tbuckley/cabot-search huggingface dataset:
In Utero Protein Therapy for an Inherited Developmental Disorder
Authors: Marja L. Mikkola
Journal: New England Journal of Medicine (2018)

Ectodermal dysplasias comprise a heterogeneous group of rare genetic diseases in which two or more derivatives of the embryonic surface ectoderm — the skin, hair, teeth, nails, or sweat or other cutaneous glands — fail to develop normally.1 Hypohidrotic ectodermal dysplasia is the most common type of ectodermal dysplasia. It is characterized by missing and malformed teeth, sparse and thin hair, and an inability to sweat caused by the sweat glands being absent or hypoplastic.2 The most prevalent cause (affecting more than 90% of persons with hypohidrotic ectodermal dysplasia) is loss of function in the X-linked gene encoding ectodysplasin A . . .
Government is too slow to act on NHS sustainability recommendations, say peers
Authors: Adrian O’Dowd
Journal: BMJ (2018)

Peers have criticised the government for delays in acting on recommendations made in a high profile report on the long term sustainability of the NHS and social care published over a year ago.

During an almost seven hour debate in the House of Lords on 26 April, many peers spoke out about the lack of progress since the select committee’s report was published in April 2017.1 The report called for the creation of an independent Office for Health and Care Sustainability, more NHS and social care funding over longer periods, and potential phasing out of the traditional partnership model of general practice.2

During the debate peers welcomed …
B-cell differentiation and IL-21 response in IL2RG/JAK3 SCID patients after hematopoietic stem cell transplantation
Authors: Alexandra M. Miggelbrink, Brent R. Logan, Rebecca H. Buckley, Roberta E. Parrott, Christopher C. Dvorak, Neena Kapoor, Hisham Abdel-Azim, Susan E. Prockop, David Shyr, Hélène Decaluwe, Imelda C. Hanson, Alfred Gillio, Blachy J. Dávila Saldaña, Hermann Eibel, Gregory Hopkins, Jolan E. Walter, Jennifer S. Whangbo, Donald B. Kohn, Jennifer M. Puck, Morton J. Cowan, Linda M. Griffith, Elie Haddad, Richard J. O’Reilly, Luigi D. Notarangelo, Sung-Yun Pai
Journal: Blood (2018)
Effectiveness of elbasvir/grazoprevir in patients with cirrhotic genotype 1 or 4 chronic hepatitis C: updated retrospective data analyses from the Trio network
Authors: M. Curry, S. Flamm, B. Bacon, S. Milligan, C. Nwankwo, N. Tsai, N. Wick, Z. Younossi, N. Afdhal
Journal: Journal of Hepatology (2018)
Predictors of Unemployment After Breast Cancer Surgery: A Systematic Review and Meta-Analysis of Observational Studies
Authors: Li Wang, Brian Y. Hong, Sean A. Kennedy, Yaping Chang, Chris J. Hong, Samantha Craigie, Henry Y. Kwon, Beatriz Romerosa, Rachel J. Couban, Susan Reid, James S. Khan, Michael McGillion, Victoria Blinder, Jason W. Busse
Journal: Journal of Clinical Oncology (2018)

Purpose Breast cancer surgery is associated with unemployment. Identifying high-risk patients could help inform strategies to promote return to work. We systematically reviewed observational studies to explore factors associated with unemployment after breast cancer surgery. Methods We searched MEDLINE, EMBASE, CINAHL, and PsycINFO to identify studies that explored risk factors for unemployment after breast cancer surgery. When possible, we pooled estimates of association for all independent variables reported by more than one study. Results Twenty-six studies (46,927 patients) reported the association of 127 variables with unemployment after breast cancer surgery. Access to universal health care was associated with higher rates of unemployment (26.6% v 15.4%; test of interaction P = .05). High-quality evidence showed that unemployment after breast cancer surgery was associated with high psychological job demands (odds ratio [OR], 4.26; 95% CI, 2.27 to 7.97), childlessness (OR, 1.30; 95% CI, 1.11 to 1.53), lower education level (OR, 1.15; 95% CI, 1.05 to 1.25), lower income level (OR, 1.46; 95% CI, 1.24 to 1.73), cancer stage II, III or IV (OR, 1.43; 95% CI, 1.13 to 1.82), and mastectomy versus breast-conserving surgery (OR, 1.18; 95% CI, 1.07 to 1.30). Moderate-quality evidence suggested an association with high physical job demands (OR, 2.11; 95%CI, 1.52 to 2.93), African-American ethnicity (OR, 1.89; 95% CI, 1.21 to 2.96), and receipt of chemotherapy (OR, 1.95; 95% CI, 1.36 to 2.79). High-quality evidence demonstrated no significant association with part-time hours, blue-collar work, tumor size, positive lymph nodes, or receipt of radiotherapy or endocrine therapy; moderate-quality evidence suggested no association with age, marital status, or axillary lymph node dissection. Conclusion Addressing high physical and psychological job demands may be important in reducing unemployment after breast cancer surgery.
Spatially confined induction of endochondral ossification by functionalized hydrogels for ectopic engineering of osteochondral tissues
Authors: Chiara Stüdle, Queralt Vallmajó-Martín, Alexander Haumer, Julien Guerrero, Matteo Centola, Arne Mehrkens, Dirk J. Schaefer, Martin Ehrbar, Andrea Barbero, Ivan Martin
Journal: Biomaterials (2018)
TCTAP A-114 New Technique of Transseptal Mitral Paravalvular Leak Closure with a Steerable Sheath (VALE Study)
Authors: Michal Kozlowski, Piotr Pysz, Magdalena Malczewska, Grzegorz Smolka, Wojciech Wojakowski
Journal: Journal of the American College of Cardiology (2018)
Treatment of adolescents genotype 4 chronic HCV infected patients with Ledipasvir/Sofosbuvir combination: A real world experience
Authors: H.E. Khayat, I. Kamal, M.H. El-Sayed, H. Ayoub, M.E. Shabrawy, A. Rizk, R. Yehia, M. Maher, Y. Fouad, D. Attia
Journal: Journal of Hepatology (2018)
Curation of the Pancreatic Ductal Adenocarcinoma Subset of the Cancer Genome Atlas Is Essential for Accurate Conclusions about Survival-Related Molecular Mechanisms
Authors: Ivana Peran, Subha Madhavan, Stephen W. Byers, Matthew D. McCoy
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Publicly available databases, for example, The Cancer Genome Atlas (TCGA), containing clinical and molecular data from many patients are useful in validating the contribution of particular genes to disease mechanisms and in forming novel hypotheses relating to clinical outcomes. Experimental Design: The impact of key drivers of cancer progression can be assessed by segregating a patient cohort by certain molecular features and constructing survival plots using the associated clinical data. However, conclusions drawn from this straightforward analysis are highly dependent on the quality and source of tissue samples, as demonstrated through the pancreatic ductal adenocarcinoma (PDAC) subset of TCGA. Results: Analyses of the PDAC-TCGA database, which contains mainly resectable cancer samples from patients in stage IIB, reveal a difference from widely known historic median and 5-year survival rates of PDAC. A similar discrepancy was observed in lung, stomach, and liver cancer subsets of TCGA. The whole transcriptome expression patterns of PDAC-TCGA revealed a cluster of samples derived from neuroendocrine tumors, which have a distinctive biology and better disease prognosis than PDAC. Furthermore, PDAC-TCGA contains numerous pseudo-normal samples, as well as those that arose from tumors not classified as PDAC. Conclusions: Inclusion of misclassified samples in the bioinformatic analyses distorts the association of molecular biomarkers with clinical outcomes, altering multiple published conclusions used to support and motivate experimental research. Hence, the stringent scrutiny of type and origin of samples included in the bioinformatic analyses by researchers, databases, and web-tool developers is of crucial importance for generating accurate conclusions. Clin Cancer Res; 24(16); 3813–9. ©2018 AACR.
Ceacam1 controls IL-2-dependent regulatory T cell induction in immune-mediated hepatitis
Authors: A. Horst, C. Wegscheid, C. Schaefers, B. Schiller, K. Neumann, S. Lunemann, A. Langeneckert, K. Oldhafer, C. Weiler-Normann, C. Schramm, K.S. Lang, B. Singer, M. Altfeld, L. Diehl, G. Tiegs
Journal: Journal of Hepatology (2018)
Viral Strategies for Targeting the Central and Peripheral Nervous Systems
Authors: Claire N. Bedbrook, Benjamin E. Deverman, Viviana Gradinaru
Journal: Annual Review of Neuroscience (2018)

Recombinant viruses allow for targeted transgene expression in specific cell populations throughout the nervous system. The adeno-associated virus (AAV) is among the most commonly used viruses for neuroscience research. Recombinant AAVs (rAAVs) are highly versatile and can package most cargo composed of desired genes within the capsid's ∼5-kb carrying capacity. Numerous regulatory elements and intersectional strategies have been validated in rAAVs to enable cell type-specific expression. rAAVs can be delivered to specific neuronal populations or globally throughout the animal. The AAV capsids have natural cell type or tissue tropism and trafficking that can be modified for increased specificity. Here, we describe recently engineered AAV capsids and associated cargo that have extended the utility of AAVs in targeting molecularly defined neurons throughout the nervous system, which will further facilitate neuronal circuit interrogation and discovery.
Detecting neurodegenerative disorders from web search signals
Authors: Ryen W. White, P. Murali Doraiswamy, Eric Horvitz
Journal: npj Digital Medicine (2018)

Neurodegenerative disorders, such as Parkinson's disease (PD) and Alzheimer's disease (AD), are important public health problems warranting early detection. We trained machine-learned classifiers on the longitudinal search logs of 31,321,773 search engine users to automatically detect neurodegenerative disorders. Several digital phenotypes with high discriminatory weights for detecting these disorders are identified. Classifier sensitivities for PD detection are 94.2/83.1/42.0/34.6% at false positive rates (FPRs) of 20/10/1/0.1%, respectively. Preliminary analysis shows similar performance for AD detection. Subject to further refinement of accuracy and reproducibility, these findings show the promise of web search digital phenotypes as adjunctive screening tools for neurodegenerative disorders.
TCTAP A-071 Sirolimus Coated Balloon Angioplasty for In-stent Restenosis in Small Coronary Arteries
Authors: Sameer Dani, Keyur Parikh, Ranjan Shetty, PrathapKumar Pillai, Jagdish Hiremath, Dinesh Shah, Gaetano Di Palma, Bernardo Cortese
Journal: Journal of the American College of Cardiology (2018)
Prospective follow up of 80 patients with addictive behaviors and advanced fibrosis after treatment of chronic HCV infection with DAA: a suboptimal management
Authors: C. Barrault, Régine Truchi, J.-B. Trabut, D. Carmona, F. Roudot, E. Gelsi, A. Bachelard, Stéphanie Dominguez, I. Rosa, C. Costentin, C. Hezode, A. Tran
Journal: Journal of Hepatology (2018)
Interferon Gamma Messenger RNA Signature in Tumor Biopsies Predicts Outcomes in Patients with Non–Small Cell Lung Carcinoma or Urothelial Cancer Treated with Durvalumab
Authors: Brandon W. Higgs, Christopher A. Morehouse, Katie Streicher, Philip Z. Brohawn, Fernanda Pilataxi, Ashok Gupta, Koustubh Ranade
Journal: Clinical Cancer Research (2018)

Abstract Purpose: To identify a predictive biomarker for durvalumab, an anti–programmed death ligand 1 (PD-L1) mAb. Experimental Design: RNA sequencing of 97 advanced-stage non–small cell lung carcinoma (NSCLC) biopsies from a nonrandomized phase Ib/II clinical trial (1108/NCT01693562) were profiled to identify a predictive signature; 62 locally advanced or metastatic urothelial cancer tumors from the same study were profiled to confirm predictive utility of the signature. Thirty NSCLC patients provided pre- and posttreatment tumors for messenger RNA (mRNA) analysis. NSCLC with ≥25% tumor cells and urothelial cancer with ≥25% tumor or immune cells stained for PD-L1 at any intensity were scored PD-L1 positive (PD-L1+). Kaplan–Meier and Cox proportional hazards analyses were used to adjust for gender, age, prior therapies, histology, ECOG status, liver metastasis, and smoking. Tumor mutation burden (TMB) was calculated using data from The Cancer Genome Atlas (TCGA). Results: In the NSCLC discovery set, a four-gene IFNγ-positive (IFNγ+) signature comprising IFNγ, CD274, LAG3, and CXCL9 was associated with higher overall response rates, longer median progression-free survival, and overall survival compared with signature-low patients. IFNγ+-signature NSCLC patients had improved survival regardless of IHC PD-L1 status. These associations were replicated in a urothelial cancer cohort. The IFNγ+ signature was induced 2-fold (P = 0.003) by durvalumab after 8 weeks of therapy in patients with NSCLC, and baseline signature was associated with TMB but not survival in TCGA data. Conclusions: The IFNγ+ mRNA signature may assist in identifying patients with improved outcomes with durvalumab, independent of PD-L1 assessed by IHC. Clin Cancer Res; 24(16); 3857–66. ©2018 AACR.
Murine hepatocytes with humanized sodium taurocholat polypeptide (NTCP) limit HDV infection in vivo independent of adaptive immune responses
Authors: M. Luetgehmann, K. Giersch, T. Volz, J. Kah, L. Allweiss, A. Lohse, J. Petersen, J. Casey, C. Sureau, M. Dandri
Journal: Journal of Hepatology (2018)
Planned organ preservation for selected T2-3 rectal cancer: French experience using chemoradiotherapy and contact xray boost.
Authors: Jean-Pierre Gerard, Nicolas N. Barbet, Catherine Dejean, Ludovic Evesque, Karine Benezery, Regis Coquard, Yann Chateau, Jocelyn Gal, Jerome Doyen, Eric François
Journal: Journal of Clinical Oncology (2018)

751 Background: The Lyon R96-02 randomized trial has demonstrated in T2-3 rectal cancer that external beam radiotherapy (EBRT) with Contact X Ray brachytherapy (CXB) boost was increasing clinical complete response, sphincter preservation and in early cases organ preservation. We report French experience in 3 radiotherapy departments using CXB boost with chemoradiotherapy (CRT) in early T2T3N0. Methods: Selection based on digital rectal examination, colonoscopy, MRI (and/or Endorectal-ultrasound). Inclusion : adenocarcinoma (distal, middle rectum), T2 T3a-b, tumor diameter ≤ 4cm, N0, M0. Treatment : CXB (80-110 Gy/3-4 fr) followed by CRT (CAP 50). Tumor response assess on week 14 : DRE, rigid rectoscopy and MRI. Clinical complete response (cCR) defined as no visible tumor, supple rectal wall and TRG 1-2 on MRI. In case of cCR a close surveillance or local excision was proposed. Results: Between 2002 -2016, 84 patients treated. Median age: 75 years, Male: 59, Female: 25. Operable patients: 69 (83%). T2 : 52, T3 : 32 (Lyon Villeurbanne : 16, Macon : 11, Nice : 57). Median follow-up time : 53 months. cCR was achieved in 94% of cases. Local excision performed in 17 patients (ypT0 : 16). At 4 years, the cancer specific survival was 82% [CI:96-70] and the local relapse rate 12% [CI: 2-22]. No isolated perirectal lymph node relapse observed. After 4 years, 3 more local relapses observed (4, 6, 7 years). Main late toxicity ( &gt; 6 months after treatment) was rectal bleeding (radiation telangiectasia) which required plasma argon coagulation in 5 patients. No TME surgery was performed and organ preservation was achieved in all cases. Bowel function was good in 85% of patients (LARS score &lt; 20). Conclusions: When combining CXB with CRT, rectal cancer T2T3a-b N0 ≤4cm achieve a high rate of cCR (≥85%) with organ preservation, good bowel function, low rate of local relapse ( &lt; 15%) and low toxicity. As rectal adenocarcinoma is radioresistant, the treatment must use a CXB boost. Like anal squamous cell cancer, planned organ preservation can be proposed to operable patients. The ongoing European OPERA trial aims at bringing evidence to this option.
Outcome of children with newly diagnosed acute lymphoblastic leukemia treated with CCLG‐ALL 2008: The first nation‐wide prospective multicenter study in China
Authors: Lei Cui, Zhi‐Gang Li, Yi‐Huan Chai, Jie Yu, Ju Gao, Xiao‐Fan Zhu, Run‐Ming Jin, Xiao‐Dong Shi, Le‐Ping Zhang, Yi‐Jin Gao, Rui‐Dong Zhang, Hu‐Yong Zheng, Shao‐Yan Hu, Ying‐Hui Cui, Yi‐Ping Zhu, Yao Zou, Margaret H. L. Ng, Yan Xiao, Jun‐Hui Li, Yong‐Hong Zhang, Hai‐Long He, Ying Xian, Tian‐You Wang, Chi‐Kong Li, Min‐Yuan Wu
Journal: American Journal of Hematology (2018)

Acute lymphoblastic leukemia (ALL) is the most common malignancy among children. The trial Chinese Children Leukemia Group (CCLG)‐ALL 2008 was a prospective clinical trial designed to improve treatment outcome of childhood ALL through the first nation‐wide collaborative study in China. Totally 2231 patients were recruited from ten tertiary hospitals in eight cities. The patients were stratified according to clinical‐biological characteristics and early treatment response. Standard risk (SR) and intermediate risk (IR) groups were treated with a modified BFM based protocol, and there was 25%‐50% dose reduction during intensification phases in the SR group. Patients in high risk (HR) group received a more intensive maintenance treatment. Minimal residual disease (MRD) monitoring with treatment adjustment was performed in two hospitals (the MRD group). Complete remission (CR) was achieved in 2100 patients (94.1%). At five years, the estimate for overall survival (OS) and event‐free survival (EFS) of the whole group was 85.3% and 79.9%, respectively. The cumulative incidence of relapse (CIR) was 15.3% at five years. The OS, EFS and CIR for the SR group were 91.5%, 87.9%, and 9.7%, respectively. The outcome of the MRD group is better than the non‐MRD group (5y‐EFS: 82.4% vs 78.3%, P = .038; 5y‐CIR: 10.7% vs 18.0%, P &lt; .001). Our results demonstrated that the large‐scale multicenter trial for pediatric ALL was feasible in China. Dose reduction in the SR group could achieve high EFS. MRD‐based risk stratification might improve the treatment outcome for childhood ALL.
Local Immunomodulation with Anti-inflammatory Cytokine-Encoding Lentivirus Enhances Functional Recovery after Spinal Cord Injury
Authors: Jonghyuck Park, Joseph T. Decker, Daniel J. Margul, Dominique R. Smith, Brian J. Cummings, Aileen J. Anderson, Lonnie D. Shea
Journal: Molecular Therapy (2018)
Deep learning Radiomics of shear wave elastography significantly improved diagnostic performance for assessing liver fibrosis in chronic hepatitis B: a prospective multicentre study
Authors: Kun Wang, Xue Lu, Hui Zhou, Yongyan Gao, Jian Zheng, Minghui Tong, Changjun Wu, Changzhu Liu, Liping Huang, Tian’an Jiang, Fankun Meng, Yongping Lu, Hong Ai, Xiao-Yan Xie, Li-ping Yin, Ping Liang, Jie Tian, Rongqin Zheng
Journal: Gut (2018)

We aimed to evaluate the performance of the newly developed deep learning Radiomics of elastography (DLRE) for assessing liver fibrosis stages. DLRE adopts the radiomic strategy for quantitative analysis of the heterogeneity in two-dimensional shear wave elastography (2D-SWE) images.A prospective multicentre study was conducted to assess its accuracy in patients with chronic hepatitis B, in comparison with 2D-SWE, aspartate transaminase-to-platelet ratio index and fibrosis index based on four factors, by using liver biopsy as the reference standard. Its accuracy and robustness were also investigated by applying different number of acquisitions and different training cohorts, respectively. Data of 654 potentially eligible patients were prospectively enrolled from 12 hospitals, and finally 398 patients with 1990 images were included. Analysis of receiver operating characteristic (ROC) curves was performed to calculate the optimal area under the ROC curve (AUC) for cirrhosis (F4), advanced fibrosis (≥F3) and significance fibrosis (≥F2).AUCs of DLRE were 0.97 for F4 (95% CI 0.94 to 0.99), 0.98 for ≥F3 (95% CI 0.96 to 1.00) and 0.85 (95% CI 0.81 to 0.89) for ≥F2, which were significantly better than other methods except 2D-SWE in ≥F2. Its diagnostic accuracy improved as more images (especially ≥3 images) were acquired from each individual. No significant variation of the performance was found if different training cohorts were applied.DLRE shows the best overall performance in predicting liver fibrosis stages compared with 2D-SWE and biomarkers. It is valuable and practical for the non-invasive accurate diagnosis of liver fibrosis stages in HBV-infected patients.NCT02313649; Post-results.
Burnout and Depression Among General Surgery Residents
Authors: Julie Ann Freischlag
Journal: JAMA Surgery (2018)

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P272Protein tyrosine phosphatase non receptor type 22 (PTPN22) function impacts neutrophil extracellular trap formation
Authors: L Kascha, T Hofbauer, M P Winter, A Panzenboeck, K Distelmaier, T Scherz, A Ondracek, C Feist, A Mangold, I M Lang
Journal: Cardiovascular Research (2018)

Background: Neutrophils undergo NETosis via peptidylarginine deiminase 4 (PAD 4) activation and release extracellular traps (NETs) into the extracellular space to combat pathogens.NETs also have a significant role in thrombotic disease.Coronary NET burden correlates positively with infarct size in ST-elevation myocardial infarction (STEMI) patients.It was reported that a missense mutation (R620W) in the protein tyrosine phosphatase non receptor type 22 (PTPN22) results in abrogated PAD4 inhibition and consecutively leads to enhanced NETosis.Deoxyribonuclease (DNase) is a natural counter mechanism against NETs.Purpose: We analyzed the effect of PTPN22 deficiency on NET formation in a murine model and studied the R620W single nucleotide polymorphism (SNP) in coronary artery disease (CAD) patients with regard to outcomes.Methods: Blood was drawn from PTPN22 knockout (KO) mice, NETosis was induced by ionomycin and compared to wildtype (WT) mice (each n¼10).NETotic neutrophils were measured by flow cytometry.DNase activity in murine plasma samples was measured by an in-house built activity assay.Furthermore, we tested the R620W SNP in 711 CAD patients who suffered from ST elevation myocardial infarction using allelic discrimination polymerase chain reaction (PCR).Results: PTPN22 KO mice displayed significantly reduced NETosis compared to WT.Interestingly, PTPN22 mice had a significantly increased plasmatic DNase activity, which correlated with reduced NETosis.CAD patients carrying the R620W showed no altered mortality compared to controls.Conclusions: In contrast to present literature, we found decreased NETosis in PTPN22 KO mice.In this ongoing project, we will further evaluate NETosis and DNase in connection to PTPN22.
Soluble serum vascular adhesion protein (sVAP)-1: A new biomarker in primary sclerosing cholangitis?
Authors: F. Saffioti, P. Trivedi, C. Weston, M. Salmi, D. Roccarina, G. Hirschfield, W. Rosenberg, A. Marshall, D. Adams, D. Thorburn
Journal: Journal of Hepatology (2018)
Platelet aggregation contributing to reperfusion injury can be prevented by normothermic ex vivo liver perfusion prior to liver transplantation
Authors: D. Kollmann, I. Linares, S. Ganesh, R. Rosales, Mátyás Hamar, P. Urbanellis, A. Wiebe, P. Yip, O. Adeyi, M. Selzner, N. Selzner
Journal: Journal of Hepatology (2018)