bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardio-ankle vascular index is more closely associated than brachial-ankle pulse wave velocity with arterial damage and risk of cardiovascular disease in patients with diabetes
Authors: Saigusa Taro , Watanabe Kentaro , Hada Yurika , Ishii Kota , Kameda Wataru , Susa Shinji , Ishizawa Kenichi , Ishihara Hisamitsu
Published: August 2022

Background

This study aimed to compare the usefulness of arterial stiffness parameters, cardio-ankle vascular index (CAVI) and brachial-ankle pulse wave velocity (baPWV), for evaluating arterial damage and risk of cardiovascular disease (CVD) in subjects with diabetes.

Methods

The study subjects were 277 patients with type 1 or type 2 diabetes. All subjects were evaluated for vascular stiffness using CAVI (n = 154) or baPWV (n = 123). Carotid intima-media thickness (IMT) and the Suita score were also measured because these are established risk factors for future CVD. Associations of both CAVI and baPWV with these established parameters were evaluated in all subjects, and then in 174 subjects with adjustment for covariates by using propensity score matching.

Results

In all subjects, CAVI and baPWV correlated significantly with both IMT (r = 0.462,P < 0.001, and r = 0.212,P = 0.019, respectively) and the Suita score (r = 0.573,P < 0.001, and r = 0.373,P < 0.001, respectively). The correlation between CAVI and IMT was more significant than that between baPWV and IMT (Z = 2.33,P = 0.020). Similarly, the correlation between CAVI and the Suita score was more significant than that between baPWV and the Suita score (Z = 2.13,P = 0.033). After adjustment by propensity score matching, significant correlations between CAVI and IMT (r = 0.432P < 0.001) and between CAVI and the Suita score (r = 0.544,P < 0.001) were preserved, though only the association between baPWV and the Suita score was significant (r = 0.289,P = 0.007) while that between baPWV and IMT showed no significance. Again, CAVI showed a significant association with the Suita score than baPWV (Z = 2.02,P = 0.043).

Conclusions

CAVI is more closely associated than baPWV with arterial damage and risk of CVD in patients with diabetes.
A case study to investigate the impact of overcrowding indices in emergency departments
Authors: Improta Giovanni , Majolo Massimo , Raiola Eliana , Russo Giuseppe , Longo Giuseppe , Triassi Maria
Published: August 2022

Background

Emergency department (ED) overcrowding is widespread in hospitals in many countries, causing severe consequences to patient outcomes, staff work and the system, with an overall increase in costs. Therefore, health managers are constantly looking for new preventive and corrective measures to counter this phenomenon. To do this, however, it is necessary to be able to characterize the problem objectively. For this reason, various indices are used in the literature to assess ED crowding. In this work, we explore the use of two of the most widespread crowding indices in an ED of an Italian national hospital, investigate their relationships and discuss their effectiveness.

Methods

In this study, two of the most widely used indices in the literature, the National Emergency Department Overcrowding Scale (NEDOCS) and the Emergency Department Working Index (EDWIN), were analysed to characterize overcrowding in the ED of A.O.R.N. “A. Cardarelli” of Naples, which included 1678 clinical cases. The measurement was taken every 15 minutes for a period of 7 days.

Results

The results showed consistency in the use of EDWIN and NEDOCS indices as measures of overcrowding, especially in severe overcrowding conditions. Indeed, in the examined case study, both EDWIN and NEDOCS showed very low rates of occurrence of severe overcrowding (2–3%). In contrast, regarding differences in the estimation of busy to overcrowded ED rates, the EDWIN index proved to be less sensitive in distinguishing these variations in the occupancy of the ED. Furthermore, within the target week considered in the study, the results show that, according to both EDWIN and NEDOCS, higher overcrowding rates occurred during the middle week rather than during the weekend. Finally, a low degree of correlation between the two indices was found.

Conclusions

The effectiveness of both EDWIN and NEDOCS in measuring ED crowding and overcrowding was investigated, and the main differences and relationships in the use of the indices are highlighted. While both indices are useful ED performance metrics, they are not always interchangeable, and their combined use could provide more details in understanding ED dynamics and possibly predicting future critical conditions, thus enhancing ED management.
Underuse of primary healthcare in France during the COVID-19 epidemic in 2020 according to individual characteristics: a national observational study
Authors: Tuppin Philippe , Lesuffleur Thomas , Constantinou Panayotis , Atramont Alice , Coatsaliou Carole , Ferrat Emilie , Canouï-Poitrine Florence , Debeugny Gonzague , Rachas Antoine
Published: August 2022

Background

The organization of healthcare systems changed significantly during the COVID-19 pandemic. The impact on the use of primary care during various key periods in 2020 has been little studied.

Methods

Using individual data from the national health database, we compared the numbers of people with at least one consultation, deaths, the total number of consultations for the population of mainland France (64.3 million) and the mean number of consultations per person (differentiating between teleconsultations and consultations in person) between 2019 and 2020. We performed analyses by week, by lockdown period (March 17 to May 10, and October 30 to December 14 [less strict]), and for the entire year. Analyses were stratified for age, sex, deprivation index, epidemic level, and disease.

Results

During the first lockdown, 26% of the population consulted a general practitioner (GP) at least once (-34% relative to 2019), 7.4% consulted a nurse (-28%), 1.6% a physiotherapist (-80%), and 5% a dentist (-95%). For specialists, consultations were down 82% for ophthalmologists and 37% for psychiatrists. The deficit was smaller for specialties making significant use of teleconsultations. During the second lockdown, the number of consultations was close to that in 2019, except for GPs (-7%), pediatricians (-8%), and nurses (+ 39%). Nurses had already seen a smaller increase in weekly consultations during the summer, following their authorization to perform COVID-19 screening tests. The decrease in the annual number of consultations was largest for dentists (-17%), physiotherapists (-14%), and many specialists (approximately 10%). The mean number of consultations per person was slightly lower for the various specialties, particularly for nurses (15.1 vs. 18.6). The decrease in the number of consultations was largest for children and adolescents (GPs: -10%, dentists: -13%). A smaller decrease was observed for patients with chronic diseases and with increasing age. There were 9% excess deaths, mostly in individuals over 60 years of age.

Conclusions

There was a marked decrease in primary care consultations in France, especially during the first lockdown, despite strong teleconsultation activity, with differences according to age and healthcare profession. The impact of this decrease in care on morbidity and mortality merits further investigation.
Comparison of anal dilatation versus no dilatation with a standardized dilator in reducing pain after hemorrhoidectomy: a randomized control trial
Authors: Sofii Imam , Darmawan Handy , Ramadhini Amelia Sophia , Kurniawan Fauzan , Hanif Ahmad Shafa
Published: August 2022

Background

Post-operative pain is the main problem of hemorrhoidectomy. An adequate pain management can promote early mobilization, fast recovery, and reduce hospitalization costs. This study aimed to investigate the role of preoperative anal dilatation using a standardized anal dilator in reducing post-operative pain.

Method

This study was conducted using randomized prospective trial with a total of 40 subjects, who were divided into 2 groups. The first group received preoperative anal dilatation using a 33 mm anal dilator for 20 min, while the second group did not. The post-operative anal pain, edema, bleeding, and incontinence were observed in the first, second, and seventh day.

Result

The post-operative pain was significantly lower in the preoperative anal dilatation group for all days of observation (p < 0.05). The difference of post-operative bleeding and edema between groups were not significant. Fecal incontinence was initially significantly higher in the preoperative anal dilatation group, but the difference was insignificant at the seventh day (p = 0.500).

Conclusion

Preoperative anal dilatation significantly reduced post-operative pain. The side effect of fecal incontinence was only temporary until the seventh day after surgery.

Trial RegistrationThis trial was registered on Thai Clinical Trials Registry (TCTR) with TCTR identification number TCTR20220314002, on 14/03/2022 (retrospectively registered).
Lung cancer coexisting with Papiliotrema flavescens infection diagnosed by next-generation sequencing: a case report
Authors: Zhang Siang , Wang Liangzhe , Han Qianyu , Sun An , Liu Xiaogang , Xue Lei
Published: August 2022

Background

Papiliotrema flavescens is a rare environmental yeast, which has been isolated from air, trees, kernels of wheat and corn, fermenting soya sauce, and cerebrospinal fluid of patient with AIDS. Additionally, it is also reported to cause subcutaneous infection in a dog. In this case, we describe primary lung adenocarcinoma coexisting with Papiliotrema flavescens infection in a female patient diagnosed by next-generation sequencing (NGS) technique, which is the first such reported case.

Case presentation

The patient was a 52-year-old female with recurrent cough for 3 months. Chest CT examination revealed a ground glass nodule of 17 * 23 * 18 mm in the right upper lung, and 3 new pulmonary nodules appeared around it 2 months later. The patient underwent right upper lobe lobectomy and pathology confirmed that the primary 2-cm-lesion in the right upper lobe was invasive lung adenocarcinoma, and two of the three surrounding lung nodules were pathologically suggestive of pulmonary fungal infection (not known in specific fungal types). Hence, the patient received empirical anti-fungal treatments with fluconazole 400 mg/day for a week and follow-up CT scanning showed no tumor progression and no relapse of fungal infection. The specific pathogen was eventually identified as Papiliotrema flavescens by the next-generation sequencing of pathogen.

Discussion and conclusion

We first reported that lung cancer coexisting with Papiliotrema flavescens infection in a female patient. The diagnosis of lung cancer with typical CT imaging features is relatively simple, while the diagnosis of lung cancer coexisting with rare fungal infection is challenging. NGS technique is an effective supplementary technique for clinical diagnosis of bacterial or fungal infectious diseases, enabling precise clinical decision-making and appropriate treatment. In this case, the lung cancer may result in a degree of immune suppression, at least locally, resulting in the formation of pulmonary fungal nodular lesions around the tumor.
M6A-related lncRNAs predict clinical outcome and regulate the tumor immune microenvironment in hepatocellular carcinoma
Authors: Chen Bo , Yang Zhan , Lang Zhichao , Tao Qiqi , Zhang Rongrong , Zhan Yating , Xu Xuantong , Zhu Kai , Zheng Jianjian , Yu Zhengping , Yu Suhui
Published: August 2022

LncRNA N6-methylandenosine (m6A) modification has been shown to be associated with the constitution of the tumor microenvironment (TME) and tumorigenesis. It’s essential to understand the mechanisms of lncRNA m6A modification in hepatocellular carcinoma (HCC) and identify relative prognostic predictors to guide therapy and explore potential therapeutic targets. Pearson correlation analysis was performed to identify m6A-related lncRNAs in 374 patients with HCC. Unsupervised cluster analysis of the potential m6A-related lncRNA-based HCC subtypes was conducted, followed by the concurrent analysis of their relationship with TME characteristics, immune checkpoints, immune features, and prognosis through single sample gene set enrichment analysis and ESTIMATE algorithm. Cox regression analyses were performed to screen prognostic m6A-related lncRNA, construct an m6A-related lncRNA signature (m6A-RLRS), and establish an integrated nomogram for the prognosis of patients with HCC. We identified 61 m6A-related lncRNAs and two HCC subtypes defined by consensus cluster of m6A-related lncRNAs with distinct clinical features. Progression-free survival (PFS), three TME-related scores, 15 immune-associated gene sets, and two immune checkpoints expression were found to be significantly different among the two subtypes. Twenty-five prognostic m6A-related lncRNAs were determined, four of which were included to establish an m6A-RLRS with favorable discrimination, and the signature was validated in the validation set and an independent FAHWMU cohort (n = 60). Furthermore, a novel nomogram combining signature and clinical predictors was generated with a C-index of 0.703, and an original ceRNA regulatory network consisting of 9 lncRNAs, 28 miRNAs, and 75 target mRNAs was constructed. Finally, the differential expression of four m6A-related lncRNA was verified by qRT-PCR. In conclusion, m6A-related lncRNA prognostic signature and molecular subtype contributes to accurately predict the prognosis of HCC and provide potential novel therapeutic targets.
Preoperative aspartate aminotransferase to albumin ratio correlates with tumor characteristics and predicts outcome of hepatocellular carcinoma patients after curative hepatectomy: a multicenter study
Authors: Peng Wei , Shen Junyi , Dai Junlong , Leng Shusheng , Xie Fei , Zhang Yu , Ran Shun , Sun Xin , Wen Tianfu
Published: August 2022

Aims

This study aimed to evaluate the clinical significance of the preoperative aminotransferase to albumin ratio (AAR) in patients with hepatocellular carcinoma (HCC) after hepatectomy.

Methods

From five hospitals, a total of 991 patients with HCC admitted between December 2014 and December 2019 were included as the primary cohort and 883 patients with HCC admitted between December 2010 and December 2014 were included as the validation cohort. The X-tile software was conducted to identify the optimal cut-off value of AAR.

Results

In the primary cohort, the optimal cut-off value of the AAR was defined as 0.7 and 1.6, respectively. Compared to patients with AAR 0.7–1.6, those with AAR > 1.6 showed significantly worse overall survival (OS) and RFS, whereas those with AAR < 0.7 showed significantly better OS and RFS (all p < 0.001). Pathologically, patients with AAR > 1.6 had more aggressive tumour characteristics, such as larger tumour size, higher incidence of microvascular invasion, and severe histologic activity, and higher AFP level than patients with AAR < 0.7. Consistently, the abovementioned clinical significance of AAR was confirmed in the validation cohort.

Conclusions

A high AAR was significantly correlated with advanced tumours and severe hepatic inflammation, and a worse prognosis of HCC.
Comparison of case-based learning combined with Rain Classroom teaching and traditional method in complete denture course for undergraduate interns
Authors: Li Xueling , Li Yanshan , Li Xiaolan , Chen Xiaodan , Yang Guihong , Yang Ling
Published: August 2022

Background

Complete denture, as an important restoration method for edentulism, is difficult to study for beginners, especially in linking the theory with clinical practice.

Objective

This study was aimed to compare the teaching effects between case-based learning combined with Rain Classroom teaching and traditional lecture method in the clinical course of complete denture prosthesis for undergraduate interns.

Methods

In a course called “Problems and treatment strategies of complete denture after wearing”, interns were divided into two groups: one for traditional lecture-based teaching with PowerPoint slideshow (the control group, n = 28); and the other for case-based learning combined with Rain Classroom teaching, which published information before class, discussed specific clinic cases in class and got real-time interns’ feedback via WeChat (the test group, n = 22). Both groups received the same exam and questionnaire survey after class. The Q&A participation of interns in class, theoretical test scores and questionnaire survey responses were used to evaluate the teaching effects. An independent sample t-test and the chi-square test or Fisher’s exact test were used for statistical analysis in this study.

Results

The Q&A participation of interns in the test group was much better than that of the control group. The average score on the theoretical test after class in the test group (72.14 ± 12.24) was significantly higher than that in the control group (61.29 ± 20.12) (P < 0.05). In the test group, 94.54% (21/22) of the interns preferred the new teaching mode.

Conclusion

Case-based learning combined with Rain Classroom teaching is helpful to enliven the classroom atmosphere, inspire studying enthusiasm, and achieve a good learning effect in both theory and clinical practice related to complete denture prosthesis.
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

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

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

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

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

Despite 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

A 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

As 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

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

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

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.
Balanced mitochondrial and cytosolic translatomes underlie the biogenesis of human respiratory complexes
Authors: Soto Iliana , Couvillion Mary , Hansen Katja G. , McShane Erik , Moran J. Conor , Barrientos Antoni , Churchman L. Stirling
Published: August 2022

Background

Oxidative phosphorylation (OXPHOS) complexes consist of nuclear and mitochondrial DNA-encoded subunits. Their biogenesis requires cross-compartment gene regulation to mitigate the accumulation of disproportionate subunits. To determine how human cells coordinate mitochondrial and nuclear gene expression processes, we tailored ribosome profiling for the unique features of the human mitoribosome.

Results

We resolve features of mitochondrial translation initiation and identify a small ORF in the 3′ UTR of MT-ND5. Analysis of ribosome footprints in five cell types reveals that average mitochondrial synthesis levels correspond precisely to cytosolic levels across OXPHOS complexes, and these average rates reflect the relative abundances of the complexes. Balanced mitochondrial and cytosolic synthesis does not rely on rapid feedback between the two translation systems, and imbalance caused by mitochondrial translation deficiency is associated with the induction of proteotoxicity pathways.

Conclusions

Based on our findings, we propose that human OXPHOS complexes are synthesized proportionally to each other, with mitonuclear balance relying on the regulation of OXPHOS subunit translation across cellular compartments, which may represent a proteostasis vulnerability.
The recombination landscape of the Khoe-San likely represents the upper limits of recombination divergence in humans
Authors: van Eeden Gerald , Uren Caitlin , Pless Evlyn , Mastoras Mira , van der Spuy Gian D. , Tromp Gerard , Henn Brenna M. , Möller Marlo
Published: August 2022

Background

Recombination maps are  important resources for epidemiological and evolutionary analyses; however, there are currently no recombination maps representing any African population outside of those with West African ancestry. We infer the demographic history for the Nama, an indigenous Khoe-San population of southern Africa, and derive a novel, population-specific recombination map from the whole genome sequencing of 54 Nama individuals. We hypothesise that there are no publicly available recombination maps representative of the Nama, considering the deep population divergence and subsequent isolation of the Khoe-San from other African groups.

Results

We show that the recombination landscape of the Nama does not cluster with any continental groups with publicly available representative recombination maps. Finally, we use selection scans as an example of how fine-scale differences between the Nama recombination map and the combined Phase II HapMap recombination map can impact the outcome of selection scans.

Conclusions

Fine-scale differences in recombination can meaningfully alter the results of a selection scan. The recombination map we infer likely represents an upper bound on the extent of divergence we expect to see for a recombination map in humans and would be of interest to any researcher that wants to test the sensitivity of population genetic or GWAS analysis to recombination map input.
Low-complexity deep unfolded neural network receiver for MIMO systems based on the probability data association detector
Authors: Souza Pedro H. C. de , Mendes Luciano L.
Published: August 2022

The interest on applications where machine learning algorithms and communications are combined has been on a rising in recent years. Machine learning and neural networks are being advocated as a way of improving the performance of several functions across all layers of future communication systems. Furthermore, in applications where complexity reduction is essential for the system feasibility at the cost of an affordable performance loss, more efficient systems might be achieved with the aid of machine learning algorithms. Signal detection for multiple-input multiple-output (MIMO) systems has become a hot topic in recent years given its prominent role in fourth and fifth generations of mobile networks. However, the computational complexity in MIMO systems can become prohibitive when the number of antennas increases. Therefore, by leveraging neural networks architectures we propose a deep unfolded detector, whereby the algorithm of the probability data association (PDA) detector is adapted and enhanced by means of neural network learning capabilities. We unveil that the proposed detector is orders-of-magnitude less complex than the PDA detector, yet presenting no severe penalties in performance in terms of bit error rate (BER).
The burden of bacterial skin infection, scabies and atopic dermatitis among urban-living Indigenous children in high-income countries: a protocol for a systematic review
Authors: Ricciardo Bernadette M. , Kessaris Heather-Lynn , Kumarasinghe Sujith Prasad , Carapetis Jonathan R. , Bowen Asha C.
Published: August 2022

Background

Bacterial skin infections and scabies disproportionately affect children in resource-poor countries as well as underprivileged children in high-income countries. Atopic dermatitis is a common childhood dermatosis that predisposes to bacterial skin infection. In Australia, at any one time, almost half of all Aboriginal and Torres Strait Islander children living remotely will have impetigo, and up to one-third will also have scabies. Yet, there is a gap in knowledge of the skin infection burden for urban-living Australian Aboriginal and Torres Strait Islander children, as well as atopic dermatitis which may be a contributing factor. The objective of this study is to provide a global background on the burden of these disorders in Indigenous urban-living children in high-income countries. These countries share a similar history of colonisation, dispossession and subsequent ongoing negative impacts on Indigenous people.

Methods

This protocol follows the Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols statement. Observational studies reporting incidence and/or prevalence data on bacterial skin infection, scabies and/or atopic dermatitis in urban-living Indigenous children in high-income countries will be included. Literature searches will be conducted in several international electronic databases (from 1990 onwards), including MEDLINE, Embase, EmCare, Web of Science and PubMed. Reference lists and citation records of all included articles will be scanned for additional relevant manuscripts. Two investigators will independently perform eligibility assessment of titles, abstract and full-text manuscripts, following which both investigators will independently extract data. Where there is disagreement, the senior author will determine eligibility. The methodological quality of selected studies will be appraised using an appropriate tool. Data will be tabulated and narratively synthesised. We expect there will be insufficient data to perform meta-analysis.

Discussion

This study will identify and evaluate epidemiological data on bacterial skin infection, scabies and atopic dermatitis in urban-living Indigenous children in high-income countries. Where available, the clinical features, risk factors, comorbidities and complications of these common childhood skin disorders will be described. The evidence will highlight the burden of disease in this population, to contribute to global burden of disease estimates and identify gaps in the current literature to provide direction for future research.

Systematic review registration

PROSPERO CRD42021277288
A novel study for hybrid pair of multivalued dominated mappings in b-multiplicative metric space with applications
Authors: Rasham Tahair , De La Sen Manuel
Published: August 2022

The aim of this paper is to prove some new fixed point results for a pair of multivalued dominated locally contractive mappings in b-multiplicative metric space. Further, fixed point theorems for multigraph-dominated mappings are also established. Some new fixed point results on a closed ball are obtained for a pair of multigraph-dominated mappings endowed with graphic structure in b-multiplicative metric space. An illustrative example is given to show the validity of the hypothesis of our obtained result. Moreover, applications for a coupled system of nonlinear Volterra-type integral equations and functional equations in dynamic programming are presented to show the novelty of our results.