bluuebunny/crossref_metadata_2025_split huggingface dataset:
Research on early warning of renal damage in hypertensive patients based on the stacking strategy
Authors: Bi Qiubo , Kuang Zemin , Haihong E. , Song Meina , Tan Ling , Tang Xinying , Liu Xing 
Published: August 2022

Abstract
Background
Among the problems caused by hypertension, early renal damage is often ignored. It can not be diagnosed until the condition is severe and irreversible damage occurs. So we decided to screen and explore related risk factors for hypertensive patients with early renal damage and establish the early-warning model of renal damage based on the data-mining method to achieve an early diagnosis for hypertensive patients with renal damage.

Methods
With the aid of an electronic information management system for hypertensive out-patients, we collected 513 cases of original, untreated hypertensive patients. We recorded their demographic data, ambulatory blood pressure parameters, blood routine index, and blood biochemical index to establish the clinical database. Then we screen risk factors for early renal damage through feature engineering and use Random Forest, Extra-Trees, and XGBoost to build an early-warning model, respectively. Finally, we build a new model by model fusion based on the Stacking strategy. We use cross-validation to evaluate the stability and reliability of each model to determine the best risk assessment model.

Results
According to the degree of importance, the descending order of features selected by feature engineering is the drop rate of systolic blood pressure at night, the red blood cell distribution width, blood pressure circadian rhythm, the average diastolic blood pressure at daytime, body surface area, smoking, age, and HDL. The average precision of the two-dimensional fusion model with full features based on the Stacking strategy is 0.89685, and selected features are 0.93824, which is greatly improved.

Conclusions
Through feature engineering and risk factor analysis, we select the drop rate of systolic blood pressure at night, the red blood cell distribution width, blood pressure circadian rhythm, and the average diastolic blood pressure at daytime as early-warning factors of early renal damage in patients with hypertension. On this basis, the two-dimensional fusion model based on the Stacking strategy has a better effect than the single model, which can be used for risk assessment of early renal damage in hypertensive patients.
Development of indicators to assess quality and patient pathways in interdisciplinary care for patients with 14 ambulatory-care-sensitive conditions in Germany
Authors: Schüttig Wiebke , Flemming Ronja , Mosler Christiane Höhling , Leve Verena , Reddemann Olaf , Schultz Annemarie , Brua Emmanuelle , Brittner Matthias , Meyer Frank , Pollmanns Johannes , Martin Johnannes , Czihal Thomas , von Stillfried Dominik , Wilm Stefan , Sundmacher Leonie 
Published: August 2022

Abstract
Background
In settings like the ambulatory care sector in Germany, where data on the outcomes of interdisciplinary health services provided by multiple office-based physicians are not always readily available, our study aims to develop a set of indicators of health care quality and utilization for 14 groups of ambulatory-care-sensitive conditions based on routine data. These may improve the provision of health care by informing discussions in quality circles and other meetings of networks of physicians who share the same patients.

Methods
Our set of indicators was developed as part of the larger Accountable Care in Deutschland (ACD) project using a pragmatic consensus approach. The six stages of the approach drew upon a review of the literature; the expertise of physicians, health services researchers, and representatives of physician associations and statutory health insurers; and the results of a pilot study with six informal network meetings of office-based physicians who share the same patients.

Results
The process resulted in a set of 248 general and disease specific indicators for 14 disease groups. The set provides information on the quality of care provided and on patient pathways, covering patient characteristics, physician visits, ambulatory care processes, pharmaceutical prescriptions and outcome indicators. The disease groups with the most indicators were ischemic heart diseases, diabetes and heart failure.

Conclusion
Our set of indicators provides useful information on patients’ health care use, health care processes and health outcomes for 14 commonly treated groups of ambulatory-care-sensitive conditions. This information can inform discussions in interdisciplinary quality circles in the ambulatory sector and foster patient-centered care.
Dynamics and structural changes of calmodulin upon interaction with the antagonist calmidazolium
Authors: Léger Corentin , Pitard Irène , Sadi Mirko , Carvalho Nicolas , Brier Sébastien , Mechaly Ariel , Raoux-Barbot Dorothée , Davi Maryline , Hoos Sylviane , Weber Patrick , Vachette Patrice , Durand Dominique , Haouz Ahmed , Guijarro J. Iñaki , Ladant Daniel , Chenal Alexandre 
Published: August 2022

Abstract
Background
Calmodulin (CaM) is an evolutionarily conserved eukaryotic multifunctional protein that functions as the major sensor of intracellular calcium signaling. Its calcium-modulated function regulates the activity of numerous effector proteins involved in a variety of physiological processes in diverse organs, from proliferation and apoptosis, to memory and immune responses. Due to the pleiotropic roles of CaM in normal and pathological cell functions, CaM antagonists are needed for fundamental studies as well as for potential therapeutic applications. Calmidazolium (CDZ) is a potent small molecule antagonist of CaM and one the most widely used inhibitors of CaM in cell biology. Yet, CDZ, as all other CaM antagonists described thus far, also affects additional cellular targets and its lack of selectivity hinders its application for dissecting calcium/CaM signaling. A better understanding of CaM:CDZ interaction is key to design analogs with improved selectivity. Here, we report a molecular characterization of CaM:CDZ complexes using an integrative structural biology approach combining SEC-SAXS, X-ray crystallography, HDX-MS, and NMR.

Results
We provide evidence that binding of a single molecule of CDZ induces an open-to-closed conformational reorientation of the two domains of CaM and results in a strong stabilization of its structural elements associated with a reduction of protein dynamics over a large time range. These CDZ-triggered CaM changes mimic those induced by CaM-binding peptides derived from physiological protein targets, despite their distinct chemical natures. CaM residues in close contact with CDZ and involved in the stabilization of the CaM:CDZ complex have been identified.

Conclusion
Our results provide molecular insights into CDZ-induced dynamics and structural changes of CaM leading to its inhibition and open the way to the rational design of more selective CaM antagonists.

Graphical abstract
Calmidazolium is a potent and widely used inhibitor of calmodulin, a major mediator of calcium-signaling in eukaryotic cells. Structural characterization of calmidazolium-binding to calmodulin reveals that it triggers open-to-closed conformational changes similar to those induced by calmodulin-binding peptides derived from enzyme targets. These results provide molecular insights into CDZ-induced dynamics and structural changes of CaM leading to its inhibition and open the way to the rational design of more selective CaM antagonists.
High-affinity SOAT1 ligands remodeled cholesterol metabolism program to inhibit tumor growth
Authors: Wang Zhihua , Wang Miaomiao , Zhang Mengxin , Xu Kaikun , Zhang Xinshuai , Xie Yi , Zhang Yiming , Chang Cheng , Li Xiaolu , Sun Aihua , He Fuchu 
Published: August 2022

Abstract

Background
Although cholesterol metabolism is a common pathway for the development of antitumor drugs, there are no specific targets and drugs for clinical use. Here, based on our previous study of sterol O-acyltransferase 1 (SOAT1) in hepatocelluar carcinoma, we sought to screen an effective targeted drug for precise treatment of hepatocelluar carcinoma and, from the perspective of cholesterol metabolism, clarify the relationship between cholesterol regulation and tumorigenesis and development.

Methods
In this study, we developed a virtual screening integrated affinity screening technology for target protein drug screening. A series of in vitro and in vivo experiments were used for drug activity verification. Multi-omics analysis and flow cytometry analysis were used to explore antitumor mechanisms. Comparative analysis of proteome and transcriptome combined with survival follow-up information of patients reveals the clinical therapeutic potential of screened drugs.

Results
We screened three compounds, nilotinib, ABT-737, and evacetrapib, that exhibited optimal binding with SOAT1. In particular, nilotinib displayed a high affinity for SOAT1 protein and significantly inhibited tumor activity both in vitro and in vivo. Multi-omics analysis and flow cytometry analysis indicated that SOAT1-targeting compounds reprogrammed the cholesterol metabolism in tumors and enhanced CD8+ T cells and neutrophils to suppress tumor growth.

Conclusions
Taken together, we reported several high-affinity SOAT1 ligands and demonstrated their clinical potential in the precision therapy of liver cancer, and also reveal the potential antitumor mechanism of SOAT1-targeting compounds.

Graphical Abstract
Noncoding RNA-mediated molecular bases of chemotherapy resistance in hepatocellular carcinoma
Authors: He Qikuan , Guo Pengyi , Bo Zhiyuan , Yu Haitao , Yang Jinhuan , Wang Yi , Chen Gang 
Published: August 2022

AbstractDespite the significant progress in decreasing the occurrence and mortality of hepatocellular carcinoma (HCC), it remains a public health issue worldwide on the basis of its late presentation and tumor recurrence. To date, apart from surgical interventions, such as surgical resection, liver transplantation and locoregional ablation, current standard antitumor protocols include conventional cytotoxic chemotherapy. However, due to the high chemoresistance nature, most current therapeutic agents show dismal outcomes for this refractory malignancy, leading to disease relapse. Nevertheless, the molecular mechanisms involved in chemotherapy resistance remain systematically ambiguous. Herein, HCC is hierarchically characterized by the formation of primitive cancer stem cells (CSCs), progression of epithelial-mesenchymal transition (EMT), unbalanced autophagy, delivery of extracellular vesicles (EVs), escape of immune surveillance, disruption of ferroptosis, alteration of the tumor microenvironment and multidrug resistance-related signaling pathways that mediate the multiplicity and complexity of chemoresistance. Of note, anecdotal evidence has corroborated that noncoding RNAs (ncRNAs) extensively participate in the critical physiological processes mentioned above. Therefore, understanding the detailed regulatory bases that underlie ncRNA-mediated chemoresistance is expected to yield novel insights into HCC treatment. In the present review, a comprehensive summary of the latest progress in the investigation of chemotherapy resistance concerning ncRNAs will be elucidated to promote tailored individual treatment for HCC patients.
STAT3-mediated upregulation of LINC00520 contributed to temozolomide chemoresistance in glioblastoma by interacting with RNA-binding protein LIN28B
Authors: Yuan Shuai , Yan Qi , Zhao Zhi-yong , Zhang Jing-long , Zhang He , Yin Hang , Yuan Zhi 
Published: August 2022

AbstractA considerable number of glioblastoma (GBM) patients developed drug resistance to Temozolomide (TMZ) during chemotherapy, resulting in therapeutic failure and tumor recurrence. However, the exact mechanism of TMZ chemoresistance in GBM is still poorly clarified. As a novel identified lncRNA, LINC00520 was located on chromosome 14 and overexpressed in multiple human cancers. This study was designed and conducted to investigate the role and underlying mechanism of LINC00520 in GBM chemoresistance to TMZ. The qRT-PCR assay demonstrated that LINC00520 was significantly overexpressed in TMZ-sensitive and/or TMZ-resistant GBM cells (P < 0.001). The silencing of LINC00520 markedly reduced the cell viability, suppressed colony formation, induced cell apoptosis and G1/S phase arrest in TMZ-resistant cells (P < 0.001). In contrast, overexpression of LINC00520 conferred TMZ-resistant phenotype of GBM cells in vitro (P < 0.001). The orthotopic xenograft model was established and the results indicated that the volume of tumor xenografts in vivo was markedly inhibited by TMZ treatment after the silencing of LINC00520 (P < 0.001). Luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay revealed a strong affinity of transcription factor STAT3 to the promoter regions of LINC00520, suggesting that STAT3 mediated the aberrant expression of LINC00520 in GBM. Further experiments demonstrated that LINC00520 could interact with RNA-binding protein LIN28B to inhibit autophagy and reduce DNA damage, thereby contributing to TMZ chemoresistance in GBM. These findings suggested that STAT3/LINC00520/LIN28B axis might be a promising target to improve TMZ chemoresistance of GBM.
What funders are doing to assess the impact of their investments in health and biomedical research
Authors: Abudu Rachel , Oliver Kathryn , Boaz Annette 
Published: August 2022

AbstractAs pressures to maximize research funding grow, biomedical research funders are increasingly tasked with demonstrating the long-term and real-world impacts of their funded research investments. Over the past three decades, research impact assessments (RIA) have emerged as an important tool for analysing the impacts of research by incorporating logic models, frameworks and indicators to track measures of knowledge production, capacity-building, development of research products, adoption of research into clinical guidelines and policies, and the realization of health, economic and social benefits. While there are currently several models for RIA within the literature, less attention has been paid to how funders can practically select and implement a RIA model to demonstrate the impacts of their own research portfolios. In this paper, a literature review was performed to understand (1) which research funders have performed RIAs of their research portfolios to date; (2) how funders have designed their assessments, including the models and tools they have used; (3) what challenges to and facilitators of success have funders found when adopting the RIA model to their own portfolio; and (4) who participates in the assessments. Forty-four papers from both published and grey literature were found to meet the review criteria and were examined in detail. There is a growing culture of RIA among funders, and included papers spanned a diverse set of funders from 10 countries or regions. Over half of funders (59.1%) used a framework to conduct their assessment, and a variety of methods for collecting impact data were reported. Issues of methodological rigour were observed across studies in the review, and this was related to numerous challenges funders faced in designing timely RIAs with quality impact data. Over a third of articles (36.4%) included input from stakeholders, yet only one article reported surveying patients and members of the public as part of the assessment. To advance RIA among funders, we offer several recommendations for increasing the methodological rigour of RIAs and suggestions for future research, and call for a careful reflection of the voices needed in an impact assessment to ensure that RIAs are having a meaningful impact on patients and the public.
Development of the Arabic Health Measures database: a bibliometric analysis of Arabic health-related measures
Authors: Albawardi Nada M. , Shaikh Quratulain , Alahaideb Wejdan , Alamasi Maryam , Aljasser Doaa , Alrasheed Lama , Alsulaiman Sultanah H. , Alghannam Abdullah F. 
Published: August 2022

Abstract
Background
To develop an open-access database of Arabic health measures intended for use by researchers and healthcare providers, along with a bibliometric analysis of the measures included in the database.

Methods
A search was conducted up to 31 December 2021 in PubMed, Embase, CINAHL, SAGE, Springer and Elsevier for published articles or abstracts with keywords “Arabic” AND “translation”, “adaptation” OR “validation”. Information on the measure and the methodology used in the study was then entered into a database. An open-access platform was developed to allow users to search for measures according to their needs. A bibliometric analysis of the articles and measures was then conducted.

Results
A total of 894 publications met the inclusion criteria. The articles discussed 716 measures that were developed using participants from at least 38 countries. The number of measures for adults was five times that for children. Mental health was the most frequent construct assessed (11.5%), followed by “function/disability” measures (10.6%). The majority of measures (54%) required 5 minutes or less to complete. Approximately 17% of the tools were available directly from the article. Saudi Arabia and Lebanon had the greatest number of publications, with 217 (23%) and 114 (12%), respectively. The majority of the publications included reporting of the validation and reliability of the instruments (64% and 56%, respectively).

Conclusions
There is a paucity of research on the quantity and quality of Arabic health measures. Similar to previous reviews, we found the number of publications on Arabic measures to be limited in comparison to those in English; however, it is encouraging that the number of publications appears to have increased steadily over the past decade. While we found the majority of publications reported on psychometric testing, we are unable to comment on the quality of the methodology used, and further investigation into this area is recommended. As the Arabic Health Measures database will facilitate the search for health instruments that have published data on their development, this will increase their visibility and use in research and clinical settings.
Feasibility of quantitative sensory testing in juvenile idiopathic arthritis
Authors: Mensink Maarten O. , Eijkelkamp Niels , Veldhuijzen Dieuwke S. , Wulffraat Nico M. 
Published: August 2022

Abstract
Objective
Juvenile Idiopathic Arthritis (JIA) is a childhood-rheumatic disease with pain as a major early complaint, and in 10–17% pain remains a major symptom. Very few data exist on sensory threshold changes at the knee in JIA, a location in which inflammation often manifests. We determined whether JIA is associated with sensory threshold changes at the knee by using Quantitative Sensory Testing (QST) and established reference values at the knee of children.

Methods
Sixteen patients with JIA aged 9–18 years with one affected knee and a patient-reported pain by Visual Analog Scale (VAS) > 10 on a 0–100 scale, and 16 healthy controls completed the study and were included for the analysis. QST was assessed in compliance with the German Research Network on Neuropathic Pain (DFNS) standard. Disease severity was determined using Juvenile Disease Activity Score (JADAS. Perceived pain was assessed with a visual analogue scale(0–100). Feasibility of QST was tested in patients aged 6–9.

Results
Under the age of 9, QST testing showed not to be feasible in 3 out of 5 JIA patients. Patients with JIA aged 9 and older reported an average VAS pain score of 54.3. QST identified a significant reduction in pressure pain threshold (PPT) and increase in cold detection threshold (CDT) compared to healthy controls. PPT is reduced in both the affected and the unaffected knee, CDT is reduced in the unaffected knee, not the affected knee.

Conclusion
In a Dutch cohort of Patients with JIA, QST is only feasible from 9 years and up. Also, sensory threshold changes at the knee are restricted to pressure pain and cold detection thresholds in Patients with JIA.

Perspective
This article shows that in a Dutch population, the extensive QST protocol is only feasible in the age group from 9 years and older, and a reduced set of QST tests containing at least pressure pain thresholds and cold detection thresholds could prove to be better suited to the pediatric setting with arthritis.
Stereotactic radiosurgery for the treatment of brainstem metastases: a multicenter retrospective study
Authors: Nicosia Luca , Navarria Piera , Pinzi Valentina , Giraffa Martina , Russo Ivana , Tini Paolo , Giaj-Levra Niccolò , Alongi Filippo , Minniti Giuseppe 
Published: August 2022

Abstract
Background
Brainstem metastases (BSM) are associated with a poor prognosis and their management represents a therapeutic challenge. BSM are often inoperable and, in absence of randomized trials, the optimal radiation treatment of BSM remains to be defined. We evaluated the efficacy and toxicity of linear accelerator (linac)-based stereotactic radiosurgery (SRS) and hypofractionated steretotactic radiotherapy (HSRT) in the treatment of BSM in a series of patients treated in different clinical centers.

Methods
We conducted a multicentric retrospective study of patients affected by 1–2 BSM from different histologies who underwent SRS/HSRT. Freedom from local progression (FLP), cancer-specific survival (CSS), overall survival (OS), and treatment-related toxicity were evaluated. In addition, predictors of treatment response and survivals were evaluated.

Results
Between 2008 and 2021, 105 consecutive patients with 111 BMS who received SRS or HSRT for 1–2 BSM were evaluated. Median follow-up time was 10 months (range 3–130). One-year FLP rate was 90.4%. At the univariate analysis, tumor volume ≤ 0.4 cc, and concurrent targeted therapy were associated with longer FLP, with combined treatment that remained a significant independent predictor [0.058, HR 0.139 (95% CI 0.0182–1.064]. Median OS and CSS were 11 months and 14.6 months, respectively. At multivariate analysis, concurrent targeted therapy administration was significantly associated with longer OS [HR 0.514 (95%CI 0.302–0.875); p = 0.01]. Neurological death occurred in 30.4% of patients, although this was due to local progression in only 3 (2.8%) patients.

Conclusion
Linac-based SRS/HSRT offers excellent local control to patients with BSM, with low treatment-related toxicity and no apparent detrimental effects on OS. When treated with ablative intent, BSM are an uncommon cause of neurological death. The present results indicates that patients with BSM should not be excluded a priori from clinical trials.