bluuebunny/crossref_metadata_2025_split huggingface dataset:
SIAH1 ubiquitination-modified HMGCR inhibits lung cancer progression and promotes drug sensitivity through cholesterol synthesis
Authors: Yuan Hongmei , Wu Hongge , Cheng Jing , Xiong Jie 
Published: April 2023

Abstract
Backgrounds
Lung cancer is one of the most frequently diagnosed cancers and the leading cause of cancer-related deaths worldwide. Deep understanding of chemoresistance will lead to remarkable progress in lung cancer treatment strategy. Cholesterol accumulation was associated with cisplatin resistance in lung cancer treatment. And we found the degree of cisplatin resistance was correlated with the expression of the cholesterol synthesis HMGCR.

Methods
We analyzed a group of 42 lung cancer patients who received cisplatin treatment after lung resection surgery. The expression of HMGCR and its correlation with cholesterol in lung cancer cell lines were determined by qRT-PCR and ELISA analyses. We focus on the function and mechanism of HMGCR in lung cancer and reveal that knockdown of HMGCR expression inhibits the proliferation, colony formation, and migration of lung cancer cell lines in vitro or in vivo and dramatically enhances the efficacy of cisplatin.

Results
Through mechanism studies, we illustrate that SIAH1, an E3 ubiquitin-protein ligase, ubiquitination modifies HMGCR and inhibits efflux protein activity via regulating cholesterol synthesis. In vivo experiments showed that SIAH1 overexpression or using HMGCR knockdown retard tumor growth and enhanced the efficacy of cisplatin. In summary, HMGCR affects cholesterol metabolism by regulating key enzymes in cholesterol synthesis, thereby reducing drug sensitivity.

Conclusion
This study indicates that lung cancer patients with lower HMGCR levels may lead to a better prognosis and provide a potential treatment by SIAH1 overexpression for lung cancer patients with cisplatin resistance.
Antioxidants-related nuclear factor erythroid 2-related factor 2 gene variants associated with HBV-related liver disease
Authors: Liu Yanqiong , Wu Qiulian , Zhang Fuyong , Qin Xue 
Published: April 2023

Abstract
Background
Accumulating evidence demonstrated that nuclear factor erythroid 2-related factor 2 (NRF2) expression plays a crucial role in the proliferation, invasion and metastasis of hepatocellular carcinoma (HCC). However, research on the effect of NRF2 genetic polymorphism on the development of chronic hepatitis B (CHB), HBV-related liver cirrhosis (LC) and HCC is still missing.

Methods
A total of 673 individuals were included in the study and classified into four groups: 110 CHB cases, 86 LC cases, 260 HCC cases, and 217 healthy controls. ​The polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing method were used to detect rs6721961 and rs6726395 polymorphisms.

Results
Patients carrying the T allele in rs6721961 were at a higher risk of HCC than individuals with the G allele compared to CHB patients (OR = 1.561, 95%CI: 1.003–2.430, P = 0.048). The statistically significant differences were also found in the rs6721961 GT genotype (OR = 2.298, 95% CI: 1.282–4.119, P = 0.005) and dominant model (OR = 2.039, 95% CI: 1.184–0.510, P = 0.010). Subgroup analysis also detected a significant association between the rs6721961 T allele and the development of HCC in older subjects (≥ 50 years) (OR = 2.148, 95% CI: 1.208–3.818, P = 0.009). Statistical analysis results indicated that subjects carrying haplotype G-A had a lower risk of HCC (OR = 0.700, 95% CI: 0.508–0.965, P = 0.028).

Conclusions
For the first time, our findings provide evidence that the NRF2 gene rs6721961 variation is a potential genetic marker of susceptibility to HCC.
Utilization of mental health services in relation to the intention to reduce chemsex behavior among clients from an integrated sexual health services center in Taiwan
Authors: Hung Yu-Ru , Chuang Tsan-Tse , Chen Tsai-Wei , Chung An-Chun , Wu Meng-Tzu , Hsu Su-Ting , Ko Nai-Ying , Strong Carol 
Published: April 2023

Abstract
Introduction
The intention of chemsex-practicing gay and bisexual men and other men who have sex with men (GBMSM) to reduce their drug use is an important factor for the utilization of harm reduction services. This study aimed to examine data from an integrated sexual health services center to understand the relationship between the intention to reduce chemsex behavior and chemsex-related utilization of mental health services among GBMSM who engage in chemsex.

Method
We used data collected from Healing, Empowerment, Recovery of Chemsex (HERO), an integrated health center in Taiwan, between November 2017 and December 2021. As the baseline, clients were asked to rate the current and ideal proportions of their sexual activities that involved the use of MDMA, ketamine, methamphetamine, GHB/GBL, or mephedrone. Having the intention to reduce chemsex was defined as having a lower proportion of ideal engagement compared to actual engagement. The data on the use of the services provided at HERO were linked to the survey responses and compared to information gathered during regular follow-up visits. Univariable and multivariable logistic regression analyses and a Poisson regression analysis were performed on the data.

Results
A total of 152 GBMSM reported engaging in chemsex, of whom 105 (69.1%) expressed the intention to reduce their chemsex behavior. Service utilization ranged from 23.0% for participating in meetings of a chemsex recovery group, 17.1% for visiting a mental health clinic, and 10.5% for using both of these services. The intention to reduce chemsex behavior significantly associated with visiting a mental health clinic (aOR = 4.68, p < 0.05), but its association with attending meetings of a chemsex recovery group was only marginally significant (aOR = 2.96, p < 0.1). Other factors that remained significantly associated with service use were a high frequency of substance use and living with HIV.

Conclusion
Comprehensive harm reduction strategies, which touch on mental health, drug use management and recovery, are needed for those who want to reduce their chemsex behavior. Public health practitioners should endeavor to raise awareness of resources that are available for people who engage in chemsex and to minimize the barriers blocking their access to the appropriate services.
Brevilin A is a potent anti-metastatic CRC agent that targets the VEGF-IL6-STAT3 axis in the HSCs-CRC interplay
Authors: Fan Xueying , Meng Mingjing , Li Baoting , Chen Hui , Tan Jincheng , Xu Keyang , Xiao Shilin , Kwan Hiu-Yee , Liu Zhongqiu , Su Tao 
Published: April 2023

Abstract
Background
More than half of the colorectal cancer (CRC) patients will develop liver metastasis that underlies the cancer mortality. In the hepatic tumor microenvironment, the interplay between CRC cells and hepatic stellate cells (HSCs), and the activation of HSCs to become carcinoma-associated fibroblasts (CAFs) will further promote the cancer development. Nevertheless, the critical signaling molecule that involved in these processes remains unknown, which hinders the development of effective therapeutic agents for the treatment of metastatic CRC (mCRC).

Methods
Conditioned medium system and co-cultured system were used to examine the interplay between CRC cells and HSCs. Luminex liquid suspension chip detection and enzyme-linked immunosorbent assay were used to screen for the mediators in the conditioned medium that facilitated the CRC-HSCs interplay and HSCs-to-CAFs differentiation. Cell and animal models were used to examine whether brevilin A inhibited CRC liver metastasis via the VEGF-IL6-STAT3 axis.

Results
In the CRC-HSCs interplay, CRC promoted HSCs-to-CAFs differentiation by releasing vascular endothelial growth factor (VEGF); and HSCs released interleukin 6 (IL6) that activated signal transducer and activator of transcription 3 (STAT3) in the CRC and hence increased the cancer metastatic potential. The functions of the VEGF-IL6-STAT3 axis in the HSCs-CRC interplay were further validated by VEGF recombinant protein and IL6 neutralizing antibody. More importantly, brevilin A, an active compound isolated from Centipeda minima (L.) A. Br. et Aschers, targeted the VEGF-IL6-STAT3 axis in the CRC-HSCs interplay, hence significantly inhibited colorectal liver metastasis and cancer growth both in vitro and in vivo.

Conclusions
We are the first to demonstrate brevilin A possesses potent anti-mCRC effect by targeting the VEGF-IL6-STAT3 axis in the CRC-HSCs interplay. Our findings not only support the development of brevilin A as a novel therapeutic agent for mCRC treatment, but also pave the path for the development of other VEGF-IL6-STAT3 targeting therapeutic strategies.
The interplay between androgens and the immune response in polycystic ovary syndrome
Authors: Shabbir Sania , Khurram Emaan , Moorthi Vedhika Sathya , Eissa Youssef Tamer Hassan , Kamal Mohammad Azhar , Butler Alexandra E. 
Published: April 2023

AbstractPolycystic ovary syndrome (PCOS) is a metabolic-reproductive-endocrine disorder that, while having a genetic component, is known to have a complex multifactorial etiology. As PCOS is a diagnosis of exclusion, standardized criteria have been developed for its diagnosis. The general consensus is that hyperandrogenism is the primary feature of PCOS and is associated with an array of physiological dysfunctions; excess androgens, for example, have been correlated with cytokine hypersecretion, adipocyte proliferation, and signaling pathway dysregulation. Another key feature of PCOS is insulin resistance, resulting in aberrant glucose and fatty acid metabolism. Additionally, the immune system plays a key role in PCOS. Hyperandrogenism stimulates some immune cells while it inhibits others, thereby disrupting the normal balance of immune cells and creating a state of chronic inflammation. This low-grade inflammation could contribute to infertility since it induces ovarian dysfunction. This dysregulated immune response in PCOS exhibits autoimmunity characteristics that require further investigation. This review paper examines the relationship between androgens and the immune response and how their malfunction contributes to PCOS.
Camrelizumab for cancers in patients living with HIV: one-single center experience
Authors: Wu Menghua , Zheng Xin , Zhang Yu , Song Jian , Zhao Jimao 
Published: April 2023

Abstract
Objectives
The primary objective was to evaluate the safety of the anti-PD-1 antibody camrelizumab in people living with HIV (PLWH); the secondary objective was to evaluate tumor response.

Methods
From May 8, 2018, to December 10, 2021, twenty-four patients with HIV and advanced cancer as well as a CD4+ T-cell count greater than or equal to 100 cells/µL were treated with camrelizumab in daily practice. We describe the demographic characteristics, safety, and clinical course of these 24 PLWH with cancer treated with camrelizumab. Safety was assessed using the current Common Terminology Criteria for Adverse Events (CTCAE). The tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1).

Results
The median number of cycles was 8 (4–26). Only two grade 3 adverse reactions were reported (no toxic deaths or immune-related deaths). Among the 24 patients, 2 (8%) complete responses and 6 (25%) partial responses were observed. 7 patients (29%) were at stable tumor status and others progressed.

Conclusions
Data from the present study strongly support the use of camrelizumab (monoclonal antibodies targeting the PD-1 pathway) in this population, as it appears to be a feasible approach with no deleterious effects on PLWH and tolerability and acceptable efficacy. In addition, these findings further support the inclusion of PLWH with cancer in clinical trials evaluating the safety and efficacy of ICIs on cancer.
Pediatric fulminant malignant hyperthermia with severe electroencephalographic abnormality and brain damage: a case report
Authors: Minami Sakura , Ikeda Azusa , Yamada Kaori , Kajihama Aya , Shimizu Hiroyuki , Nagafuchi Hiroyuki 
Published: April 2023

Abstract
Background
Malignant hyperthermia is an extremely dangerous condition that can occur with exposure to volatile inhalant anesthetics and depolarizing muscle relaxants, and that requires immediate intervention. Neurological complications have rarely been reported, with no reports of electroencephalographic abnormalities or encephalopathy. Here, we report a case of severe electroencephalographic abnormality in the acute phase of malignant hyperthermia that eventually led to diffuse cerebral cortical damage.

Case presentation
A 15-month-old Japanese boy underwent a Rastelli procedure to correct a double-outlet right ventricle and pulmonary atresia. Sevoflurane was used for induction and maintenance of anesthesia during surgery. After withdrawal from the heart–lung machine, his body temperature rose at a rate of 0.1 ℃/minute, and when he left the operating room, his core body temperature had reached 42 ℃. After admission to the intensive care unit, tachycardia, high PaCO2, and progressive metabolic acidosis were observed. A clinical grading scale score of 63 indicated malignant hyperthermia, and dantrolene was administered. The pupils were dilated, and the electroencephalogram showed persistent generalized continuous multifocal spikes. Midazolam, levetiracetam, and fosphenytoin were administered without improvement, and thiamylal and ketamine were infused continuously. After the electroencephalogram shifted to burst suppression, the epileptic firing gradually decreased, and the background electroencephalogram became lower in amplitude. Magnetic resonance imaging of the head performed after the patient was hemodynamically stable suggested diffuse cerebral cortical damage. Severe mental retardation, hypertonia, and quadriplegia were observed as neurological complications.

Conclusions
In this case, despite the use of high-dose anticonvulsants, the patient showed severe electroencephalogram abnormality, resulting in diffuse cortical damage. Hyperthermia is known to damage the central nervous system by causing increased brain pressure and cerebral edema, which may have triggered the severe neuronal excitation that we observed in this case. The presence of systemic inflammatory response syndrome and the patient’s background, including young age and ethnicity, might also have been factors. Malignant hyperthermia can be complicated by encephalopathy, and continuous electroencephalogram monitoring should be considered.
Self-Compacting Concrete with Partially Substitution of Waste Marble: A Review
Authors: Ahmad Jawad , Zhou Zhiguang , Deifalla Ahmed Farouk 
Published: April 2023

AbstractSelf-compacting concrete (SCC) is also seen as unsustainable since it uses a lot of natural resources. Recent researchers have focused on lowering construction costs and partially replacing cement with industrial waste. It is possible to effectively use various industrial wastes in concrete as cement or aggregates. Among these wastes, waste marble (WM) is a useful choice, and researchers have been interested in using WM in concrete for a couple of years. However, to pinpoint the advantages and recent advancements of research on WM as an ingredient of SCC, a comprehensive study is necessary. Therefore, the purpose of this study is to do a compressive evaluation of WM as an SCC ingredient. The review includes a general introduction to SCC and WM, the filling and passing capability of SCC, strength properties of SCC, durability, and microstructure analysis of SCC. According to the findings, WM improved the concrete strength and durability of SCC by up to 20% substitution due to micro-filling and pozzolanic reaction. Finally, the review also identifies research gaps for future investigations.
Exactly how free? Constrained choices and product ranges of medieval copper-alloy objects found between the Meuse and Loire rivers (9th–16th centuries CE)
Authors: Saussus Lise , Thomas Nicolas , Bourgarit David 
Published: April 2023

Abstract
This contribution synthesises the PIXE and ICP-AES elemental analyses carried out on a large dataset, comprising of 300 copper-alloy objects dating mainly to the Late Middle Ages. The objects are drawn from heritage institutions and archaeological contexts in various regions between the Meuse and the Loire rivers (France and Belgium). This investigation focuses on the main elements that make up the alloys (Cu, Zn, Sn, Pb). Past studies have often defined the composition of an alloy as an intentional choice, however in this paper we aim to identify the constraints in alloy manufacture in a bid to understand the degree of freedom enjoyed by craftsmen during this period. We will also evaluate to what degree the constraints imposed by technique, economic conditions and social requirement, affected production in a complex multifactorial system. We have opted to define alloys by object type, functional area and social context, by chronology and product ranges. For cast table- and the kitchenware, we have observed that alloys and the objects are standardised on a trans-regional scale. Conversely, the hammered objects are produced with a greater freedom, leading to a new hypothesis regarding specific workshop practices. Finally, we will propose a predictive model for cast objects that we hope is better suited for the study of heritage objects, their materials and their production processes, to be verified in future studies. This approach emphasises the importance of considering everything that makes an object what it is: its function, status and place in the market, when researching heritage materials.
Exploring investor-business-market interplay for business success prediction
Authors: Gangwani Divya , Zhu Xingquan , Furht Borko 
Published: April 2023

AbstractThe success of the business directly contributes towards the growth of the nation. Hence it is important to evaluate and predict whether the business will be successful or not. In this study, we use the company’s dataset which contains information from startups to Fortune 1000 companies to create a machine learning model for predicting business success. The main challenge of business success prediction is twofold: (1) Identifying variables for defining business success; (2) Feature selection and feature engineering based on Investor-Business-Market interrelation to provide a successful outcome of the predictive modeling. Many studies have been carried out using only the available features to predict business success, however, there is still a challenge to identify the most important features in different business angles and their interrelation with business success. Motivated by the above challenge, we propose a new approach by defining a new business target based on the definition of business success used in this study and develop additional features by carrying out statistical analysis on the training data which highlights the importance of investments, business, and market features in forecasting business success instead of using only the available features for modeling. Ensemble machine learning methods as well as existing supervised learning methods were applied to predict business success. The results demonstrated a significant improvement in the overall accuracy and AUC score using ensemble methods. By adding new features related to the Investor-Business-Market entity demonstrated good performance in predicting business success and proved how important it is to identify significant relationships between these features to cover different business angles when predicting business success.
Graphical Abstract
Effect of intravenous fluid volume on biomarkers of endothelial glycocalyx shedding and inflammation during initial resuscitation of sepsis
Authors: Macdonald Stephen , Bosio Erika , Keijzers Gerben , Burrows Sally , Hibbs Moira , O’Donoghue Helen , Taylor David , Mukherjee Ashes , Kinnear Frances , Smart Lisa , Ascencio-Lane Juan-Carlos , Litton Edward , Fraser John , Shapiro Nathan I. , Arendts Glenn , Fatovich Daniel ,   The REFRESH Trial Investigators, McCutcheon David , Leonard Anton , Burcham Jonathan , Bellomo Rinaldo , Arendts Glenn , Litton Edward , Harley Amanda , Winearls James , Ascencio-Lane Juan Carlos , Brown Simon , Cooper David , Fatovich Daniel , Vlad Ioana , Wibrow Bradley , Anstey Matthew , Hazelwood Sarah 
Published: April 2023

Abstract
Purpose
To investigate the effect of IV fluid resuscitation on endothelial glycocalyx (EG) shedding and activation of the vascular endothelium and inflammation.

Materials and methods
A planned biomarker sub-study of the REFRESH trial in which emergency department (ED) patients) with suspected sepsis and hypotension were randomised to a restricted fluid/early vasopressor regimen or IV fluid resuscitation with later vasopressors if required (usual care). Blood samples were collected at randomisation (T0) and at 3 h (T3), 6 h (T6)- and 24 h (T24) for measurement of a range of biomarkers if EG shedding, endothelial cell activation and inflammation.

Results
Blood samples were obtained in 95 of 99 enrolled patients (46 usual care, 49 restricted fluid). Differences in the change in biomarker over time between the groups were observed for Hyaluronan (2.2-fold from T3 to T24, p = 0.03), SYN-4 (1.5-fold from T3 to T24, P = 0.01) and IL-6 (2.5-fold from T0 to T3, p = 0.03). No difference over time was observed between groups for the other biomarkers.

Conclusions
A consistent signal across a range of biomarkers of EG shedding or of endothelial activation or inflammation was not demonstrated. This could be explained by pre-existing EG shedding or overlap between the fluid volumes administered in the two groups in this clinical trial.
Trial registration Australia New Zealand Clinical Trials Registry ACTRN126160000006448 Registered 12 January 2016.
Data-driven resuscitation training using pose estimation
Authors: Weiss Kerrin E. , Kolbe Michaela , Nef Andrina , Grande Bastian , Kalirajan Bravin , Meboldt Mirko , Lohmeyer Quentin 
Published: April 2023

Abstract
Background
Cardiopulmonary resuscitation (CPR) training improves CPR skills while heavily relying on feedback. The quality of feedback can vary between experts, indicating a need for data-driven feedback to support experts. The goal of this study was to investigate pose estimation, a motion detection technology, to assess individual and team CPR quality with the arm angle and chest-to-chest distance metrics.

Methods
After mandatory basic life support training, 91 healthcare providers performed a simulated CPR scenario in teams. Their behaviour was simultaneously rated based on pose estimation and by experts. It was assessed if the arm was straight at the elbow, by calculating the mean arm angle, and how close the distance between the team members was during chest compressions, by calculating the chest-to-chest distance. Both pose estimation metrics were compared with the expert ratings.

Results
The data-driven and expert-based ratings for the arm angle differed by 77.3%, and based on pose estimation, 13.2% of participants kept the arm straight. The chest-to-chest distance ratings by expert and by pose estimation differed by 20.7% and based on pose estimation 63.2% of participants were closer than 1 m to the team member performing compressions.

Conclusions
Pose estimation-based metrics assessed learners’ arm angles in more detail and their chest-to-chest distance comparably to expert ratings. Pose estimation metrics can complement educators with additional objective detail and allow them to focus on other aspects of the simulated CPR training, increasing the training’s success and the participants’ CPR quality.

Trial registration
Not applicable.