bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Gender Gap in Market Work Hours Among Canadians: Examining Essential(ist) Linkages to Parenting Time and Household Labour Hours
Authors: Buchanan Tom , McFarlane Adian , Das Anupam 
Published: November 2019

Using 2015 Canadian time diary data, we analyse how the gender gap in market work hours is linked to gender inequality in parenting time and household labour hours (N = 2,296). Among Canadians who are 15–34 years of age, we examine three family groupings, single without children, married without children and married with children. For the married with children group, we focus on respondents with at least one child aged 0–4 years. We find that the gender gap in market work is not significant for those single and married without children. For the married without children group, a gender gap exists for household labour. This suggests that a gender gap in household labour exists prior to the onset of children. As expected, a large gender gap in market work presents itself for married/common law respondents with young children. Half of the gender gap in market work is explained by household labour hours and parenting time. Our study demonstrates that time allocations contribute substantively to gender inequality in market work. Yet, the large unexplained part of the gap suggests that this issue is larger and more complex than mere bargaining decisions about domestic and market time. JEL: I24, J13, J16, C10
Noninvasive ventilation failure in patients with hypoxemic respiratory failure: the role of sepsis and septic shock
Authors: Duan Jun , Chen Lijuan , Liang Guopeng , Shu Weiwei , Li Liucun , Wang Ke , Wang Shengyu , Liu Xiaoyi , He Chunfeng , He Dehua , Chen Qimin , Wei Bilin , Chen Baixu , Shu Yuzhen , Tian Yao , Fan Liping , Han Xiaoli , Zhang Rui , Yang Xiangmei , Peng Yan , Wan Dong , Chen Xiaoying , Ye Lin , Tian Shijing , Huang Qiong , Jiang Lei , Bai Linfu , Zhou Lintong 
Published: November 2019

Background: Sepsis and septic shock are common in noninvasive ventilation (NIV) patients. However, studies on the association between sepsis and NIV failure are lacking. Methods: A prospective multi-center observational study was performed in 16 Chinese intensive care units (ICUs). Patients who used NIV due to hypoxemic respiratory failure were enrolled. Sepsis and septic shock were diagnosed according to the guideline of sepsis-3. Results: A total of 519 patients were enrolled. Sepsis developed in 365 patients (70%) and septic shock developed in 79 patients (15%). However, 75 patients (14%) had no sepsis. NIV failure was 23%, 38%, and 61% in patients, with no sepsis, sepsis, and septic shock, respectively. Multivariate analysis found that sepsis [odds ratio (OR) = 1.95, 95% confidence interval (CI): 1.06–3.61] and septic shock (OR = 2.47, 95% CI: 1.12–5.45) were independently associated with NIV failure. In sepsis and septic shock population, the NIV failure was 13%, 31%, 37%, 53%, and 67% in patients with sequential organ failure assessment (SOFA) scores of ⩽2, 3–4, 5–6, 7–8, and ⩾9, respectively. Patients with nonpulmonary induced sepsis had similar NIV failure rate compared with those with pulmonary induced sepsis, but had higher proportion of septic shock (37% versus 10%, p ⩽ 0.01) and lower ICU mortality (10% versus 22%, p ⩽ 0.01). Conclusions: Sepsis was associated with NIV failure in patients with hypoxemic respiratory failure, and the association was stronger in septic shock patients. NIV failure increased with the increase of organ dysfunction caused by sepsis. The reviews of this paper are available via the supplemental material section.
Sport-Specific Associations of Specialization and Sex With Overuse Injury in Youth Athletes
Authors: Post Eric G. , Biese Kevin M. , Schaefer Daniel A. , Watson Andrew M. , McGuine Timothy A. , Brooks M. Alison , Bell David R. 
Published: November 2019

Background: Significant evidence has emerged that sport specialization is associated with an increased risk of overuse injury in youth athletes. Several recommendations exist to reduce the risk of overuse injury in youth sports, but the risk of overuse injuries may be dependent on specific movements required by a given sport. Hypotheses: Associations between specialized sport participation and overuse injury will exist in volleyball athletes but not soccer or basketball athletes. Female athletes will be more likely to report an overuse injury in the previous year, regardless of sport. Study Design: Cross-sectional study. Level of Evidence: Level 3. Methods: Youth athletes between the ages of 12 and 18 years were recruited in-person at club team tournaments, competitions, and events around the state of Wisconsin during the 2016-2017 school year. Participants were asked to complete an anonymous questionnaire that consisted of (1) participant demographics, (2) sport specialization status, (3) monthly and weekly sport volume, and (4) sport-related injury history in the previous year. Results: A total of 716 youth athletes completed the questionnaire (70.8% female; mean age, 14.21 ± 1.50 years; 43.2% basketball, 19.4% soccer, 37.4% volleyball; 41.8% highly specialized; 32.3% reported overuse injury in the previous year). Sex was associated with overuse injury among basketball athletes, with female basketball athletes nearly 4 times more likely to report an overuse injury compared with male basketball athletes (odds ratio, [OR], 3.7; 95% CI, 2.1-6.6; P < 0.001). High specialization (OR, 2.3; 95% CI, 1.1-4.9; P = 0.02) and participating in a single sport for more than 8 months per year (OR, 2.0; 95% CI, 1.1-3.5; P < 0.05) were associated with overuse injury only among volleyball athletes. Conclusion: Specialization and exceeding 8 months per year in a single sport was associated with overuse injury in volleyball, which is one of the most popular youth sports for female athletes. Specialization was not associated with overuse injury in basketball or soccer athletes. Female basketball athletes were nearly 4 times more likely to report a history of overuse injury compared with male basketball athletes. The sex of a youth athlete and the sport that he or she plays may influence the risk of overuse injury associated with sport specialization. Clinical Relevance: Youth athletes, parents, and clinicians should be aware that the potential risks of specialization might vary based on the athlete’s sport and sex.
Biology and Application of Genome Editing
Authors: Zhang Feng 
Published: November 2019

Precision genome editing, which can be used to alter specific DNA sequences, is a powerful tool for understanding the molecular circuitry underlying cellular processes. Over the past several years, we and others have harnessed microbial CRISPR-Cas systems for use as platforms for a range of genome manipulations, including single and multiplex gene knockout, gene activation, and large-scale screening applications. Recently, we discovered and characterized several novel CRISPR systems that target RNA, including the CRISPR-Cas13 family. We developed a toolbox for RNA modulation based on Cas13, including methods for highly specific RNA knockdown, transcript imaging, and precision base editing. During our initial characterization of Cas13, we observed that Cas13 also exhibits so-called non-specific "collateral" RNase activity in vitro, which we capitalized on to create SHERLOCK, a highly sensitive and specific CRISPR diagnostic platform. We are continuing to refine and extend CRISPR-based technologies as well as explore microbial diversity to find new enzymes and systems that can be adapted for use as molecular biology tools and novel therapeutics.

Disclosures
Zhang: Arbor Biotechnologies: Consultancy, Equity Ownership; Sherlock Biosciences: Consultancy, Equity Ownership; Pairwise Plants: Consultancy, Equity Ownership; Beam Therapeutics: Consultancy, Equity Ownership; Editas Medicine: Consultancy, Equity Ownership.
A Complicated Neighborhood: Insights into the Hodgkin Lymphoma Microenvironment
Authors: Gandhi Maher K. 
Published: November 2019

Classical Hodgkin Lymphoma (cHL) is a heterogenous and complex biological entity. Whereas early studies focussed on characterization of the Reed-Sternberg (RS) cell, there is now increasing recognition of the importance of the tumor microenvironment (TME). This critical but only partially understood component of cHL biology is likely to impact pathogenesis, chemo-sensitivity and long-term outcome. Here, the non-malignant infiltrate is variably comprised of macrophages, regulatory T cells, and stroma, with the relative composition varying by histological sub-type. Notably, relative to other B cell lymphomas, cHL expresses high levels of immune checkpoint receptors such as PD-1 and LAG3, and immune checkpoint ligands such as PD-L1, PD-L2, the latter of which are frequently the subject of genetic amplifications. Hence the bi-directional relationship between the microenvironment and the malignant cell is now a valid target. Breakthroughs in our understanding of the TME in cHL have contributed to its status as the 'poster-child' for how checkpoint blockade can de-activate tumor-tolerance to induce meaningful clinical benefit. A further layer of complexity within the TME is the potential aetiological relationship between cHL and the Epstein-Barr virus, a ubiquitous virus found to reside within the RS cells in 40% of cases, particularly in those cases that have mixed cellularity. Unlike benign EBV-infected B cells, within RS cells the virus is in a highly aberrant latency state with expression of the viral oncoprotein LMP1, a virus that is known to induce immunosuppression and drive PD-L1 expression through the NFkB and the JAK-STAT pathways. But numerous unanswered mechanistic questions remain, not least in the light of the frequent genetically driven deficiencies in antigen presentation present in RS cells, particularly in cases of nodular sclerosing disease. This has reignited debate about the relative roles of adaptive and innate immunity in this disease. Remaining questions that need to be addressed include the evolution of the interaction between the TME and the malignant compartment during the course of cHL, the role of other immune checkpoints and their impact on combinatorial immune based strategies, and the contribution to immune-evasion played by stromal cells. Further understanding will assist the rational development of new immune-based strategies, and potentially one day a chemo-free regimen that is as clinically efficacious but less toxic than current chemotherapies.

Disclosures
Gandhi: Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Honoraria, Research Funding; Roche: Honoraria, Other: Travel Support; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria.
Analyzing How Elderly Acute Myeloid Leukemia Patients Are Treated, an Institutional Experience
Authors: Willner Christopher Allen , Chisti Mohammad Muhsin , Soriano Michaela , Huang James 
Published: November 2019

Rationale: Treatment of acute myelogenous leukemia (AML) remains a challenge in elderly populations, those with comorbid conditions, and patients with poor performance status indices. The optimal choice for induction therapy as well as further agent selection is unclear, and current guidelines recommend enrollment in a controlled clinical trial.
Methods: Institutional cases of AML via an electronic medical record query performed in November 2017 containing cases of AML in patients 65 years of age or greater from 01/01/2000 to 06/21/2017 were extracted. Instances of acute myelogenous leukemia were identified by ICD codes. Age, gender, induction therapy, cytogenetics, molecular analyses, and overall survival were collected.
Results: A total of 61 cases of AML in patients aged 65 or greater were identified, with those having incomplete data being excluded from analysis. The mean age of included patients was 78.9 years of age, 35 were male and 26 were female. 60 confirmed deaths were recorded. 26 patients received conventional 7+3 (42.6%), 22 received a hypomethylating agent (HMA) (31.1%), 16 (26.2%) did not receive treatment.
Conclusion: Our institutional data showed overall survival was significantly longer when treated with 7+3, 354 days (95% CI [93, 614]), vs. 61 days (95% CI [15, 107]). Similarly, OS was significantly longer when treated with HMA, 303 days (95% CI [23, 583]). Risk of death, accordingly, was as follows: 7+3 HR .347 (.179-.672), HMA HR .348 (.173-.703). Our institutional mortality data reasonably reflected SEER data analysis reported by Medeiros et al concerning untreated patients, but trended toward a greater OS for those treated with 7+3 or HMA. Registry data, as well as our institutional data, demonstrate a survival benefit to intensive chemotherapy and palliative chemotherapy, while controlled trials have not shown this benefit consistently in elderly populations. Practices regarding induction therapy vary greatly between institutions. Determination of which elderly patients to treat with intensive therapy remains difficult.
References:
Almeida AM, Ramos F. Acute myeloid leukemia in the older adults. Leuk Res Rep. 2016;6:1-7.
Eleni LD, Nicholas ZC, Alexandros S. Challenges in treating older patients with acute myeloid leukemia. J Oncol. 2010;2010:943823.
Medeiros BC, Satram-hoang S, Hurst D, Hoang KQ, Momin F, Reyes C. Big data analysis of treatment patterns and outcomes among elderly acute myeloid leukemia patients in the United States. Ann Hematol. 2015;94(7):1127-38.

Disclosures
Chisti: Eli Lilly: Speakers Bureau; Medscape: Honoraria; UpToDate: Honoraria.
Hereditary Hemolytic Anemias Other Than Thalassemia: Single Center Experience
Authors: Ozdemir Gul Nihal , Kilic Mehmet Akif 
Published: November 2019

Aim: The aim of this study was to evaluate the demographic information, clinical and hematologic findings and treatment response of patients diagnosed with hereditary hemolytic anemias other than thalassemia at a single center.
Materials and Methods: A total of 157 children with a diagnosis of hereditary hemolytic anemia except thalassemia were included. Patients' files were reviewed retrospectively. Demographic, clinical and laboratory characteristics, family history, complications, history of splenectomy and cholecystectomy, splenectomy response, use of chelating agents and other treatments, first transfusion age and transfusion frequency of patients were evaluated. Mean, standard deviation, median and 25-75 percentile values were used when descriptive analysis were presented. Mann Whitney U and Kruskal Wallis Tests were used for nonparametric groups. Pearson Chi Square and Fisher Tests were used when categorical comparisons were made. A value of P <0.05 was considered statistically significant.
Results: Of the 157 patients , 101 patients (64,3%) had hereditary spherocytosis, 39 patients had (24,8%) glucose-6 phosphate dehydrogenase deficiency (G6PD), 15 patients had (9,6%) sickle cell anemia and 2 patients had (1.3%) pyruvate kinase deficiency. Sixty-one patients (38,9%) were girls and 96 were boys (61,1%). Median age of diagnosis was 10 months (range 1-188 months). Of 97 patients whom family history was questioned, 63 (64.9%) had family history. Most common complaint at diagnosis was paleness. Eighty-two patients had splenomegaly. Twenty-two patients (14%) had cholecystectomy and 56 patients (35.7%) had splenectomy on follow-up. The most frequent indication for splenectomy was hereditary spherocytosis. Fifty-eight (36.9%) patients required regular transfusion. Mean ferritin level of all was 506.3±1175.0. Patients with pyruvate kinase had the highest ferritin levels. Erythropoietin was used for 1 patient with hereditary spherocytosis in infancy without a response. Ten of 15 patients with sickle cell anemia were using hydroxyurea. Thirteen percent of all were using chelating agents.
Conclusion: Hereditary spherocytosis and G6PD deficiency were the most common hereditary hemolytic anemias except thalassemia in our center. Family history was more frequent in hereditary spherocytosis compared to other hereditary hemolytic anemias. Patients with G6PD deficiency were diagnosed earlier than other hereditary hemolytic anemias. Hereditary spherocytosis was the most common indication for splenectomy and eliminated/decreased transfusion requirement in 96%. Patients with other hemolytic anemias had lower iron load compared to thalassemia except pyruvate kinase deficiency patients.

Disclosures
No relevant conflicts of interest to declare.
Correlation between Changes in Cardiac Iron and Hepatic Iron in Pediatric Patients with Thalassemia Major
Authors: Pepe Alessia , Meloni Antonella , Filosa Aldo , Pistoia Laura , Casini Tommaso , Lisi Roberto , Putti Maria Caterina , Maggio Aurelio , Gerardi Calogera , Fina Priscilla , Positano Vincenzo , Casale Maddalena 
Published: November 2019

Introduction. A prospective magnetic resonance imaging (MRI) study demonstrated a good control of myocardial iron overload (MIO) in terms of prevention and treatment in children with thalassemia major (TM).
The aim of the present study was to evaluate if changes in MIO were related to baseline hepatic iron or changes in hepatic iron overload (HIO).
Methods. We considered 68 TM patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) project with less than 18 years at the first MRI scan and who performed a follow-up (FU) study at 18±3 months.
Myocardial and hepatic iron burdens were quantified by the T2* technique. The value of 20 ms was used as conservative normal value for the global T2* value. Liver T2* values were converted into liver iron concentration (LIC) values. A LIC<3 mg/g/dw indicated significant no HIO, between 3 and 7 mg/g/dw mild HIO, between 7 and 15 mg/g/dw moderate HIO, and ≥15 mg/g/dw severe HIO.
Results. Thirty-six patients were females and mean age at the time of the baseline MRI was 13.74±3.09 years. Baseline global heart T2* values were 29.72±11.21 ms and 16 (23.5%) patients showed significant baseline MIO.
The percentage changes in global heart T2* values per month in the whole patient population were 0.66±1.70 and they resulted significantly higher in the 16 patients with significant baseline MIO versus the patients with no baseline MIO (1.99±2.53% vs 0.25±1.09% ms; P=0.002).
Percentage changes in global heart T2* values per month were not influenced by initial MRI LIC values (R=0.048; P=0.695) (Figure 1A) and were comparable among the 4 groups of patients identified on the basis of baseline MRI LIC values (14 no HIO: 0.29±1.12% vs 21 mild HIO: 0.75±1.56% vs 15 moderate HIO: 0.82±2.03% vs 18 severe HIO: 0.71±2.00%; P=0.876).
Percentage changes in global heart T2* values per month were not associated to final MRI LIC values (R=-0.134; P=0.277) (Figure 1B).
The correlation between % changes in global heart T2* and MRI LIC values did not reach the statistical significance (R=-0.244; P=0.067) (Figure 1C).
In patients with baseline MIO no correlation was found between % changes in global heart T2* values per month and initial MRI LIC values (R=-0.325; P=0.219) or % changes in MRI LIC values per month (R=-0.353; P=0.180).
Conclusion. In pediatric TM patients changes in cardiac iron are not correlated to baseline MRI LIC values and changes in hepatic iron. So, our data seem not supporting the hypothesis for which it is necessary to clean the liver before removing iron from the heart.
Figure 1

Disclosures
Pepe: Chiesi Farmaceutici S.p.A., ApoPharma Inc., and Bayer: Other: No profit support.
Pancreatic Iron and Glucidic Metabolism in Thalassemia Major
Authors: Pepe Alessia , Pistoia Laura , Campisi Saveria , Sarli Roberto , Giovangrossi Piera , Guerrini Giulia , Mattei Roberto , Maggio Aurelio , Visceglie Domenico , Carrai Valentina , Peritore Giuseppe , Positano Vincenzo , Meloni Antonella 
Published: November 2019

Background. A preliminary study involving 59 patients demonstrated that pancreatic iron assessed by magnetic resonance imaging (MRI) was the strongest overall predictor of glucose dysregulation in thalassemia major (TM) patients.
Aim. In the present multicenter study we explored systematically the link between pancreatic iron and glucidic metabolism in a large cohort of TM patients.
Methods. We considered 705 TM patients (372 F, mean age 37.00±9.95 years) enrolled in the E-MIOT (Extension-Myocardial Iron Overload in Thalassemia) project. T2* measurements were performed over pancreatic head, body and tail and global value was the mean. The pattern of disturbances of glucose metabolism was assessed by means of the oral glucose tolerance test (OGTT).
Results. According to OGTT results, 546 patients (77.4%) had normal glucose tolerance (NGT), 14 (2.0%) had isolated impaired fasting glucose (IFG), 29 (4.1%) had impaired glucose tolerance (IGT), and 116 (16.5%) had diabetes mellitus (DM).
None of the 85 patients (12.1%) without pancreatic iron overload (global pancreas T2*≥26 ms) had IGT or DM (Figure 1). The 84.6% of patients with NGT had pancreatic iron overload. The global pancreatic T2* values were significantly higher in patients with NGT than in patients with DM (13.58±11.08 ms versus 8.09±4.72 ms, P&lt;0.0001).
Receiver operator characteristic (ROC) analysis showed that a global pancreas T2*&lt;13.73 ms was the optimal cutoff for predicting an abnormal OGTT, with an area under the curve (AUC) of 0.62.
Global pancreas T2* values showed a weak significant correlation with insulin values (R=0.160; P=0.002) and homeostasis model assessment-insulin resistance (HOMA-IR) index (R=0.122; P=0.019).
Conclusion. A normal global pancreas T2* value has a negative predictive value of 100% for IGT and DM. The low specificity of pancreatic iron overload for glucose dysregulation seems to support the hypothesis that a latency time is need before pancreatic iron burden could give impaired glucose tolerance and overt diabetes mellitus.
Figure 1

Disclosures
Pepe: Chiesi Farmaceutici S.p.A., ApoPharma Inc., and Bayer: Other: No profit support.