bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

AbstractPilz 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

Abstract
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

AbstractInherited 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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.