bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced VWF clearance in low VWF pathogenesis: limitations of the VWFpp/VWF:Ag ratio and clinical significance
Authors: Doherty Dearbhla , Lavin Michelle , Byrne Mary , Nolan Margaret , O’Sullivan Jamie M. , Ryan Kevin , O’Connell Niamh M. , Haberichter Sandra L. , Christopherson Pamela A. , Di Paola Jorge , James Paula D. , O’Donnell James S. 
Published: May 2022

AbstractIncreased von Willebrand factor (VWF) clearance plays a key role in the pathogenesis of type 1 and type 2 von Willebrand disease (VWD). However, the pathological mechanisms involved in patients with mild to moderate reductions in plasma VWF:Ag (range, 30-50 IU/dL; low VWF) remain poorly understood. In this study, we investigated the hypothesis that enhanced VWF clearance may contribute to the pathobiology of low VWF. Patients with low VWF were recruited to the LoVIC study after ethics approval and receipt of informed consent. Desmopressin was administered IV in 75 patients, and blood samples were drawn at baseline and at the 1-hour and 4-hour time points. As defined by recent ASH/ISTH/NHF/WFH guidelines, 20% of our low-VWF cohort demonstrated significantly enhanced VWF clearance. Importantly, from a clinical perspective, this enhanced VWF clearance was seen after desmopressin infusion, but did not affect the steady-state VWF propeptide (VWFpp)-to-VWF antigen (VWF:Ag) ratio (VWFpp/VWF:Ag) in most cases. The discrepancy between the VWFpp/VWF:Ag ratio and desmopressin fall-off rates in patients with mild quantitative VWD may have reflected alteration in VWFpp clearance kinetics. Finally, bleeding scores were significantly lower in patients with low VWF with enhanced VWF clearance, compared with those in whom reduced VWF biosynthesis represented the principle pathogenic mechanism. This trial was registered at http://www.clinicaltrials.gov as #NCT03167320.
Modulation of the Drosophila transcriptome by developmental exposure to alcohol
Authors: Morozova Tatiana V. , Shankar Vijay , MacPherson Rebecca A. , Mackay Trudy F. C. , Anholt Robert R. H. 
Published: May 2022

AbstractBackgroundPrenatal exposure to ethanol can cause fetal alcohol spectrum disorder (FASD), a prevalent, preventable pediatric disorder. Identifying genetic risk alleles for FASD is challenging since time, dose, and frequency of exposure are often unknown, and manifestations of FASD are diverse and evident long after exposure.Drosophila melanogasteris an excellent model to study the genetic basis of the effects of developmental alcohol exposure since many individuals of the same genotype can be reared under controlled environmental conditions.ResultsWe used 96 sequenced, wild-derived inbred lines from theDrosophila melanogasterGenetic Reference Panel (DGRP) to profile genome-wide transcript abundances in young adult flies that developed on ethanol-supplemented medium or standard culture medium. We found substantial genetic variation in gene expression in response to ethanol with extensive sexual dimorphism. We constructed sex-specific genetic networks associated with alcohol-dependent modulation of gene expression that include protein-coding genes, Novel Transcribed Regions (NTRs, postulated to encode long non-coding RNAs) and female-specific coordinated regulation of snoRNAs that regulate pseudouridylation of ribosomal RNA. We reared DGRP lines which showed extreme upregulation or downregulation of snoRNA expression during developmental alcohol exposure on standard or ethanol supplemented medium and demonstrated that developmental exposure to ethanol has genotype-specific effects on adult locomotor activity and sleep.ConclusionsThere is significant and sex-specific natural genetic variation in the transcriptional response to developmental exposure to ethanol in Drosophila that comprises networks of genes affecting nervous system development and ethanol metabolism as well as networks of regulatory non-coding RNAs.
Healthcare utilisation for elderly people at the onset of the COVID-19 pandemic in South Korea
Authors: Park K. , Byeon J. , Yang Y. , Cho H. 
Published: May 2022

Abstract
Background
At the onset of the coronavirus disease 2019 (COVID-19) pandemic, health care systems were severely disrupted in many countries and in particular, elderly people vulnerable to COVID-19 may have been reluctant to receive their medical treatment.

Methods
We conducted interrupted time series analyses (ITSA) using nationwide medical claim data between January 2020 and July 2020, with focus on different disease categories for the patients of 65 to 84-year-olds, i.e., acute upper respiratory infections (AURIs) vs. chronic diseases.

Results
AURIs and chronic diseases showed a sharp contrast with respect to the change in healthcare service utilisation. First, the utilisation rate for chronic diseases changed little whereas for AURIs it dropped by 20.4% year-over-year (yoy) at the onset of the pandemic (week 6, 2020). Second, as social distancing relaxed (week 17, 2020), the AURIs patients trended up and even reached to 7.8% above yoy whereas no significant change found for chronic diseases.

Conclusions
The uninterrupted treatment for chronic diseases in contrast to the AURIs implies that the governmental and public responses to the pandemic outbreak worked for efficient healthcare provision to patients in needs of regular check-ups and treatment in the middle of an infectious disease crisis.
Renal artery thrombosis in SARS-CoV-2 infection: a case report
Authors: Huang Huayan , Lin Chunguang , Chen Yongdong , Wu Xiuting , Lin Miaomiao , Chen Siqi , Li Kai 
Published: May 2022

Abstract
Background
Coronavirus disease 2019 (COVID-19) is identified as the pneumonia and acute respiratory distress syndrome caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). The intravascular thrombotic phenomena related to the COVID-19 are emerging as an important complication that contribute to significant mortality.

Case presentation
We present a 62-year-old man with severe COVID-19 and type 2 diabetes. After symptomatic and supportive treatment, the respiratory function was gradually improved. However, the patient suddenly developed abdominal pain, and the enhanced CT scan revealed renal artery thrombosis. Given the risk of surgery and the duration of the disease, clopidogrel and heparin sodium were included in the subsequent treatment. The patient recovered and remained stable upon follow-up.

Conclusions
Thrombosis is at a high risk in patients with severe COVID-19 pneumonia because of hypercoagulable state, blood stasis and endothelial injury. Thrombotic events caused by hypercoagulation status secondary to vascular endothelial injury deserves our attention. Because timely anticoagulation can reduce the risk of early complications, as illustrated in this case report.
A real-world retrospective study of the use of Ki-67 testing and treatment patterns in patients with HR+, HER2− early breast cancer in the United States
Authors: Brown Jacqueline , Scardo Savannah , Method Michael , Schlauch Dan , Misch Amanda , Picard Shaita , Hamilton Erika , Jones Suzanne , Burris Howard , Spigel David 
Published: May 2022

Abstract
Background
The National Comprehensive Cancer Network recommends that patients with hormone receptor-positive early breast cancer be considered for adjuvant endocrine therapy (ET) after primary treatment like surgical excision. Adjuvant chemotherapy (CT) use primarily depends on risk of recurrence. Biomarkers such as Ki-67 potentially have most value in patients with intermediate risk factors, such as involvement of 1–3 positive nodes. This study evaluated the use of Ki-67 testing and treatment patterns in patients with HR+, human epidermal growth factor receptor 2-negative early breast cancer.

Methods
This was an observational retrospective cohort study of patients with electronic medical records from January 2010 to August 2018 treated for HR+, HER2− early breast cancer at Sarah Cannon sites in the United States (US). Overall, 567 patients were randomly selected after using the eligibility criteria: female or male ≥18 years, without distant metastases, and with available physician and pathology reports. Multivariable logistic regression was used to investigate factors predicting Ki-67 testing and test results. Descriptive analyses were applied to treatment patterns.

Results
Multivariable logistic regression analyses found no clinical or pathological factors that predicted whether Ki-67 testing had been ordered by physicians. Of all tested patients (N = 130), having Grade-2 tumors (OR, 7.95 [95% CI: 2.05, 30.9]; p = 0.0027) or Grade-3 tumors (OR, 95.3 [95% CI, 11.9, 760.7]; p < 0.001) at initial diagnosis was a predictor of high Ki-67 expression (≥20%). Ki-67 expression was tested in 23.6% (61/258) of patients with 1–3 positive nodes; 54.1% of them (33/61) had high Ki-67 expression (≥20%). While having a higher grade tumor predicted high Ki-67 (≥20%), 28.6% of patients with Grade-1 tumors also had high Ki-67 expression. Neo-adjuvant therapy was received by 16.0% of patients (91/567), most of whom (66/91; 72.5%) received CT alone. Adjuvant therapy, either endocrine and/or chemotherapy, was received by 92.6% (525/567) of patients and by 67.0% (61/91) of those who received neo-adjuvant therapy. Most (428/525, 81.5%) received ET in the adjuvant treatment setting.

Conclusions
High grade tumors predicted high Ki-67 (≥20%) expression, but Ki-67 testing was not widely used in these US patients. Most HR+, HER2− early breast cancers were treated with adjuvant ET, with or without CT.
Long-term outcome and relapse patterns in Ewing sarcoma patients with extensive lung/pleural metastases after a complete response to systemic therapy
Authors: Xu Jie , Zhi Xin , Xie Lu , Sun Xin , Liu Xingyu , Liu Kuisheng , Guo Wei 
Published: May 2022

Abstract
Background
Ewing sarcoma (ES) is sensitive to systemic therapy, including chemotherapy and anti-angiogenesis Tyrosine Kinase Inhibitors(aaTKIs). However, the prognosis of patients with metastatic disease remains poor. Recurrence or distant metastasis after a complete response (CR) or near-CR due to systemic therapy is not rare.

Methods
We reviewed data from 187 ES patients between 2014–2019 treated at a single institute in China. Patients with extensive lung/pleural metastases (L/Pmeta) who had a CR or near-CR after first- or second-line chemotherapy with or without aaTKIs were retrospectively enrolled. Event-free survival (EFS) and overall survival (OS) were determined using the Kaplan–Meier method. For patients who had L/P recurrence, images were reviewed to define the exact location of each recurrent lesion, compared with the primary L/P lesion before chemotherapy and summarized as the relapse pattern.

Results
Seventeen patients and 21 cases of CR/nCR (5 by VDC/IE, 3 by VIT, and 13 by AVI) were finally analyzed. Median follow-up for surviving patients was 39.6 (range, 14.5–60.9) months. Median EFS and OS were 9.3 (95% confidence interval [CI], 2.0–16.6) months and 37.5 (95% CI, 21.8–53.1) months, respectively. The 2-year EFS was 19% and the 2-year OS was 70.6%, respectively. Most patients (82.4%) received whole lung irradiation (WLI). Lung/pleural relapse occurred in 71.4% (15/21) of CR/nCR cases. Most notably, all recurrent lesions exactly coincided with the original metastatic lesions before chemotherapy (exactly in situ) in 9 of the 15 recurrent cases, which was thus the major relapse pattern, whereas 42.9% had distant metastases other than L/Pmeta.

Conclusions
Survival of ES patients with extensive L/Pmeta remains poor, even if they have a CR after systemic therapy. Recurrence exactly in situ is the major relapse pattern. WLI is not sufficient to prevent local recurrence in lung or pleura. More aggressive local treatment for metastatic lesions is warranted.
Hemodynamic parameters after Delayed Cord Clamping (DCC) in term neonates: a prospective observational study
Authors: Gupta Bhvya , Yengkhom Rameshwor , Banait Nishant , Chetan Chinmay , Pareek Prince , Suryawanshi Pradeep 
Published: May 2022

Abstract
Background
Delayed cord clamping (DCC) is practiced worldwide, as standard care in both term and preterm babies. Our aim was to determine the hemodynamic effects of DCC on transitional circulation.

Material and methods
This prospective observational study was carried out in a tertiary care hospital, at Pune, India, from May 2018 to October 2019.Term neonates born during the study period were included. The primary outcome variables of the study were right ventricular output (RVO), left ventricular output (LVO), superior vena cava (SVC) flow (ml/kg/min) and heart rate(HR) at 12 ± 6 and 48 ± 6 h of life measured by point of care functional echocardiography. Inter-observer and intra-observer variability was calculated for these parameters.

Results
Out of a total of 2744 deliveries during the study period, 620 babies were included. Mean gestational age of the enrolled babies was 38.96 ± 1.08 weeks and mean birth weight was 2.9 ± 0.39 kg. Mean heart rate of babies recorded at 12 ± 6 h of life was 127 beats per minute (bpm) whereas it was 128 bpm at 48 ± 6 h of life. RVO {mean (SD)} was 209.55(44.89) and 205.85(46.35) ml/kg/min, LVO {mean (SD)} was 133.68(31.15) and 134.78(29.84) ml/kg/min whereas SVC flow {mean (SD)} was 106.85(26.21) and 109.29(25.11) ml/kg/min at 12 ± 6 and 48 ± 6 h of life respectively. There was good intra-observer agreement in all the variables.
SGA babies had a significantly higher heart rate at 12 ± 6 h of life as compared to AGA babies, although this difference in heart rate could not be appreciated at 48 ± 6 h of life. However SGA babies had a higher LVO, RVO and SVC flow than AGA babies at both the time points of observation.

Conclusion
After DCC there is less fluctuation in the hemodynamic parameters (heart rate, cardiac output) at the two time points of observation.. As compared to AGA babies, SGA babies had a significantly higher baseline heart rate, LVO, RVO and SVC flow. LVO of SGA babies after delayed cord clamping is found to be significantly lower than LVO seen in other studies, favoring the cardio-stabilizing effect of DCC.

Brief rationale
This is the first study with a large sample size evaluating the hemodynamic effects of DCC in term neonates by functional echocardiography. The normative data of heart rate and cardiac output of term, stable babies with small for gestational age(SGA) as a special subgroup undergoing DCC requires further evaluation.
Determinants of the evolutions of behaviours, school adjustment and quality of life in autistic children in an adapted school setting: an exploratory study with the International Classification of Functioning, disability and health (ICF)
Authors: Schneider Stéphanie , Clément Céline , Goltzene Marc-André , Meyer Nicolas , Gras-Vincendon Agnès , Schröder Carmen M. , Coutelle Romain 
Published: May 2022

Abstract
Background
Previous studies about Quality of Life (QoL) in autistic children (ASD) have put forward the negative impact of factors such as Autism Spectrum Disorder (ASD) severity, psychiatric comorbidities and adaptive behaviour impairment. However, little is known about the relation of these factors to school adjustment, measured with the International Classification of Functions disability and health (ICF) framework (World Health Organization, 2001), and QoL evolutions. Thus, this study aimed at investigating the determinants of behaviours, school adjustment and QoL changes in 32 children in an ASD inclusion program over one academic year.

Methods
Using Bayesian methods, we studied the impact of ASD severity, psychiatric comorbidities, adaptive behaviour level and a diagnosis of Pathological Demand Avoidance (PDA) on evolutions of behaviour, school adjustment (measured with the ICF) and QoL.

Results
As predicted, adequate adaptive behaviour levels were associated with better progress of behaviours and school adjustment whereas psychiatric comorbidities were related to worse outcome of school adjustment. Contrary to our hypotheses, severe ASD was associated to better evolution of adjustment at school. PDA was not discriminant. We did not find any association between the studied factors and the evolution of QoL over the academic year.

Conclusion
Our results show that the assessment of adaptive behaviour levels, psychiatric comorbidities and ASD severity level may be useful predictors to discriminate of school adjustment evolution (assessed by teachers within the ICF model) over a one-year period in autistic children. The assessment of this time course of school adjustment was sensitive to change and adapted to differentiate evolutions in an inclusive education framework. The investigation of quality of school life of autistic children as well as its determinants may therefore be relevant to improving academic adaptation. However, further research in larger groups, over longer periods and in different personalized school settings for autistic children is needed.
Correlates of influenza vaccination among underserved Latinx middle-aged and older adults: a cross-sectional survey
Authors: Bazargan Mohsen , Martinez-Hollingsworth Adrienne , Cobb Sharon , Kibe Lucy W. 
Published: May 2022

Abstract
Background
Vaccination is a powerful tool in the fight against seasonal influenza, among underserved, middle-age and older, Latinx adults. Yet, vaccine hesitancy and inconsistent uptake in this population continues to represent a substantial challenge to public health. A better understanding of factors impacting influenza vaccination behaviors in this group could result in more effective messaging and initiatives promoting universal vaccination among Latinx.

Methods
In this cross-sectional survey, we explore correlates of influenza vaccination uptake among underserved, Latinx, older adults. Our focus was on the role of socio-demographics, living arrangements, financial strain, access and satisfaction with medical care, and the presence of major chronic conditions in terms of vaccine uptake. Middle-aged and older Latinx residents diagnosed with diabetes and/or hypertension (n=165), were recruited from the South Los Angeles Service Plan Area (SPA), a historically under-resourced community. Bi-variate and multi-variate logistical regression were performed on survey data to explore independent correlates of influenza vaccination.

Results
Almost half of underserved Latinx older adults in our study (45%) reported influenza vaccination within the 12 months prior to the study. The majority (~85%) reported receiving this recommendation from their primary care provider. However, thirty percent (30%) of those receiving this advice did not get the vaccine. A decreased likelihood of vaccination was significantly associated with living alone (p-value=0.026), lacking Medicare coverage (0.028), or higher levels of financial strain (0.020). Difficulty accessing medical care (p-value=0.008) or dissatisfaction with these experiences (p-value=0.001) were also strongly associated with decreased likelihood of vaccination. Participants diagnosed with COPD had 9.5 (CI: 1.76 – 51.3) higher odds of being vaccinated compared to those without; no correlation was detected for other chronic conditions.

Conclusion
The high number of unvaccinated Latinx participants receiving a vaccine recommendation from a provider is consistent with studies among other ethnic/racial minority older adults and highlights the pivotal role of the provider in influenza vaccine adoption. Additional findings reflect negative impact of Social Determinates of Health on preventive care efforts in this group. Further efforts to quantify these associations are needed to explore structural and human factors impacting influenza vaccine uptake.
The absence of IL-9 reduces allergic airway inflammation by reducing ILC2, Th2 and mast cells in murine model of asthma
Authors: Li Yan , Lan Feng , Yang Yiran , Xu Yingjie , Chen Yalin , Qin Xiaofeng , Lv Zhe , Wang Wei , Ying Sun , Zhang Luo 
Published: May 2022

AbstractAllergic asthma is an allergic inflammatory disease of the airways, in which numerous cell types and cytokines have been shown to contribute to pathogenesis of the disease. Although increased expression of IL-9 has been shown to influence the activity of structural as well as eosinophils and mast cells in asthma, the influence of IL-9 on function of ILC2 and Th2 cells remains unclear. This study therefore aimed to elucidate the role of IL-9 on ILC2 and Th2 cells using a murine model of asthma. A murine model of asthma was established using wild type (WT) and IL-9-deficient (Il9−/−) transgenic mice sensitized to house dust mite (HDM). Bronchoalveolar lavage fluid (BALF) and lung tissues were collected, and analysed for inflammatory cells (eosinophils, mast cells, Th2 cells and ILC2 cells), histopathological changes, and several cytokines. HDM challenge significantly increased accumulation of ILC2 cells, Th2 cells and mast cells, as well as goblet cell hyperplasia, and the expression of cytokines IL-4, IL-5 and IL-13, but not IFN-γ, in WT mice compared to saline-challenged control group. In contrast, all pathological changes, including infiltration of ILC2 cells, Th2 cells and mast cells, were significantly attenuated in HDM-challenged Il9−/− mice. Furthermore, the number of Ki67+ILC2 cells, Ki67+Th2 cells and Ki67+mast cells were significantly reduced in the absence of IL-9 signalling. These data suggest that IL-9 promotes the proliferation and type 2 cytokine production of type 2 cells in the murine models of asthma, and therefore might be a potential therapeutic target for asthma treatment.
Development of the German social attitude barriers and facilitators to participation-scales: an analysis according to the Rasch model
Authors: Upegui-Arango Luz Dary , Mainz Verena , Gecht Judith , Mueller Christian-Andreas , Quack Valentin , Heinemann Allen W. , Boecker Maren 
Published: May 2022

Abstract
Background
Social attitudes experienced by people with disabilities can strongly impact upon their health and quality of life. The extent to which social attitude measurement transcends specific cultures is unknown. Thus, the aim of the study was to develop German item banks to assess social attitude barriers and facilitators to participation and compare the construct definition with that developed in the United States.

Methods
The American version of the two item banks assessing social attitudes that act as barriers and facilitators in persons with disabilities was translated into German and culturally adapted. The sample consisted of 410 in- and outpatients treated for spinal diseases at a German University Hospital. The psychometric properties of the resulting 53 items-item pool were evaluated using Rasch analysis. A special focus was placed on the investigation of unidimensionality, local independence, differential item functioning (DIF) and targeting. To evaluate convergent and divergent validity correlations with perceived social support, depression and pain interference were calculated.

Results
Unlike the American version, both the barriers and facilitators item banks had to be divided into two subscales assessing attitudes that individuals with disabilities experience as being directed towards them (individual perception) or attitudes that respondents experience as being directed towards people with disabilities as a social group (societal perception). Four unidimensional scales were constructed. Fit to the Rasch model required item deletion and forming testlets to account for extensive local dependence. There was no evidence of DIF with regard to gender or age. Targeting of the subscales was moderate to good.

Conclusions
Results support a distinction between social attitudes at the individual and societal level, allowing a more specific assessment than is possible when this distinction is ignored.