bluuebunny/crossref_metadata_2025_split huggingface dataset:
A referral pathway for potentially abnormal neurodevelopment in children with heart disease in the United Kingdom: a Delphi consensus
Authors: Hoskote Aparna , Wray Jo , Banks Victoria , Brown Katherine , Lakhanpaul Monica 
Published: April 2020

IntroductionChildren with congenital heart disease have complex medical and neurodevelopmental needs. We aimed to develop a multi-professional consensus-based referral pathway applicable to action the results of the brief developmental assessment (BDA), a validated early recognition tool, that categorises the neurodevelopmental status as green (appropriate for age), amber (equivocal) or red (delayed) in children aged between 4 months and 5 years.MethodsA Delphi consensus survey detailing two scenarios—a child categorised as delayed (red) and another as equivocal (amber) on administration of the BDA at the time of discharge from the tertiary centre—was sent to 80 expert professionals from primary, secondary and tertiary care seeking agreement on next steps and referral pathways. An iterative process was proposed with a pre-defined rule of 75% for consensus.ResultsThe survey was completed by 77 Delphi panel experts in Round 1, 73 in Round 2 and 70 in Round 3. Consensus was achieved (1) for the child with amber or red BDA, the child should be under the care of a paediatrician with expertise in cardiology (PEC) (or general paediatrician if no PEC) based at their local hospital, (2) for the child with red BDA, the PEC should initiate referral to community services at first assessment, (3) for child with amber BDA, a re-assessment by the health visitor should occur within 1–2 months, with referral to community services and notification to the PEC if on-going concerns.ConclusionsThe Delphi process enabled a consensus to be reached between health professionals on referral pathways for specialist neurodevelopmental assessment/treatment for children with heart disease, in response to amber or red BDA results. The agreed referral pathway, if implemented, could underpin a national guideline to address and intervene on the neurodevelopmental difficulties in children with heart disease.
Diversity in NHS clinical leadership: Is better talent management the route to gender balance?
Authors: Gilmartin Molly , Woods Niamh , Patel Shruti , Brummell Zoe 
Published: April 2020

MethodologyThrough interviews with seven senior female clinical leaders, insights were gained regarding the importance of and need for gender diversity in leadership. These interviews looked at the skills, access and opportunities required to ensure that gender diversity exists and is successful in senior clinical leadership positions.ConclusionGender diversity in leadership can be enhanced through the combination of several measures; Increased mentorship, talent management, training and network opportunities, improvements to advertising, interview panel diversity and succession planning.
Impact of tricuspid regurgitation on postoperative outcomes after non-cardiac surgeries
Authors: Parikh Parth , Banerjee Kinjal , Ali Ambreen , Anumandla Anil , Patel Aditi , Jobanputra Yash , Menon Venu , Griffin Brian , Tuzcu E Murat , Kapadia Samir 
Published: April 2020

ObjectiveTricuspid regurgitation (TR) severity has known adverse implications, its impact on patients undergoing non-cardiac surgery (NCS) remains unclear. We sought to determine the impact of TR on patient outcomes after NCS.MethodsWe performed a retrospective cohort study in patients undergoing NCS. Outcomes in patients with moderate or severe TR were compared with no/trivial TR after adjusting for baseline characteristics and revised cardiac risk index (RCRI). The primary outcome was defined as 30-day mortality and heart failure (HF), while the secondary outcome was long-term mortality.ResultsOf the 7064 patients included, 312 and 80 patients had moderate and severe TR, respectively. Thirty-day mortality was higher in moderate TR (adjusted OR 2.44, 95% CI 1.25 to 4.76) and severe TR (OR 2.85, 95% CI 1.04 to 7.79) compared with no/trivial TR. There was no difference in 30-day HF in patients with moderate TR (OR 1.48, 95% CI 0.90 to 2.44) or severe TR (OR 1.42, 95% CI 0.60 to 3.39). The adjusted HR for long-term mortality in moderate TR was 1.55 (95% CI 1.31 to 1.82) and 1.87 (95% CI 1.40 to 2.50) for severe TR compared with no/trivial TR.ConclusionIncreasing TR severity has higher postoperative 30-day mortality in patients undergoing NCS, independent of RCRI risk factors, ejection fraction or mitral regurgitation. Severity of TR should be considered in risk stratification for patients undergoing NCS.
Correlates of tobacco product reuptake and relapse among youth and adults in the USA: findings from the PATH Study Waves 1–3 (2013–2016)
Authors: Edwards Kathryn C , Kasza Karin A , Tang Zhiqun , Stanton Cassandra A , Sharma Eva , Halenar Michael J , Taylor Kristie A , Donaldson Elisabeth A , Hull Lynn C , Bansal-Travers Maansi , Limpert Jean , Zandberg Izabella , Gardner Lisa D , Borek Nicolette , Kimmel Heather L , Compton Wilson M , Hyland Andrew 
Published: April 2020

ObjectiveThis study examines sociodemographic and tobacco use correlates of reuptake and relapse to tobacco use across a variety of tobacco products (cigarettes, electronic nicotine delivery systems, cigars, hookah and smokeless tobacco) among the US population.DesignData were drawn from the first three waves (2013–2016) of the Population Assessment of Tobacco and Health Study, a nationally representative, longitudinal cohort study of US youth (ages 12–17) and adults (ages 18+). Reuptake (past 30-day use among previous tobacco users) and relapse (current use among former established users; adults only) were examined among previous users of at least one type of tobacco product at Wave 1 (W1) or Wave 2 (W2) (n=19 120 adults, n=3039 youth). Generalised estimating equations were used to evaluate the association between demographic and tobacco use characteristics at baseline, with reuptake/relapse at follow-up, over two 1-year periods (W1–W2 and W2–Wave 3).ResultsAny tobacco product reuptake occurred in 7.8% of adult previous users and 30.3% of youth previous users. Correlates of any tobacco reuptake included being male, non-Hispanic black and bisexual in adults, but race and sexual orientation were not consistent findings in youth. Among recent former users, relapse rates were greater (32.9%). Shorter time since last use and greater levels of tobacco dependence showed the strongest association with any tobacco relapse.DiscussionContinued clinical and public health efforts to provide adults with tools to cope with tobacco dependence symptoms, especially within the first year or two after quitting, could help prevent relapse.
Correlates of tobacco product initiation among youth and adults in the USA: findings from the PATH Study Waves 1–3 (2013–2016)
Authors: Kasza Karin A , Edwards Kathryn C , Tang Zhiqun , Stanton Cassandra A , Sharma Eva , Halenar Michael J , Taylor Kristie A , Donaldson Elisabeth , Hull Lynn C , Day Hannah , Bansal-Travers Maansi , Limpert Jean , Zandberg Izabella , Gardner Lisa D , Hammad Hoda T , Borek Nicolette , Kimmel Heather L , Compton Wilson M , Hyland Andrew 
Published: April 2020

ObjectiveTo report on demographic and tobacco product use correlates of tobacco product initiation (cigarettes, electronic nicotine delivery systems (ENDS), cigars, hookah and smokeless tobacco) among the US population.DesignData were from the first three waves (2013–2016) of the Population Assessment of Tobacco and Health Study, a nationally representative, longitudinal cohort study of US youth (aged 12–17 years) and adults (aged 18+ years). Never users of at least one type of tobacco product at Wave 1 (W1, 2013/14) or Wave 2 (W2, 2014/15) were included (n=12 987 youth; n=25 116 adults). Generalised estimating equations were used to evaluate the association between demographic and tobacco product use characteristics at baseline, and tobacco product initiation at follow-up (ever, past 30 day (P30D), frequent (use on 20 or more of thepast 30 days)) over two 1-year periods (W1–W2 and W2–Wave 3).ResultsYouth aged 15–17 years were more likely than youth aged 12–14 years and adults aged 18–24 years were more likely than older adults to initiate P30D tobacco use across products; non-heterosexuals were more likely than heterosexuals to initiate P30D cigarette and ENDS use. Older adults were more likely than young adults, and males were more likely than females, to be frequent users of ENDS on initiation. Ever use of another tobacco product predicted P30D initiation of each tobacco product.DiscussionOther tobacco product use and age predict P30D tobacco initiation across products whereas associations with other demographic characteristics vary by product. Continued contemporary evaluation of initiation rates within the changing tobacco product marketplace is important.
MRI findings and surgical treatment of a carpal synovial cyst in a dog
Authors: Tzounos Caitlin , Taeymans Olivier , Quinn Rob , Haimel Georg 
Published: April 2020

A male neutered pug aged 3 years and 3 months presented with a 4‐month history of persistent left thoracic limb lameness, which was associated with a firm swelling on the palmerolateral aspect of the carpus. MRI confirmed a fluid‐filled structure, which appeared to be associated with the joint space. The structure was surgically excised. Histopathology confirmed a true synovial cyst. Follow‐up by telephone and email with the owner 18 months after surgery confirmed the patient was clinically well, with complete resolution of the lameness and no recurrence of swelling. This report discusses the MRI characteristics and successful treatment of a carpal synovial cyst causing lameness in the absence of osteoarthritis. There was long‐term resolution of clinical signs with surgical excision of the cyst.
Effect of particle size and CO2 treatment of waste cement powder on properties of cement paste
Authors: Mehdizadeh Hamideh , Ling Tung-Chai , Cheng Xiongfei , Mo Kim Hung 
Published: April 2020

This paper studies the role of CO2 treatment and the impact of particle size (<75 μm and 75–150 μm) of waste cement powder (WCP) with different cement replacement content (0%, 5%, 10%, 15%, 20%, and 30%) on the physical properties and microstructure of blended cement paste. The results show that carbonation of WCP can effectively increase the flowability of paste due to the formation of calcite and decrease the porosity of WCP microstructure, while the water demand to achieve the same workability decreases with increasing size of WCP particles. Cement paste containing decreased particles of carbonated waste cement powder possesses a higher 28 day compressive strength due to formation of a higher amount of calcite and hydration products, based on the thermogravimetric analysis.
Genetic and Circulating Biomarker Data Improve Risk Prediction for Pancreatic Cancer in the General Population
Authors: Kim Jihye , Yuan Chen , Babic Ana , Bao Ying , Clish Clary B. , Pollak Michael N. , Amundadottir Laufey T. , Klein Alison P. , Stolzenberg-Solomon Rachael Z. , Pandharipande Pari V. , Brais Lauren K. , Welch Marisa W. , Ng Kimmie , Giovannucci Edward L. , Sesso Howard D. , Manson JoAnn E. , Stampfer Meir J. , Fuchs Charles S. , Wolpin Brian M. , Kraft Peter 
Published: April 2020

Abstract

Background:
Pancreatic cancer is the third leading cause of cancer death in the United States, and 80% of patients present with advanced, incurable disease. Risk markers for pancreatic cancer have been characterized, but combined models are not used clinically to identify individuals at high risk for the disease.

Methods:
Within a nested case–control study of 500 pancreatic cancer cases diagnosed after blood collection and 1,091 matched controls enrolled in four U.S. prospective cohorts, we characterized absolute risk models that included clinical factors (e.g., body mass index, history of diabetes), germline genetic polymorphisms, and circulating biomarkers.

Results:
Model discrimination showed an area under ROC curve of 0.62 via cross-validation. Our final integrated model identified 3.7% of men and 2.6% of women who had at least 3 times greater than average risk in the ensuing 10 years. Individuals within the top risk percentile had a 4% risk of developing pancreatic cancer by age 80 years and 2% 10-year risk at age 70 years.

Conclusions:
Risk models that include established clinical, genetic, and circulating factors improved disease discrimination over models using clinical factors alone.

Impact:
Absolute risk models for pancreatic cancer may help identify individuals in the general population appropriate for disease interception.
Cyclophilin A Inhibitor Debio-025 Targets Crk, Reduces Metastasis, and Induces Tumor Immunogenicity in Breast Cancer
Authors: Davra Viralkumar , Saleh Tamjeed , Geng Ke , Kimani Stanley , Mehta Dhriti , Kasikara Canan , Smith Brendan , Colangelo Nicholas W. , Ciccarelli Bryan , Li Hong , Azzam Edouard I. , Kalodimos Charalampos G. , Birge Raymond B. , Kumar Sushil 
Published: April 2020

Abstract

The Crk adaptor protein, a critical modifier of multiple signaling pathways, is overexpressed in many cancers where it contributes to tumor progression and metastasis. Recently, we have shown that Crk interacts with the peptidyl prolyl cis-trans isomerase, Cyclophilin A (CypA; PP1A) via a G219P220Y221 (GPY) motif in the carboxyl-terminal linker region of Crk, thereby delaying pY221 phosphorylation and preventing downregulation of Crk signaling. Here, we investigate the physiologic significance of the CypA/Crk interaction and query whether CypA inhibition affects Crk signaling in vitro and in vivo. We show that CypA, when induced under conditions of hypoxia, regulates Crk pY221 phosphorylation and signaling in cancer cell lines. Using nuclear magnetic resonance spectroscopy, we show that CypA binds to the Crk GPY motif via the catalytic PPII domain of CypA, and small-molecule nonimmunosuppressive inhibitors of CypA (Debio-025) disrupt the CypA–CrkII interaction and restores phosphorylation of Crk Y221. In cultured cell lines, Debio-025 suppresses cell migration, and when administered in vivo in an orthotopic model of triple-negative breast cancer, Debio-025 showed antitumor efficacy either alone or in combination with anti-PD-1 mAb, reducing both tumor volume and metastatic lung dispersion. Furthermore, when analyzed by NanoString immune profiling, treatment of Debio-025 with anti-PD-1 mAb increased both T-cell signaling and innate immune signaling in tumor microenvironment.

Implications:
These data suggest that pharmacologic inhibition of CypA may provide a promising and unanticipated consequence in cancer biology, in part by targeting the CypA/CrkII axis that regulates cell migration, tumor metastasis, and host antitumor immune evasion.
Genetic Ablation of HLA Class I, Class II, and the T-cell Receptor Enables Allogeneic T Cells to Be Used for Adoptive T-cell Therapy
Authors: Kagoya Yuki , Guo Tingxi , Yeung Brian , Saso Kayoko , Anczurowski Mark , Wang Chung-Hsi , Murata Kenji , Sugata Kenji , Saijo Hiroshi , Matsunaga Yukiko , Ohashi Yota , Butler Marcus O. , Hirano Naoto 
Published: April 2020

Abstract
Adoptive immunotherapy can induce sustained therapeutic effects in some cancers. Antitumor T-cell grafts are often individually prepared in vitro from autologous T cells, which requires an intensive workload and increased costs. The quality of the generated T cells can also be variable, which affects the therapy's antitumor efficacy and toxicity. Standardized production of antitumor T-cell grafts from third-party donors will enable widespread use of this modality if allogeneic T-cell responses are effectively controlled. Here, we generated HLA class I, HLA class II, and T-cell receptor (TCR) triple-knockout (tKO) T cells by simultaneous knockout of the B2M, CIITA, and TRAC genes through Cas9/sgRNA ribonucleoprotein electroporation. Although HLA-deficient T cells were targeted by natural killer cells, they persisted better than HLA-sufficient T cells in the presence of allogeneic peripheral blood mononuclear cells (PBMC) in immunodeficient mice. When transduced with a CD19 chimeric antigen receptor (CAR) and stimulated by tumor cells, tKO CAR-T cells persisted better when cultured with allogeneic PBMCs compared with TRAC and B2M double-knockout T cells. The CD19 tKO CAR-T cells did not induce graft-versus-host disease but retained antitumor responses. These results demonstrated the benefit of HLA class I, HLA class II, and TCR deletion in enabling allogeneic-sourced T cells to be used for off-the-shelf adoptive immunotherapy.
Mammalian SWI/SNF Complex Genomic Alterations and Immune Checkpoint Blockade in Solid Tumors
Authors: Abou Alaiwi Sarah , Nassar Amin H. , Xie Wanling , Bakouny Ziad , Berchuck Jacob E. , Braun David A. , Baca Sylvan C. , Nuzzo Pier Vitale , Flippot Ronan , Mouhieddine Tarek H. , Spurr Liam F. , Li Yvonne Y. , Li Taiwen , Flaifel Abdallah , Steinharter John A. , Margolis Claire A. , Vokes Natalie I. , Du Heng , Shukla Sachet A. , Cherniack Andrew D. , Sonpavde Guru , Haddad Robert I. , Awad Mark M. , Giannakis Marios , Hodi F. Stephen , Liu X. Shirley , Signoretti Sabina , Kadoch Cigall , Freedman Matthew L. , Kwiatkowski David J. , Van Allen Eliezer M. , Choueiri Toni K. 
Published: April 2020

AbstractPrior data have variably implicated the inactivation of the mammalian SWItch/Sucrose Non-Fermentable (mSWI/SNF) complex with increased tumor sensitivity to immune checkpoint inhibitors (ICI). Herein, we examined the association between mSWI/SNF variants and clinical outcomes to ICIs. We correlated somatic loss-of-function (LOF) variants in a predefined set of mSWI/SNF genes (ARID1A, ARID1B, SMARCA4, SMARCB1, PBRM1, and ARID2) with clinical outcomes in patients with cancer treated with systemic ICIs. We identified 676 patients from Dana-Farber Cancer Institute (DFCI, Boston, MA) and 848 patients from a publicly available database from Memorial Sloan Kettering Cancer Center (MSKCC, New York, NY) who met the inclusion criteria. Multivariable analyses were conducted and adjusted for available baseline factors and tumor mutational burden. Median follow-up was 19.6 (17.6–22.0) months and 28.0 (25.0–29.0) months for the DFCI and MSKCC cohorts, respectively. Seven solid tumor subtypes were examined. In the DFCI cohort, LOF variants of mSWI/SNF did not predict improved overall survival (OS), time-to-treatment failure (TTF), or disease control rate. Only patients with renal cell carcinoma with mSWI/SNF LOF showed significantly improved OS and TTF with adjusted HRs (95% confidence interval) of 0.33 (0.16–0.7) and 0.49 (0.27–0.88), respectively, and this was mostly driven by PRBM1. In the MSKCC cohort, where only OS was captured, LOF mSWI/SNF did not correlate with improved outcomes across any tumor subtype. We did not find a consistent association between mSWI/SNF LOF variants and improved clinical outcomes to ICIs, suggesting that mSWI/SNF variants should not be considered as biomarkers of response to ICIs.
Sorting Nexin 10 Mediates Metabolic Reprogramming of Macrophages in Atherosclerosis Through the Lyn-Dependent TFEB Signaling Pathway
Authors: You Yan , Bao Wei-Lian , Zhang Su-Lin , Li Hai-Dong , Li Hui , Dang Wen-Zhen , Zou Si-Li , Cao Xin-Yue , Wang Xu , Liu Li-Xin , Jiang Hualiang , Qu Le-Feng , Zheng Mingyue , Shen Xiaoyan 
Published: April 2020

Rationale:
SNX10 (sorting nexin 10) has been reported to play a critical role in regulating macrophage function and lipid metabolism.

Objective:
To investigate the precise role of SNX10 in atherosclerotic diseases and the underlying mechanisms.

Methods and Results:

SNX10 expression was compared between human healthy vessels and carotid atherosclerotic plaques. Myeloid cell-specific SNX10 knockdown mice were crossed onto the APOE
−/−
(apolipoprotein E) background and atherogenesis (high-cholesterol diet-induced) was monitored for 16 weeks. We found that SNX10 expression was increased in atherosclerotic lesions of aortic specimens from humans and APOE
−/−
mice. Myeloid cell-specific SNX10 deficiency (Δ knockout [KO]) attenuated atherosclerosis progression in APOE
−/−
mice. The population of anti-inflammatory monocytes/macrophages was increased in the peripheral blood and atherosclerotic lesions of ΔKO mice. In vitro experiments showed that SNX10 deficiency-inhibited foam cell formation through interrupting the internalization of CD36, which requires the interaction of SNX10 and Lyn-AKT (protein kinase B). The reduced Lyn-AKT activation by SNX10 deficiency promoted the nuclear translocation of TFEB (transcription factor EB), thereby enhanced lysosomal biogenesis and LAL (lysosomal acid lipase) activity, resulting in an increase of free fatty acids to fuel mitochondrial fatty acid oxidation. This further promoted the reprogramming of macrophages and shifted toward the anti-inflammatory phenotype.

Conclusions:
Our data demonstrate for the first time that SNX10 plays a crucial role in diet-induced atherogenesis via the previously unknown link between the Lyn-Akt-TFEB signaling pathway and macrophage reprogramming, suggest that SNX10 may be a potentially promising therapeutic target for atherosclerosis treatment.
Chronic Disease Burden After Congenital Heart Surgery: A 47‐Year Population‐Based Study With 99% Follow‐Up
Authors: Raissadati Alireza , Haukka Jari , Pätilä Tommi , Nieminen Heta , Jokinen Eero 
Published: April 2020

Background

Postoperative morbidity is an increasingly important outcome measure of patients who have undergone congenital heart surgery (
CHS
). We examined late postoperative morbidity after
CHS
on the basis of patients’ government‐issued medical special reimbursement rights.

Methods and Results

Between 1953 and 2009, 10 635 patients underwent
CHS
at <15 years of age in Finland. We excluded early deaths and mental disabilities. Noncyanotic and cyanotic defects were divided into simple and severe groups, respectively. We obtained 4 age‐, sex‐, birth time–, and hospital district–matched control subjects per patient. The Social Insurance Institution of Finland provided data on all medical special reimbursement rights granted between 1966 and 2012. Follow‐up started at the first operation and ended at death, date of emigration, or December 31, 2012. A total of 8623 patients met inclusion criteria. Follow‐up was 99.9%. A total of 3750 patients (43%) required special reimbursements rights for a chronic disease. Cardiovascular disease was the most common late morbidity among patients (28%), followed by obstructive pulmonary disease (9%), neurologic disease (3%), and psychiatric disease (2%). Heart failure (simple hazard ratio [HR], 56.3 [95%
CI,
35.4–89.7]; severe HR, 918.0 [95% CI, 228.9–3681.7]) and arrhythmia (simple HR, 11.0 [95% CI, 7.1–17.0]; severe HR, 248.0 [95% CI, 61.3–1002.7]) were the most common cardiovascular morbidities. Hypertension was common among patients with coarctation of the aorta (13%; incidence risk ratio [RR], 8.9; 95%
CI,
7.5–10.7). Psychiatric disease was more common among simple defects, particularly ventricular septal defects.

Conclusions

Chronic cardiac and noncardiac sequelae are common after
CHS
regardless of the severity of the defect, underscoring the importance of long‐term follow‐up of all patients after
CHS
.