metabolic biomarkers from plasma PBMC, which selectively discriminated BD from healthy control and patients with similar symptoms (recurrent mouth ulcers with/without genital ulcers). The strong correlation was determined between the BD activity and the lipid molecules. These findings may lead to the development for diagnostic and prognostic biomarkers based on a better understanding of the BD pathomechanism.
Sperm DNA methylome abnormalities occur both pre- and post-treatment in men with Hodgkin disease and testicular cancer
Authors: Chan Donovan , Oros Klein Kathleen , Riera-Escamilla Antoni , Krausz Csilla , O’Flaherty Cristian , Chan Peter , Robaire Bernard , Trasler Jacquetta M. 
Published: January 2023

Abstract
Background
Combination chemotherapy has contributed to increased survival from Hodgkin disease (HD) and testicular cancer (TC). However, questions concerning the quality of spermatozoa after treatment have arisen. While studies have shown evidence of DNA damage and aneuploidy in spermatozoa years following anticancer treatment, the sperm epigenome has received little attention. Our objectives here were to determine the impact of HD and TC, as well as their treatments, on sperm DNA methylation. Semen samples were collected from community controls (CC) and from men undergoing treatment for HD or TC, both before initiation of chemotherapy and at multiple times post-treatment. Sperm DNA methylation was assessed using genome-wide and locus-specific approaches.

Results
Imprinted gene methylation was not affected in the sperm of HD or TC men, before or after treatment. Prior to treatment, using Illumina HumanMethylation450 BeadChip (450 K) arrays, a subset of 500 probes was able to distinguish sperm samples from TC, HD and CC subjects; differences between groups persisted post-treatment. Comparing altered sperm methylation between HD or TC patients versus CC men, twice as many sites were affected in TC versus HD men; for both groups, the most affected CpGs were hypomethylated. For TC patients, the promoter region of GDF2 contained the largest region of differential methylation. To assess alterations in DNA methylation over time/post-chemotherapy, serial samples from individual patients were compared. With restriction landmark genome scanning and 450 K array analyses, some patients who underwent chemotherapy showed increased alterations in DNA methylation, up to 2 to 3 years post-treatment, when compared to the CC cohort. Similarly, a higher-resolution human sperm-specific assay that includes assessment of environmentally sensitive regions, or “dynamic sites,” also demonstrated persistently altered sperm DNA methylation in cancer patients post-treatment and suggested preferential susceptibility of “dynamic” CpG sites.

Conclusions
Distinct sperm DNA methylation signatures were present pre-treatment in men with HD and TC and may help explain increases in birth defects reported in recent clinical studies. Epigenetic defects in spermatozoa of some cancer survivors were evident even up to 2 years post-treatment. Abnormalities in the sperm epigenome both pre- and post-chemotherapy may contribute to detrimental effects on future reproductive health.
Genetic, DNA methylation, and immune profile discrepancies between early-stage single primary lung cancer and synchronous multiple primary lung cancer
Authors: Yu Fenglei , Huang Xiaojie , Zhou Danting , Zhao Zhenyu , Wu Fang , Qian Banglun , Wang Qiang , Chen Juan , Liang Qingchun , Jiang Yi , Ding Qi , He Qiongzhi , Tang Jingqun , Wang Xiang , Liu Wenliang , Chen Chen 
Published: January 2023

Abstract
Background
To explore the possible carcinogenesis and help better diagnose and treat patients with synchronous multiple primary lung cancers (sMPLC), we systematically investigated the genetic and DNA methylation profiles of early-stage sMPLC and single primary lung cancer (SPLC) and explored the immune profiles in the tumor microenvironment.

Methods
Hundred and ninety-one patients with 191 nodules in the SPLC group and 132 patients with 295 nodules in the sMPLC group were enrolled. All the samples were subjected to wide panel-genomic sequencing. Genome-wide DNA methylation was assessed using the Infinium Human Methylation 850 K BeadChip. RNA-seq and CIBERSORT analyses were performed to identify the immune characteristics in these two groups.

Results
Lesions from sMPLC patients had lower TMB levels than that from SPLC patients. sMPLC had a similar genetic mutational landscape with SPLC, despite some subgroup genetic discrepancies. Distinct DNA methylation patterns were identified between the two groups. The differentially methylated genes were related to immune response pathways. RNA-seq analyses revealed more immune-related DEGs in sMPLC. Accordingly, more immune-related biological processes and pathways were identified in sMPLC. Aberrant DNA methylation was associated with the abnormal expression of immune-related genes. CIBERSORT analysis revealed the infiltration of immune cells was different between the two groups.

Conclusion
Our study for the first time demonstrated genetic, epigenetic, and immune profile discrepancies between sMPLC and SPLC. Relative to the similar genetic mutational landscape, the DNA methylation patterns and related immune profiles were significantly different between sMPLC and SPLC, indicating their essential roles in the initiation and development of sMPLC.