bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physical activity and television watching in relation to semen quality in young men
Authors: Gaskins Audrey Jane , Mendiola Jaime , Afeiche Myriam , Jørgensen Niels , Swan Shanna H , Chavarro Jorge E 
Published: February 2013

BackgroundSemen quality appears to have declined over the past decades but reasons for this decline are unresolved. The concurrent increase in sedentary behaviour may be a contributing factor. The objective of this study was to evaluate the relationship of physical activity and television (TV) watching with sperm parameters in a population of young, healthy men.MethodsMen aged 18–22 years (n=189) from the Rochester Young Men's Study (2009–2010) participated in this analysis. Physical activity (h/week of moderate and vigorous exercise) and TV watching (h/week of TV, video or DVD watching) over the past 3 months were assessed via questionnaire. Semen quality was assessed by sperm concentration, motility, morphology and total sperm count.ResultsSperm concentration and total sperm count were directly related to physical activity after multivariable adjustment (p-trend=0.01 and 0.04); men in the highest quartile of moderate-to-vigorous activity (≥15 h/week) had 73% (95% CI 15% to 160%) higher sperm concentration than men in the lowest quartile (<5 h/week). TV watching was inversely associated with sperm concentration and total sperm count in multivariable analyses (p-trend=0.05 and 0.06); men in the highest quartile of TV watching (>20 h/week) had 44% (95% CI 15 to 63%) lower sperm concentration than men in the lowest quartile (0 h/week). These measures of physical and leisure time activities were not significantly associated with sperm motility or morphology.ConclusionsIn this population of healthy men, higher moderate-to-vigorous activity and less TV watching were significantly associated with higher total sperm count and sperm concentration.
Frequent alcohol, nicotine or cannabis use is common in young persons presenting for mental healthcare: a cross-sectional study
Authors: Hermens Daniel F , Scott Elizabeth M , White Django , Lynch Marta , Lagopoulos Jim , Whitwell Bradley G , Naismith Sharon L , Hickie Ian B 
Published: February 2013

ObjectivesTo determine the prevalence of recent alcohol, nicotine or cannabis use in young persons presenting for mental healthcare.DesignA cross-sectional study of young people seeking mental healthcare completed self-report questionnaires regarding their use of alcohol, nicotine or cannabis.SettingData were collected from two sites as part of the nationalheadspaceservices programme.Participants2122 young people aged 12–30 years provided information as part of a patient register; a subset of N=522 participants also provided more detailed information about their patterns of alcohol use.Outcome measuresPrevalence levels of recent alcohol, nicotine or cannabis use within relevant age bands (12–17, 18–19 and 20–30) or primary diagnostic categories.ResultsThe rates for useat least weeklyof alcohol for the three age bands were 12%, 39% and 45%, and for cannabis 7%, 14% and 18%, respectively. The rates ofdailynicotine use for the three age bands were 23%, 36% and 41%. The pattern of alcohol use was characterised by few abstainers as well as many risky drinkers. Age of onset across all three substances was approximately 15 years. Individuals who used any of the three substances more frequently were likely to be older, male or have psychotic or bipolar disorders.ConclusionsFrequent use of alcohol, nicotine or cannabis in young people seeking mental healthcare is common. Given the restricted legal access, the patterns of use in those aged 12–17 years are particularly notable. Reductions in substance use needs to be prioritised within services for at-risk young people.
HAMPI
Authors: Kiezun Adam , Ganesh Vijay , Artzi Shay , Guo Philip J. , Hooimeijer Pieter , Ernst Michael D. 
Published: February 2013

Many automatic testing, analysis, and verification techniques for programs can be effectively reduced to a constraint-generation phase followed by a constraint-solving phase. This separation of concerns often leads to more effective and maintainable software reliability tools. The increasing efficiency of off-the-shelf constraint solvers makes this approach even more compelling. However, there are few effective and sufficiently expressive off-the-shelf solvers for string constraints generated by analysis of string-manipulating programs, so researchers end up implementing their own ad-hoc solvers.
To fulfill this need, we designed and implemented Hampi, a solver for string constraints over bounded string variables. Users of Hampi specify constraints using regular expressions, context-free grammars, equality between string terms, and typical string operations such as concatenation and substring extraction. Hampi then finds a string that satisfies all the constraints or reports that the constraints are unsatisfiable.

We demonstrate Hampi's expressiveness and efficiency by applying it to program analysis and automated testing. We used Hampi in static and dynamic analyses for finding SQL injection vulnerabilities in Web applications with hundreds of thousands of lines of code. We also used Hampi in the context of automated bug finding in C programs using dynamic systematic testing (also known as concolic testing). We then compared Hampi with another string solver, CFGAnalyzer, and show that Hampi is several times faster. Hampi's source code, documentation, and experimental data are available at http://people.csail.mit.edu/akiezun/hampi
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A CD90+ Tumor-Initiating Cell Population with an Aggressive Signature and Metastatic Capacity in Esophageal Cancer
Authors: Tang Kwan Ho , Dai Yong Dong , Tong Man , Chan Yuen Piu , Kwan Pak Shing , Fu Li , Qin Yan Ru , Tsao Sai Wah , Lung Hong Lok , Lung Maria L. , Tong Daniel K. , Law Simon , Chan Kwok Wah , Ma Stephanie , Guan Xin Yuan 
Published: February 2013

AbstractTumor-initiating cells (TIC), also known as cancer stem cells, are regarded widely as a specific subpopulation of cells needed for cancer initiation and progression. TICs have yet to be identified in esophageal tumors that have an increasing incidence in developed countries. Here, we report a CD90+ cell population found in esophageal squamous cell carcinoma (ESCC), which is endowed with stem cell–like properties and high tumorigenic and metastatic potential. mRNA profiling of these cells suggested pathways through which they drive tumor growth and metastasis, with deregulation of an Ets-1/MMP signaling pathway and epithelial–mesenchymal transition figuring prominently. These cells possessed higher self-renewal activity and were sufficient for tumor growth, differentiation, metastasis, and chemotherapeutic resistance. CD90+ TICs were isolated and characterized from ESCC clinical specimens as well as ESCC cell lines. In freshly resected clinical specimens, they represented a rare cell population, the levels of which correlated with strong family histories and lymph node metastasis. Our results prompt further study of this CD90+ population of esophageal TICs as potential therapeutic targets. Cancer Res; 73(7); 2322–32. ©2013 AACR.
Sunlight UV-Induced Skin Cancer Relies upon Activation of the p38α Signaling Pathway
Authors: Liu Kangdong , Yu Donghoon , Cho Yong-Yeon , Bode Ann M. , Ma Weiya , Yao Ke , Li Shengqing , Li Jixia , Bowden G. Tim , Dong Ziming , Dong Zigang 
Published: February 2013

Abstract
The activation of cellular signal transduction pathways by solar ultraviolet (SUV) irradiation plays a vital role in skin tumorigenesis. Although many pathways have been studied using pure ultraviolet A (UVA) or ultraviolet B (UVB) irradiation, the signaling pathways induced by SUV (i.e., sunlight) are not understood well enough to permit improvements for prevention, prognosis, and treatment. Here, we report parallel protein kinase array studies aimed at determining the dominant signaling pathway involved in SUV irradiation. Our results indicated that the p38-related signal transduction pathway was dramatically affected by SUV irradiation. SUV (60 kJ UVA/m2/3.6 kJ UVB/m2) irradiation stimulates phosphorylation of p38α (MAPK14) by 5.78-fold, MSK2 (RPS6KA4) by 6.38-fold, and HSP27 (HSPB1) by 34.56-fold compared with untreated controls. By investigating the tumorigenic role of SUV-induced signal transduction in wild-type and p38 dominant-negative (p38 DN) mice, we found that p38 blockade yielded fewer and smaller tumors. These results establish that p38 signaling is critical for SUV-induced skin carcinogenesis. Cancer Res; 73(7); 2181–8. ©2013 AACR.
Human Regulatory T Cells Do Not Suppress the Antitumor Immunity in the Bone Marrow: A Role for Bone Marrow Stromal Cells in Neutralizing Regulatory T Cells
Authors: Guichelaar Teun , Emmelot Maarten E. , Rozemuller Henk , Martini Bianka , Groen Richard W.J. , Storm Gert , Lokhorst Henk M. , Martens Anton C. , Mutis Tuna 
Published: February 2013

Abstract
Purpose: Regulatory T cells (Tregs) are potent tools to prevent graft-versus-host disease (GVHD) induced after allogeneic stem cell transplantation or donor lymphocyte infusions. Toward clinical application of Tregs for GVHD treatment, we investigated the impact of Tregs on the therapeutic graft-versus-tumor (GVT) effect against human multiple myeloma tumors with various immunogenicities, progression rates, and localizations in a humanized murine model.
Experimental Design: Immunodeficient Rag2−/−γc−/− mice, bearing various human multiple myeloma tumors, were treated with human peripheral blood mononuclear cell (PBMC) alone or together with autologous ex vivo cultured Tregs. Mice were analyzed for the in vivo engraftment, homing of T-cell subsets, development of GVHD and GVT. In additional in vitro assays, Tregs that were cultured together with bone marrow stromal cells were analyzed for phenotype and functions.
Results: Treatment with PBMC alone induced variable degrees of antitumor response, depending on the immunogenicity and the growth rate of the tumor. Coinfusion of Tregs did not impair the antitumor response against tumors residing within the bone marrow, irrespective of their immunogenicity or growth rates. In contrast, Tregs readily inhibited the antitumor effect against tumors growing outside the bone marrow. Exploring this remarkable phenomenon, we discovered that bone marrow stroma neutralizes the suppressive activity of Tregs in part via production of interleukin (IL)-1β/IL-6. We furthermore found in vitro and in vivo evidence of conversion of Tregs into IL-17–producing T cells in the bone marrow environment.
Conclusions: These results provide new insights into the Treg immunobiology and indicate the conditional benefits of future Treg-based therapies. Clin Cancer Res; 19(6); 1467–75. ©2012 AACR.
Abnormal Lung Function in Adults With Congenital Heart Disease: Prevalence, Relation to Cardiac Anatomy, and Association With Survival
Authors: Alonso-Gonzalez Rafael , Borgia Francesco , Diller Gerhard-Paul , Inuzuka Ryo , Kempny Aleksander , Martinez-Naharro Ana , Tutarel Oktay , Marino Philip , Wustmann Kerstin , Charalambides Menelaos , Silva Margarida , Swan Lorna , Dimopoulos Konstantinos , Gatzoulis Michael A. 
Published: February 2013

Background—
Restrictive lung defects are associated with higher mortality in patients with acquired chronic heart failure. We investigated the prevalence of abnormal lung function, its relation to severity of underlying cardiac defect, its surgical history, and its impact on outcome across the spectrum of adult congenital heart disease.

Methods and Results—

A total of 1188 patients with adult congenital heart disease (age, 33.1±13.1 years) undergoing lung function testing between 2000 and 2009 were included. Patients were classified according to the severity of lung dysfunction based on predicted values of forced vital capacity. Lung function was normal in 53% of patients with adult congenital heart disease, mildly impaired in 17%, and moderately to severely impaired in the remainder (30%). Moderate to severe impairment of lung function related to complexity of underlying cardiac defect, enlarged cardiothoracic ratio, previous thoracotomy/ies, body mass index, scoliosis, and diaphragm palsy. Over a median follow-up period of 6.7 years, 106 patients died. Moderate to severe impairment of lung function was an independent predictor of survival in this cohort. Patients with reduced force vital capacity of at least moderate severity had a 1.6-fold increased risk of death compared with patients with normal lung function (
P
=0.04).

Conclusions—
A reduced forced vital capacity is prevalent in patients with adult congenital heart disease; its severity relates to the complexity of the underlying heart defect, surgical history, and scoliosis. Moderate to severe impairment of lung function is an independent predictor of mortality in contemporary patients with adult congenital heart disease.
Assembling Old Tricks for New Tasks: A Neural Model of Instructional Learning and Control
Authors: Huang Tsung-Ren , Hazy Thomas E. , Herd Seth A. , O'Reilly Randall C. 
Published: February 2013

Abstract
We can learn from the wisdom of others to maximize success. However, it is unclear how humans take advice to flexibly adapt behavior. On the basis of data from neuroanatomy, neurophysiology, and neuroimaging, a biologically plausible model is developed to illustrate the neural mechanisms of learning from instructions. The model consists of two complementary learning pathways. The slow-learning parietal pathway carries out simple or habitual stimulus–response (S-R) mappings, whereas the fast-learning hippocampal pathway implements novel S-R rules. Specifically, the hippocampus can rapidly encode arbitrary S-R associations, and stimulus-cued responses are later recalled into the basal ganglia-gated pFC to bias response selection in the premotor and motor cortices. The interactions between the two model learning pathways explain how instructions can override habits and how automaticity can be achieved through motor consolidation.
Operative Treatment of Nonunion Following Distal Fibula and Medial Malleolar Ankle Fractures
Authors: Khurana Sonya , Karia Raj , Egol Kenneth A. 
Published: February 2013

Background: The purpose of this study was to evaluate the outcomes following operative treatment of nonunited rotational distal fibula and medial malleolar ankle fractures. Methods: Seventeen patients were identified as having a nonunion of a rotational ankle fracture. All patients were evaluated clinically, radiographically, and functionally with the Short Musculoskeletal Functional Assessment (SMFA) questionnaire. They were divided into lateral and medial malleolus groups and compared with 44 patients following a nonoperative (SE2/3) ankle fracture and 25 patients who underwent operative fixation of their SE4 ankle fracture for functional comparison. Results: Two of the 17 patients were excluded. The patients in the medial malleolar group were notably older than those in the other groups. Nonunions included 12 distal fibulas and 3 medial malleoli. All patients were treated with open reduction with plate and screw fixation or screw fixation alone. Adjunctive grafting was performed in all but 2 cases. The average time to healing was 5.2 months post surgery. At latest follow-up, mean 33.9 months, all nonunions had resolved. Standardized SMFA scores differed notably among the groups in the Bothersome, Emotional, and Mobility categories. There was no difference between lateral malleolar nonunion patients and surgically treated SE4 patients. Conclusions: Reports of nonunions of fractures of lateral and medial malleoli have been rarely reported. Operative treatment of these nonunions in this study led to reliable bony healing. Patients who underwent surgery for these nonunions ultimately had similar outcomes and range of motion compared with patients who underwent operative treatment for acute ankle fractures. Level of Evidence: Level III, retrospective comparative series.
Injectable Treatments for Noninsertional Achilles Tendinosis
Authors: Gross Christopher E. , Hsu Andrew R. , Chahal Jaskarndip , Holmes George B. 
Published: February 2013

Background: Although there has been a recent increase in interest regarding injectable therapy for noninsertional Achilles tendinosis, there are currently no clear treatment guidelines for managing patients with this condition. The objective of this study was (1) to conduct a systematic review of clinical outcomes following injectable therapy of noninsertional Achilles tendinosis, (2) to identify patient-specific factors that are prognostic of treatment outcomes, (3) to provide treatment recommendations based on the best available literature, and (4) to identify knowledge deficits that require further investigation. Methods: We searched MEDLINE (1948 to March week 1 2012) and EMBASE (1980 to 2012 week 9) for clinical studies evaluating the efficacy of injectable therapies for noninsertional Achilles tendinosis. Specifically, we included randomized controlled trials and cohort studies with a comparative control group. Data abstraction was performed by 2 independent reviewers. The Oxford Level of Evidence Guidelines and GRADE recommendations were used to rate the quality of evidence and to make treatment recommendations. Results: Nine studies fit the inclusion criteria for our review, constituting 312 Achilles tendons at final follow-up. The interventions of interest included platelet-rich plasma (n = 54), autologous blood injection (n = 40), sclerosing agents (n = 72), protease inhibitors (n = 26), hemodialysate (n = 60), corticosteroids (n = 52), and prolotherapy (n = 20). Only 1 study met the criteria for a high-quality randomized controlled trial. All of the studies were designated as having a low quality of evidence. While some studies showed statistically significant effects of the treatment modalities, often studies revealed that certain injectables were no better than a placebo. Conclusions: The literature surrounding injectable treatments for noninsertional Achilles tendinosis has variable results with conflicting methodologies and inconclusive evidence concerning indications for treatment and the mechanism of their effects on chronically degenerated tendons. Prospective, randomized studies are necessary in the future to guide Achilles tendinosis treatment recommendations using injectable therapies. Level of Evidence: Level II, systematic review.
Prevalence of brain magnetic resonance imaging meeting Barkhof and McDonald criteria for dissemination in space among headache patients
Authors: Liu Syrone , Kullnat Jonathan , Bourdette Dennis , Simon Jack , Kraemer Dale F , Murchison Charles , Hamilton Bronwyn E 
Published: February 2013

Background: Incidental T2 white matter hyperintensities (WMHs) in headache patients on brain magnetic resonance imaging (MRI) may prompt concern for demyelinating disease. Objective: We reviewed brain MRI studies in patients with headaches without known demyelinating disease to determine the prevalence meeting imaging criteria for multiple sclerosis (MS) using two different definitions of “juxtacortical” and “periventricular”. Methods: Consecutive patients undergoing pre- and post-contrast MRI for headaches over a 25-month period were retrospectively identified. Exclusions included patients under age 10 and over 55 years or with known demyelinating disorder. Patients were classified as meeting: 1) Barkhof and 2) 2010 McDonald dissemination in space criteria for MS based on: FLAIR/T2 scans for WMH and enhanced T1-weighted images for enhancement. Both groups were further differentiated by defining “periventricular” and “juxtacortical” as WMH contacting ventricle and cortex (Barkhof “touching”, McDonald “touching”) versus WMH within 3 mm (Barkhof – 3 mm, McDonald – 3 mm). Results: 326/564 (58%) studies met inclusion criteria. WMH prevalence was 168/326 (51.53%). Barkhof “touching” criteria were met in 4/168 (2.4%) and in 12/168 (7.1%) of the 3 mm group. McDonald criteria were met in 41/168 (24.4%) for “touching” and 58/168 (34.5%) for 3 mm, respectively. Conclusion: Barkhof and McDonald criteria were met in 2.4–7.1% and 24.4–34.5%, respectively.
Plasma Epstein-Barr virus DNA predicts outcome in advanced Hodgkin lymphoma: correlative analysis from a large North American cooperative group trial
Authors: Kanakry Jennifer A. , Li Hailun , Gellert Lan L. , Lemas M. Victor , Hsieh Wen-son , Hong Fangxin , Tan King L. , Gascoyne Randy D. , Gordon Leo I. , Fisher Richard I. , Bartlett Nancy L. , Stiff Patrick , Cheson Bruce D. , Advani Ranjana , Miller Thomas P. , Kahl Brad S. , Horning Sandra J. , Ambinder Richard F. 
Published: February 2013

Key Points
Plasma EBV-DNA is highly concordant with EBV tumor status in Hodgkin lymphoma. Plasma EBV-DNA has prognostic significance in Hodgkin lymphoma, both before therapy and at month 6 of follow-up.
Combining BCR-ABL1 transcript levels at 3 and 6 months in chronic myeloid leukemia: implications for early intervention strategies
Authors: Neelakantan Pratap , Gerrard Gareth , Lucas Claire , Milojkovic Dragana , May Philippa , Wang Lihui , Paliompeis Christos , Bua Marco , Reid Alistair , Rezvani Katayoun , O'Brien Stephen , Clark Richard , Goldman John , Marin David 
Published: February 2013

Key Points
Response to TKIs can be accurately established by measuring the 3-month transcript level. An additional measurement of the transcript level at 6 months adds very little useful clinical information to the 3-month result.