bluuebunny/crossref_metadata_2025_split huggingface dataset:
BCOR Binding to MLL-AF9 Is Essential for Leukemia via Altered EYA1, SIX, and MYC Activity
Authors: Schmidt Charles R. , Achille Nicholas J. , Kuntimaddi Aravinda , Boulton Adam M. , Leach Benjamin I. , Zhang Shubin , Zeleznik-Le Nancy J. , Bushweller John H. 
Published: July 2020

Abstract

MLL is a target of chromosomal translocations in acute leukemias with poor prognosis. The common MLL fusion partner AF9 (MLLT3) can directly bind to AF4, DOT1L, BCOR, and CBX8. To delineate the relevance of BCOR and CBX8 binding to MLL-AF9 for leukemogenesis, here we determine protein structures of AF9 complexes with CBX8 and BCOR, and show that binding of all four partners to AF9 is mutually exclusive. Using the structural analyses, we identify point mutations that selectively disrupt AF9 interactions with BCOR and CBX8. In bone marrow stem/progenitor cells expressing point mutant CBX8 or point mutant MLL-AF9, we show that disruption of direct CBX8/MLL-AF9 binding does not impact in vitro cell proliferation, whereas loss of direct BCOR/MLL-AF9 binding causes partial differentiation and increased proliferation. Strikingly, loss of MLL-AF9/BCOR binding abrogated its leukemogenic potential in a mouse model. The MLL-AF9 mutant deficient for BCOR binding reduces the expression of the EYA1 phosphatase and the protein level of c-Myc. Reduction in BCOR binding to MLL-AF9 alters a MYC-driven gene expression program, as well as altering expression of SIX-regulated genes, likely contributing to the observed reduction in the leukemia-initiating cell population.

Significance:
Direct recruitment of BCOR to MLL-AF9 is essential for leukemia via EYA1 phosphatase regulation, altering MYC and SIX gene expression programs. Specific partner binding (AF4, DOT1L, and BCOR) contributes in distinct ways to MLL leukemia. This may provide a rationale for combination DOT1L and EYA1 inhibition for MLL fusion leukemia treatment.
This article is highlighted in the In This Issue feature, p. 127
Electrocardiogram Standards for Children and Young Adults Using
Z
-Scores
Authors: Bratincsák András , Kimata Chieko , Limm-Chan Blair N. , Vincent Kevin P. , Williams Matthew R. , Perry James C. 
Published: July 2020

Background:

Normative ECG values for children are based on relatively few subjects and are not standardized, resulting in interpersonal variability of interpretation. Recent advances in digital technology allow a more quantitative, reproducible assessment of ECG variables. Our objective was to create the foundation of normative ECG standards in the young utilizing
Z
-scores.

Methods:
One hundred two ECG variables were collected from a retrospective cohort of 27 085 study subjects with no known heart condition, ages 0 to 39 years. The cohort was divided into 16 age groups by sex. Median, interquartile range, and range were calculated for each variable adjusted to body surface area.

Results:

Normative standards were developed for all 102 ECG variables including heart rate; P, R, and T axis; R-T axis deviation; PR interval, QRS duration, QT, and QTc interval; P, Q, R, S, and T amplitudes in 12 leads; as well as QRS and T wave integrals. Incremental
Z
-score values between –2.5 and 2.5 were calculated to establish upper and lower limits of normal. Historical ECG interpretative concepts were reassessed and new concepts observed.

Conclusions:

Electronically acquired ECG values based on the largest pediatric and young adult cohort ever compiled provide the first detailed, standardized, quantitative foundation of traditional and novel ECG variables. Expression of ECG variables by
Z
-scores lends an objective and reproducible evaluation without interpreter bias that can lead to more confident establishment of ECG-disease correlations and improved automated ECG readings in high-volume cardiac screening efforts in the young.

Graphic Abstract:

A
graphic abstract
is available for this article.
Could Anti‐Hypertensive Drug Therapy Affect the Clinical Prognosis of Hypertensive Patients With COVID‐19 Infection? Data From Centers of Southern Italy
Authors: Sardu Celestino , Maggi Paolo , Messina Vincenzo , Iuliano Pasquale , Sardu Antonio , Iovinella Vincenzo , Paolisso Giuseppe , Marfella Raffaele 
Published: July 2020

BACKGROUND
Coronavirus disease 2019 (COVID‐19) is the cause of a pandemic disease, with severe acute respiratory syndrome by binding target epithelial lung cells through angiotensin‐converting enzyme 2 in humans. Thus, patients with hypertension with COVID‐19 could have worse prognosis. Indeed, angiotensin‐converting enzyme inhibitors and/or angiotensin receptor blockers may interfere with angiotensin‐converting enzyme 2 expression/activity. Thus, patients with hypertension undergoing angiotensin‐converting enzyme inhibitor and/or angiotensin receptor blockers drug therapy may be at a higher risk of contracting a serious COVID‐19 infection and should be monitored. Moreover, in the present study we investigated the effects of angiotensin‐converting enzyme inhibitor versus angiotensin receptor blockers versus calcium channel blockers on clinical outcomes as mechanical ventilation, intensive care unit admissions, heart injury, and death in 62 patients with hypertension hospitalized for COVID‐19 infection.

METHODS AND RESULTS

The multicenter study was prospectively conducted at Department of Infectious Diseases of Sant'Anna Hospital of Caserta, and of University of Campania "Luigi Vanvitelli" of Naples, at Department of Advanced Surgical and Medical Sciences of University of Campania "Luigi Vanvitelli," Naples, and at General Medical Assistance Unit "FIMG," Naples, Italy. Lowest values of left ventricle ejection fraction predicted deaths (1.142, 1.008–1.294,
P
<0.05), while highest values of interleukin‐6 predicted the admission to intensive care unit (1.617, 1.094–2.389), mechanical ventilation (1.149, 1.082–1.219), heart injuries (1.367, 1.054–1.772), and deaths (4.742, 1.788–8.524).

CONCLUSIONS
Anti‐hypertensive drugs didn't affect the prognosis in patients with COVID‐19. Consequently, tailored anti‐inflammatory and immune therapies in addition to chronic antihypertensive therapy, could prevent a worse prognosis, as well as improve the clinical outcomes in patients with hypertension with COVID‐19 infection.
A Review on Treatment-Related Brain Changes in Aphasia
Authors: Schevenels Klara , Price Cathy J. , Zink Inge , De Smedt Bert , Vandermosten Maaike 
Published: July 2020

Abstract
Numerous studies have investigated brain changes associated with interventions targeting a range of language problems in patients with aphasia. We strive to integrate the results of these studies to examine (1) whether the focus of the intervention (i.e., phonology, semantics, orthography, syntax, or rhythmic-melodic) determines in which brain regions changes occur; and (2a) whether the most consistent changes occur within the language network or outside, and (2b) whether these are related to individual differences in language outcomes. The results of 32 studies with 204 unique patients were considered. Concerning (1), the location of treatment-related changes does not clearly depend on the type of language processing targeted. However, there is some support that rhythmic-melodic training has more impact on the right hemisphere than linguistic training. Concerning (2), we observed that language recovery is not only associated with changes in traditional language-related structures in the left hemisphere and homolog regions in the right hemisphere, but also with more medial and subcortical changes (e.g., precuneus and basal ganglia). Although it is difficult to draw strong conclusions, because there is a lack of systematic large-scale studies on this topic, this review highlights the need for an integrated approach to investigate how language interventions impact on the brain. Future studies need to focus on larger samples preserving subject-specific information (e.g., lesion effects) to cope with the inherent heterogeneity of stroke-induced aphasia. In addition, recovery-related changes in whole-brain connectivity patterns need more investigation to provide a comprehensive neural account of treatment-related brain plasticity and language recovery.
Barriers to Impact Factor Growth in Two Major Psychiatry Journals in India
Authors: D’cruz Migita , Andrade Chittaranjan 
Published: July 2020

Background: Despite exponential growth in Indian research, Indian journals have low impact factors. A previous study by one of the authors (CA) of this paper showed that articles published in the Indian Journal of Psychiatry (IJP) under-referenced previously published relevant papers in the same journal. Based on this, we decided to investigate the citation characteristics of contemporary scientific articles published in the Indian Journal of Psychological Medicine (IJPM). Methods: The citation characteristics of scientific articles published in 2018 (Vol 40, issues 1–6) in the IJPM were examined to determine how well the authors cited relevant articles published during the past ten years in the IJPM and the IJP. Results: There were 145 and 142 citation-worthy articles in the IJPM and the IJP, respectively; of these, 85.5% and 65.5%, respectively, had not been cited. Conclusions: Authors publishing in the IJPM under-reference previous relevant research published in the IJPM and IJP. This suggests unawareness of, deliberate disregard of, or even disdain for prior Indian research in the field. Additionally, if Indian researchers do not cite previous Indian research in the field published in Indian journals, the citation metrics of Indian journals will not grow.
Tenecteplase versus alteplase after acute ischemic stroke at high age
Authors: Thommessen Bente , Næss Halvor , Logallo Nicola , Kvistad Christopher E , Waje-Andreassen Ulrike , Ihle-Hansen Hege , Ihle-Hansen Håkon , Thomassen Lars , Morten Rønning Ole 
Published: July 2020

Background Stroke prevalence is increasing with age. Alteplase is the only agent approved for thrombolytic treatment for patients with ischemic stroke, including patients ≥80 years. In the present study, the aim was to compare efficacy and safety of tenecteplase and alteplase in patients ≥80 years. Methods Data from the Norwegian Tenecteplase Stroke Trial, a randomized controlled trial comparing alteplase and tenecteplase, were assessed. Results Of the 273 patients ≥80 years included, mean age was 85.5 years. In the intention-to-treat analyses, 43.1% receiving tenecteplase and 39.9% receiving alteplase reached excellent functional outcome (modified Rankin Scale score 0–1) after 3 months (odds ratio (OR) 1.14, 95% confidence interval (CI) 0.70–1.85, p=0.59). No significant differences among patients in the two treatment groups regarding frequency of symptomatic intracranial hemorrhage during the first 48 h were identified (11 (8.5%) in the tenecteplase group, 10 (7.0%) in the alteplase group, OR 1.23, 95% CI 0.50–3.00, p 0.65). Death within 3 months occurred in 18 patients (14.3%) in the tenecteplase group and in 21 (15.3%) in the alteplase group (p 0.84). After excluding stroke mimics, the proportion of patients with excellent functional outcome was 44.1% in the tenecteplase group and 34.4% in the alteplase group (OR 1.50 CI 0.90–2.52, p 0.12). Conclusion No differences in the efficacy and safety of tenecteplase versus alteplase in patients ≥80 years were identified. Trial registration Clinicaltrials.gov (NCT01949948)
Pediatric Palate Fractures: An Assessment of Patterns and Management at a Level 1 Trauma Center
Authors: Gala Zachary , Halsey Jordan N. , Kapadia Kavita , Otaguro Lauren , Hoppe Ian C. , Lee Edward S. , Granick Mark S. 
Published: July 2020

Study Design: Literature discussing palate fractures in the pediatric population is limited. We performed a retrospective review of pediatric palatal fractures at our institution to better understand the impact of this fracture pattern in the pediatric patient. Objectives: The goal of our study is to analyze our institutional experience with pediatric palate fractures, focusing on epidemiology, concomitant injuries, and fracture management. Methods: Records were collected for all palatal fractures in pediatric patients diagnosed between 2000 and 2016 at an urban Level I trauma center. Patient imaging was reviewed. Demographic characteristics and inpatient clinical data were recorded. Results: Nine pediatric patients were diagnosed with fracture of the bony palate. Average age was twelve with male predominance (66%). Pedestrian struck injuries (33%) and motor vehicle accidents (33%) were the most common etiologies. Five patients sustained skull fractures. Three patients were found to have intracranial hemorrhage, two required emergent bolt placement. Two patients sustained cervical spine injury. One patient had severe facial hemorrhage requiring embolization. According to the Hendrickson classification, there were three type I fractures, two type II fractures, one type III fracture, one type IV fracture, and one type V fracture. Lefort I and/or alveolar fracture was present in every patient. Four patients underwent surgical treatment with open reduction and restoration of facial height with maxillomandibular fixation. Three patients underwent concomitant mandible fracture repair. Conclusions: Pediatric palatal fractures are rare and are usually accompanied by devastating concomitant injuries. Surgical repair of the palate in the pediatric patient is often necessary to restore facial height.
Invasive Hemodynamic Characteristics in Patients Undergoing Transcatheter Tricuspid Valve-In-Valve Implantation for Treatment of Tricuspid Stenosis
Authors: Patel Krishan , Sadeghi Soraya , Aboulhosn Jamil 
Published: July 2020

Background: We sought to describe invasive hemodynamic measurements in patients with tricuspid stenosis (TS) undergoing transcatheter tricuspid valve-in-valve (TVIV) implantation immediately pre- and postimplantation. Development of TS in patients who have undergone surgical tricuspid valve replacement with a bioprosthetic valve is a serious complication that leads to elevated right atrial (RA) pressures and decreased cardiac output. Transcatheter TVIV implantation is a viable alternative to surgical tricuspid valve replacement, but data on the hemodynamic consequences of TVIV for the treatment of severe TS are currently limited to echocardiographic assessment of Doppler-derived gradients. Methods: Eleven patients undergoing transcatheter TVIV implantation with moderate to severe bioprosthetic valve stenosis were selected for retrospective review. Right atrial mean pressure, right ventricular (RV) systolic and end-diastolic pressure, mean diastolic RA-RV pressure gradient, pulmonary artery capillary wedge pressure, pulmonary artery systolic, end-diastolic and mean pressures, and pulmonary artery pulsatility index (PAPi) both before and after transcatheter valve placement were collected from catheterization reports. Results: After transcatheter TVIV implantation, the mean TS gradient decreased significantly ( P < .01), while the mean RV end-diastolic pressure increased ( P = .046). Pulmonary artery pulsatility index also increased as the TS was relieved ( P = .039). Conclusions: Tricuspid valve-in-valve implantation results in immediate relief of TS, leading to increased RV preload with resultant augmentation of RV and pulmonary pressures. Increased PAPi following the procedure demonstrates acute improvement in RV output but remains low due to the failure of the RA pressure to decline significantly immediately following intervention.
Efficacy of Nitric Oxide Administration in Attenuating Ischemia/Reperfusion Injury During Neonatal Cardiopulmonary Bypass
Authors: Elzein Chawki , Urbas Cynthia , Hughes Bonnie , Li Yi , Lefaiver Cheryl , Ilbawi Michel , Vricella Luca 
Published: July 2020

Objective: Nitric oxide (NO) plays several protective roles in ischemia/reperfusion (I/R) injury. Neonates undergoing the Norwood procedure are subject to develop I/R injury due to the immaturity of their organs and the potential need to interrupt or decrease systemic flow during surgery. We hypothesized that NO administration during cardiopulmonary bypass (CPB) ameliorates the I/R and could help the postoperative recovery after the Norwood procedure. Methods: Twenty-four neonates who underwent a Norwood procedure were enrolled in a prospective randomized blinded controlled trial to receive NO (12 patients) or placebo (12 patients) into the oxygenator of the CPB circuit during the Norwood procedure. Markers of I/R injury were collected at baseline (T0), after weaning from CPB before modified ultrafiltration (T1), after modified ultrafiltration (T2), and at 12 hours (T3) and 24 hours (T4) after surgery, and they were compared between both groups, as well as other postoperative clinical variables. Results: There was no difference in age, weight, anatomical diagnosis, CPB, and aortic cross-clamp time between both groups. Troponin levels were lower in the study group at T1 (0.62 ± 58 ng/mL vs 0.87 ± 0.58 ng/mL, P = .31) and became significantly lower at T2 (0.36 ± 0.32 ng/mL vs 0.97 ± 0.48 ng/mL, P = .009).There were no significant differences between both groups for all other markers. Despite a lower troponin level, there was no difference in inotropic scores or ventricular function between both groups. Time to start diuresis, time to sternal closure and extubation, and intensive care unit and hospital stay were not different between both groups. Conclusion: Systemic administration of NO during the Norwood procedure has myocardial protective effects (lower Troponin levels) but we observed no effect on postoperative recovery. Larger sample size may be needed to show clinical differences.
Attitudes to Cardiac Xenotransplantation by Pediatric Heart Surgeons and Physicians
Authors: Padilla Luz A. , Sorabella Robert A. , Carlo Waldemar F. , Dabal Robert J. , Rhodes Leslie , Cleveland David C. , Cooper David K. , Paris Wayne 
Published: July 2020

Background: Cardiac transplantation in early childhood is limited by scarcity of organ donors. Advances in cardiac xenotransplantation (XTx) research suggest that xenografts may one day represent an alternative to allografts. We sought to determine the attitudes among surgeons and cardiologists in the field of pediatric cardiac transplantation toward the potential use of XTx if this clinical option were to become a reality. Methods: A Likert-scale anonymous survey addressing the use of XTx in pediatric patients was sent to members of the Congenital Heart Surgeons (CHS) Society and the Pediatric Heart Transplant Society. Results were described and compared between the two surgeon/physician groups. Results: Ninety-two CHS and 42 pediatric transplant cardiologists (PTC) responded (N = 134). The potential acceptance of XTx was high in both groups, assuming risks and results were similar to those of cardiac allotransplantation (88% CHS vs 81% PTC; P = .07). When asked if they would recommend a xenograft, if the results were anticipated to be inferior to those of cardiac allotransplantation, as a bridge to a human heart, potential acceptance fell dramatically but remained higher among CHS than PTC (41% vs 17%, p 0.02). Approximately only one-third of CHS and half of PTC preferred primary cardiac XTx for hypoplastic left heart syndrome if there was no waitlist time and had similar outcomes to allotransplantation. Conclusions: Our findings suggest that potential acceptance of XTx by CHS and PTC would not be a major barrier if XTx demonstrated similar outcomes to allotransplantation. Acceptance by other congenital heart stakeholders remains to be investigated.
Multiple performance pressure inconsistency, resource slack, and the firm’s R&D investment: A behavioral agency theory perspective
Authors: Diwei Lv David , Chen Weihong , Lan Hailin 
Published: July 2020

In the process of operation, firms will face different types of performance pressure. The inconsistency among multiple performance pressure signals has an important impact on resource allocation and R&D investment. However, at present, studies on the impact of multiple performance pressures on the firm’s resource allocation and R&D investment are very limited, and few studies have analyzed the impact of inconsistencies among multiple performance pressure signals on the firm’s R&D investment. Given this research gap, this article empirically tested a model from the perspective of behavioral agency theory, in which inconsistency in long- and short-term performance pressure facilitates the accumulation of organizational slack. We further test the impact of an increase in organizational slack on the firms’ R&D investment intensity and find that this effect is stronger when the level of managerial ownership is comparatively low. These results together indicate that high inconsistency in performance pressure and low managerial ownership jointly facilitate the accumulation of organizational slack, enabling firms to go beyond local search and have more slack searches in the face of multiple performance pressure, which is conducive to an increase in R&D investment. JEL CLASSIFICATION: M10.
Parent Experiences Caring for a Child With Bronchiolitis: A Qualitative Study
Authors: Campbell Alyson , Hartling Lisa , Louie-Poon Samantha , Scott Shannon D 
Published: July 2020

Background: Bronchiolitis is an acute lower respiratory infection, with significant impacts on children and families and strains on the health care system. Understanding parents’ experiences and information needs caring for a child with bronchiolitis is crucial to highlight misconceptions or issues contributing to the high burden. The objective of this qualitative study was to describe parents’ experiences caring for a child with bronchiolitis. Methods: Qualitative description guided this study. Participants were recruited from the Stollery Children’s Hospital emergency department (ED), a specialized pediatric ED in a major Canadian urban center. Semi-structured interviews were conducted with 15 parents. Results: Five major themes were identified: (a) their children’s symptoms and behaviors, (b) bronchiolitis affects the entire family, (c) factors influencing parent’s decision to go to ED, (d) ED experience for parents and their children, and (e) bronchiolitis treatment and management. Interviews revealed bronchiolitis has significant effects on both children and families and parents are generally unaware of bronchiolitis symptoms, treatment, and management. Conclusions: Our study highlights that parents have knowledge deficits when it comes to recognizing the presence and severity of bronchiolitis symptoms. Parents would benefit from having more evidence-based resources to enhance their knowledge about the nature of bronchiolitis.