bluuebunny/crossref_metadata_2025_split huggingface dataset:
HCC prediction models in chronic hepatitis B patients receiving entecavir or tenofovir: a systematic review and meta-analysis
Authors: Xu Xiaolan , Jiang Lushun , Zeng Yifan , Pan Liya , Lou Zhuoqi , Ruan Bing 
Published: August 2023

Abstract
Background
Our study aimed to compare the predictive performance of different hepatocellular carcinoma (HCC) prediction models in chronic hepatitis B patients receiving entecavir or tenofovir, including discrimination, calibration, negative predictive value (NPV) in low-risk, and proportion of low-risk.

Methods
We conducted a systematic literature research in PubMed, EMbase, the Cochrane Library, and Web of Science before January 13, 2022. The predictive performance was assessed by area under receiver operating characteristic curve (AUROC), calibration index, negative predictive value, and the proportion in low-risk. Subgroup and meta-regression analyses of discrimination and calibration were conducted. Sensitivity analysis was conducted to validate the stability of the results.

Results
We identified ten prediction models in 23 studies. The pooled 3-, 5-, and 10-year AUROC varied from 0.72 to 0.84, 0.74 to 0.83, and 0.76 to 0.86, respectively. REAL-B, AASL-HCC, and HCC-RESCUE achieved the best discrimination. HCC-RESCUE, PAGE-B, and mPAGE-B overestimated HCC development, whereas mREACH-B, AASL-HCC, REAL-B, CAMD, CAGE-B, SAGE-B, and aMAP underestimated it. All models were able to identify people with a low risk of HCC accurately. HCC-RESCUE and aMAP recognized over half of the population as low-risk. Subgroup analysis and sensitivity analysis showed similar results.

Conclusion
Considering the predictive performance of all four aspects, we suggest that HCC-RESCUE was the best model to utilize in clinical practice, especially in primary care and low-income areas. To confirm our findings, further validation studies with the above four components were required.
Global serum profiling: an opportunity for earlier cancer detection
Authors: Sala Alexandra , Cameron James M. , Brennan Paul M. , Crosbie Emma J. , Curran Tom , Gray Ewan , Martin-Hirsch Pierre , Palmer David S. , Rehman Ihtesham U. , Rattray Nicholas J. W. , Baker Matthew J. 
Published: August 2023

AbstractThe advances in cancer research achieved in the last 50 years have been remarkable and have provided a deeper knowledge of this disease in many of its conceptual and biochemical aspects. From viewing a tumor as a ‘simple’ aggregate of mutant cells and focusing on detecting key cell changes leading to the tumorigenesis, the understanding of cancer has broadened to consider it as a complex organ interacting with its close and far surroundings through tumor and non-tumor cells, metabolic mechanisms, and immune processes. Metabolism and the immune system have been linked to tumorigenesis and malignancy progression along with cancer-specific genetic mutations. However, most technologies developed to overcome the barriers to earlier detection are focused solely on genetic information. The concept of cancer as a complex organ has led to research on other analytical techniques, with the quest of finding a more sensitive and cost-effective comprehensive approach. Furthermore, artificial intelligence has gained broader consensus in the oncology community as a powerful tool with the potential to revolutionize cancer diagnosis for physicians. We herein explore the relevance of the concept of cancer as a complex organ interacting with the bodily surroundings, and focus on promising emerging technologies seeking to diagnose cancer earlier, such as liquid biopsies. We highlight the importance of a comprehensive approach to encompass all the tumor and non-tumor derived information salient to earlier cancer detection.
The effect of a customised digital adherence tool on HIV treatment outcomes in young people living with HIV (YPLHIV) in Blantyre, Malawi: a protocol for a randomised controlled trial
Authors: Msosa Takondwa Charles , Swai Iraseni , Sumari-de Boer Marion , Ngowi Kennedy , F. Rinke de Wit Tobias , Aarnoutse Rob , Nliwasa Marriott 
Published: August 2023

Abstract
Background
People living with HIV (PLHIV) have to take lifelong antiretroviral treatment, which is often challenging. Young people living with HIV (YPLHIV) have the lowest viral load suppression rates in Malawi and globally, mostly due to poor treatment adherence. This is a result of complex interactions of multiple factors unique to this demographic group. The use of digital health interventions, such as real-time medication monitor (RTMM)-based digital adherence tools (DATs), could improve ART adherence in YPLHIV and subsequently improve viral load suppression which in turn could lead to reduced HIV-associated morbidity and mortality.

Aim
To provide the evidence base for a digital adherence intervention to improve treatment outcomes in YPLHIV on ART.

Objectives
1. The primary objective is to determine the efficacy of a customised DAT compared to the standard of care in improving ART adherence in YPLHIV.
2. The secondary objective is to determine the efficacy of the customised DAT compared to the standard of care in improving viral load suppression in YPLHIV.

Methodology
This will be a parallel open-label randomised control controlled two-arm trial in which non-adherent YPLHIV in selected ART facilities in Blantyre will be randomised in a 1:1 ratio to a customised DAT and standard care arms and followed up for 9 months. The primary outcome is the proportion adherent at 9 months (> = 95% by pill count), and the secondary outcome is the proportion with viral load suppressed at 9 months (< 200 copies/ml).

Discussion
There is a paucity of good quality evidence on effective digital health interventions to improve ART adherence and viral load suppression in YPLHIV globally and particularly in HIV high-burden settings like Malawi. This study will provide good-quality evidence on the effectiveness of a customised DAT in improving ART adherence and viral load suppression in this important demographic.

Trial registration
The trial has been registered in the Pan African Clinical Trials Registry number: PACTR202303867267716 on 23 March 2023 and can be accessed through the following URL: https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=25424. All items from the WHO Trial Registration Data Set are described in this manuscript.
Effects of multimodal exercise program on postural balance in patients with chronic obstructive pulmonary disease: study protocol for a randomized controlled trial
Authors: Daros dos Santos Tamires , Pasqualoto Adriane Schmidt , Cardoso Dannuey Machado , Da Cruz Ivana Beatrice Mânica , Moresco Rafael Noal , Ferreira da Silveira Aron , Martins de Albuquerque Isabella 
Published: August 2023

Abstract
Background
Evidence has shown that patients with chronic obstructive pulmonary disease present significant deficits in the control of postural balance when compared to healthy subjects. In view of this, it is pertinent to investigate the effects of different therapeutic strategies used alone or in association with pulmonary rehabilitation with the potential to improve postural balance and other outcomes with clinical significance in patients with chronic obstructive pulmonary disease. This study will investigate the effects of an 8-week (short-term) multimodal exercise program [inspiratory muscle training (IMT) plus neuromuscular electrical stimulation (NMES)] on postural balance in patients with chronic obstructive pulmonary disease enrolled in a pulmonary rehabilitation program compared to individualized addition of IMT or NMES to pulmonary rehabilitation or standard pulmonary rehabilitation.

Methods
This is a randomized, single-blind, 4-parallel-group trial. Forty patients with chronic obstructive pulmonary disease will be included prospectively to this study during a pulmonary rehabilitation program. Patients will be randomly assigned to one of four groups: multimodal exercise program (IMT + NMES + pulmonary rehabilitation group) or (IMT + pulmonary rehabilitation group) or (NMES + pulmonary rehabilitation group) or standard pulmonary rehabilitation group. Patients will receive two sessions per week for 8 weeks. The primary outcome will be static postural balance and secondary outcomes will include as follows: static and dynamic postural balance, fear of falling, muscle strength and endurance (peripheral and respiratory), functional capacity, health-related quality of life, muscle architecture (quadriceps femoris and diaphragm), and laboratory biomarkers.

Discussion
This randomized clinical trial will investigate the effects of adding of short-term multimodal exercise program, in addition to pulmonary rehabilitation program, in postural balance in patients with chronic obstructive pulmonary disease enrolled in a pulmonary rehabilitation. Furthermore, this randomized control trial will enable important directions regarding the effectiveness of short-term intervention as part of the need to expand the focus of pulmonary rehabilitation to include balance management in chronic obstructive pulmonary disease patients which will be generated.

Trial registration
ClinicalTrials.gov NCT04387318. Registered on May 13, 2020.
Differences in the position of endometriosis-associated and non-associated ovarian cancer relative to the uterus
Authors: Saida Tsukasa , Mori Kensaku , Ishiguro Toshitaka , Saida Yukihisa , Satoh Toyomi , Nakajima Takahito 
Published: August 2023

Abstract
Background
Preoperative assessment of the histological type of ovarian cancer is essential to determine the appropriate treatment strategy. Tumor location may be helpful in this regard. The purpose of this study was to compare the position of endometriosis-associated (EAOCs) and non-associated (non-EAOCs) ovarian cancer relative to the uterus using MRI.

Methods
This retrospective study included patients with pathologically confirmed malignant epithelial ovarian tumors who underwent MRI at our hospital between January 2015 and January 2023. T2-weighted images of the sagittal and axial sections of the long axis of the uterine body were used for the analysis. Three blinded experienced radiologists independently interpreted the images and assessed whether the ovarian tumor was attached to the uterus, and the angle between the uterus and the tumor was measured. The presence of attachment and the measured angles were compared for each histology. In addition, the angles between EAOCs, including endometrioid carcinomas (ECs) and clear cell carcinomas (CCCs), were compared with non-EAOCs.

Results
In total, 184 women (mean age, 56 years; age range, 20–91 years) were evaluated. High-grade serous carcinomas (HGSCs) were significantly smaller than the others and had significantly less uterine attachment than CCCs (p < 0.01 for all readers). According to the mean of the measured angles, CCCs were positioned significantly more posteriorly than HGSCs and mucinous carcinomas (p < 0.02), and EAOCs were positioned significantly more posteriorly to the uterus than non-EAOCs (p < 0.01).

Conclusion
HGSCs are often not attached to the uterus, and EAOCs are positioned more posteriorly to the uterus than non-EAOCs.

Critical relevance statement
High-grade serous carcinomas were often not attached to the uterus, and endometriosis-associated ovarian cancers were positioned more posteriorly to the uterus than non-endometriosis-associated ovarian cancers.

Key points
• The position of the ovarian tumor can be determined using MRI.
• High-grade serous carcinomas had less attachment to the uterus.
• Endometriosis-associated cancers were positioned more posteriorly to the uterus.
• The location of ovarian tumors is helpful in estimating histology.

Graphical abstract
Symptomatic calcified chronic subdural hematoma in an elderly patient: a case report
Authors: Tefera Esayas Adefirs , Assefa Mezgebu Alemneh , Molla Yohannis Derbew 
Published: August 2023

Abstract
Introduction
Calcified chronic subdural hematoma is a rare and infrequent diagnosis made in clinical practice according to the literature. Calcification of chronic subdural hematoma is found more frequently in children and young adults than in the aged. The proposed mechanism of calcification may involve poor circulation and absorption in the subdural space together with intravascular thrombosis and prolonged existence of the hematoma in the subdural space.

Clinical presentation
An 84-year-old Ethiopian male patient presented with progressive right-sided body weakness of 8-month duration. The weakness started in the right lower extremity and progressively involved the upper extremity. Associated with the above complaint, he had had also a globalized headache of the same duration. Pre- and post-contrast brain computed tomography scans showed a right hemispheric extra-axial collection that crossed the suture line, with a maximum depth of 2.3 cm. Subsequently, craniotomy and hematoma evacuation were carried out and the patient was discharged improved.

Conclusion
The most common symptom of calcified chronic subdural hematoma is headache followed by lethargy, confusion, memory impairment weakness, and seizures. A diminished level of consciousness is relatively common and motor deficits are usually manifested as hemiparesis or gait disturbance. Most calcified chronic subdural hematomas can be diagnosed by computed tomography or magnetic resonance imaging and differentiated from the usual chronic subdural hematoma by imaging studies and gross pathology. Surgical treatment is advised in symptomatic patients when feasible, and often results in neurological improvement. Here we presented a patient with an uncommon calcified chronic subdural hematoma, which was successfully evacuated, resulting in a good recovery.
SDF-1 and NOTCH signaling in myogenic cell differentiation: the role of miRNA10a, 425, and 5100
Authors: Mierzejewski Bartosz , Grabowska Iwona , Michalska Zuzanna , Zdunczyk Kamila , Zareba Franciszek , Irhashava Aliksandra , Chrzaszcz Marta , Patrycy Magdalena , Streminska Wladyslawa , Janczyk-Ilach Katarzyna , Koblowska Marta , Iwanicka-Nowicka Roksana , Gromadka Agnieszka , Kowalski Kamil , Ciemerych Maria Anna , Brzoska Edyta 
Published: August 2023

Abstract
Background
Skeletal muscle regeneration is a complex process regulated by many cytokines and growth factors. Among the important signaling pathways regulating the myogenic cell identity are these involving SDF-1 and NOTCH. SDF-1 participates in cell mobilization and acts as an important chemoattractant. NOTCH, on the other hand, controls cell activation and myogenic determination of satellite cells. Knowledge about the interaction between SDF-1 and NOTCH signaling is limited.

Methods
We analyzed two populations of myogenic cells isolated from mouse skeletal muscle, that is, myoblasts derived from satellite cells (SCs) and muscle interstitial progenitor cells (MIPCs). First, microRNA level changes in response to SDF-1 treatment were analyzed with next-generation sequencing (NGS). Second, myogenic cells, i.e., SC-derived myoblasts and MIPCs were transfected with miRNA mimics, selected on the basis of NGS results, or their inhibitors. Transcriptional changes, as well as proliferation, migration, and differentiation abilities of SC-derived myoblasts and MIPCs, were analyzed in vitro. Naive myogenic potential was assessed in vivo, using subcutaneous engrafts and analysis of cell contribution to regeneration of the skeletal muscles.

Results
SDF-1 treatment led to down-regulation of miR10a, miR151, miR425, and miR5100 in myoblasts. Interestingly, miR10a, miR425, and miR5100 regulated the expression of factors involved in the NOTCH signaling pathway, including Dll1, Jag2, and NICD. Furthermore, miR10a, miR425, and miR5100 down-regulated the expression of factors involved in cell migration: Acta1, MMP12, and FAK, myogenic differentiation: Pax7, Myf5, Myod, Mef2c, Myog, Musk, and Myh3. However, these changes did not significantly affect myogenic cell migration or fusion either in vitro or in vivo, except when miR425 was overexpressed, or miR5100 inhibitor was used. These two molecules increased the fusion of MIPCs and myoblasts, respectively. Furthermore, miR425-transfected MIPC transplantation into injured skeletal muscle resulted in more efficient regeneration, compared to control cell transplantation. However, skeletal muscles that were injected with miR10a transfected myoblasts regenerated less efficiently.

Conclusions
SDF-1 down-regulates miR10a, miR425, and miR5100, what could affect NOTCH signaling, differentiation of myogenic cells, and their participation in skeletal muscle regeneration.
Fibroblast-to-cardiomyocyte lactate shuttle modulates hypertensive cardiac remodelling
Authors: Wei Tong , Guo Yuetong , Huang Chenglin , Sun Mengwei , Zhou Bin , Gao Jing , Shen Weili 
Published: August 2023

Abstract
Background
Cardiac fibroblasts (CFs) and cardiomyocytes are the major cell populations in the heart. CFs not only support cardiomyocytes by producing extracellular matrix (ECM) but also assimilate myocardial nutrient metabolism. Recent studies suggest that the classical intercellular lactate shuttle may function in the heart, with lactate transported from CFs to cardiomyocytes. However, the underlying mechanisms regarding the generation and delivery of lactate from CFs to cardiomyocytes have yet to be explored.

Results
In this study, we found that angiotensin II (Ang II) induced CFs differentiation into myofibroblasts that, driven by cell metabolism, then underwent a shift from oxidative phosphorylation to aerobic glycolysis. During this metabolic conversion, the expression of amino acid synthesis 5-like 1 (GCN5L1) was upregulated and bound to and acetylated mitochondrial pyruvate carrier 2 (MPC2) at lysine residue 19. Hyperacetylation of MPC2k19 disrupted mitochondrial pyruvate uptake and mitochondrial respiration. GCN5L1 ablation downregulated MPC2K19 acetylation, stimulated mitochondrial pyruvate metabolism, and inhibited glycolysis and lactate accumulation. In addition, myofibroblast-specific GCN5L1-knockout mice (GCN5L1fl/fl: Periostin-Cre) showed reduced myocardial hypertrophy and collagen content in the myocardium. Moreover, cardiomyocyte-specific monocarboxylate transporter 1 (MCT1)-knockout mice (MCT1fl/fl: Myh6-Cre) exhibited blocked shuttling of lactate from CFs to cardiomyocytes and attenuated Ang II-induced cardiac hypertrophy.

Conclusions
Our findings suggest that GCN5L1-MPC2 signalling pathway alters metabolic patterns, and blocking MCT1 interrupts the fibroblast-to-cardiomyocyte lactate shuttle, which may attenuate cardiac remodelling in hypertension.

Graphical Abstract
Meta-analysis of preclinical measures of efficacy in immune checkpoint blockade therapies and comparison to clinical efficacy estimates
Authors: Tenorio-Pedraza Juan Miguel , Lippert Jörg , Burghaus Rolf , Scheerans Christian 
Published: August 2023

Abstract
Background
Despite the successes of checkpoint inhibitors targeting T-cell receptors, clinical efficacy is highly cancer-dependent and subject to high inter-individual variability in treatment outcome. The ability to predict the clinical success in different cancer indications is therefore an important capability for successful clinical development. In this meta-analysis, the main goal was to identify factors that modified the clinical efficacy estimates of checkpoint blockade therapies derived from preclinical animal data to improve the robustness and reliability of such estimates.

Methods
To this end, animal studies testing checkpoint inhibitors (anti-PD-1, anti-PD-L1, anti-CTLA-4) were identified in PubMed ranging from 1.01.2000 to 31.12.2018. The eligibility criteria included the reporting of the Kaplan–Meier estimates of survival and the number of mice used in each experiment. A mixed-effects model was fitted to the preclinical and clinical data separately to determine potential sources of bias and heterogeneity between studies.

Results
A total of 160 preclinical studies comprising 13,811 mice were selected, from which the hazard ratio (HR) and the median survival ratio (MSR) were calculated. Similarly, clinical Phase III studies of checkpoint inhibitors were identified in PubMed and the ClinicalTrials.gov database ranging from 1.01.2010 to 31.12.2020. This resulted in 62 clinical studies representing 43,135 patients subjected to 8 therapies from which overall survival (OS) and progression-free survival (PFS) hazard ratios were obtained. Using a mixed-effects model, different factors were tested to identify sources of variability between estimates. In the preclinical data, the tumor cell line and individual study were the main factors explaining the heterogeneity. In the clinical setting, the cancer type was influential to the inter-study variability. When using the preclinical estimates to predict clinical estimates, the cancer-type specific estimates of treatment effect using the MSRs better approximated the observed clinical estimates than the HR-derived predictions.

Conclusions
This has strong implications on the design of ICB preclinical studies with respect to sample size determination, selection of cancer cell lines and labs to run the experiments and the choice of efficacy measure.
Patient experience of spontaneous intracranial hypotension (SIH): qualitative interviews for concept elicitation
Authors: Amrhein Timothy J. , McFatrich Molly , Ehle Kate , Malinzak Michael D. , Gray Linda , Kranz Peter G. , Weant E. Hope , Zigler Christina K. 
Published: August 2023

Abstract
Background & objectives
Spontaneous intracranial hypotension (SIH) is an underdiagnosed and debilitating condition caused by a spinal cerebrospinal fluid (CSF) leak. Although SIH can lead to substantial morbidity and disability, little data exists about patients’ perspectives. Without hearing directly from patients, our understanding of the full experience of having SIH is limited, as is our ability to identify and use appropriate patient-reported outcome measures (PROMs) within clinical care and research. The purpose of this study was to conduct qualitative interviews with confirmed SIH patients to fully describe their experiences and identify relevant concepts to measure.

Methods
Patients were recruited from an SIH specialty clinic at a large, U.S.-based healthcare center. Patients undergoing an initial consultation who were ≥ 18 years old, English-speaking, met the International Classification of Headache Disorders-3 criteria for SIH, and had a brain MRI with contrast that was positive for SIH were eligible to participate. During semi-structured qualitative interviews with a trained facilitator, participants were asked to describe their current SIH symptoms, how their experiences with SIH had changed over time, and the aspects of SIH that they found most bothersome. Analysts reviewed the data, created text summaries, and wrote analytic reports.

Results
Fifteen participants completed interviews. Common symptoms reported by patients included headache, tinnitus, ear fullness/pressure/pain, and neck or interscapular pain. Patients reported that their symptoms worsened over the course of their day and with activity. The most bothersome aspect of SIH was disruption to daily activities and limits to physical activities/exercise, which were severe. With regard to symptoms, the most bothersome and impactful included physical pain and discomfort (including headache), as well as fatigue.

Conclusions
Patients reported a diverse set of symptoms that were attributed to SIH, with devastating impacts on functioning and high levels of disability. Researchers considering use of PROMs for SIH should consider inclusion of both symptom scales and aspects of functioning, and future work should focus on evaluating the validity of existing measures for this patient population using rigorous qualitative and quantitative methods in diverse samples. Additionally, these data can be used to assist clinicians in understanding the impacts of SIH on patients.