bluuebunny/crossref_metadata_2025_split huggingface dataset:
How I treat dysfibrinogenemia
Authors: Casini Alessandro , de Moerloose Philippe 
Published: April 2021

AbstractCongenital dysfibrinogenemia (CD) is caused by structural changes in fibrinogen that modify its function. Diagnosis is based on discrepancy between decreased fibrinogen activity and normal fibrinogen antigen levels and is confirmed by genetic testing. CD is caused by monoallelic mutations in fibrinogen genes that lead to clinically heterogenous disorders. Most patients with CD are asymptomatic at the time of diagnosis, but the clinical course may be complicated by a tendency toward bleeding and/or thrombosis. Patients with a thrombosis-related fibrinogen variant are particularly at risk, and, in such patients, long-term anticoagulation should be considered. Management of surgery and pregnancy raise important and difficult issues. The mainstay of CD treatment remains fibrinogen supplementation. Antifibrinolytic agents are part of the treatment in some specific clinical settings. In this article, we discuss 5 clinical scenarios to highlight common clinical challenges. We detail our approach to establishing a diagnosis of CD and discuss strategies for the management of bleeding, thrombosis, surgery, and pregnancy.
Molecular classification improves risk assessment in adult BCR-ABL1–negative B-ALL
Authors: Paietta Elisabeth , Roberts Kathryn G. , Wang Victoria , Gu Zhaohui , Buck Georgina A. N. , Pei Deqing , Cheng Cheng , Levine Ross L. , Abdel-Wahab Omar , Cheng Zhongshan , Wu Gang , Qu Chunxu , Shi Lei , Pounds Stanley , Willman Cheryl L. , Harvey Richard , Racevskis Janis , Barinka Jan , Zhang Yanming , Dewald Gordon W. , Ketterling Rhett P. , Alejos David , Lazarus Hillard M. , Luger Selina M. , Foroni Letizia , Patel Bela , Fielding Adele K. , Melnick Ari , Marks David I. , Moorman Anthony V. , Wiernik Peter H. , Rowe Jacob M. , Tallman Martin S. , Goldstone Anthony H. , Mullighan Charles G. , Litzow Mark R. 
Published: April 2021

Abstract
Genomic classification has improved risk assignment of pediatric, but not adult B-lineage acute lymphoblastic leukemia (B-ALL). The international UKALLXII/ECOG-ACRIN E2993 (#NCT00002514) trial accrued 1229 adolescent/adult patients with BCR-ABL1− B-ALL (aged 14 to 65 years). Although 93% of patients achieved remission, 41% relapsed at a median of 13 months (range, 28 days to 12 years). Five-year overall survival (OS) was 42% (95% confidence interval, 39, 44). Transcriptome sequencing, gene expression profiling, cytogenetics, and fusion polymerase chain reaction enabled genomic subtyping of 282 patient samples, of which 264 were eligible for trial, accounting for 64.5% of E2993 patients. Among patients with outcome data, 29.5% with favorable outcomes (5-year OS 65% to 80%) were deemed standard risk (DUX4-rearranged [9.2%], ETV6-RUNX1/-like [2.3%], TCF3-PBX1 [6.9%], PAX5 P80R [4.1%], high-hyperdiploid [6.9%]); 50.2% had high-risk genotypes with 5-year OS of 0% to 27% (Ph-like [21.2%], KMT2A-AFF1 [12%], low-hypodiploid/near-haploid [14.3%], BCL2/MYC-rearranged [2.8%]); 20.3% had intermediate-risk genotypes with 5-year OS of 33% to 45% (PAX5alt [12.4%], ZNF384/-like [5.1%], MEF2D-rearranged [2.8%]). IKZF1 alterations occurred in 86% of Ph-like, and TP53 mutations in patients who were low-hypodiploid (54%) and BCL2/MYC-rearranged (33%) but were not independently associated with outcome. Of patients considered high risk based on presenting age and white blood cell count, 40% harbored subtype-defining genetic alterations associated with standard- or intermediate-risk outcomes. We identified distinct immunophenotypic features for DUX4-rearranged, PAX5 P80R, ZNF384-R/-like, and Ph-like genotypes. These data in a large adult B-ALL cohort treated with a non–risk-adapted approach on a single trial show the prognostic importance of genomic analyses, which may translate into future therapeutic benefits.
Rate of thrombosis in children and adolescents hospitalized with COVID-19 or MIS-C
Authors: Whitworth Hilary , Sartain Sarah E. , Kumar Riten , Armstrong Katherine , Ballester Lance , Betensky Marisol , Cohen Clay T. , Diaz Rosa , Diorio Caroline , Goldenberg Neil A. , Jaffray Julie , Keegan Jacquelyn , Malone Kendra , Randolph Adrienne G. , Rifkin-Zenenberg Stacey , Leung Wendy Seto , Sochet Anthony , Srivaths Lakshmi , Zia Ayesha , Raffini Leslie 
Published: April 2021

Abstract
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with thrombotic complications in adults, but the incidence of COVID-19-related thrombosis in children and adolescents is unclear. Most children with acute COVID-19 have mild disease, but coagulopathy has been associated with multisystem inflammatory syndrome in children (MIS-C), a postinfectious complication. We conducted a multicenter retrospective cohort study to determine the incidence of thrombosis in children hospitalized with COVID-19 or MIS-C and evaluate associated risk factors. We classified patients into 1 of 3 groups for analysis: COVID-19, MIS-C, or asymptomatic SARS-CoV-2. Among a total of 853 admissions (COVID-19, n = 426; MIS-C, n = 138; and asymptomatic SARS-CoV-2, n = 289) in 814 patients, there were 20 patients with thrombotic events (TEs; including 1 stroke). Patients with MIS-C had the highest incidence (9 [6.5%] of 138) vs COVID-19 (9 [2.1%] of 426) or asymptomatic SARS-CoV-2 (2 [0.7%] of 289). In patients with COVID-19 or MIS-C, a majority of TEs (89%) occurred in patients age ≥12 years. Patients age ≥12 years with MIS-C had the highest rate of thrombosis at 19% (9 of 48). Notably, 71% of TEs that were not present on admission occurred despite thromboprophylaxis. Multivariable analysis identified the following as significantly associated with thrombosis: age ≥12 years, cancer, presence of a central venous catheter, and MIS-C. In patients with COVID-19 or MIS-C, hospital mortality was 2.3% (13 of 564), but it was 28% (5 of 18) in patients with TEs. Our findings may help inform pediatric thromboprophylaxis strategies.
Impact of dark tetrad personality traits on nascent entrepreneurial behavior: the mediating role of entrepreneurial intention
Authors: Cai Li , Murad Majid , Ashraf Sheikh Farhan , Naz Shumaila 
Published: April 2021

AbstractThe impact of negative personality traits on entrepreneurial intention and entrepreneurial behavior has become a research focus in the field of entrepreneurship. This study aimed to identify the influence of dark tetrad personality traits on the nascent entrepreneurial behavior and the mediating role of entrepreneurial intention. This study used partial least square-structural equation modeling (PLS-SEM) to test the hypotheses on a sample of 347 undergraduate and postgraduate university students from China. The results of this study revealed that narcissism, psychopathy, Machiavellianism, and sadism have a positive and significant influence on nascent entrepreneurial behavior and entrepreneurial intention, which significantly partially mediates the relationship between dark tetrad and nascent entrepreneurial behavior. The finding of the study implies China’s higher education and policymakers to unlock the hidden potential of its youth. This study contributes to the emerging literature on psychology and entrepreneurship and provides evidence that individuals with a high level of dark tetrad are more likely to be involved in entrepreneurial action.
Short‐term outcomes in children following emergency department visits for minor injuries sustained at home
Authors: Molloy Matthew J , Shields Wendy , Stevens Molly W , Gielen Andrea C 
Published: April 2021

AbstractBackgroundMinor injuries are very common in the pediatric population and often occur in the home environment. Despite its prevalence, little is known about outcomes in children following minor injury at home. Understanding the impact of these injuries on children and their families is important for treatment, prevention, and policy. The objectives of our study were (1) To describe the distribution of short-term outcomes following pediatric minor injuries sustained at home and (2) To explore the relationship of injury type and patient and household demographics with these outcomes.MethodsChildren (n = 102) aged 0–7 years with a minor injury sustained at home were recruited in an urban pediatric emergency department as part of the Child Housing Assessment for a Safer Environment (CHASE) observational study. Each patient had a home visit following the emergency department visit, where five parent-reported outcomes were assessed. Relationships were explored with logistic regression.ResultsThe most common type of injury was soft tissue (57.8 %). 13.2 % of children experienced ≥ 7 days of pain, 21.6 % experienced ≥ 7 days of abnormal activity, 8.9 % missed ≥ 5 days of school, 17.8 % of families experienced ≥ 7 days of disruption, and 9.1 % of parents missed ≥ 5 days of work. Families reported a total of 120 missed school days and 120 missed work days. Children who sustained a burn had higher odds of experiencing pain (OR 6.97), abnormal activity (OR 8.01), and missing school (OR 8.71). The parents of children who sustained a burn had higher odds of missing work (OR 14.97).ConclusionsFamilies of children suffering a minor injury at home reported prolonged pain and changes in activity as well as significant school and work loss. In this cohort, burns were more likely than other minor injuries to have these negative short-term outcomes reported and represent an important target for interventions. The impact of these injuries on missed school and disruption of parental work warrants further consideration.
Three thousand year paleo-tsunami history of the southern part of the Japan Trench
Authors: Higaki Hokuto , Goto Kazuhisa , Yanagisawa Hideaki , Sugawara Daisuke , Ishizawa Takashi 
Published: April 2021

AbstractThis study conducted a field survey and multiproxy analyses on sediment cores retrieved from the Kobatake-ike pond in Choshi City, Chiba Prefecture, Japan. Kobatake-ike pond is located at a high elevation (i.e., 11 m above present-day sea level) and faces the southern part of the Japan Trench. Three event sand layers were detected within the continuous mud and peat sequences of 3000 years. Based on the multi-proxy analyses, including mineralogical composition, diatom assemblages, and geochemical markers, these sedimentological events were associated with past tsunamis. The most recent event was a sandy layer and is attributed to the AD 1677 Enpo tsunami, which was reported by an earlier study conducted in the pond. Our results demonstrated that two older sand layers are associated with large tsunamis that struck the Choshi area in AD 896–1445 and in BC 488–AD 215. In addition, the age ranges of these events seem to overlap that of large earthquakes and tsunamis known from the central part of the Japan Trench. This implies a possible spatiotemporal relation of earthquake generations between the central and southern parts of the Japan Trench. However, since the error ranges of the ages of tsunami deposits at the southern and central parts of the Japan Trench are still large, further investigation is required to clarify the relations of large earthquakes in both areas.
Does the macro design of an implant affect the accuracy of template-guided implantation? A prospective clinical study
Authors: Schnutenhaus Sigmar , Edelmann Cornelia , Rudolph Heike 
Published: April 2021

Abstract
Background
An implant prosthesis aims to ensure the best possible rehabilitation of function and esthetics following tooth loss. Template-guided insertion is used to achieve an optimal position of the implant with regard to prosthetic restorability, bone availability, and condition of the surrounding soft tissues. The accuracy of template-guided implant placement is subject to various influencing factors.
The clinically achievable accuracy depending on the macro design of the implant body was investigated in this prospective clinical study.

Material and methods
In this prospective clinical study, 20 implants were placed in 20 patients. The implant had a pronounced conical outer geometry (Conelog ProgressiveLine, Camlog Wimsheim, Germany). Data from a study using an implant with a distinct cylindrical outer geometry were used as a comparison group (Conelog ScrewLine, Camlog, Wimsheim, Germany). The clinically achieved implant position was compared with the planned position.

Results
The evaluation of the two-dimensional deviations in direction resulted in the following mean values (standard deviation) at the shoulder: 0.42 mm (0.33) in the buccolingual direction, 0.27 mm (0.25) in the mesiodistal direction, and 0.68 mm (0.55) in the apicocoronal direction. The mean angular deviation was 4.1° (2.3). The three-dimensional (3D) deviation was 0.94 mm (0.53) at the shoulder and 1.36 mm (0.62) at the apex of the implant.
Significant differences between implants with different macro designs were found in the apicocoronal direction. In connection to this, a significant 3D deviation was found at the implant shoulder.

Conclusions
Significant differences in height were found between the groups. The study had shown that the macro design of an implant has no influence on accuracy in all other directions. Overall, the implants showed a high level of accuracy and a low variation in values. The values were in the range determined by the template-guided insertion system in numerous other investigations. This provides good predictability of prosthetic rehabilitation.

Trial registration
German Register for Clinical Studies (DRKS-ID: DRKS000018939). Date of registration: November 11, 2019.
Nutritional status among orphans and vulnerable children aged 6 to 59 months in Addis Ababa, Ethiopia: a community-based cross-sectional study
Authors: Berr Nina , Nigatu Yemisrach , Dereje Nebiyu 
Published: April 2021

Abstract
Background
Childhood undernutrition is a global problem contributing to more than a third of under-five mortality. Orphans and vulnerable children (OVC) fare worse than children living with their parents. However, the nutritional and healthcare needs of OVC are under-recognized in Ethiopia.

Methods
A community-based cross-sectional study was conducted among OVC aged 6 to 59 months. Multi-stage sampling technique was applied to select the households and eligible children included in the study (n = 584). An interviewer-administered questionnaire and anthropometric measurements were carried out. The proportions of stunting, wasting and underweight were determined based on the WHO Z-score cut-off. Factors associated with stunting were identified by Multivariable binary logistic regression analysis.

Results
The prevalence of stunting, wasting and underweight were 35.1% (95% CI; 31.3–39.1%), 4.7% (95% CI; 3.2–6.7%) and 12.0% (95% CI; 9.6–14.9%), respectively. Stunting was significantly associated with initiation of complementary feeding after 12 months of age (AOR = 3.61; 95% CI 1.16–14.11), household food insecurity (AOR = 1.90; 95% CI 1.10–3.17), unplanned pregnancy (AOR = 1.90; 95% CI 1.03–3.42), age ≥ 2 years (AOR = 1.80; 95% CI 1.25–2.67), caretaker’s age ≤ 25 years (AOR = 1.50; 95% CI 1.03–2.16) and employment of the caretaker (AOR = 1.50; 95% CI 1.03–2.26).

Conclusion
The prevalence of all forms of undernutrition among OVC was significantly higher than the national estimate that has been reported by consecutive Ethiopian Demographic and Health Surveys (EDHS). Policy makers and programmers working on nutritional interventions should give due emphasis to address the unmet need of OVC and focus on interventions which enhance household food security and caretaker’s awareness on child feeding and pregnancy planning.
Genetic polymorphism of HLA-G gene (G*01:03, G*01:04, and G*01:05N) in Iraqi patients with inflammatory bowel disease (ulcerative colitis and Crohn’s disease)
Authors: Abdul-Hussein Sarah S. , Ali Ekhlass N. , Zaki Neihaya H. , Ad’hiah Ali H. 
Published: April 2021

Abstract
Background
Human leukocyte antigen-G (HLA-G) has been proposed to influence susceptibility to inflammatory bowel disease (IBD). Therefore, the genetic association between HLA-G alleles and two clinical phenotypes of IBD (ulcerative colitis [UC] and Crohn’s disease [CD]) was evaluated in Iraqi patients. A case-control study was performed on 50 UC and 50 CD patients and 100 healthy controls (HC). Three HLA-G alleles (G*01:03, G*01:04, and G*01:05N) were determined using sequence-specific polymerase chain reaction assay followed by product digestion with restriction endonucleases (Hinf-I, BseR-I, and PpuM-I, respectively).

Results
The G*01:03 allele was not detected in IBD patients (UC and CD) or HC, while G*01:04 and G*01:05N alleles showed polymorphic frequencies. The allele G*01:04 was significantly associated with susceptibility to UC (odds ratio [OR] = 2.55; 95% confidence interval [CI] = 1.27–5.13; corrected probability [pc] = 0.018) and CD (OR = 4.45; 95% CI = 2.11–9.41; pc < 0.001). The allele G*01:05N was also associated with increased risk of UC (OR = 4.17; 95% CI = 1.32–13.21; pc = 0.032) and CD (OR = 4.75; 95% CI = 1.53–14.78; pc = 0.014). These associations were more pronounced in IBD (UC + CD), and a significantly increased risk for IBD was found with the alleles G*01:04 (OR = 3.32; 95% CI = 1.86–5.95; pc < 0.001) and G*01:05N (OR = 4.46; 95% CI = 1.59–12.47; pc = 0.008). A stratification of IBD patients according to some demographic and clinical characteristics revealed that frequencies of both alleles showed no significant differences between the subgroups of patients in each stratum. Soluble HLA-G was not influenced by HLA-G alleles in patients or HC. UC was an exception, and the presence of G*01:04 allele was associated with a significantly higher mean of soluble HLA-G compared to patients without the allele (189.6 ± 24.0 vs. 168.6 ± 27.2 ng/mL; p = 0.033).

Conclusion
This study indicated that HLA-G*01:04 and HLA-G*01:05N alleles may influence susceptibility to UC and CD in Iraqi patients.
Eyes closed, aDrosophilap47 homolog, is essential for photoreceptor morphogenesis
Authors: Sang Tzu-Kang , Ready Donald F. 
Published: April 2021

Starting with a mutation impacting photoreceptor morphogenesis, we identify here a Drosophila gene, eyes closed (eyc), as a fly homolog of p47, a protein co-factor of the p97 ATPase implicated in membrane fusion. Temporal misexpression of Eyc during rhabdomere extension early in pupal life results in inappropriate retention of normally transient adhesions between developing rhabdomeres. Later Eyc misexpression results in endoplasmic reticulum proliferation and inhibits rhodopsin transport to the developing photosensitive membrane. Loss of Eyc function results in a lethal failure of nuclear envelope assembly in early zygotic divisions. Phenotypes resulting from eyc mutations provide the first in vivo evidence for a role for p47 in membrane biogenesis.Movies available on-line
Theheartstringsmutation in zebrafish causes heart/fin Tbx5 deficiency syndrome
Authors: Garrity Deborah M. , Childs Sarah , Fishman Mark C. 
Published: April 2021

Holt-Oram syndrome is one of the autosomal dominant human ‘heart-hand’ disorders, with a combination of upper limb malformations and cardiac defects. Holt-Oram syndrome is caused by mutations in the TBX5 gene, a member of a large family of T-box transcription factors that play important roles in cell-type specification and morphogenesis. In a screen for mutations affecting zebrafish cardiac function, we isolated the recessive lethal mutant heartstrings, which lacks pectoral fins and exhibits severe cardiac dysfunction, beginning with a slow heart rate and progressing to a stretched, non-functional heart.We mapped and cloned the heartstrings mutation and find it to encode the zebrafish ortholog of the TBX5 gene. The heartstrings mutation causes premature termination at amino acid 316. Homozygous mutant embryos never develop pectoral fin buds and do not express several markers of early fin differentiation. The total absence of any fin bud differentiation distinguishes heartstrings from most other mutations that affect zebrafish fin development, suggesting that Tbx5 functions very early in the pectoral fin induction pathway. Moderate reduction of Tbx5 by morpholino causes fin malformations, revealing an additional early requirement for Tbx5 in coordinating the axes of fin outgrowth. The heart of heartstrings mutant embryos appears to form and function normally through the early heart tube stage, manifesting only a slight bradycardia compared with wild-type siblings. However, the heart fails to loop and then progressively deteriorates, a process affecting the ventricle as well as the atrium.Relative to mammals, fish require lower levels of Tbx5 to produce malformed appendages and display whole-heart rather than atrial-predominant cardiac defects. However, the syndromic deficiencies of tbx5 mutation are remarkably well retained between fish and mammals.
Cues from neuroepithelium and surface ectoderm maintain neural crest-free regions within cranial mesenchyme of the developing chick
Authors: Golding Jon P. , Dixon Monica , Gassmann Martin 
Published: April 2021

Within the developing vertebrate head, neural crest cells (NCCs) migrate from the dorsal surface of the hindbrain into the mesenchyme adjacent to rhombomeres (r)1 plus r2, r4 and r6 in three segregated streams. NCCs do not enter the intervening mesenchyme adjacent to r3 or r5, suggesting that these regions contain a NCC-repulsive activity.We have used surgical manipulations in the chick to demonstrate that r3 neuroepithelium and its overlying surface ectoderm independently help maintain the NCC-free zone within r3 mesenchyme. In the absence of r3, subpopulations of NCCs enter r3 mesenchyme in a dorsolateral stream and an ectopic cranial nerve forms between the trigeminal and facial ganglia. The NCC-repulsive activity dissipates/degrades within 5-10 hours of r3 removal. Initially, r4 NCCs more readily enter the altered mesenchyme than r2 NCCs, irrespective of their maturational stage. Following surface ectoderm removal, mainly r4 NCCs enter r3 mesenchyme within 5 hours, but after 20 hours the proportions of r2 NCCs and r4 NCCs ectopically within r3 mesenchyme appear similar.
Defining epithelial-mesenchymal transitions in animal development
Authors: Sheng Guojun 
Published: April 2021

ABSTRACT
Over 50 years after its discovery in early chick embryos, the concept of epithelial-mesenchymal transition (EMT) is now widely applied to morphogenetic studies in both physiological and pathological contexts. Indeed, the EMT field has witnessed exponential growth in recent years, driven primarily by a rapid expansion of cancer-oriented EMT research. This has led to EMT-based therapeutic interventions that bear the prospect of fighting cancer, and has given developmental biologists new impetus to investigate EMT phenomena more closely and to find suitable models to address emerging EMT-related questions. Here, and in the accompanying poster, I provide a brief summary of the current status of EMT research and give an overview of EMT models that have been used in developmental studies. I also highlight dynamic epithelialization and de-epithelialization events that are involved in many developmental processes and that should be considered to provide a broader perspective of EMT. Finally, I put forward a set of criteria to separate morphogenetic phenomena that are EMT-related from those that are not.