bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence‐searching capability among health care professionals: a comparative study
Authors: Chi Szu-Yu , Tsai Yu-Shiun , Fang Tien-Pei , Tung Tao-Hsin , Chi Ching-Chi
Published: February 2021

Background

Evidence-based practice is among core competencies of health care professionals (HCPs). However, the levels of evidence-searching capability may differ among various disciplines of HCPs as they receive different education and trainings for various durations in medical schools and teaching hospitals.

Methods

This study aimed to compare the evidence-searching capability among different disciplines of HCPs and identify which aspects need to be reinforced. From a teaching hospital, we recruited 80 HCPs of various disciplines and compared their evidence-searching capability by using a validated scale. To examine if sex and education levels affect evidence-searching capability, we performed a multiple linear regression analysis with collinearity diagnostics.

Results

Physicians and pharmacists performed significantly better than other disciplines in the seven formative assessment items and the summative item (allP < 0.05). No collinearity was detected between discipline and age nor level of education. Except for the 2nd formative assessment item (correlation coefficient 0.24 ± 0.12,P = 0.04), participant’s levels of education did not affect evidence-searching capability. Age was associated with lower evidence-searching capability in five formative and the summative assessment items.

Conclusions

We found a better evidence-searching capability among physicians and pharmacists than other HCPs who may require more training on evidence-searching skills. Also, evidence-searching skills training should be provided to HCPs irrespective of age and education levels.
Evaluating the effects of electronic health records system adoption on the performance of Malaysian health care providers
Authors: Salleh Mohd Idzwan Mohd , Abdullah Rosni , Zakaria Nasriah
Published: February 2021

Background

The Ministry of Health of Malaysia has invested significant resources to implement an electronic health record (EHR) system to ensure the full automation of hospitals for coordinated care delivery. Thus, evaluating whether the system has been effectively utilized is necessary, particularly regarding how it predicts the post-implementation primary care providers’ performance impact.

Methods

Convenience sampling was employed for data collection in three government hospitals for 7 months. A standardized effectiveness survey for EHR systems was administered to primary health care providers (specialists, medical officers, and nurses) as they participated in medical education programs. Empirical data were assessed by employing partial least squares-structural equation modeling for hypothesis testing.

Results

The results demonstrated that knowledge quality had the highest score for predicting performance and had a large effect size, whereas system compatibility was the most substantial system quality component. The findings indicated that EHR systems supported the clinical tasks and workflows of care providers, which increased system quality, whereas the increased quality of knowledge improved user performance.

Conclusion

Given these findings, knowledge quality and effective use should be incorporated into evaluating EHR system effectiveness in health institutions. Data mining features can be integrated into current systems for efficiently and systematically generating health populations and disease trend analysis, improving clinical knowledge of care providers, and increasing their productivity. The validated survey instrument can be further tested with empirical surveys in other public and private hospitals with different interoperable EHR systems.
Post-acute care use patterns among Hospital Service Areas by older adults in the United States: a cross-sectional study
Authors: Dean Julianna M. , Hreha Kimberly , Hong Ickpyo , Li Chih-Ying , Jupiter Daniel , Prochaska John , Reistetter Timothy
Published: February 2021

Background

Despite the success of stroke rehabilitation services, differences in service utilization exist. Some patients with stroke may travel across regions to receive necessary care prescribed by their physician. It is unknown how availability and combinations of post-acute care facilities in local healthcare markets influence use patterns. We present the distribution of skilled nursing, inpatient rehabilitation, and long-term care hospital services across Hospital Service Areas among a national stroke cohort, and we describe drivers of post-acute care service use.

Methods

We extracted data from 2013 to 2014 of a national stroke cohort using Medicare beneficiaries (174,498 total records across 3232 Hospital Service Areas). Patients’ ZIP code of residence was linked to the facility ZIP code where care was received. If the patient did not live in the Hospital Service Area where they received care, they were considered a “traveler”. We performed multivariable logistic regression to regress traveling status on the care combinations available where the patient lived.

Results

Although 73.4% of all Hospital Service Areas were skilled nursing-only, only 23.5% of all patients received care in skilled nursing-only Hospital Service Areas; 40.8% of all patients received care in Hospital Service Areas with only inpatient rehabilitation and skilled nursing, which represented only 18.2% of all Hospital Service Areas. Thirty-five percent of patients traveled to a different Hospital Service Area from where they lived. Regarding “travelers,” for those living in a skilled nursing-only Hospital Service Area, 49.9% traveled for care to Hospital Service Areas with only inpatient rehabilitation and skilled nursing. Patients living in skilled nursing-only Hospital Service Areas had more than five times higher odds of traveling compared to those living in Hospital Service Areas with all three facilities.

Conclusions

Geographically, the vast majority of Hospital Service Areas in the United States that provided rehabilitation services for stroke survivors were skilled nursing-only. However, only about one-third lived in skilled nursing-only Hospital Service Areas; over 35% traveled to receive care. Geographic variation exists in post-acute care; this study provides a foundation to better quantify its drivers. This study presents previously undescribed drivers of variation in post-acute care service utilization among Medicare beneficiaries—the “traveler effect”.
Health services utilization and out-of-pocket (OOP) expenditures in public and private facilities in Pakistan: an empirical analysis of the 2013–14 OOP health expenditure survey
Authors: Khalid Faraz , Raza Wajeeha , Hotchkiss David R. , Soelaeman Rieza H.
Published: February 2021

Background

As low- and middle-income countries progress toward Universal Health Coverage, there is an increasing focus on measuring out-of-pocket (OOP) expenditure and health services utilization within countries. While there have been several reforms to improve health services coverage and financial protection in Pakistan, there is limited empirical research comparing OOP expenditure and health services utilization between public and private facilities and exploring their determinants, a knowledge gap addressed in this study.

Methods

We used data from 2013-14 OOP Health Expenditure Survey, a population-based household survey carried out for Pakistan’s National Health Accounts. The analysis included 7969 encounters from 4293 households. We conducted bivariate analyses to describe patterns of care utilization, estimated annualized expenditures by type and sector of care, and assessed expenditure composition. We used multivariable logistic regression modeling to identify factors associated with sector of care and generalized linear model (GLM) with log link and gamma distribution to identify determinants of OOP expenditures stratified by type of care (inpatient and outpatient).

Results

Most encounters (82.5%) were in the private sector and were for outpatient visits (85%). Several public-private differences were observed in annualized expenditures and expenditure components. Logistic regression results indicate males, wealthier individuals, Punjab and Sindh residents, and those in smaller households were more likely to access private outpatient care. In the inpatient model, rural residents were more likely to use a private provider, while Khyber Pakhtunkhwa residents were less likely to use private care. GLM results indicate private sector inpatient expenditures were approximately PKR 6660 (USD 61.8) higher than public sector expenditures, but no public-private differences were observed for outpatient expenditures. Several demographic factors were significantly associated with outpatient and inpatient expenditures. Of note, expenditures increased with increasing wealth, decreased with increasing household size, and differed by province and region.

Conclusions

This is the first study comprehensively investigating how healthcare utilization and OOP expenditures vary by sector, type of care, and socio-economic characteristics in Pakistan. The findings are expected to be particularly useful for the next phase of social health protection programs and supply side reforms, as they highlight sub-populations with higher OOP and private sector utilization.
G-quadruplexes: a promising target for cancer therapy
Authors: Kosiol Nils , Juranek Stefan , Brossart Peter , Heine Annkristin , Paeschke Katrin
Published: February 2021

DNA and RNA can fold into a variety of alternative conformations. In recent years, a particular nucleic acid structure was discussed to play a role in malignant transformation and cancer development. This structure is called a G-quadruplex (G4). G4 structure formation can drive genome instability by creating mutations, deletions and stimulating recombination events. The importance of G4 structures in the characterization of malignant cells was currently demonstrated in breast cancer samples. In this analysis a correlation between G4 structure formation and an increased intratumor heterogeneity was identified. This suggests that G4 structures might allow breast cancer stratification and supports the identification of new personalized treatment options. Because of the stability of G4 structures and their presence within most human oncogenic promoters and at telomeres, G4 structures are currently tested as a therapeutic target to downregulate transcription or to block telomere elongation in cancer cells. To date, different chemical molecules (G4 ligands) have been developed that aim to target G4 structures. In this review we discuss and compare G4 function and relevance for therapeutic approaches and their impact on cancer development for three cancer entities, which differ significantly in their amount and type of mutations: pancreatic cancer, leukemia and malignant melanoma. G4 structures might present a promising new strategy to individually target tumor cells and could support personalized treatment approaches in the future.
mRNA vaccine for cancer immunotherapy
Authors: Miao Lei , Zhang Yu , Huang Leaf
Published: February 2021

mRNA vaccines have become a promising platform for cancer immunotherapy. During vaccination, naked or vehicle loaded mRNA vaccines efficiently express tumor antigens in antigen-presenting cells (APCs), facilitate APC activation and innate/adaptive immune stimulation. mRNA cancer vaccine precedes other conventional vaccine platforms due to high potency, safe administration, rapid development potentials, and cost-effective manufacturing. However, mRNA vaccine applications have been limited by instability, innate immunogenicity, and inefficient in vivo delivery. Appropriate mRNA structure modifications (i.e., codon optimizations, nucleotide modifications, self-amplifying mRNAs, etc.) and formulation methods (i.e., lipid nanoparticles (LNPs), polymers, peptides, etc.) have been investigated to overcome these issues. Tuning the administration routes and co-delivery of multiple mRNA vaccines with other immunotherapeutic agents (e.g., checkpoint inhibitors) have further boosted the host anti-tumor immunity and increased the likelihood of tumor cell eradication. With the recent U.S. Food and Drug Administration (FDA) approvals of LNP-loaded mRNA vaccines for the prevention of COVID-19 and the promising therapeutic outcomes of mRNA cancer vaccines achieved in several clinical trials against multiple aggressive solid tumors, we envision the rapid advancing of mRNA vaccines for cancer immunotherapy in the near future. This review provides a detailed overview of the recent progress and existing challenges of mRNA cancer vaccines and future considerations of applying mRNA vaccine for cancer immunotherapies.
Correction to: A novel protein encoded by a circular RNA circPPP1R12A promotes tumor pathogenesis and metastasis of colon cancer via Hippo-YAP signaling
Authors: Zheng Xiao , Chen Lujun , Zhou You , Wang Qi , Zheng Zhuojun , Xu Bin , Wu Chen , Zhou Qi , Hu Wenwei , Wu Changping , Jiang Jingting
Published: February 2021

An amendment to this paper has been published and can be accessed via the original article.
Pellino1 promoted inflammation in lung injury model of sepsis by TRAF6/ NF-κB signal pathway
Authors: Liu Xiaqing , Lin Zhengfang , Xu Yufeng
Published: February 2021

Background

This study was designed to investigate the role of Pellino1 in lung injury model of sepsis and its anti-inflammation mechanism.

Method:

C57BL/6 male mice (6–7 weeks old) and Pellino1−/− male mice were subjected to laparotomy followed by extracorporeal cecum mobilization and ligation. THP-1 cells were treated with 500 ng/ml of LPS for 4 h. Both mRNA and protein expression of Pellino1 was increased at time dependence in lung tissue of lung injury model of sepsis mice. Knockout of Pellino1 attenuated lung injury and inhibited inflammation of sepsis mice. While Pellino1 protein enhanced lung injury and increased inflammation of sepsis mice. Pellino1 promoted inflammation in in vitro model of lung injury by TRAF6/ NF-κB signal pathway.

Result

TRAF6 inhibitor attenuated the effects of Pellino1 on inflammation and lung injury in mice of sepsis. Similarly, NF-κB inhibitor also suppressed the effects of Pellino1 on inflammation and lung injury in mice of sepsis. The activation of TRAF6 or induction of NF-κB attenuated the effects of Pellino1 on inflammation in in vitro model of sepsis. The inhibition of TRAF6 or suppression of NF-κB reduced the effects of Pellino1 on inflammation in in vitro model of sepsis.

Conclusions

These results suggested that Pellino1 promoted inflammation in lung injury model of sepsis by TRAF6/ NF-κB signal pathway.
A paclitaxel and microRNA-124 coloaded stepped cleavable nanosystem against triple negative breast cancer
Authors: Chen Chuanrong , Shen Ming , Liao Hongze , Guo Qianqian , Fu Hao , Yu Jian , Duan Yourong
Published: February 2021

Background

Triple negative breast cancer (TNBC) is one of the most biologically aggressive breast cancers and lacks effective treatment options, resulting in a poor prognosis. Therefore, studies aiming to explore new therapeutic strategies for advanced TNBC are urgently needed. According to recent studies, microRNA-124 (miR124) not only inhibits tumour growth but also increases the sensitivity of TNBC to paclitaxel (PTX), suggesting that a platform combining PTX and miR124 may be an advanced solution for TNBC.

Results

Herein, we constructed a stepped cleavable calcium phosphate composite lipid nanosystem (CaP/LNS) to codeliver PTX and miR124 (PTX/miR124-NP). PTX/miR124-NP exhibited superior tumor microenvironment responsive ability, in which the surface PEG layer was shed in the mildly acidic environment of tumor tissues and exposed oligomeric hyaluronic acid (o-HA) facilitated the cellular uptake of CaP/LNS by targeting the CD44 receptor on the surface of tumor cells. Inside tumour cells, o-HA detached from CaP/LNS due to the reduction of disulfide bonds by glutathione (GSH) and inhibited tumour metastasis. Then, PTX and miR124 were sequentially released from CaP/LNS and exerted synergistic antitumour effects by reversing the Epithelial-Mesenchymal Transition (EMT) process in MDA-MB-231 cells. Moreover, PTX/miR124-NP showed significant antitumour efficiency and excellent safety in mice bearing MDA-MB-231 tumours.

Conclusion

Based on these results, the codelivery of PTX and miR124 by the CaP/LNS nanosystem might be a promising therapeutic strategy for TNBC.
Administration route governs the therapeutic efficacy, biodistribution and macrophage targeting of anti-inflammatory nanoparticles in the lung
Authors: Wang Lu , Rao Yafei , Liu Xiali , Sun Liya , Gong Jiameng , Zhang Huasheng , Shen Lei , Bao Aihua , Yang Hong
Published: February 2021

Background

Uncontrolled inflammation is a central problem for many respiratory diseases. The development of potent, targeted anti-inflammatory therapies to reduce lung inflammation and re-establish the homeostasis in the respiratory tract is still a challenge. Previously, we developed a unique anti-inflammatory nanodrug, P12 (made of hexapeptides and gold nanoparticles), which can attenuate Toll-like receptor-mediated inflammatory responses in macrophages. However, the effect of the administration route on its therapeutic efficacy and tissue distribution remained to be defined.

Results

In this study, we systematically compared the effects of three different administration routes [the intratracheal (i.t.), intravenous (i.v.) and intraperitoneal (i.p.)] on the therapeutic activity, biodistribution and pulmonary cell targeting features of P12. Using the LPS-induced ALI mouse model, we found that the local administration route via i.t. instillation was superior in reducing lung inflammation than the other two routes even treated with a lower concentration of P12. Further studies on nanoparticle biodistribution showed that the i.t. administration led to more accumulation of P12 in the lungs but less in the liver and other organs; however, the i.v. and i.p. administration resulted in more nanoparticle accumulation in the liver and lymph nodes, respectively, but less in the lungs. Such a lung favorable distribution was also determined by the unique surface chemistry of P12. Furthermore, the inflammatory condition in the lung could decrease the accumulation of nanoparticles in the lung and liver, while increasing their distribution in the spleen and heart. Interestingly, the i.t. administration route helped the nanoparticles specifically target the lung macrophages, whereas the other two administration routes did not.

Conclusion

The i.t. administration is better for treating ALI using nanodevices as it enhances the bioavailability and efficacy of the nanodrugs in the target cells of the lung and reduces the potential systematic side effects.
Health-related quality of life of people living with HIV/AIDS: the role of social inequalities and disease-related factors
Authors: Nigusso Fikadu Tadesse , Mavhandu-Mudzusi Azwihangwisi Helen
Published: February 2021

Background

Health-related quality of life (HRQoL) serves as a direct measure of individuals’ health, life expectancy and the impact that the utilization of health care has on quality of life. The purpose of this study is to assess the HRQoL of people living with HIV (PLHIV), and to ascertain its association with the social inequalities and clinical determinants among people living with HIV in Benishangul Gumuz Regional State, Ethiopia.

Methods

A cross-sectional study was conducted between December 2016 and February 2017; 390 people at two referral hospitals and three health centers participated in the study. The Patient-Reported Outcomes Measurement Information System Global Health Scale (PROMIS Global 10) was used to measure key HRQoL domains. Global Physical Health (GPH) and Global Mental Health (GPH) summary scores were employed. GPH and GMH summary scores below 50 (the standardized mean score) were determined as poor HRQoL. Bivariate and multivariate logistic regression analyses were used to identify factors associated with GPH and GMH summary scores.

Results

This study included 259 (66.4%) females and 131 (33.6%) males. The GPH summary scores ranged from 16.2 to 67.7 with a mean of 48.8 (SD = 8.9). Almost 44.6% of the study population has a GPH summary score of below 50; the GMH summary scores ranged from 28.4 to 67.6 with a mean of 50.8 (SD = 8.1). About 41.8% of the study population has a GMH summary score of below 50. Unemployment, household food insecurity and comorbidities with HIV were associated with both poor GPH and poor GMH summary scores. Age below 25 years and being a member of Christian fellowship were inversely associated with poor GPH. The least wealth index score and CD4 count below 350 cells/mL were also associated with poor GMH.

Conclusion

Overall, socioeconomic inequalities and HIV-related clinical factors play an important role in improving the HRQoL of PLHIV. Many of these determinants are alterable risk factors. Appropriate strategies can improve the holistic management of chronic HIV care and maximize PLHIVs’ HRQoL. Such strategies require the adoption of comprehensive interventions, including policies and programmes that would improve the health, wellbeing and livelihood of PLHIV.
Identification of susceptibility loci for cardiovascular disease in adults with hypertension, diabetes, and dyslipidemia
Authors: Song Youhyun , Choi Ja-Eun , Kwon Yu-Jin , Chang Hyuk-Jae , Kim Jung Oh , Park Da-Hyun , Park Jae-Min , Kim Seong-Jin , Lee Ji Won , Hong Kyung-Won
Published: February 2021

Background

Hypertension (HTN), diabetes mellitus (DM), and dyslipidemia (DL) are well-known risk factors of cardiovascular disease (CVD), but not all patients develop CVDs. Studies have been limited investigating genetic risk of CVDs specific to individuals with metabolic diseases. This study aimed to identify disease-specific and/or common genetic loci associated with CVD susceptibility in chronic metabolic disease patients.

Methods

We conducted a genome-wide association study (GWAS) of a multiple case–control design with data from the City Cohort within Health EXAminees subcohort of the Korean Genome and Epidemiology Study (KoGES_HEXA). KoGES_HEXA is a population-based prospective cohort of 173,357 urban Korean adults that had health examinations at medical centers. 42,393 participants (16,309 HTN; 5,314 DM; 20,770 DL) were analyzed, and each metabolic disease group was divided into three CVD case-controls: coronary artery disease (CAD), ischemic stroke (IS), and cardio-cerebrovascular disease (CCD). GWASs were conducted for each case–control group with 7,975,321 imputed single nucleotide polymorphisms using the Phase 3 Asian panel from 1000 Genomes Project, by logistic regression and controlled for confounding variables. Genome-wide significant levels were implemented to identify important susceptibility loci.

Results

Totaling 42,393 individuals, this study included 16,309 HTN (mean age [SD], 57.28 [7.45]; 816 CAD, 398 IS, and 1,185 CCD cases), 5,314 DM (57.79 [7.39]; 361 CAD, 153 IS, and 497 CCD cases), and 20,770 DL patients (55.34 [7.63]; 768 CAD, 295 IS, and 1,039 CCD cases). Six genome-wide significant CVD risk loci were identified, with relatively large effect sizes: 1 locus in HTN (HTN-CAD: 17q25.3/CBX8-CBX4 [OR, 2.607; P = 6.37 × 10−9]), 2 in DM (DM-IS: 4q32.3/MARCH1-LINC01207 [OR, 5.587; P = 1.34 × 10−8], and DM-CCD: 17q25.3/RPTOR [OR, 3.511; P = 1.99 × 10−8]), and 3 in DL (DL-CAD: 9q22.2/UNQ6494-LOC101927847 [OR, 2.282; P = 7.78 × 10−9], DL-IS: 3p22.1/ULK4 [OR, 2.162; P = 2.97 × 10−8], and DL-CCD: 2p22.2/CYP1B1-CYP1B1-AS1 [OR, 2.027; P = 4.24 × 10−8]).

Conclusions

This study identified 6 susceptibility loci and positional candidate genes for CVDs in HTN, DM, and DL patients using an unprecedented study design. 1 locus (17q25.3) was commonly associated with CAD. These associations warrant validation in additional studies for potential therapeutic applications.
Performance of BioFire array or QuickVue influenza A + B test versus a validation qPCR assay for detection of influenza A during a volunteer A/California/2009/H1N1 challenge study
Authors: McIlwain David R. , Chen Han , Apkarian Maria , Affrime Melton , Bock Bonnie , Kim Kenneth , Mukherjee Nilanjan , Nolan Garry P. , McNeal Monica M.
Published: February 2021

Background

Influenza places a significant burden on global health and economics. Individual case management and public health efforts to mitigate the spread of influenza are both strongly impacted by our ability to accurately and efficiently detect influenza viruses in clinical samples. Therefore, it is important to understand the performance characteristics of available assays to detect influenza in a variety of settings. We provide the first report of relative performance between two products marketed to streamline detection of influenza virus in the context of a highly controlled volunteer influenza challenge study.

Methods

Nasopharyngeal swab samples were collected during a controlled A/California/2009/H1N1 influenza challenge study and analyzed for detection of virus shedding using a validated qRT-PCR (qPCR) assay, a sample-to-answer qRT-PCR device (BioMerieux BioFire FilmArray RP), and an immunoassay based rapid test kit (Quidel QuickVue Influenza A + B Test).

Results

Relative to qPCR, the sensitivity and specificity of the BioFire assay was 72.1% [63.7–79.5%, 95% confidence interval (CI)] and 93.5% (89.3–96.4%, 95% CI) respectively. For the QuickVue rapid test the sensitivity was 8.5% (4.8–13.7%, 95% CI) and specificity was 99.2% (95.6–100%, 95% CI).

Conclusion

Relative to qPCR, the BioFire assay had superior performance compared to rapid test in the context of a controlled influenza challenge study.
Are CSF CXCL13 concentrations solely dependent on intrathecal production? A commentary on “Chemokine CXCL13 in serum, CSF, and blood–CSF barrier function”
Authors: DiSano Krista D. , Gilli Francesca , Pachner Andrew R.
Published: February 2021

Pilz et al. (Fluids Barriers CNS 17:7; 2020) investigated how CSF CXCL13 concentrations are influenced by CXCL13 serum concentrations and blood-CSF barrier (BCSFB) function, comparing the impact of serum CXCL13 levels and Qalbumin (CSF albumin/serum albumin) on CSF CXCL13 among patients with CNS inflammation categorized as CXCL13 negative, low, medium, or high. Among all CXCL13 groups, their results showed no correlation between CSF CXCL13 concentrations and serum CXCL13 or Qalbumin. The authors argue that, in contrast to other proteins, CXCL13 passage across the BCSFB does not occur, regardless of BCSFB function, and is instead solely influenced by intrathecal production. In contrast to the authors’ findings, in our studies including both non-inflammatory neurological disorders (NIND; n = 62) and multiple sclerosis (MS) patients we observed a significant correlation between serum CXCL13 concentrations and CSF CXCL13 concentrations. We review several observations which may underlie these contrasting results, including (1) the impact of serum CXCL13 concentrations on CSF CXCL13 in patients with lower intrathecal CXCL13 production and thus lower CXCL13 concentrations (i.e. NIND and MS), (2) the proposed diffusion dynamics of the small molecule CXCL13 across the BCSFB, and (3) differing definitions of negative versus elevated CSF CXCL13 concentrations determined by an assay’s relative sensitivity. In conclusion, we argue that for patients with moderately elevated CSF CXCL13 concentrations, serum CXCL13 concentrations influence CSF CXCL13 levels, and thus the appropriate corrections including incorporation of CSF/serum ratios and Qalbumin values should be utilized.
RDmap: a map for exploring rare diseases
Authors: Yang Jian , Dong Cong , Duan Huilong , Shu Qiang , Li Haomin
Published: February 2021

Background

The complexity of the phenotypic characteristics and molecular bases of many rare human genetic diseases makes the diagnosis of such diseases a challenge for clinicians. A map for visualizing, locating and navigating rare diseases based on similarity will help clinicians and researchers understand and easily explore these diseases.

Methods

A distance matrix of rare diseases included in Orphanet was measured by calculating the quantitative distance among phenotypes and pathogenic genes based on Human Phenotype Ontology (HPO) and Gene Ontology (GO), and each disease was mapped into Euclidean space. A rare disease map, enhanced by clustering classes and disease information, was developed based on ECharts.

Results

A rare disease map called RDmap was published at http://rdmap.nbscn.org. Total 3287 rare diseases are included in the phenotype-based map, and 3789 rare genetic diseases are included in the gene-based map; 1718 overlapping diseases are connected between two maps. RDmap works similarly to the widely used Google Map service and supports zooming and panning. The phenotype similarity base disease location function performed better than traditional keyword searches in an in silico evaluation, and 20 published cases of rare diseases also demonstrated that RDmap can assist clinicians in seeking the rare disease diagnosis.

Conclusion

RDmap is the first user-interactive map-style rare disease knowledgebase. It will help clinicians and researchers explore the increasingly complicated realm of rare genetic diseases.
Dominant mutations in MIEF1 affect mitochondrial dynamics and cause a singular late onset optic neuropathy
Authors: Charif Majida , Wong Yvette C. , Kim Soojin , Guichet Agnès , Vignal Catherine , Zanlonghi Xavier , Bensaid Philippe , Procaccio Vincent , Bonneau Dominique , Amati-Bonneau Patrizia , Reynier Pascal , Krainc Dimitri , Lenaers Guy
Published: February 2021

Inherited optic neuropathies are the most common mitochondrial diseases, leading to neurodegeneration involving the irreversible loss of retinal ganglion cells, optic nerve degeneration and central visual loss. Importantly, properly regulated mitochondrial dynamics are critical for maintaining cellular homeostasis, and are further regulated by MIEF1 (mitochondrial elongation factor 1) which encodes for MID51 (mitochondrial dynamics protein 51), an outer mitochondrial membrane protein that acts as an adaptor protein to regulate mitochondrial fission. However, dominant mutations in MIEF1 have not been previously linked to any human disease. Using targeted sequencing of genes involved in mitochondrial dynamics, we report the first heterozygous variants in MIEF1 linked to disease, which cause an unusual form of late-onset progressive optic neuropathy characterized by the initial loss of peripheral visual fields. Pathogenic MIEF1 variants linked to optic neuropathy do not disrupt MID51’s localization to the outer mitochondrial membrane or its oligomerization, but rather, significantly disrupt mitochondrial network dynamics compared to wild-type MID51 in high spatial and temporal resolution confocal microscopy live imaging studies. Together, our study identifies dominant MIEF1 mutations as a cause for optic neuropathy and further highlights the important role of properly regulated mitochondrial dynamics in neurodegeneration.
A multicenter, randomized phase III trial of hetrombopag: a novel thrombopoietin receptor agonist for the treatment of immune thrombocytopenia
Authors: Mei Heng , Liu Xiaofan , Li Yan , Zhou Hu , Feng Ying , Gao Guangxun , Cheng Peng , Huang Ruibin , Yang Linhua , Hu Jianda , Hou Ming , Yao Yazhou , Liu Li , Wang Yi , Wu Depei , Zhang Liansheng , Zheng Changcheng , Shen Xuliang , Hu Qi , Liu Jing , Jin Jie , Luo Jianmin , Zeng Yun , Gao Sujun , Zhang Xiaohui , Zhou Xin , Shi Qingzhi , Xia Ruixiang , Xie Xiaobao , Jiang Zhongxing , Gao Li , Bai Yuansong , Li Yan , Xiong Junye , Li Runzi , Zou Jianjun , Niu Ting , Yang Renchi , Hu Yu
Published: February 2021

Background

Hetrombopag, a novel thrombopoietin receptor agonist, has been found in phase I studies to increase platelet counts and reduce bleeding risks in adults with immune thrombocytopenia (ITP). This phase III study aimed to evaluate the efficacy and safety of hetrombopag in ITP patients.

Methods

Patients who had not responded to or had relapsed after previous treatment were treated with an initial dosage of once-daily 2.5 or 5 mg hetrombopag (defined as the HETROM-2.5 or HETROM-5 group) or with matching placebo in a randomized, double-blind, 10-week treatment period. Patients who received placebo and completed 10 weeks of treatment switched to receive eltrombopag, and patients treated with hetrombopag in the double-blind period continued hetrombopag during the following open-label 14-week treatment. The primary endpoint was the proportion of responders (defined as those achieving a platelet count of ≥ 50 × 109/L) after 8 weeks of treatment.

Results

The primary endpoint was achieved by significantly more patients in the HETROM-2.5 (58.9%; odds ratio [OR] 25.97, 95% confidence interval [CI] 9.83–68.63; p < 0.0001) and HETROM-5 (64.3%; OR 32.81, 95% CI 12.39–86.87; p < 0.0001) group than in the Placebo group (5.9%). Hetrombopag was also superior to placebo in achieving a platelet response and in reducing the bleeding risk and use of rescue therapy throughout 8 weeks of treatment. The durable platelet response to hetrombopag was maintained throughout 24 weeks. The most common adverse events were upper respiratory tract infection (42.2%), urinary tract infection (17.1%), immune thrombocytopenic purpura (17.1%) and hematuria (15%) with 24-week hetrombopag treatment.

Conclusions

In ITP patients, hetrombopag is efficacious and well tolerated with a manageable safety profile.

Trial registration Clinical trials.gov NCT03222843, registered July 19, 2017, retrospectively registered.
Temporal changes in the epidemiology, management, and outcome from acute respiratory distress syndrome in European intensive care units: a comparison of two large cohorts
Authors:   the SOAP and ICON Investigators, Sakr Yasser , François Bruno , Solé-Violan Jordi , Kotfis Katarzyna , Jaschinski Ulrich , Estella Angel , Leone Marc , Jakob Stephan M. , Wittebole Xavier , Fontes Luis E. , de Melo Gurgel Miguel , Midega Thais , Vincent Jean-Louis , Ranieri V. Marco
Published: February 2021

Background

Mortality rates for patients with ARDS remain high. We assessed temporal changes in the epidemiology and management of ARDS patients requiring invasive mechanical ventilation in European ICUs. We also investigated the association between ventilatory settings and outcome in these patients.

Methods

This was a post hoc analysis of two cohorts of adult ICU patients admitted between May 1–15, 2002 (SOAP study, n = 3147), and May 8–18, 2012 (ICON audit, n = 4601 admitted to ICUs in the same 24 countries as the SOAP study). ARDS was defined retrospectively using the Berlin definitions. Values of tidal volume, PEEP, plateau pressure, and FiO2 corresponding to the most abnormal value of arterial PO2 were recorded prospectively every 24 h. In both studies, patients were followed for outcome until death, hospital discharge or for 60 days.

Results

The frequency of ARDS requiring mechanical ventilation during the ICU stay was similar in SOAP and ICON (327[10.4%] vs. 494[10.7%], p = 0.793). The diagnosis of ARDS was established at a median of 3 (IQ: 1–7) days after admission in SOAP and 2 (1–6) days in ICON. Within 24 h of diagnosis, ARDS was mild in 244 (29.7%), moderate in 388 (47.3%), and severe in 189 (23.0%) patients. In patients with ARDS, tidal volumes were lower in the later (ICON) than in the earlier (SOAP) cohort. Plateau and driving pressures were also lower in ICON than in SOAP. ICU (134[41.1%] vs 179[36.9%]) and hospital (151[46.2%] vs 212[44.4%]) mortality rates in patients with ARDS were similar in SOAP and ICON. High plateau pressure (> 29 cmH2O) and driving pressure (> 14 cmH2O) on the first day of mechanical ventilation but not tidal volume (> 8 ml/kg predicted body weight [PBW]) were independently associated with a higher risk of in-hospital death.

Conclusion

The frequency of and outcome from ARDS remained relatively stable between 2002 and 2012. Plateau pressure > 29 cmH2O and driving pressure > 14 cmH2O on the first day of mechanical ventilation but not tidal volume > 8 ml/kg PBW were independently associated with a higher risk of death. These data highlight the continued burden of ARDS and provide hypothesis-generating data for the design of future studies.
Uniportal and three-portal video-assisted thoracic surgery pulmonary lobectomy for early-stage lung cancer (UNIT trial): study protocol of a single-center randomized trial
Authors: Mendogni Paolo , Mazzucco Alessandra , Palleschi Alessandro , Rosso Lorenzo , Righi Ilaria , Carrinola Rosaria , Damarco Francesco , Privitera Emilia , Fumagalli Jacopo , Bonitta Gianluca , Nosotti Mario , Tosi Davide
Published: February 2021

Background

Video-assisted thoracoscopic surgery (VATS) lobectomy is currently the recommended approach for treating early-stage non-small cell lung cancer (NSCLC). Different VATS approaches have been proposed so far, and the actual advantages of one technique over the other are still under debate. The aim of our study is to compare postoperative pain and analgesic drug consumption in uniportal VATS and triportal VATS for pulmonary lobectomy in early-stage lung cancer patients.

Methods

This study is a single-center, prospective, two-arm, parallel-group, randomized controlled trial. It is designed to compare uniportal video-assisted thoracic surgery (u-VATS) and three-port video-assisted thoracic surgery (t-VATS) in terms of postoperative pain. The trial will enroll 120 patients with a 1:1 randomization. The primary outcome is the assessment of analgesic drug consumption. Secondary outcomes are postoperative pain measurement, evaluation of postoperative pulmonary function, and metabolic recovery after pulmonary lobectomy.

Discussion

The choice of which VATS approach to adopt for treating patients undergoing pulmonary resection mostly depends on the surgeon’s preferences; therefore, it is hard to prove whether one VATS technique is superior to the other. Moreover, postoperative analgesic protocols vary consistently among different centers. To date, only a few studies have evaluated the effects of the most popular VATS techniques. There is no evidence about the difference between multiport VATS and u-VATS in terms of postoperative pain. We hope that the results of our trial will provide valuable information on the outcomes of these different surgical approaches.

Trial registration

ClinicalTrials.gov NCT03240250. Registered on 07 August 2017; retrospectively registered.
Effects of a 90-min educational intervention for patients with insect venom allergy: a prospective controlled pilot study
Authors: Schoeben Lisa-Sophie , Mohr Nicole , Bubak Corinna , Schmieder Astrid , Schaarschmidt Marthe-Lisa
Published: February 2021

Background

Anaphylactic sting reactions need a prompt management. A structured educational intervention for patients with insect sting allergy has not been implemented so far. The purpose of this study was to analyze the effects of a structured 90-min educational intervention for patients with insect sting allergy.

Methods

Patients with an insect venom allergy were offered to participate in a structured 90-min group education (intervention group (IG)) or to attend a control group (CG). The patients’ subjective self-assurance in using the emergency medication, the willingness to always carry the emergency medication, the mental health status, absolute one-time willingness-to-pay (WTP) for complete cure, a disease knowledge assessment and a simulation test to examine the ability to manage an acute sting reaction were estimated at baseline (t0) and at follow-up (t1) as outcome parameters.

Results

55 patients participated in the IG (n = 25, 52.0% female, mean age 55.9 years) or the CG (n = 30, 56.7% female, mean age 52.0 years). Both arms showed a significant gain in self-assurance in using the emergency medication (IG: 6.1 at t0 vs. 8.6 at t1, p < 0.0001 and CG: 7.1 vs. 8.0, p = 0.0062) and ability to manage an acute sting reaction (IG: 6.7 vs. 11.4, p < 0.0001 and CG: 9.0 vs. 10.5, p = 0.0002) at t1. However, trained participants showed a significantly higher gain in the respective parameters. There were no significant changes regarding the remaining examined outcome parameters.

Conclusions

Patients who are willing to invest 90 min in a patient education intervention benefit significantly by an increased subjective and objective empowerment to manage an acute sting reaction.
GPR4 signaling is essential for the promotion of acid-mediated angiogenic capacity of endothelial progenitor cells by activating STAT3/VEGFA pathway in patients with coronary artery disease
Authors: Ouyang Shun , Li Yan , Wu Xing , Wang Yan , Liu Fanmao , Zhang Jianning , Qiu Yumin , Zhou Zhe , Wang Zhichao , Xia Wenhao , Lin Xiufang
Published: February 2021

Background

Patients with coronary artery disease (CAD) are characterized by a decline in vascular regeneration, which is related to the dysfunction of endothelial progenitor cells (EPCs). G-protein-coupled receptor 4 (GPR4) is a proton-sensing G-protein-coupled receptor (GPCR) that contributes to neovascularization in acidic microenvironments. However, the role of GPR4 in regulating the angiogenic capacity of EPCs from CAD patients in response to acidity generated in ischemic tissue remains completely unclear.

Methods

The angiogenic capacity of EPCs collected from CAD patients and healthy subjects was evaluated in different pH environments. The GPR4 function of regulating EPC-mediated angiogenesis was analyzed both in vitro and in vivo. The downstream mechanisms were further investigated by genetic overexpression and inhibition.

Results

Acidic environment prestimulation significantly enhanced the angiogenic capacity of EPCs from the non-CAD group both in vivo and in vitro, while the same treatment yielded the opposite result in the CAD group. Among the four canonical proton-sensing GPCRs, GPR4 displays the highest expression in EPCs. The expression of GRP4 was markedly lower in EPCs from CAD patients than in EPCs from non-CAD individuals independent of acid stimulation. The siRNA-mediated knockdown of GPR4 with subsequent decreased phosphorylation of STAT3 mimicked the impaired function of EPCs from CAD patients at pH 6.4 but not at pH 7.4. Elevating GPR4 expression restored the neovessel formation mediated by EPCs from CAD patients in an acidic environment by activating STAT3/VEGFA signaling. Moreover, the beneficial impact of GPR4 upregulation on EPC-mediated angiogenic capacity was abrogated by blockade of the STAT3/VEGFA signaling pathway.

Conclusions

Our present study demonstrated for the first time that loss of GPR4 is responsible for the decline in proton sensing and angiogenic capacity of EPCs from CAD patients. Augmentation of GPR4 expression promotes the neovessel formation of EPCs by activating STAT3/VEGF signaling. This finding implicates GPR4 as a potential therapeutic target for CAD characterized by impaired neovascularization in ischemic tissues.
The impact of physical activity and exercise interventions for physical health in people with cystic fibrosis: protocol for a systematic review
Authors: Tomlinson Owen W. , Denford Sarah , Barker Alan R. , Schneiderman Jane E. , Campisi Emma S. , Douglas Helen , Rand Sarah , McNarry Melitta A. , Mackintosh Kelly A. , Williams Craig A.
Published: February 2021

Background

Cystic fibrosis (CF) is a genetically inherited, life-limiting condition, affecting ~90,000 people globally. Physical activity (PA) and exercise form an integral component of CF management, and have been highlighted by the CF community as an area of interest for future research. Previous reviews have solely focused on PA or structured exercise regimens independent of one another, and thus a comprehensive assessment of the physical health benefits of all PA, including exercise, interventions, is subsequently warranted. Therefore, the purpose of this review is to evaluate the effects of both PA and exercise upon outcomes of physical health and healthcare utilisation in people with CF.

Methods

A systematic review has been registered and reported in line with Preferred Reporting Items for Systematic Reviews and Meta-Analysis-P guidelines. This will include randomised control trials on the effects of PA and exercise, relative to usual treatment, upon people with CF. Primary outcomes will include variables associated with fitness, PA, lung health, inflammation, body composition, glycaemic control and patient-reported outcomes. Secondary outcomes will include adverse events and healthcare utilisation. Searches will be undertaken in Ovid MEDLINE, OVID EMBASE, PsychINFO, ERIC, SPORTDiscus, ASSIA, CCTR, CINHAL and Web of Science databases, and will be searched from date of inception onwards. Two reviewers will independently screen citations and abstracts, and full-texts, for inclusion and data extraction, respectively. Methodological quality will be assessed using the Cochrane Risk of Bias-2 tool. If feasible, random-effects meta-analyses will be conducted where appropriate. Additional analyses will explore potential sources of heterogeneity, such as age, sex, and disease severity.

Discussion

This systematic review will build on previous research, by comprehensively assessing the impact of both PA and exercise upon physical health and healthcare utilisation in people with CF. Results of this review will be utilised to inform discussions that will ultimately result in a consensus document on the impact of physical activity and exercise for people with CF.

Systematic review registration

PROSPERO CRD42020184411
Retraction Note: Existence of global solutions to a quasilinear Schrödinger equation with general nonlinear optimal control conditions
Authors: Hu Yisheng , Qin Songhai , Liu Zhibin , Wang Yi
Published: February 2021

This article has been retracted. Please see the Retraction Notice for more detail: 10.1186/s13661-021-01502-z
Finite time stability and sliding mode control for uncertain variable fractional order nonlinear systems
Authors: Jiang Jingfei , Li Hongkui , Zhao Kun , Cao Dengqing , Guirao Juan L. G.
Published: February 2021

This paper deals with the finite time stability and control for a class of uncertain variable fractional order nonlinear systems. The variable fractional Lyapunov direct method is developed to provide the basis for the stability proof of the system considered. The sliding mode control method is applied for robust control of uncertain variable fractional order systems; furthermore, the chattering phenomenon is avoided. And the finite time stability of the systems under control law is proved based on the proposed stability criterion. Finally, numerical simulations are proposed and the efficiency of the controller is verified.
Emden–Fowler-type neutral differential equations: oscillatory properties of solutions
Authors: Bazighifan Omar , Almutairi Alanoud
Published: February 2021

In this paper, we study the oscillation of a class of fourth-order Emden–Fowler delay differential equations with neutral term. Using the Riccati transformation and comparison method, we establish several new oscillation conditions. These new conditions complement a number of results in the literature. We give examples to illustrate our main results.
Higher order solitary solutions to the meta-model of diffusively coupled Lotka–Volterra systems
Authors: Timofejeva Inga , Telksnys Tadas , Navickas Zenonas , Marcinkevicius Romas , Ragulskis Minvydas
Published: February 2021

A meta-model of diffusively coupled Lotka–Volterra systems used to model various biomedical phenomena is considered in this paper. Necessary and sufficient conditions for the existence ofnth order solitary solutions are derived via a modified inverse balancing technique. It is shown that as the highest possible solitary solution ordernis increased, the number of nonzero solution parameter values remains constant for solitary solutions of order$n>3$n>3. Analytical and computational experiments are used to illustrate the obtained results.