bluuebunny/crossref_metadata_2025_split huggingface dataset:
Possible apixaban-induced leukocytoclastic vasculitis
Authors: Daul Brandon , Petersen Greta , Butler Jared 
Published: August 2020

Abstract

Purpose
The development of leukocytoclastic vasculitis (LCV) during apixaban therapy in a female patient being treated for deep vein thrombosis (DVT) is reported.

Summary
A 74-year-old Caucasian woman weighing 102 kg presented to a walk-in clinic with complaints of mild pain and swelling in her left leg for 2 weeks. She was diagnosed as having left lower-extremity DVT. The direct oral anticoagulant (DOAC) apixaban (10 mg twice daily for 7 days, then 5 mg twice daily for 3 months) was prescribed. At 1-week follow-up the patient stated that her DVT symptoms were slowly improving and reported that small areas of red rash had appeared bilaterally on her lower extremities. On day 23 of apixaban therapy, the patient presented to a walk-in clinic with a complaint that the rash had progressively worsened. The rash was diagnosed as LCV by dermatology consult. On day 24 of therapy, apixaban use was discontinued and the patient was initiated on rivaroxaban (20 mg daily) for the remainder of DVT treatment. LCV was found to be progressively improving on day 73, with trace petechiae. Rivaroxaban was used through the end of DVT treatment without further reports of LCV.

Conclusion
A female patient who developed LCV while taking apixaban for treatment of DVT was successfully transitioned to rivaroxaban therapy, leading to resolution of LCV and successful completion of DVT treatment without recurrence of LCV.
Structural basis of SARS-CoV-2 spike protein induced by ACE2
Authors: Meirson Tomer , Bomze David , Markel Gal 
Published: August 2020

Abstract

Motivation
The recent emergence of the novel SARS-coronavirus 2 (SARS-CoV-2) and its international spread pose a global health emergency. The spike (S) glycoprotein binds ACE2 and promotes SARS-CoV-2 entry into host cells. The trimeric S protein binds the receptor using the receptor-binding domain (RBD) causing conformational changes in S protein that allow priming by host cell proteases. Unraveling the dynamic structural features used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal novel therapeutic targets. Using structures determined by X-ray crystallography and cryo-EM, we performed structural analysis and atomic comparisons of the different conformational states adopted by the SARS-CoV-2-RBD.

Results
Here, we determined the key structural components induced by the receptor and characterized their intramolecular interactions. We show that κ-helix (polyproline-II) is a predominant structure in the binding interface and in facilitating the conversion to the active form of the S protein. We demonstrate a series of conversions between switch-like κ-helix and β-strand, and conformational variations in a set of short α-helices which affect the hinge region. These conformational changes lead to an alternating pattern in conserved disulfide bond configurations positioned at the hinge, indicating a possible disulfide exchange, an important allosteric switch implicated in viral entry of various viruses, including HIV and murine coronavirus. The structural information presented herein enables to inspect and understand the important dynamic features of SARS-CoV-2-RBD and propose a novel potential therapeutic strategy to block viral entry. Overall, this study provides guidance for the design and optimization of structure-based intervention strategies that target SARS-CoV-2.

Availability and implementation
We have implemented the proposed methods in an R package freely available at https://github.com/Grantlab/bio3d.

Supplementary information
Supplementary data are available at Bioinformatics online.
Lateralized Cerebral Processing of Abstract Linguistic Structure in Clear and Degraded Speech
Authors: Meng Qingqing , Hegner Yiwen Li , Giblin Iain , McMahon Catherine , Johnson Blake W 
Published: August 2020

Abstract
Human cortical activity measured with magnetoencephalography (MEG) has been shown to track the temporal regularity of linguistic information in connected speech. In the current study, we investigate the underlying neural sources of these responses and test the hypothesis that they can be directly modulated by changes in speech intelligibility. MEG responses were measured to natural and spectrally degraded (noise-vocoded) speech in 19 normal hearing participants. Results showed that cortical coherence to “abstract” linguistic units with no accompanying acoustic cues (phrases and sentences) were lateralized to the left hemisphere and changed parametrically with intelligibility of speech. In contrast, responses coherent to words/syllables accompanied by acoustic onsets were bilateral and insensitive to intelligibility changes. This dissociation suggests that cerebral responses to linguistic information are directly affected by intelligibility but also powerfully shaped by physical cues in speech. This explains why previous studies have reported widely inconsistent effects of speech intelligibility on cortical entrainment and, within a single experiment, provided clear support for conclusions about language lateralization derived from a large number of separately conducted neuroimaging studies. Since noise-vocoded speech resembles the signals provided by a cochlear implant device, the current methodology has potential clinical utility for assessment of cochlear implant performance.
Ambrosia Beetle (Coleoptera: Curculionidae) Communities and Frass Production in ʻŌhiʻa (Myrtales: Myrtaceae) Infected With Ceratocystis (Microascales: Ceratocystidaceae) Fungi Responsible for Rapid ʻŌhiʻa Death
Authors: Roy Kylle , Jaenecke Kelly A , Peck Robert W 
Published: August 2020

Abstract
Rapid ʻŌhiʻa Death (ROD) is a deadly disease that is threatening the native Hawaiian keystone tree species, ʻōhiʻa lehua (Metrosideros polymorpha Gaudich). Ambrosia beetles (Curculionidae: Scolytinae) and their frass are hypothesized to play a major role in the spread of ROD, although their ecological niches and frass production within trees and across the landscape are not well understood. We characterized the beetle communities and associated frass production from bolts (tree stem sections) representative of entire individual ʻōhiʻa trees from multiple locations across Hawaiʻi Island by rearing beetles and testing their frass for viable ROD-causing fungi. Additionally, we estimated frass production for three beetle species by weighing their frass over time. We found that Xyleborinus saxesenii (Ratzburg), Xyleborus affinis Eichhoff, Xyleborus ferrugineus (Fabricius), Xyleborus perforans (Wollaston), and Xyleborus simillimus Perkins were commonly found on ROD-infected ʻōhiʻa and each produced frass containing viable Ceratocystis propagules. The Hawaiʻi Island endemic beetle and the only native ambrosia beetle associated with ʻōhiʻa, X. simillimus, was limited to high elevations and appeared to utilize similar tree heights or niche dimensions as the invasive X. ferrugineus. Viable Ceratocystis propagules expelled in frass were found throughout entire tree bole sections as high as 13 m. Additionally, we found that X. ferrugineus produced over 4× more frass than X. simillimus. Our results indicate the ambrosia beetle community and their frass play an important role in the ROD pathosystem. This information may help with the development and implementation of management strategies to control the spread of the disease.
Poor quality of life in patients with and without frailty: co-prevalence and prognostic implications in patients undergoing percutaneous coronary interventions and cardiac catheterization
Authors: Kanwar Amrit , Roger Veronique L , Lennon Ryan J , Gharacholou S Michael , Singh Mandeep 
Published: August 2020

Abstract

Aims
We hypothesize that poor quality of life (QOL) is highly prevalent in frail older adults and is associated with worse prognosis.

Methods and results
Predismissal standardized tests for frailty and QOL were prospectively administered to patients included in two cohorts. In Cohort 1, 629 patients ≥65 years who underwent percutaneous coronary intervention (PCI) from 2005 to 2008, frailty (Fried criteria), and QOL [SF-36 and Seattle Angina Questionnaires (SAQ)] were ascertained. Cohort 2 included 921 patients ≥55 years who underwent cardiac catheterization (535 had PCI) from 2014 to 2018 and frailty was determined by Rockwood criteria and QOL by single-item, self-reported health questionnaire. In Cohort 1, 19% were frail and 20% patients in Cohort 2 were frail with a frailty index &gt;0.30. The median SAQ for physical limitation (58.9 vs. 82.2, P &lt; 0.001), physical (29.5 vs. 43.9, P &lt; 0.001), and mental (49.2 vs. 57.4, P &lt; 0.001) component scores of SF-36 in Cohort 1 were lower and self-rating of fair/poor health (56% vs 18%, P &lt; 0.001) in Cohort 2 was significantly higher in frail patients. As compared to patients without frailty, frail patients were five times more likely (59% vs. 11%, P &lt; 0.001) in Cohort 1 and seven times more likely (56% vs. 8%) in Cohort 2 to be classified with poor QOL. Age- and gender-adjusted 3-year all-cause death and death or myocardial infarction (MI) was significantly higher for patients undergoing PCI with frailty; [hazard ratio (95% confidence interval) death, 4.20 (2.63–6.68, P &lt; 0.001) and death or MI hazard ratio (HR) 2.72 (1.91–3.87, P &lt; 0.001)] and with poor QOL [HR death 2.47 (1.59–3.84, P &lt; 0.001)] and death or MI 1.61 (1.16–2.24, P &lt; 0.001). There was no significant interaction between frailty and QOL (P = 0.64) and only modest attenuation was observed when considered together indicating their independent prognostic influence.

Conclusion
In elderly patients undergoing cardiac catheterization or PCI, poor QOL is seen more frequently in frail patients. Both frailty and poor QOL had significant and independent association with long-term survival.
Anomalous left coronary artery from the pulmonary artery: modified extra-anatomic reimplantation
Authors: Albadi Waleed , Kreitmann Bernard , Roubertie François 
Published: August 2020

Abstract
The anomalous origin of the left coronary artery from the pulmonary artery in the position of a non-facing coronary sinus is extremely rare. The anatomical position of the ectopic ostia will determine which is the appropriate operative approach to create a dual-coronary supply. This report describes a technique of modified extra-anatomical rerouting using autologous pericardium patch and pulmonary artery flap to create a neo-composite coronary trunk passing anterior to the right ventricular outflow tract.
Immigrants’ First Names and Perceived Discrimination: A Contribution to Understanding the Integration Paradox
Authors: Tuppat Julia , Gerhards Jürgen 
Published: August 2020

Abstract
Many studies have shown that better-educated immigrants more frequently report perceived discrimination in the host country than less-educated immigrants. Two different explanations for this discrimination paradox, which is a subcase of the so-called integration paradox, are discussed in the literature. First, with increasing integration, immigrants’ sensitivity to discrimination processes changes. Second, more integrated immigrants are more exposed to discrimination as they have more frequent contact with the majority society, and thus, more actual opportunities for perceived discrimination. We argue that exposure is only effective if immigrants are recognizable as such. Besides other characteristics, first names serve as an indicator of immigrant background. We use respondents’ first name as an exogenous variation in exposure. By analyzing data from the German Socio-Economic Panel (N = 32,043), we show that (i) immigrants with first names considered uncommon in the host country report discrimination disproportionately frequently, (ii) the discrimination paradox is only evident if a name as a marker indicating ethnicity exists, and (iii) there is no such interaction between first name and education, if immigrants are recognizable by phenotypical markers.
Length of Hospital Stay for Hip Fracture and 30-Day Mortality in People With Alzheimer’s Disease: A Cohort Study in Finland
Authors: Lavikainen Piia , Koponen Marjaana , Taipale Heidi , Tanskanen Antti , Tiihonen Jari , Hartikainen Sirpa , Tolppanen Anna-Maija 
Published: August 2020

AbstractBackgroundPersons with Alzheimer’s disease (AD) are at higher risk of hip fractures (HFs) than general older population and have worse prognosis after HF. Hospital stays after HF have shortened along time. We investigated the association between length of hospital stay after HF and mortality after discharge among persons with AD.MethodThe MEDALZ cohort includes all Finnish community dwellers who received clinically verified AD diagnosis in 2005–2011 (N = 70 718). Patients who experienced first HF after AD diagnosis in 2005‒2015 (n = 6999) were selected. Length of hospital stay for HF was measured as a sum of the consecutive days spent in hospital after HF until discharge. Outcome was defined as death within 30 days after hospital discharge.ResultsMean of overall length of hospital stay after a HF decreased from 52.6 (SD 62.9) days in 2005 to 19.6 (SD 23.1) days in 2015. Shortest treatment decile (1‒4 days) had the highest risk of death within 30 days after discharge (adjusted hazard ratio [aHR] 2.76; 95% confidence interval [CI] 1.66–4.60) in addition to second (5‒6 days; aHR 2.52; 95% CI 1.50–4.23) and third (7‒10 days; aHR 2.22; 95% CI 1.34–3.69) deciles when compared to the sixth decile of length of stays (21‒26 days).ConclusionsAmong persons with AD, shorter length of hospital stay after HF was associated with an increased risk of death after discharge. After acute HF treatment, inpatient rehabilitation or proper care and services in home need to be organized to older persons with AD.
Optimal processing for seismic noise correlations
Authors: Fichtner Andreas , Bowden Daniel , Ermert Laura 
Published: August 2020

SUMMARYA wide spectrum of processing schemes is commonly applied during the calculation of seismic noise correlations. This is intended to suppress large-amplitude transient and monochromatic signals, to accelerate convergence of the correlation process or to modify raw correlations into more plausible approximations of interstation Green’s functions. Many processing schemes, such as one-bit normalization or various other nonlinear normalizations, clearly break the linear physics of seismic wave propagation. This naturally raises the question: To what extent are the resulting noise correlations physically meaningful quantities? In this contribution, we demonstrate that commonly applied processing methods may indeed introduce an unphysical component into noise correlations. This affects not only noise correlation amplitudes but also, to a lesser extent, time-dependent phase information. The profound consequences are that most processed correlations cannot be entirely explained by any combination of Earth structure and noise sources, and that inversion results may thus be polluted. The positive component of our analysis is a new and easily applicable method that allows us to modify any existing processing such that it becomes optimal in the sense of (1) completely avoiding the unphysical component while (2) approximating the result of the original processing as closely as possible. The resulting optimal schemes can be derived purely on the basis of observed noise, without any knowledge of or assumptions on the nature of noise sources. In addition to the theoretical analysis, we present illustrative real-data examples from the Irish National Seismic Network and the Lost Hills array in Central California. We anticipate that optimal processing schemes may be most useful in applications that exploit complete correlation waveforms, amplitudes and weak arrivals, or small (time-dependent) phase shifts.
Tofacitinib in Patients with Ulcerative Colitis: Inflammatory Bowel Disease Questionnaire Items in Phase 3 Randomized Controlled Induction Studies
Authors: Dubinsky Marla C , DiBonaventura Marco , Fan Haiyun , Bushmakin Andrew G , Cappelleri Joseph C , Maller Eric , Thorpe Andrew J , Salese Leonardo , Panés Julian 
Published: August 2020

Abstract

Background
Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We examined the effect of tofacitinib induction treatment on Inflammatory Bowel Disease Questionnaire (IBDQ) items in adults with moderate to severe UC.

Methods
Data were pooled from the randomized, 8‑week, double-blind, phase 3 OCTAVE Induction 1 and 2 studies. The IBDQ was self-administered by patients at baseline, week 4, and week 8, with higher scores indicating better health-related quality of life (HRQoL). Change from baseline in IBDQ items was analyzed for 10 mg of tofacitinib twice daily (BID) vs placebo using a linear mixed-effects model, with no multiplicity adjustment performed. Effect sizes were calculated. Subgroup analyses by tumor necrosis factor inhibitor (TNFi) experience were performed.

Results
Significant improvements (nominal P &lt; 0.05) were observed in all IBDQ items with 10 mg of tofacitinib BID vs placebo at weeks 4 and 8. For the overall population, the largest treatment differences across all items were reported for “bowel movements been loose” at weeks 4 and 8, and “problem with rectal bleeding” at week 8 (mean treatment differences all 1.1; both in bowel symptoms domain). These items also showed the largest effect sizes. Treatment benefits were generally slightly numerically higher in TNFi-experienced vs TNFi-naïve patients.

Conclusions
Tofacitinib induction therapy improved all IBDQ items vs placebo in patients with UC, reflecting improvements in HRQoL, with greatest benefits reported in bowel symptoms domain items (Funded by Pfizer Inc; OCTAVE Induction 1 and OCTAVE Induction 2; ClinicalTrials.gov, NCT01465763 and NCT01458951, respectively).
Status of Gene Methylation and Polymorphism in Different Courses of Ulcerative Colitis and Their Comparison with Sporadic Colorectal Cancer
Authors: Liu Chen , Yuan Zi-Ying , Yuan Hao , Wu Ke-Xiang , Cao Bin , Ren Ke-Yu , Cui Ming-Juan , Liu Jun-Heng , Chen Hai-Xing , Pang Yao-Wei 
Published: August 2020

Abstract

Background
The objective of this study is to explore the common genetic and epigenetic mechanism of ulcerative colitis (UC) and sporadic colorectal cancer (SCRC) by observing genes methylation level and single nucleotide polymorphisms (SNPs) of different disease courses in UC and SCRC.

Methods
Two hundred subjects were enrolled, including 40 in the healthy control (HC) group, 50 in the short disease course UC group (SUC), 52 in the long disease course UC group (LUC), and 58 in the SCRC group. Methylation-specific polymerase chain reaction was used to detect the methylation of MINT1 and cyclooxygenase 2 (COX-2) gene. Single nucleotide polymorphisms of interleukin (IL)-23R rs10889677 and IL-1β rs1143627 were detected by Sanger sequencing.

Results
Compared with HCs (32.5%), methylation level of MINT1 was significantly increased in SCRC (67.2%; P = 0.001) and was a risk factor for CRC (odds ratio, [OR] 4.26). The methylation ratios of COX-2 were 95.0%, 58.0%, 23.1%, and 24.1% in HC, SUC, LUC, and SCRC, respectively, which were negatively correlated with the disease course of UC (r = −0.290). Hypermethylation of COX-2 was a protective factor for SUC (OR, 0.11), LUC (OR, 0.02), and SCRC (OR, 0.03; P &lt; 0.05). Compared with HCs, rs10889677 allele A was a risk factor for SUC and LUC, and rs1143627 allele T was a protective factor for SUC and LUC. Genotype TT was a protective factor for SUC.

Conclusion
The hypomethylation of COX-2 gene was a common risk factor and epigenetic modification for UC and SCRC, which might be one of the mechanisms through which UC patients were susceptible to CRC. The hypermethylation of MINT1 was a risk factor for SCRC but not for UC; alleles of IL-23Rrs10889677 and IL-1βrs1143627 were related to UC but not to SCRC.
Serum miRNAs Are Pharmacodynamic Biomarkers Associated With Therapeutic Response in Pediatric Inflammatory Bowel Disease
Authors: Batra Suruchi K , Heier Christopher R , Diaz-Calderon Lina , Tully Christopher B , Fiorillo Alyson A , van den Anker John , Conklin Laurie S 
Published: August 2020

Abstract

Background
We sought to identify microRNAs (miRNAs) associated with response to anti-TNF-α or glucocorticoids in children with inflammatory bowel disease (IBD) to generate candidate pharmacodynamic and monitoring biomarkers.

Methods
Clinical response was assessed by Pediatric Crohn’s Disease Activity Index and Pediatric Ulcerative Colitis Activity Index. Quantitative real-time polymerase chain reaction via Taqman Low-Density Array cards were used to identify miRNAs in a discovery cohort of responders (n = 11) and nonresponders (n = 8). Seven serum miRNAs associated with clinical response to treatment, along with 4 previously identified (miR-146a, miR-146b, miR-320a, miR-486), were selected for further study. Candidates were assessed in a validation cohort of serum samples from IBD patients pre- and post-treatment and from healthy controls. Expression of miRNA was also analyzed in inflamed mucosal biopsies from IBD patients and non-IBD controls.

Results
Discovery cohort analysis identified 7 miRNAs associated with therapeutic response: 5 that decreased (miR-126, miR-454, miR-26b, miR-26a, let-7c) and 2 that increased (miR-636, miR-193b). In the validation cohort, 7 of 11 candidate miRNAs changed in the same direction with response to anti-TNF-α therapies, glucocorticoids, or both. In mucosal biopsies, 7 out of 11 miRNAs were significantly increased in IBD vs healthy controls.

Conclusions
Five candidate miRNAs associated with clinical response and mucosal inflammation in pediatric IBD patients were identified (miR-126, let-7c, miR-146a, miR-146b, and miR-320a). These miRNAs may be further developed as pharmacodynamic and response monitoring biomarkers for use in clinical care and trials.
Experience using intravenous posaconazole in paediatric and young adult oncology patients
Authors: Lambrix Arathi A , Swanson Hope D , Pauley Jennifer L , Bragg Allison W , Carias Delia C , Bourque Melissa S , Zhou Yinmei , Cheng Cheng , Greene William L , Maron Gabriela 
Published: August 2020

AbstractBackgroundPosaconazole exhibits broad-spectrum antifungal activity. An IV formulation became available in 2014. Few studies describing the use of this formulation exist in patients under the age of 18 years. This study describes our experience using IV posaconazole in paediatric and young adult cancer patients.MethodsThis single-centre retrospective chart review evaluated patients who received IV posaconazole and had at least one posaconazole plasma concentration obtained after five or more days with a consistent dosage. Relationships between doses required to achieve a plasma concentration of ≥1 µg/mL and patient age, weight and body surface area (BSA) were evaluated. The clinical record was reviewed to identify descriptions of any adverse events.ResultsTwenty-five patients were analysed, with a median age of 10.5 years (range 1.9–22.9 years; 92% were &lt;18 years). All patients were able to achieve a posaconazole plasma concentration ≥1 µg/mL during their treatment course. The daily mg/kg/day dose required to achieve the target concentration decreased significantly with increasing age of the patient (P = 0.018). Assessment of dosage based on BSA suggested a requirement of 225 mg/m2/day across all age groups &lt;18 years. Adverse events documented in the clinical record were consistent with those described with the oral formulations. No CNS toxicities were observed with use of IV posaconazole.ConclusionsConcentrations ≥1 µg/mL are achievable and a BSA-based dosing approach may allow a consistent empirical dose for patients &lt;18 years of age. Therapeutic drug monitoring is recommended to ensure patients achieve therapeutic concentrations.