bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase 2 study of ruxolitinib and decitabine in patients with myeloproliferative neoplasm in accelerated and blast phase
Authors: Mascarenhas John O. , Rampal Raajit K. , Kosiorek Heidi E. , Bhave Rupali , Hexner Elizabeth , Wang Eunice S. , Gerds Aaron , Abboud Camille N. , Kremyanskaya Marina , Berenzon Dimitry , Odenike Olatoyosi , Farnoud Noushin , Krishnan Aishwarya , Weinberg Rona Singer , McGovern Erin , Salama Mohamed E. , Najfeld Vesna , Medina-Martinez Juan S. , Arango Ossa Juan E. , Levine Max F. , Zhou Yangyu , Sandy Lonette , Heaney Mark L. , Levine Ross L. , Mesa Ruben A. , Dueck Amylou C. , Hoffman Ronald 
Published: October 2020

Abstract
Myeloproliferative neoplasms (MPN) that have evolved into accelerated or blast phase disease (MPN-AP/BP) have poor outcomes with limited treatment options and therefore represent an urgent unmet need. We have previously demonstrated in a multicenter, phase 1 trial conducted through the Myeloproliferative Neoplasms Research Consortium that the combination of ruxolitinib and decitabine is safe and tolerable and is associated with a favorable overall survival (OS). In this phase 2 trial, 25 patients with MPN-AP/BP were treated at the recommended phase 2 dose of ruxolitinib 25 mg twice daily for the induction cycle followed by 10 mg twice daily for subsequent cycles in combination with decitabine 20 mg/m2 for 5 consecutive days in a 28-day cycle. Nineteen patients died during the study follow-up. The median OS for all patients on study was 9.5 months (95% confidence interval, 4.3-12.0). Overall response rate (complete remission + incomplete platelet recovery + partial remission) was 11/25 (44%) and response was not associated with improved survival. We conclude that the combination of decitabine and ruxolitinib was well tolerated, demonstrated favorable OS, and represents a therapeutic option for this high-risk patient population. This trial was registered at www.clinicaltrials.gov as #NCT02076191.
Daytime sleepiness predicts inflammation and ambulatory blood pressure in sleep apnoea
Authors: Pak Victoria M. , Butts Brittany , Hertzberg Vicki , Collop Nancy , Quyyumi Arshed A. , Cox John , Rogers Ann , Dunbar Sandra B. 
Published: October 2020

IntroductionSleepiness in obstructive sleep apnoea is associated with cardiovascular risk; however, the biological mechanisms are not known. This study explored whether those with subjective sleepiness have increased plasma tumour necrosis factor-related protein 1 (C1qTNF1), a novel adipose-derived hormone (adipokine), and 24-h ambulatory blood pressure (ABP) compared to those without sleepiness in newly diagnosed, treatment-naïve participants with obstructive sleep apnoea.MethodsOverall, 94 participants were included in the analysis. Participants completed the Epworth Sleepiness Scale (ESS), 24-h ABP was monitored, and plasma C1qTNF1 was measured. Sleepy participants were defined as ESS≥10 and nonsleepy as ESS<10. Multiple linear regression was used to explore differences in C1qTNF1, and 24-h mean arterial pressure (MAP) between sleepy and nonsleepy participants, adjusting for age, sex, body mass index, apnoea–hypopnoea index, and smoking status.ResultsC1qTNF1 was significantly higher in sleepy participants (n=57) compared to nonsleepy participants (n=37) (β=0.41 NPX, 95% CI 0.02, 0.80; p=0.04). The 24-h MAP was significantly higher in sleepy participants compared to nonsleepy participants (β=4.06 mmHg, 95% CI 0.36, 7.77; p=0.03).ConclusionsOur findings show that sleepiness is associated with inflammation and higher 24-h MAP in sleep apnoea.
Validation of a composed COVID-19 chest radiography score: the CARE project
Authors: Giraudo Chiara , Cavaliere Annachiara , Fichera Giulia , Weber Michael , Motta Raffaella , Pelloso Michela , Tosato Francesca , Lupi Amalia , Calabrese Fiorella , Carretta Giovanni , Cattelan Anna Maria , De Conti Giorgio , Cianci Vito , Navalesi Paolo , Plebani Mario , Rea Federico , Vettor Roberto , Vianello Andrea , Stramare Roberto 
Published: October 2020

ObjectivesThe aim of this study was to validate a composed coronavirus disease 2019 (COVID-19) chest radiography score (CARE) based on the extension of ground-glass opacity (GG) and consolidations (Co), separately assessed, and to investigate its prognostic performance.MethodsCOVID-19-positive patients referring to our tertiary centre during the first month of the outbreak in our area and with a known outcome were retrospectively evaluated. Each lung was subdivided into three areas and a three-grade score assessing the extension of GG and Co was used. The CARE was derived from the sum of the subscores. A mixed-model ANOVA withpost hocBonferroni correction was used to evaluate whether differences related to the referring unit (emergency room, COVID-19 wards and intensive care unit (ICU)) occurred. Logistic regression analyses were used to investigate the impact of CARE, patients’ age and sex on the outcome. To evaluate the prognostic performance of CARE, receiver operating characteristic curves were computed for the entire stay and at admission only.ResultsA total of 1203 chest radiographs of 175 patients (120 males; mean age 67.81±15.5 years old) were examined. On average, each patient underwent 6.8±10.3 radiographs. Patients in ICU as well as deceased patients showed higher CARE scores (p<0.05, each). Age, Co and CARE significantly influenced the outcome (p<0.05 each). The CARE demonstrated good accuracy (area under the curve (AUC)=0.736) using longitudinal data as well as at admission only (AUC=0.740). A CARE score of 17.5 during hospitalisation showed 75% sensitivity and 69.9% specificity.ConclusionsThe CARE was demonstrated to be a reliable tool to assess the severity of pulmonary involvement at chest radiography with a good prognostic performance.
Multicentre feasibility of multiple-breath washout in preschool children with cystic fibrosis and other lung diseases
Authors: Stahl Mirjam , Joachim Cornelia , Kirsch Ines , Uselmann Tatjana , Yu Yin , Alfeis Nadine , Berger Christiane , Minso Rebecca , Rudolf Isa , Stolpe Cornelia , Bovermann Xenia , Liboschik Lena , Steinmetz Alena , Tennhardt Dunja , Dörfler Friederike , Röhmel Jobst , Unorji-Frank Klaudia , Rückes-Nilges Claudia , von Stoutz Bianca , Naehrlich Lutz , Kopp Matthias V. , Dittrich Anna-Maria , Sommerburg Olaf , Mall Marcus A. 
Published: October 2020

BackgroundMultiple-breath washout (MBW)-derived lung clearance index (LCI) detects early cystic fibrosis (CF) lung disease. LCI was used as an end-point in single- and multicentre settings at highly experienced MBW centres in preschool children. However, multicentre feasibility of MBW in children aged 2–6 years, including centres naïve to this technique, has not been determined systematically.MethodsFollowing central training, 91 standardised nitrogen MBW investigations were performed in 74 awake preschool children (15 controls, 46 with CF, and 13 with other lung diseases), mean age 4.6±0.9 years at investigation, using a commercially available device across five centres in Germany (three experienced, two naïve to the performance in awake preschool children) with central data analysis. Each MBW investigation consisted of several measurements.ResultsOverall success rate of MBW investigations was 82.4% ranging from 70.6% to 94.1% across study sites. The number of measurements per investigation was significantly different between sites ranging from 3.7 to 6.2 (p<0.01), while the mean number of successful measurements per investigation was comparable with 2.1 (range, 1.9 to 2.5; p=0.46). In children with CF, the LCI was increased (median 8.2, range, 6.7–15.5) compared to controls (median 7.3, range 6.5–8.3; p<0.01), and comparable to children with other lung diseases (median 7.9, range, 6.6–13.9; p=0.95).ConclusionThis study demonstrates that multicentre MBW in awake preschool children is feasible, even in centres previously naïve, with central coordination to assure standardised training, quality control and supervision. Our results support the use of LCI as multicentre end-point in clinical trials in awake preschoolers with CF.
Differences among families in craniofacial shape at early life-stages of Arctic charr (Salvelinus alpinus)
Authors: Beck Samantha V. , Räsänen Katja , Leblanc Camille A. , Skúlason Skúli , Jónsson Zophonías O. , Kristjánsson Bjarni K. 
Published: October 2020

AbstractBackgroundOrganismal fitness can be determined at early life-stages, but phenotypic variation at early life-stages is rarely considered in studies on evolutionary diversification. The trophic apparatus has been shown to contribute to sympatric resource-mediated divergence in several taxa. However, processes underlying diversification in trophic traits are poorly understood. Using phenotypically variable Icelandic Arctic charr (Salvelinus alpinus), we reared offspring from multiple families under standardized laboratory conditions and tested to what extent family (i.e. direct genetic and maternal effects) contributes to offspring morphology at hatching (H) and first feeding (FF). To understand the underlying mechanisms behind early life-stage variation in morphology, we examined how craniofacial shape varied according to family, offspring size, egg size and candidate gene expression.ResultsCraniofacial shape (i.e. the Meckel’s cartilage and hyoid arch) was more variable between families than within families both across and within developmental stages. Differences in craniofacial morphology between developmental stages correlated with offspring size, whilst within developmental stages only shape at FF correlated with offspring size, as well as female mean egg size. Larger offspring and offspring from females with larger eggs consistently had a wider hyoid arch and contracted Meckel’s cartilage in comparison to smaller offspring.ConclusionsThis study provides evidence for family-level variation in early life-stage trophic morphology, indicating the potential for parental effects to facilitate resource polymorphism.
Preventing mother to child transmission of HIV: lessons learned from China
Authors: Dong Yu , Guo Wei , Gui Xien , Liu Yanbin , Yan Yajun , Feng Ling , Liang Ke 
Published: October 2020

Abstract
Background
The program for the prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) was launched in 2003 in China, but few studies have been conducted to describe the panorama of PMTCT. We investigated the rate and associated factors of mother-to-child transmission (MTCT) in China from 2004 to 2018.

Methods
HIV-infected pregnant women from two areas in China between 2004 and 2018 were enrolled. Antiretrovirals (ARVs) were provided to the mothers and their babies, and the children were followed and tested for HIV.

Results
In total, 857 mothers and their 899 children were enrolled, and the overall MTCT rate was 6.6% (95% CI 5.0–8.2). The MTCT rates of nonintervention, only formula feeding (FF), infant prophylaxis (IP) + FF, single dosage antiretrovirals (sdARVs) + IP + FF, zidovudine (AZT) alone+IP + FF and prenatal combination antiretroviral therapy (cART) + IP + FF were 36.4, 9.4, 10.0, 5.7, 3.8 and 0.3%, respectively. The MTCT rate declined over time. No ARVs, CD4 count < 200/μL, low birth weight, and breastfeeding were associated with MTCT of HIV. For different ARVs, a higher MTCT rate was observed for AZT alone, sdARVs, and no ARVs compared to cART for pregnant women.

Conclusions
Although the overall MTCT rate remains relatively high, the real-world effect of prenatal cART+IP + FF in China has exerted the same protective effects in high-income countries. With the extension of prenatal cART for pregnant women with HIV, the MTCT rate of HIV has gradually declined in China. However, the coverage of prenatal cART for pregnant women should be further improved. The effect of only post-exposure prophylaxis for infants was limited.
Retraction of transporting bone segment during Ilizarov bone transport
Authors: Ma Yunhong , Yin Qudong , Wu Yongwei , Wang Zongnan , Sun Zhenzhong , Gu Sanjun , Rui Yongjun , Han Xiaofei 
Published: October 2020

AbstractBackgroundRetraction of transporting bone segment (TBS) may occur when the fixator of the TBS is removed prior to full consolidation of the distracted callus, which has adverse effect on the healing of the docking site. However, there are few reports on the retraction of TBS. The purpose of this study is to analyze the causes and risk factors of the retraction of TBS.MethodsThe clinical data of 37 cases with tibial bone defect treated by Ilizarov bone transport were analyzed retrospectively, in whom the TBS fixator was removed prior to full consolidation of the distracted callus and union of the docking site. Bivariate correlation was used to analyze relationship between the retraction distance of TBS and potential risk factors including age, gender, course, length of bone defect, number of operations, size of TBS, transport distance, timing and time interval of removal of TBS fixator. Risk factors with significant level were further identified using multivariate linear regression.ResultsBivariate correlation showed that the timing of removal was negatively correlated with the retraction distance, and the time interval and transport distance were positively correlated with the retraction distance(p < 0.05), the age, gender, course, length of bone defect, size of TBS and number of operations were not correlated with the retraction distance(p > 0.05). Multivariate linear regression of the 3 risk factors showed that the timing of removal and time interval were the main risk factors affecting the retraction distance (p < 0.05), but the transport distance was not (p > 0.05).ConclusionThe traction forces of TBS endured from the soft tissues and the unconsolidated distracted callus have elastic properties, which can make retraction of TBS. The timing of removal and time interval are the main risk factors of the retraction of TBS. In the case of early removal, another external fixation or quickly converted to internal fixation should be performed to avoid the adverse effect of more retraction.
Horizontal inequity in the use and access to health care in Uruguay
Authors: González Cecilia , Triunfo Patricia 
Published: October 2020

Abstract
Background
In 2007 Uruguay began a reform in the health sector towards the construction of a National Integrated Health System (SNIS), based on public insurance with private and public provision. The main objective of the reform was to universalize access to health services.

Methods
Data comes from the first National Health Survey conducted in 2014 and available since 2016. Concentration indices are calculated for different indicators of use and access to medical services, for the population 18 years of age and older, and for different subgroups (age, sex, region and type of coverage). The indices are decomposed into need and non-need variables and the contribution of each of them to total inequality is analyzed. Horizontal inequity is calculated.

Results
Results show pro-rich inequality for medical consultations, medical analysis, medication use and non-access due to costs. Type of health coverage is the variable that explains most of the inequality: private coverage is pro-rich while public coverage is pro-poor. Income does not appear as significant to explain inequality, except for access issues.
From the population subgroups’ analysis, there is no evidence of inequality for the group of 60 years old or more. On the other hand, studies such as Pap Smear and prostate, which may be associated with preventive studies,, shows pro-rich inequality and, in both cases, the main contribution is given by income.

Conclusions
The analysis of health inequity shows pro-rich inequity in medical consultations, medical analysis, medication use and lack of access due to costs. The type of health coverage explains these inequalities; in particular, private coverage is pro-rich. These results suggest that the type of health coverage are capturing the income factor, since higher income individuals will be more likely to be treated in the private system.
Treatment monitoring of colorectal cancer by integrated analysis of plasma concentration and sequencing of circulating tumor DNA
Authors: Yeh Yu-Min , Lin Peng-Chan , Lee Chung-Ta , Chen Shang-Hung , Lin Bo-Wen , Lin Shao-Chieh , Chen Po-Chuan , Chan Ren-Hao , Shen Meng-Ru 
Published: October 2020

AbstractCirculating cell-free DNA (cfDNA) analysis is an important tool for cancer monitoring. The patient-specific mutations identified in colorectal cancer (CRC) tissues are usually used to design the cfDNA analysis. Despite high specificity in predicting relapse, the sensitivity in most studies is around 40–50%. To improve this weakness, we designed a cfDNA panel according to the CRC genomic landscape and recurrent-specific mutations. The pathological variants in cfDNA samples from 60 CRC patients were studied by a next-generation sequencing (NGS) method incorporating the dual molecular barcode. Interestingly, patients in the disease positive group had a significantly higher cfDNA concentration than those in the disease negative group. Based on receiver operating characteristic analysis, the cfDNA concentration of 7 ng/mL was selected into the analytical workflow. The sensitivity in determining the disease status was 72.4%, which represented a considerable improvement on prior studies, and the specificity remained high at 80.6%. Compared to standard imaging and laboratory studies, earlier detection of residual disease and clinical benefits were shown on two cases by this cfDNA assay. We conclude this integrative framework of cfDNA analytical pipeline with a satisfactory sensitivity and specificity could be used in postoperative CRC surveillance.
Best practices for variant calling in clinical sequencing
Authors: Koboldt Daniel C. 
Published: October 2020

AbstractNext-generation sequencing technologies have enabled a dramatic expansion of clinical genetic testing both for inherited conditions and diseases such as cancer. Accurate variant calling in NGS data is a critical step upon which virtually all downstream analysis and interpretation processes rely. Just as NGS technologies have evolved considerably over the past 10 years, so too have the software tools and approaches for detecting sequence variants in clinical samples. In this review, I discuss the current best practices for variant calling in clinical sequencing studies, with a particular emphasis on trio sequencing for inherited disorders and somatic mutation detection in cancer patients. I describe the relative strengths and weaknesses of panel, exome, and whole-genome sequencing for variant detection. Recommended tools and strategies for calling variants of different classes are also provided, along with guidance on variant review, validation, and benchmarking to ensure optimal performance. Although NGS technologies are continually evolving, and new capabilities (such as long-read single-molecule sequencing) are emerging, the “best practice” principles in this review should be relevant to clinical variant calling in the long term.
miR-137 boosts the neuroprotective effect of endothelial progenitor cell-derived exosomes in oxyhemoglobin-treated SH-SY5Y cells partially via COX2/PGE2 pathway
Authors: Li Yuchen , Wang Jinju , Chen Shuzhen , Wu Pei , Xu Shancai , Wang Chunlei , Shi Huaizhang , Bihl Ji 
Published: October 2020

Abstract
Background
We have previously verified the beneficial effects of exosomes from endothelial progenitor cells (EPC-EXs) in ischemic stroke. However, the effects of EPC-EXs in hemorrhagic stroke have not been investigated. Additionally, miR-137 is reported to regulate ferroptosis and to be involved in the neuroprotection against ischemic stroke. Hence, the present work explored the effects of miR-137-overexpressing EPC-EXs on apoptosis, mitochondrial dysfunction, and ferroptosis in oxyhemoglobin (oxyHb)-injured SH-SY5Y cells.

Methods
The lentiviral miR-137 was transfected into EPCs and then the EPC-EXs were collected. RT-PCR was used to detect the miR-137 level in EPCs, EXs, and neurons. The uptake mechanisms of EPC-EXs in SH-SY5Y cells were explored by the co-incubation of Dynasore, Pitstop 2, Ly294002, and Genistein. After the transfection of different types of EPC-EXs, flow cytometry and expression of cytochrome c and cleaved caspase-3 were used to detect the apoptosis of oxyHb-injured neurons. Neuronal mitochondrial function was assessed by reactive oxygen species (ROS) level, mitochondrial membrane potential (MMP) depolarization, and cellular ATP content. Cell ferroptosis was measured by lipid peroxidation, iron overload, degradation of glutathione, and glutathione peroxidase 4. Additionally, recombinational PGE2 was used to detect if activation of COX2/PGE2 pathway could reverse the protection of miR-137 overexpression.

Results
The present work showed (1) EPC-EXs could be taken in by SH-SY5Y cells via caveolin-/clathrin-mediated pathways and macropinocytosis; (2) miR-137 was decreased in neurons after oxyHb treatment, and EXsmiR-137 could restore the miR-137 levels; (3) EXsmiR-137 worked better than EXs in reducing the number of apoptotic neurons and pro-apoptotic protein expression after oxyHb treatment; (4) EXsmiR-137 are more effective in improving the cellular MMP, ROS, and ATP level; (5) EXsmiR-137, but not EXs, protected oxyHb-treated SH-SY5Y cells against lipid peroxidation, iron overload, degradation of glutathione, and glutathione peroxidase 4; and (6) EXsmiR-137 suppressed the expression of the COX2/PGE2 pathway, and activation of the pathway could partially reverse the neuroprotective effects of EXsmiR-137.

Conclusion
miR-137 overexpression boosts the neuroprotective effects of EPC-EXs against apoptosis and mitochondrial dysfunction in oxyHb-treated SH-SY5Y cells. Furthermore, EXsmiR-137 rather than EXs can restore the decrease in miR-137 levels and inhibit ferroptosis, and the protection mechanism might involve the miR-137-COX2/PGE2 signaling pathway.
Cardiovascular risk in patients with severe mental illness in Italy
Authors: Salvi Virginio , Aguglia Andrea , Barone-Adesi Francesco , Bianchi Davide , Donfrancesco Chiara , Dragogna Filippo , Palmieri Luigi , Serafini Gianluca , Amore Mario , Mencacci Claudio 
Published: October 2020

Abstract

Background
Patients with severe mental illness (SMI), such as schizophrenia or bipolar disorders, are more frequently affected by metabolic syndrome and cardiovascular (CV) diseases than the general population, with a significant reduction in life expectancy. Beyond metabolic syndrome, quantifying the risk of CV morbidity in the long-term may help clinicians to put in place preventive strategies. In this study, we assessed 10-year CV risk in patients with SMI and healthy individuals using an algorithm validated on the Italian general population.

Methods
Patients aged 35–69 years diagnosed with SMI were consecutively recruited from psychiatric acute care units. Single CV risk factors were assessed, and 10-year CV risk calculated by means of the CUORE Project 10-year CV risk algorithm, based on the combination of the following risk factors: age, systolic blood pressure, total and high-density lipoprotein cholesterol, diabetes, smoking habit, and hypertensive treatment. Patients’ data were compared with those from the general population. The 10-year CV risk was log-transformed, and multivariable linear regression was used to estimate mean ratios, adjusting for age, and education.

Results
Three hundred patients and 3,052 controls were included in the analysis. Among men, the 10-year CV risk score was very similar between patients with SMI and the general population (mean ratio [MR]: 1.02; 95%CI 0.77–1.37), whereas a 39% increase in 10-year CV risk was observed in women with SMI compared to the general population (MR: 1.39; 95%CI 1.16–1.66).

Conclusions
In our study, women with SMI were consistently more at risk than the general population counterpart, even at younger age.