tbuckley/cabot-search huggingface dataset:
Effect of Attendance of the Child on Body Weight, Energy Intake, and Physical Activity in Childhood Obesity Treatment
Authors: Kerri N. Boutelle, Kyung E. Rhee, June Liang, Abby Braden, Jennifer Douglas, David Strong, Cheryl L. Rock, Denise E. Wilfley, Leonard H. Epstein, Scott J. Crow
Journal: JAMA Pediatrics (2017)

<h3>Importance</h3> Family-based weight loss treatment (FBT) is considered the gold-standard treatment for childhood obesity and is provided to the parent and child. However, parent-based treatment (PBT), which is provided to the parent without the child, could be similarly effective and easier to disseminate. <h3>Objective</h3> To determine whether PBT is similarly effective as FBT on child weight loss over 24 months. Secondary aims evaluated the effect of these 2 treatments on parent weight loss, child and parent dietary intake, child and parent physical activity, parenting style, and parent feeding behaviors. <h3>Design, Setting, and Participants</h3> Randomized 2-arm noninferiority trial conducted at an academic medical center, University of California, San Diego, between July 2011 and July 2015. Participants included 150 overweight and obese 8- to 12-year-old children and their parents. <h3>Interventions</h3> Both PBT and FBT were delivered in 20 one-hour group meetings with 30-minute individualized behavioral coaching sessions over 6 months. Treatments were similar in content; the only difference was the attendance of the child. <h3>Main Outcomes and Measures</h3> The primary outcome measure was child weight loss (body mass index [BMI] and BMI<i>z</i>score) at 6, 12, and 18 months post treatment. Secondary outcomes were parent weight loss (BMI), child and parent energy intake, child and parent physical activity (moderate to vigorous physical activity minutes), parenting style, and parent feeding behaviors. <h3>Results</h3> One hundred fifty children (mean BMI, 26.4; mean BMI<i>z</i>score, 2.0; mean age, 10.4 years; 66.4% girls) and their parent (mean BMI, 31.9; mean age, 42.9 years; 87.3% women; and 31% Hispanic, 49% non-Hispanic white, and 20% other race/ethnicity) were randomly assigned to either FBT or PBT. Child weight loss after 6 months was −0.25 BMI<i>z</i>scores in both PBT and FBT. Intention-to-treat analysis using mixed linear models showed that PBT was noninferior to FBT on all outcomes at 6-, 12-, and 18-month follow-up with a mean difference in child weight loss of 0.001 (95% CI, −0.06 to 0.06). <h3>Conclusions and Relevance</h3> Parent-based treatment was as effective on child weight loss and several secondary outcomes (parent weight loss, parent and child energy intake, and parent and child physical activity). Parent-based treatment is a viable model to provide weight loss treatment to children. <h3>Trial Registration</h3> Clinicaltrials.gov Identifier:NCT01197443
The value of computerised neurocognitive testing at medical clearance to return to play following a sport-related concussion in youth ice hockey players
Authors: Amanda M Black, Brian L Brooks, Regan S McLeod, Luz Palacios-Derflingher, Kathryn J Schneider, Tracy A Blake, Kirsten A Taylor, Willem H Meeuwisse, Carolyn A Emery
Journal: British Journal of Sports Medicine (2017)

Objective To determine the value of the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) tool in measuring neurocognitive recovery following concussion. Design Nested case-control. Setting Sport Medicine Centre, Alberta, Canada. Participants Ice hockey players (n=96; 88.5% male, 11-17 years old) following concussion who completed ImPACT at baseline and medical clearance to return to play (RTP) were compared to controls (n=31) matched for age, sex, and testing time interval. Assessment of risk factors Players who sustained a concussion were referred to a study physician for assessment and RTP clearance based on clinical assessment and SCAT2/3. Physicians were blinded to ImPACT scores. Outcome measures ImPACT composite scores were measured (i.?e., verbal memory, visual memory, reaction time, visual motor) at each time interval [i.e., baseline and RTP (cases)/second measurement (controls)]. Between-interval ImPACT reliable change scores (80%CI) were compared. Main results At RTP (Median days since injury: 22, range: 2–84), 43/96 (44.8%) concussed players and 11/31 (35.5%) controls had ≥1 composite scores reliably worse than at baseline. Conditional logistic regression analysis (n=31 matched pairs) did not demonstrate a difference in the odds of having ≥1 reliably worse composite score between concussed and controls [OR=2.00 (95% CI: 0.5–8.0)] or ≥1 reliably better composite score [OR=1.2 (95% CI: 0.37–3.93)]. Conclusions The utility of baseline ImPACT scores in medical decisions to RTP may be limited by the reliability of composite scores in youth populations. Caution is warranted when interpreting ImPACT scores post-concussion on an individual level using baseline performance. Future research including multivariable analyses is warranted in a larger sample. Competing interests Brian Brooks is a co-author of a paediatric memory test for which he receives royalties. No financial interests in ImPACT are declared. None for all other authors.
Profiling head accelerations using triaxial accelerometery during ‘bodies in front’ training play: a preliminary study of the sport of rugby league
Authors: Stephen J Atkins, Ian Bentley, Howard T Hurst, Mark E Mark E, Cassandra Richardson, Jonathan K Sinclair
Journal: British Journal of Sports Medicine (2017)

Objective To provide unique descriptive information on head accelerations, both linear and rotational, during ‘bodies in front’ training play. Design A convenience sample were tested using a cross-sectional design. Players wore a triaxial accelerometer (XPatch, X2 Biosystems, Seattle) during two sessions of training gameplay (session duration 142±26 min). Accelerometers were affixed on the left side of the head, at a point approximate to the external occipital protuberance. Setting Testing was undertaken at an elite performance training centre. Participants 20 elite, professional, rugby league players. Main outcome measures Minimum recordable accelerations were set at 10 g (linear acceleration) and 25 rads s -2 (rotational acceleration). Results A total of 1256 recorded ‘hits’ were analysed, excluding evident artefacts. No player was reported to have suffered a concussion. Player ‘loading’ was 46±33 hits per session (range 7–170). Average linear (14.9±8.8 g) and rotational (532±347 rads s -2 ) accelerations were not significantly different between training sessions (P&gt;0.05). Frequency of hits are summarised in the table below. Abstact 20 Table 1 Linear acceleration (g) Cumulative% Rotational acceleration (rads s –2 ) Cumulative% 10–20 92.6 25–500 64.7 21–40 5.4 501–1000 27.5 41–60 0.7 1001–2000 5.4 61–80 0.5 2001–3000 1.6 81–100 0.4 3001–4000 0.8 &gt;101 0.4 &gt;4001 0 Conclusions The majority of head accelerations occurred within lower ‘sub-concussive’ zones. This confirms existing research findings from other sports. Whilst few accelerations occurred in higher zones, there were a number of very high loading impacts observed in ‘hit up forward’ positions. Our research confirms the suitability of using portable accelerometers in determining head accelerations in full-contact, ‘armourless’, invasion games. Competing interests None.
Purpuric Drug Eruptions Caused by Epidermal Growth Factor Receptor Inhibitors for Non–Small Cell Lung Cancer
Authors: Yung-Tsu Cho, Kai-Lung Chen, Yi-Shuan Sheen, Che-Wen Yang, Jau-Yu Liau, Yu-Pin Cheng, Chia-Yu Chu
Journal: JAMA Dermatology (2017)

Purpuric skin lesions have only rarely been reported in patients receiving epidermal growth factor receptor inhibitors. However, their clinical and histopathologic presentations have varied considerably.To characterize purpuric skin eruptions caused by epidermal growth factor receptor inhibitors.This prospective study enrolled 32 patients who presented to an integrated dermato-oncologic clinic in a tertiary referral medical center with purpuric skin lesions after using epidermal growth factor receptor inhibitors from January 1, 2013, through December 31, 2015.Epidermal growth factor receptor tyrosine kinase inhibitors, including gefitinib, erlotinib, and afatinib.Clinical presentations, histopathologic features, laboratory examinations, and treatment outcomes of patients with purpuric drug eruptions.Thirty-two patients, 14 with purpuric drug eruptions without pustules (mean [SD] age, 60 [11] years; 12 female and 2 male) and 18 with purpuric drug eruptions with pustules (mean [SD] age, 64 [11] years; 12 female and 6 male), were identified. The median time to development of skin lesions was 3.5 months. The clinical presentations were characterized by purpuric macules, papules, and confluent plaques predominantly on the lower extremities. Pustules in various sizes could be found in 18 patients (56%). Eleven patients (34%) had skin lesions that covered places other than the lower extremities. Eczema craquelé-like features developed in 13 patients (41%). Bacterial pathogens were frequently identified in these skin lesions. Among them, Staphylococcus aureus was the most predominant and was found in 20 patients (63%), commonly in those with cutaneous pustules. Epidermal dysmaturation, neutrophil exocytosis, perivascular infiltration of lymphocytes and neutrophils, red blood cell extravasation, and plumping endothelium were the main histopathologic features. The expressions of filaggrin and human β-defensin 2 in lesional skin of these patients were markedly reduced. All patients improved after receiving at least 1 week of systemic antibiotic treatment; the doses of epidermal growth factor receptor inhibitors were also changed for 14 patients (44%).Purpuric drug eruptions caused by epidermal growth factor receptor inhibitors are uncommon and have characteristic clinical and histopathologic presentations. The role of bacterial pathogens in this reaction is important and requires further exploration.
TRTH-05. PREDICTORS OF SUCCESS OF PHASE 2 PAEDIATRIC ONCOLOGY CLINICAL TRIALS
Authors: Laura Franshaw, Maria Tsoli, Jennifer Byrne, Siva Sivarajasingam, Murray Norris, Glenn Marshall, David Ziegler
Journal: Neuro-Oncology (2017)

The rarity of childhood cancer, and high cure rates, mean only a limited number of novel therapies can be tested in patients with relapsed or refractory disease. Despite this, most novel therapeutic strategies fail in early phase trials. Of those that successfully pass through the different stages of clinical development, there is little evidence to identify the factors that influenced success. To better improve clinical success rates, we examined the impact of 23 preclinical and trial design variables for their influence on the success of 135 Phase 2 paediatric oncology clinical trials. Trial success was determined by an objective assessment of patient response, with data analysed using Fisher’s Exact or Pearson’s Chi-Square tests, and multivariate analysis using logistic regression models. For 61% of trials (83/135), no relevant preclinical experiments were performed. For those trials where preclinical studies were carried out (52/135 [39%]), there was no evidence the conduct of any preclinical experiments made the trial more likely to succeed. The only factors that positively influenced success related to trial design. Trials that evaluated patients with a single histological cancer type were significantly more likely to succeed than those that assessed multiple cancer types (67% versus 47%, 27%, and 17% for 1, 2–3, 4–7 and 8+; P<0·005). Liquid or solid tumour trials were more successful than central nervous system trials, or combined trials (67%, 61%, 37%, and 23%; P=0·005). Trials of combination therapies were more successful than single agents (70% versus 28%; P<0·005). Trials initiated based on adult studies were less likely to be successful, whereas trials initiated based on prior paediatric studies were more successful. Overall, the results of this study have the potential to change the way not only preclinical research is conducted and assessed prior to trial initiation but how clinical research is designed and performed moving forward.
PDTM-06. TARGETED CATALYTIC INHIBITION OF EZH2 SYNERGIZES WITH LOW-DOSE PANOBINOSTAT IN MALIGNANT RHABDOID TUMOR
Authors: Dean Popovski, Catherine R Cochrane, Elizabeth M Algar, Anette Szczepny, W Samantha Jayasekara, David M Ashley, Peter Downie, D Neil Watkins, Jason E Cain
Journal: Neuro-Oncology (2017)

Malignant Rhabdoid Tumor (MRT) is a rare pediatric cancer predominant in the kidney and CNS that is resistant to current treatment regimes. MRT is genetically characterized by homozygous inactivation of SMARCB1, a core subunit of the SWI/SNF chromatin-remodeling complex. Next-generation sequencing data demonstrates SMARCB1 loss is the primary driver mutation, implicating epigenetic dysregulation in pathogenesis of MRT. Recently, we showed that sustained treatment of MRT cell lines with low-dose Panobinostat (LBH589), inhibited tumor growth through driving multi-lineage differentiation in vitro and in vivo. Furthermore, physiological re-expression of SMARCB1 in G401 MRT cells phenocopied the low-dose LBH589 treatment and led to growth inhibition, senescence and terminal differentiation in vitro and in vivo. EZH2, a core subunit of the Polycomb Repressive Complex 2, confers transcriptional silencing via methylation at Lysine 27 of Histone 3 (H3K27me3), and is a transcriptional target of SMARCB1. Interestingly, EZH2 expression and H3K27me3 were drastically reduced following sustained low-dose LBH589 treatment and re-expression of SMARCB1 in G401 MRT cells. Sustained siRNA knockdown of EZH2 in G401 cells demonstrated similar cellular growth reduction and changes in mRNA expression as those observed following low-dose LBH589 treatment and SMARCB1 re-expression. However, MRT cells treated with EZH2-catalytic inhibitor GSK-126, had no effect on EZH2 expression and moderately reduced cell growth and H3K27me3 at doses 1nM-10μM suggesting important non-catalytic EZH2 function. Interestingly, MRT cells treated in combination with low-dose LBH589 and GSK-126, had diminished EZH2 and H3K27me3 expression and exhibited reduced cell growth in vitro compared to single agent controls, revealing a synergistic relationship. In vivo xenograft models of low-dose LBH589 and GSK-126 treatment produced a marked reduction in tumor growth, not observed with single agent treatments. This data positions EZH2 as an important mediator of MRT proliferation and provides evidence for dual therapeutic targeting of EZH2 with low-dose HDACi in MRT.
Chimeric antigen receptor modified T cells that target chemokine receptor CCR4 as a therapeutic modality for T‐cell malignancies
Authors: Liyanage P. Perera, Meili Zhang, Masao Nakagawa, Michael N. Petrus, Michiyuki Maeda, Marshall E. Kadin, Thomas A. Waldmann, Pin‐Yu Perera
Journal: American Journal of Hematology (2017)

With the emerging success of treating CD19 expressing B cell malignancies with ex vivo modified, autologous T cells that express CD19-directed chimeric antigen receptors (CAR), there is intense interest in expanding this evolving technology to develop effective modalities to treat other malignancies including solid tumors. Exploiting this approach to develop a therapeutic modality for T cell malignancies for which the available regimens are neither curative, nor confer long term survival we generated a lentivirus-based CAR gene transfer system to target the chemokine receptor CCR4 that is over-expressed in a spectrum of T cell malignancies as well as in CD4+ CD25+ Foxp3+ T regulatory cells that accumulate in the tumor microenvironment constituting a barrier against anti-tumor immunity. Ex vivo modified, donor-derived T cells that expressed CCR4 directed CAR displayed antigen-dependent potent cytotoxicity against patient-derived cell lines representing ATL, CTCL, ALCL and a subset of HDL. Furthermore, these CAR T cells also eradicated leukemia in a mouse xenograft model of ATL illustrating the potential utility of this modality in the treatment of a wide spectrum of T cell malignancies.
A Case–Control Study of Maternal Polybrominated Diphenyl Ether (PBDE) Exposure and Cryptorchidism in Canadian Populations
Authors: Cynthia G. Goodyer, Shirley Poon, Katarina Aleksa, Laura Hou, Veronica Atehortua, Amanda Carnevale, Roman Jednak, Sherif Emil, Darius Bagli, Sumit Dave, Barbara F. Hales, Jonathan Chevrier
Journal: Environmental Health Perspectives (2017)

Background: Polybrominated diphenyl ethers (PBDEs) are flame retardants found in North American household products during the past four decades. These chemicals leach out in dust as products age, exposing individuals daily through inhalation and ingestion. Animal studies suggest that PBDEs disrupt sex hormones and adversely affect development of the reproductive system. Objectives: In the present study, we examined whether there is a link between maternal hair PBDE concentrations and the risk of cryptorchidism (undescended testes) in male infants; testis descent is known to be dependent on androgens. Methods: Full-term male infants were recruited through clinics in Montreal, Toronto, and London, Canada. Boys with cryptorchidism at 3–18 months of age (n=137) were identified by pediatric urologists and surgeons; similar-aged controls (n=158) had no genitourinary abnormalities as assessed by pediatricians. Eight BDE congeners (BDE-28, -47, -99, -100, -153, -154, -183, -209) were measured by GC-MS (gas chromatography–mass spectrometry) in maternal hair samples collected at the time of recruitment. Results: The ∑PBDE geometric mean for maternal hair was 45.35 pg/mg for controls and 50.27 pg/mg for cases; the concentrations of three BDEs (BDE-99, -100, and -154) were significantly higher in cases than controls in unadjusted models. In adjusted models, every 10-fold increase in the concentration of maternal hair BDE-99 [OR=2.53 (95% CI: 1.29, 4.95)] or BDE-100 [OR=2.45 (95% CI: 1.31, 4.56)] was associated with more than a doubling in the risk of cryptorchidism. BDE-154 [OR=1.88 (95% CI: 1.08, 3.28)] was also significant. Conclusions: Our results suggest that maternal exposure to BDE-99, -100, and -154 may be associated with abnormal migration of testes in the male fetus. This may be due to the anti-androgenic properties of the PBDEs. https://doi.org/10.1289/EHP522
An Uncommon Occupational Lesion
Authors: Agnès Dupret-Bories, Vincent Sibaud, Aymeric André
Journal: JAMA Surgery (2017)

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Epidemiology of athletic trainer services for concussions among us high school student-athletes
Authors: Erin B Wasserman, Zachary Y Kerr, Thomas P Dompier
Journal: British Journal of Sports Medicine (2017)

Objective This study examined athletic trainer (AT) services for sports-related concussion among high school (HS) student-athletes during the 2011/12–2013/14 academic years. Design Descriptive epidemiology. Setting Concussion data originated from the National Athletic Trainers Injury and Outcomes Network (NATION), a US-wide surveillance program comprised of a convenience sample of 127 HS. All concussions were diagnosed and reported by ATs. Participants Our sample included 1662 concussions with service data among HS student-athletes from 22 sports; 48.0% were in football; 8.2% were recurrent. Of 607 concussions in sex-comparable sports, 52.7% were among females. Assessment of risk factors We examined outcome measures by sport (American football vs. non-football), sex, and whether the concussion was reported as recurrent. Outcome measures ATs reported the number and types of AT room visits and services. We compared the means of these measures by sport, sex, and recurrence using independent samples t-tests. Main results There were 15,698 AT room visits reported (mean=9.5 per concussion; Standard Deviation [SD]=7.4). ATs provided an average 1.2 (SD=0.3) services per visit. No differences existed by sport or recurrence. In sex-comparable sports, females had a mean 12.2 (SD=10.5) visits compared to 9.5 (SD=7.0) among males (p&lt;0.001). No sex differences existed in services per visit. Conclusions There are more AT room visits per concussion among females than males in sex-comparable sports. This is likely related to previous research finding symptom resolution time is longer in females than males. Identifying concussions that will require more AT services may help with resource allocation and planning for ATs. Competing interests This project was funded by the National Athletic Trainers’ Association Research and Education Foundation (NATAREF), and the Central Indiana Corporate Partnership (CICP) Foundation in cooperation with BioCrossroads. The content of this report is solely the responsibility of the authors and does not necessarily reflect the views of the NATAREF, CICP Foundation or BioCrossroads.
Phase Ib Pilot Study to Evaluate Reparixin in Combination with Weekly Paclitaxel in Patients with HER-2–Negative Metastatic Breast Cancer
Authors: Anne F. Schott, Lori J. Goldstein, Massimo Cristofanilli, Pier Adelchi Ruffini, Susan McCanna, James M. Reuben, Raymond P. Perez, Giraldo Kato, Max Wicha
Journal: Clinical Cancer Research (2017)

Abstract Purpose: Chemokine receptor 1 (CXCR1) is recognized as an actionable receptor selectively expressed by breast cancer stem cells (BCSCs). Reparixin is an investigational allosteric inhibitor of chemokine receptors 1 and 2 (CXCR1/2), and demonstrates activity against BCSCs in human breast cancer xenografts. This phase Ib clinical trial examined dose, safety, and pharmacokinetics of paclitaxel plus reparixin therapy, and explored effects of reparixin on BCSCs in patients with metastatic breast cancer (MBC) (trial registration ID: NCT02001974). Experimental Design: Eligible patients had MBC and were candidates for paclitaxel therapy. Study treatment included a 3-day run-in with reparixin oral tablets three times a day, followed by paclitaxel 80 mg/m2/week (days 1, 8, and 15 for 28-day cycle) + reparixin tablets three times a day for 21/28 days; three dose cohorts were examined in a 3+3 dose escalation schema. Additional patients were recruited into an expansion cohort at the recommended phase II dose to further explore pharmacokinetics, safety, and biological effects of the combination therapy. Results: There were neither G4–5 adverse events nor serious adverse events related to study therapy and no interactions between reparixin and paclitaxel to influence their respective pharmacokinetic profiles. A 30% response rate was recorded, with durable responses &amp;gt;12 months in two patients. Exploratory biomarker analysis was inconclusive for therapy effect on BCSCs. Conclusions: Weekly paclitaxel plus reparixin in MBC appeared to be safe and tolerable, with demonstrated responses in the enrolled population. Dose level 3, 1200 mg orally three times a day, was selected for further study in a randomized phase II trial (NCT02370238). Clin Cancer Res; 23(18); 5358–65. ©2017 AACR.