bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dietary factors and pediatric multiple sclerosis: A case-control study
Authors: Pakpoor Julia , Seminatore Brandon , Graves Jennifer S , Schreiner Teri , Waldman Amy T , Lotze Timothy E , Belman Anita , Greenberg Benjamin M , Weinstock-Guttman Bianca , Aaen Gregory , Tillema Jan-Mendelt , McDonald Jamie C , Hart Janace , Ness Jayne M , Harris Yolanda , Rubin Jennifer , Candee Meghan , Krupp Lauren , Gorman Mark , Benson Leslie , Rodriguez Moses , Chitnis Tanuja , Mar Soe , Kahn Ilana , Rose John , Carmichael Suzan L , Roalstad Shelly , Waltz Michael , Casper T Charles , Waubant Emmanuelle ,   for the US Network of Pediatric Multiple Sclerosis Centers
Published: June 2017

Background: The role of diet in multiple sclerosis (MS) is largely uncharacterized, particularly as it pertains to pediatric-onset disease. Objective: To determine the association between dietary factors and MS in children. Methods: Pediatric MS patients and controls were recruited from 16 US centers (MS or clinically isolated syndrome onset before age 18, <4 years from symptom onset and at least 2 silent lesions on magnetic resonance imaging). The validated Block Kids Food Screener questionnaire was administered 2011–2016. Chi-squared test compared categorical variables, Kruskal–Wallis test compared continuous variables, and multivariable logistic regression analysis was performed. Results: In total, 312 cases and 456 controls were included (mean ages 15.1 and 14.4 years). In unadjusted analyses, there was no difference in intake of fats, proteins, carbohydrates, sugars, fruits, or vegetables. Dietary iron was lower in cases ( p = 0.04), and cases were more likely to consume below recommended guidelines of iron (77.2% of cases vs 62.9% of controls, p < 0.001). In multivariable analysis, iron consumption below recommended guidelines was associated with MS (odds ratio = 1.80, p < 0.01). Conclusion: Pediatric MS cases may be less likely to consume sufficient iron compared to controls, and this warrants broader study to characterize a temporal relationship. No other significant difference in intake of most dietary factors was found.
Pediatric-onset multiple sclerosis and other acquired demyelinating syndromes of the central nervous system in Denmark during 1977–2015: A nationwide population-based incidence study
Authors: Boesen Magnus Spangsberg , Magyari Melinda , Koch-Henriksen Nils , Thygesen Lau Caspar , Born Alfred Peter , Uldall Peter Vilhelm , Blinkenberg Morten 
Published: June 2017

Background: The incidence of acquired demyelinating syndromes (ADS) including multiple sclerosis (MS) has never been investigated in a Danish pediatric population. Objectives: We estimated the nationwide age- and sex-specific incidence of pediatric ADS including MS. Methods: Data were sourced from the Danish Multiple Sclerosis Registry, providing cases of pediatric MS for 1977–2015, and the National Patient Register, providing cases of ADS during 2008–2015. All medical records were reviewed to validate the register-based diagnoses. Results: We identified 364 cases of pediatric MS occurring during 1977–2015 (incidence rate = 0.79 per 100,000 person-years). MS was exceptionally rare before puberty, but the incidence rose considerably from 9 years in girls and 11 years in boys. The female-to-male ratio was 2.5; the median age at onset was 16 years (range = 7–17 years). The MS incidence rate was relatively stable through the study period. During 2008–2015, we identified 219 ADS cases. The incidence was 2.29 per 100,000 person-years with considerable differences in the age peaks for the separate ADS. Conclusion: The incidence rates of MS and other ADS in Denmark were higher than those reported for some other European countries. Referral bias and classification differences may account for this disparity, in particular the age-intervals and the definition of onset.
Venous flaps for coverage of traumatic soft tissue defects of the hand: a systematic review
Authors: Wharton R. , Creasy H. , Bain C. , James M. , Fox A. 
Published: June 2017

A PRISMA-guided systematic review was performed of all published cases that detail the use of venous flaps for soft tissue reconstruction of the hand following trauma. Outcome measures examined included flap survival rates, venous congestion, and return to theatre. Database searches were performed on Medline, Embase, AHMED, CINAHL. A total of 381 articles were identified. Data were extracted from 45 articles that met inclusion criteria. A total of 756 flaps were described and their data analysed. A total of 75% of flaps were arterialized and 25% were pure venous flaps. There was no difference in survival rate for arterialized or pure venous flaps. Unplanned return to theatre occurred in 5.3% due to flap compromise or necrosis. Early venous congestion was present in 60% of cases. Total early failure requiring re-operation occurred in 19 flaps (2.5%) of cases. Venous flaps offer a versatile and well-tolerated reconstructive option. Early venous congestion is common, but can be managed non-operatively. Level of evidence: II
Revision shoulder arthroplasty for failed humeral head resurfacing hemiarthroplasty
Authors: Thangarajah Tanujan , Ajami Sara , Coathup Melanie , Blunn Gordon W. , Higgs Deborah , Falworth Mark , Lambert Simon 
Published: June 2017

Background The purpose of the present study was to analyze and report the clinical outcomes following revision shoulder arthroplasty for failed humeral head resurfacing hemiarthroplasty (HHRH). Methods All patients who underwent revision shoulder arthroplasty for failed HHRH at our institution were retrospectively reviewed. Twenty-two shoulders in 20 patients were available for analysis. Mean age at the time of HHRH was 60 years (range 42 years to 75 years). The cohort consisted of 17 females and three males. Results The mean time from HHRH to revision was 5 years (range 1 year to 8 years). Mean age at the time of revision surgery was 62 years (range 44 years to 80 years). Patients were followed-up for a mean of 3.3 years (range 2 years to 4 years) after revision. Following revision surgery, there was an increase in forward elevation from 67° (range 0° to 130°) to 97° (range 40° to 160°) ( p = 0.04). This was accompanied by an improvement in both the Oxford Shoulder Score and the subjective shoulder value, which increased from 13 (range 2 to 28) to 39 (range 24 to 48) ( p = 0.000) and from 23 (range 0 to 65) to 79 (range 25 to 100) ( p = 0.000) respectively. Conclusions Revision shoulder arthroplasty for failed HHRH improves functional outcome.
A Preliminary Study Comparing Microfracture and Local Adherent Transplantation of Autologous Adipose-Derived Stem Cells Followed by Intraarticular Injection of Platelet-Rich Plasma for the Treatment of Chondral Defects in Rabbits
Authors: Spakova Timea , Amrichova Judita , Plsikova Jana , Harvanova Denisa , Hornak Slavomir , Ledecky Valent , Rosocha Jan 
Published: June 2017

Objective This study aimed to compare microfracture and application of adipose-derived stem cells (ADSCs) by local adherent technique enhanced by platelet-rich plasma (PRP) to provide a new approach for the repair of cartilage defect. Design Full-thickness cylindrical defects were created in the medial femoral condyle in 9 New Zealand White rabbits (5 months old, 4.65 ± 0.20 kg). Two groups of rabbits ( n = 3) were either treated with ADSCs (Group 1) or the microfracture technique (Group 2) following intraarticular injection of PRP 3 times in weekly intervals. Rabbits in control group ( n = 3) remained untreated. The outcome was assessed macroscopically, histologically, and immunohistochemically. Results At the end of week 12, Group 1 showed better defect filling compared with Group 2. Specimens treated with the combination of ADSCs and PRP exhibited significant differences from the other groups in all criteria of International Cartilage Repair Society macroscopic scoring system. Conclusions Intraarticular injection of autologous PRP in combination with transplantation of autologous ADSCs by local adherent technique enhances the quality of cartilage defect repair with better results in comparison with microfracture surgery in a rabbit model.
Platelet amyloid precursor protein is a modulator of venous thromboembolism in mice
Authors: Canobbio Ilaria , Visconte Caterina , Momi Stefania , Guidetti Gianni Francesco , Zarà Marta , Canino Jessica , Falcinelli Emanuela , Gresele Paolo , Torti Mauro 
Published: June 2017

Key Points
APP is dispensable for platelet activation and arterial thrombosis. APP is an important novel regulator of vein thrombosis and controls coagulation and neutrophil extracellular traps formation.
Cichorium intybus L. promotes intestinal uric acid excretion by modulating ABCG2 in experimental hyperuricemia
Authors: Wang Yu , Lin Zhijian , Zhang Bing , Nie Anzheng , Bian Meng 
Published: June 2017

Abstract
Background
Excessive production and/or reduced excretion of uric acid could lead to hyperuricemia, which could be a major cause of disability. Hyperuricemia has received increasing attention in the last few decades due to its global prevalence. Cichorium intybus L., commonly known as chicory, is a perennial herb of the asteraceae family. It was previously shown to exert potent hypouricemic effects linked with decreasing uric acid formation in the liver by down-regulating the activity of xanthine oxidase, and increasing uric acid excretion by up-regulating the renal OAT3 mRNA expression. The present study aimed to evaluate its extra-renal excretion and possible molecular mechanism underlying the transporter responsible for intestinal uric acid excretion in vivo.

Methods
Chicory was administered intragastrically to hyperuricemic rats induced by drinking 10% fructose water. The uricosuric effect was evaluated by determining the serum uric acid level as well as the intestinal uric acid excretion by HPLC. The location and expression levels of ATP-binding cassette transporter, sub-family G, member 2 (ABCG2) in jejunum and ileum were analyzed.

Results
The administration of chicory decreased the serum uric acid level significantly and increased the intestinal uric acid excretion obviously in hyperuricemic rats induced by 10% fructose drinking. Staining showed that ABCG2 was expressed in the apical membrane of the epithelium and glands of the jejunum and ileum in rats. Further examination showed that chicory enhanced the mRNA and protein expressions of ABCG2 markedly in a dose-dependent manner in jejunum and ileum.

Conclusion
These findings indicate that chicory increases uric acid excretion by intestines, which may be related to the stimulation of intestinal uric acid excretion via up-regulating the mRNA and protein expressions of ABCG2.
Transcriptional and epigenetic regulation of T cell hyporesponsiveness
Authors: Pereira Renata M , Hogan Patrick G , Rao Anjana , Martinez Gustavo J 
Published: June 2017

Abstract
Naive CD8+ T cells differentiate into effector and memory cytolytic T cells (CTLs) during an acute infection. In contrast, in scenarios of persistent antigen stimulation, such as chronic infections and cancer, antigen-specific CTLs show a gradual decrease in effector function, a phenomenon that has been termed CD8+ T cell “exhaustion” or “dysfunction.” Another hyporesponsive state, termed “anergy”, is observed when T cells are activated in the absence of positive costimulatory signals. Among the many negative regulators induced in hyporesponsive T cells are inhibitory cell–surface receptors, such as PD-1, LAG-3, CTLA-4, and TIM-3; “checkpoint blockade” therapies that involve treatment of patients with cancer with blocking antibodies to those receptors show considerable promise in the clinic because the blocking antibodies can mitigate hyporesponsiveness and promote tumor rejection. In this review, we describe recent advances in our molecular understanding of these hyporesponsive states. We review evidence for the involvement of diverse transcription factors, metabolic programs, and chromatin accessibility changes in hyporesponsive T cells, and we discuss how checkpoint blockade therapies affect the molecular program of CD8+ T cell exhaustion.
Routine molecular screening of advanced refractory cancer patients: An analysis of the first 2490 patients of the ProfiLER study.
Authors: Tredan Olivier , Corset Veronique , Wang Qing , Varnier Romain , Pacaud Camille , Torroja Alexia , Luppi Nicolas , Ezzalfani Monia , Myard Magali , Jiang Xiaojun , Attignon Valéry , Pissaloux Daniel , Baudet Christian , Cassier Philippe Alexandre , Fayette Jérôme , Carbonnaux Mélodie , Bonneville-Levard Alice , Viari Alain , Pérol David , Blay Jean-Yves ,   LYric Profiler Author's Group
Published: June 2017

LBA100 Background: ProfiLER (NCT01774409) is a molecular profiling clinical trial exploring cancer cell genomic alterations in pts with advanced disease to guide treatment. Methods: Pts with confirmed diagnosis of advanced cancers are eligible. DNA extracted from either archival or fresh collected tumor samples was analyzed by targeted exon sequencing of 60 cancer related genes and whole genome array comparative genomic hybridization (CGH). A multidisciplinary molecular board analyzes genomic data and recommends molecular targeted therapies (MTT) when actionable alterations are found. Results: As of Jan 2017, 2490 pts (55% female, median age 59, range 1-90) were consented; 1826 (73.3%) tumors were analyzed, 301 (12%) are ongoing (not done in 363 pts (14.6%) for technical issues). Tumor types were colorectal (10.3%), gyneco (9.5%), breast (8.8%), head & neck (7.1%) carcinomas, sarcomas (7.1%) and brain tumors (6.5%). 940/1826 pts (51.5%) had at least 1 actionable mutation (AM): 579 pts with only one AM, while 358 with 2 or more AM (up to 6). Mutations (including substitutions and small indels), amplifications and homozygous deletions (HD) were observed respectively in 55.3%, 42.1% and 25.5% of tumor samples. The most common AM were on KRAS (n = 156; 8.5%), PIK3CA (n = 150; 8.2%), CDKN2A HD (n = 174; 9.5% ), PTEN HD (n = 49, 2.7%), CCND1 (n = 97; 5.3%), FGFR1 (n = 56; 3.1%), MDM2 (n = 53; 2.9%), HER2 (n = 42; 2.3%) and HER1(n = 41; 2.2%). MTT were recommended in 644 pts. Among them, 101 (gyn [28%], GI [18%], breast [12%]) initiated a recommended MTT. Collection of treatment data is ongoing for 202 pts. MTT received were mTOR inhibitors (39%), anti-angiogenic TKI (21%), EGFR TKI (9.8%), inhibitors of cell cycle (6.9%). Best responses were CR (n = 2, 2.3%), PR (n = 13, 15.1%), SD (n = 29, 33.7%), PD (n = 42, 48.8%), with a median PFS of 2.8 months (95% IC: 2.2-3.5). 24% are alive progression free at 6 months. Updated data will be presented at the meeting. Conclusions: In this series of 2490 cancer pts, CGH and NGS identified actionable alterations on 51% of pts, with treatment recommendation in 35%. Most patients treated derived benefit from the recommended MTT, but these represent a minority of the whole population screened. Clinical trial information: NCT01774409.
SCORAD III: Randomized noninferiority phase III trial of single-dose radiotherapy (RT) compared to multifraction RT in patients (pts) with metastatic spinal canal compression (SCC).
Authors: Hoskin Peter , Misra Vivek , Hopkins Kirsten , Holt Tanya , Brown Gillian , Arnott Seonaid , Shibu Thomas Sharon , Reczko Krystyna , Beare Sandy , Lopes Andre , Forsyth Sharon 
Published: June 2017

LBA10004 Background: SCC is a common complication of metastatic cancer. Most pts receive RT to improve neurological function and mobility and to relieve pain. There is no standard schedule (RT ranges from single dose 8Gy to 40Gy in 20 fractions). SCORAD III was conducted to show whether a single fraction is as effective as multifraction RT without compromising patient outcomes. Methods: Pts from 43 UK and 4 Australian sites were randomized (1:1) to receive external beam spinal canal RT as a single dose of 8Gy or 20Gy in 5 fractions; stratified by RT center, ambulatory status (AS), site of primary, and presence or absence of nonskeletal metastases. Eligible pts had spinal cord or cauda equina (C1-S2) compression confirmed by MRI/CT scan, treatable within a single radiation field, life expectancy >8 weeks (wks), no previous RT to the same area. Primary endpoint was AS at wk 8: graded 1 (full function) to 4 (no/flicker motor power). The noninferiority margin was 11% for comparing the proportion of patients with AS 1 or 2 at wk 8 (whether maintained from baseline or improved from AS 3-4). Results: 688 pts were randomized Feb 2008 to Apr 2016 (n=345 single dose, n=343 multifraction). 73% were male; median age 70 years; ambulatory with/without walking aids 66%; 44% prostate, 18% lung, 11% breast, 11% gastrointestinal. Baseline characteristics were balanced. 69.5% (114/164 pts evaluable at wk 8) single dose vs. 73.3% (129/176) multifraction had AS 1-2 at wk 8 (risk difference: -3.78%, 90%CI -11.85 to 4.28). Importantly, overall survival (OS) was very similar: median OS 12.4 wks single dose vs. 13.7 multifraction, (hazard ratio 1.02 [95%CI 0.86-1.21], p=0.81). Proportion of pts with adverse events was similar for grade 3-4 (20.6% single dose vs. 20.4% multifraction), but grade 1-2 events were lower with single dose (51.0% vs. 56.9%). Conclusions: Using a single dose of 8Gy in pts with metastatic SCC was as effective as multiple fractions for AS at 8 wks and OS. We now recommend using single dose RT in this setting, with the major benefit of requiring only a single instead of multiple hospital visits, important when considering the short survival in these pts. Clinical trial information: 97108008.
Performance of a high-intensity 508-gene circulating-tumor DNA (ctDNA) assay in patients with metastatic breast, lung, and prostate cancer.
Authors: Razavi Pedram , Li Bob T. , Abida Wassim , Aravanis Alex , Jung Byoungsok , Shen Ronglai , Hou Chenlu , De Bruijn Ino , Gnerre Sante , Lim Raymond S. , Reales Dalicia , Maddala Tara , Berger Michael F. , Riely Gregory J. , Scher Howard I. , Novotny William F. , Solit David B. , Lee Mark , Reis-Filho Jorge S. , Baselga Jose 
Published: June 2017

LBA11516 Background: ctDNA assays can noninvasively assess tumor burden and biology by identifying tumor-derived somatic alterations. For broad applicability, including early cancer detection, an unprecedented high-intensity approach (ultra-deep sequencing of plasma cell-free DNA (cfDNA) with broad genomic coverage) is needed to address intra-patient and population-level heterogeneity. We present initial results with this approach in patients (pts) with metastatic breast (BC), non-small cell lung (NSCLC), and castration-resistant prostate cancer (CRPC). Methods: Blood and tissue were prospectively collected w/in 6 wks with no intervening therapy change from pts with de novo or progressive cancer. cfDNA and white blood cell (WBC) genomic DNA from each pt were sequenced with a 508-gene panel (2 Mb; >60,000X raw depth). cfDNA variant calling used molecular barcoding for error correction and filtering for WBC variants. Tissue was sequenced using the MSK-IMPACT assay (410 genes, 1.4 Mb, >500X depth) blinded to plasma/WBC sequencing. Variants were classified as clonal or subclonal based on tumor sequencing in BC and NSCLC. Results: Of 161 eligible pts, 124 (39 BC, 41 NSCLC, and 44 CRPC) were evaluable for concordance. In tissue, 864 variants were detected across the 3 tumor types, with 627 (73%) also detected in plasma: single nucleotide variants/indels - 75%, fusions - 67%, and copy number alterations - 58%. In 90% of pts, at least 1 of the variants detected in tumor tissue was also detected in plasma: BC - 97%, NSCLC - 85%, CRPC - 84%. Most actionable mutations detected in tissue were also detected in plasma (54/71, 76%; SNVs only: 28/31, 90%). A subset of driver mutations (eg. in ESR1, PIK3CA, ERBB2, EGFR) were observed in plasma but not tissue. Clonal variants in tissue were more likely to be detected in plasma than subclonal variants (p<.001). Conclusions: This novel, high-intensity ctDNA assay enabled broad detection of genomic variants in plasma at high rates of concordance with corresponding tumor tissue, providing strong evidence for tumor-derivation of these signals. This study will inform development of a high-intensity sequencing approach for early cancer detection.
The efficacy of larotrectinib (LOXO-101), a selective tropomyosin receptor kinase (TRK) inhibitor, in adult and pediatric TRK fusion cancers.
Authors: Hyman David Michael , Laetsch Theodore Willis , Kummar Shivaani , DuBois Steven G. , Farago Anna F. , Pappo Alberto S. , Demetri George D. , El-Deiry Wafik S. , Lassen Ulrik Niels , Dowlati Afshin , Brose Marcia S. , Boni Valentina , Turpin Brian , Nagasubramanian Ramamoorthy , Cruickshank Scott , Cox Michael Craig , Ku Nora C. , Hawkins Douglas S. , Hong David S. , Drilon Alexander E. 
Published: June 2017

LBA2501 Background: Larotrectinib is the first selective small-molecule pan-TRK inhibitor. TRK fusions appear oncogenic independent of tumor lineage, are widely distributed across cancers, and affect all ages. We present an integrated dataset from 3 studies intended to support regulatory approval. Methods: All NTRK fusion pts with RECIST measurable disease enrolled to the adult (NCT02122913, n=8) and pediatric (NCT02637687, n=12) phase I trials and adult/adolescent phase 2 trial (NCT02576431, n=35) were analyzed. TRK fusion status was determined by local testing prior to enrollment. Pts were dosed predominantly at 100mg BID on a continuous 28-day schedule. Primary objective was investigator-assessed overall response rate (ORR) per RECIST v1.1. Secondary endpoints included duration of response (DOR) and safety. Data were cut on 31-JAN-2017. Results: 55 TRK fusion pts (12 peds, 43 adult, range: 4 mo.-76 yrs) were enrolled (median priors=2). Fusions involved NTRK1 (n=25), NTRK2 (n=1), and NTRK3 (n=29), and 14 unique partners. 13 discrete tumor types were treated: salivary (12), sarcoma (10), infantile fibrosarcoma (7), lung (5), thyroid (5), colon (4), melanoma (4), cholangio (2), GIST (2), and other (4). For the 46 pts evaluated to date, the ORR was 78% (95% CI: 64%–89%) with responses in 12 unique tumor types. Responses are ongoing in 29/33 (88%) pts, excluding 3 peds pts whose DOR was censored at attempted curative resection. A median DOR has not been reached as the majority of responders remain on treatment without progression. The longest responder remains on treatment at 23 mos., 8 pts remain in response at >12 mos., and 16 pts at >6 mos. NTRK solvent front mutations were detected in all 4 pts to develop acquired resistance. The most common TEAEs were fatigue (30%), dizziness (28%), and nausea (28%). 5 (11%) pts required dose reductions. Conclusions: Larotrectinib has demonstrated consistent and durable antitumor activity in TRK fusion cancers, across a wide range of ages and tumor types, and was well-tolerated. Larotrectinib could be the first targeted therapy developed in a tissue type-agnostic manner, and the first developed simultaneously in adults and pediatrics. Clinical trial information: NCT02576431, NCT02122913, NCT02637687.