bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atypical age-related cortical thinning in episodic migraine
Authors: Chong Catherine D , Dodick David W , Schlaggar Bradley L , Schwedt Todd J 
Published: April 2014

Background Prior studies demonstrate reduced cortical thickness and volume in migraineurs. However, the effect of age on cortical thickness has not been assessed in migraineurs. In this study we investigated whether the process of aging on cortical thickness affects migraineurs differently compared to age-matched healthy controls, i.e. whether aging exacerbates cortical thinning in migraineurs. Methods Cortical thickness was estimated using a general linear model vertex-by-vertex approach for 32 healthy controls (mean age = 35.3 years; SD = 11.6) and 27 episodic migraine patients (mean age = 33.6 years; SD = 12.3). Results were modeled using a main effect analysis to estimate the effect of age on cortical thickness for each group separately, and an age-by-group analysis to estimate differences in age-related cortical thinning between migraine patients and normal controls. Results Although migraineurs and normal controls both have expected age-related thinning in many regions along the cortical mantle, migraineurs have age-related thinning of regions that do not thin in healthy controls, including: bilateral postcentral, right fusiform, and right temporal pole areas. Cortical thinning of these regions is more prominent with advancing age. Conclusion Results suggest that migraine is associated with atypical cortical aging, suggesting that the migraine disease process interacts with aging to affect cortical integrity.
Magnetic Resonance Imaging Findings in the Symptomatic Hips of Younger Retired National Football League Players
Authors: Domb Benjamin G. , Jackson Timothy J. , Carter Christopher C. , Jester Jon R. , Finch Nathan A. , Stake Christine E. 
Published: April 2014

Background: American football players have an increased level of risk for hip injuries because of the high level of contact, biomechanical load, and anatomic strain placed on the hip joint. Many injuries are attributed to soft tissue injury rather than intra-articular lesions. However, because of improved imaging and increased knowledge, physicians are attributing unexplained hip pain to intra-articular lesions with increasing frequency. Purpose: To assess the prevalence of pathologic intra-articular hip lesions in a younger, retired National Football League (NFL) player cohort evaluated for persistent hip pain. Study Design: Case series; Level of evidence, 4. Methods: A retrospective chart review was performed of magnetic resonance imaging (MRI) on retired NFL players evaluated at an orthopaedic clinic for persistent hip pain. All MRIs were performed at the same location and reviewed by the same independent radiologist. The study included 62 hips; MRI was used to evaluate 27 hips, and MRI arthrogram was used to evaluate 35 hips. Images were assessed for labral tears, chondral lesions, ligamentum teres (LT) tears, bone cysts, osteophytes, loose bodies, trochanteric bursitis, and alpha angle. Player demographics, including position and seasons played, were recorded. Results: From February 2011 to December 2012, a total of 50 retired players from the NFL (average age, 33 years; range, 27-39 years) received impairment evaluations assessing all symptomatic joints. Thirty-eight (76%) players had hip complaints and underwent a dedicated hip MRI. Twenty-four players (63%) had bilateral hip pain, for a total of 62 hips evaluated. There were 55 (89%) labral tears, 61 (98%) chondral lesions, and 50 (81%) partial or complete LT tears identified on MRI. Additional findings included 3 (5%) hips with osteophytes, 9 (14.5%) with subchondral bone cysts, and 3 (5%) with paralabral cysts. None of the players were found to have trochanteric bursitis or loose bodies. Fifty-eight of 62 alpha angles could be measured, for a mean of 59° (range, 39°-77°). The majority of players were defensive players (63%), while the remainder were offensive players (34%) and 1 special teams player. Position breakdown was as follows: 29% were defensive backs, 16% played the defensive line, 18% were linebackers, 13% were fullbacks, 11% were wide receivers, 5% played the offensive line, and the remaining 8% were kickers, running backs, and quarterbacks. Conclusion: This study demonstrated a high incidence of intra-articular pathologic lesions of the hip in a younger cohort of retired NFL players. The majority of players had bilateral hip pain. The most common finding was chondral lesions, followed by labral tears. Future research is needed to further elucidate incidence and treatment outcomes using prospective studies examining active and retired players with hip-related injuries.
Do we treat individuals as patients or as potential donors? A phenomenological study of healthcare professionals’ experiences
Authors: Orøy Aud , Strømskag Kjell Erik , Gjengedal Eva 
Published: April 2014

Background: Organ donation and transplantation have made it possible to both save life and to improve the quality of life for a large number of patients. In the last years there has been an increasing gap between the number of patients who need organs and organs available for transplantation, and the focus worldwide has been on how to meet the organ shortage. This also rises some ethical challenges. Objective: The objective of this study was to explore healthcare professionals' experience of ethics related to care and interaction with critically ill patients with severe brain injuries and their families. Research design: A hermeneutic phenomenological approach was used to explore the participants' experiences. Methods for collecting data were a combination of participant observations and in-depth interviews. Participants and research context: Two ICUs in a Norwegian university hospital were recruited for data collection. A total of 12 cases were observed, and 32 of the healthcare professionals involved were interviewed. Ethical considerations: The study was approved by the Regional Committee for Research Ethics. Permission to the study in the ICUs was obtained from the Chief Physician in the two ICUs respectively. The right of the participants was ensured by written, voluntary, and informed consent. Findings: From the thematic analysis, a structure of the participants' experiences emerged as a process. While the patients' condition was clarified through phases of prognostic ambiguity, gradual clarification and prognostic certainty, interaction with the families was characterized by ambiguity that involved withholding. The prognostic process had a great impact on how the healthcare professionals interacted with the family. The interaction challenged the participants' caring values in various ways and captured an important structure in their experiences of the ethical interaction with the patients' families. These challenges distinguish caring for families in donation situations from caring for relatives of critically ill patients in general. Discussion: In the discussion we have illuminated how professional ethics may be threatened by more pragmatic and utilitarian arguments contained in regulations and transplant act. Conclusion: Ethical questions should be discussed more both in educations of healthcare professionals and in clinical practice.
The Efficacy of Sulodexide in the Prevention of Postthrombotic Syndrome
Authors: Luzzi Roberta , Belcaro Gianni , Dugall Mark , Hu Shu , Arpaia Guido , Ledda Andrea , Ippolito Edmondo , Corsi Marcello , Ricci Andrea , Cotellese Roberto , Agus Giovanni , Errichi Bruno M. , Cornelli Umberto , Cesarone M. Rosaria , Hosoi Morio 
Published: April 2014

Aim: The aim of this open, observational registry was to evaluate the effects of antithrombotic treatment on the development of postthrombotic syndrome (PTS): the effects of “standard management” (SM; according to International Union of Angiology guidelines) were compared to SM in association with sulodexide or aspirin. Methods: Postthrombotic syndrome occurrence was observed in 3 nonparallel groups after deep venous thrombosis (DVT); the registry started after the end of the anticoagulation period. The target was to observe the occurrence of PTS in 5 years. Three possible options were suggested to the patients, and the patients and their caregivers defined the type of management. A group of 167 patients was involved in the SM with reevaluation every 6 months; the sulodexide group included 124 patients and the aspirin group included 48 patients. Results: The 3 groups were clinically similar and comparable for age and sex distribution. Of the 167 patients in the SM group, 154 patients completed 60 months of follow-up. The percentage of patients with PTS in the SM group ranged from 14.9% (1 year after the end of anticoagulation) to 19.5% (60 months). In the nonparallel group using sulodexide (124 comparable patients at inclusion; 115 at 60 months), the percentage of PTS was variable from 8.8% (1 year after anticoagulants) to 12.17% at 60 months. These percentages are significantly lower than those observed with SM. In the nonparallel aspirin group (48 patients at inclusion and 34 at 54 months), there was a PTS incidence of 23.5% at 54 months (vs 12.17% in the sulodexide group and 18.23% in the SM group). The incidence of PTS was significantly higher in comparison with the other 2 groups. The incidence of PTS was lower in the sulodexide group in comparison with the 2 other groups. Conclusions: Sulodexide administration after DVT appears to be effective in preventing PTS in association with recommended management and a number of recurrent DVTs. Modalities of treatment, dosages, and timing of administration should be explored in more comprehensive and complete studies.
Hypertriglyceridemia and hyperglycemia induced by capecitabine: A report of two cases and review of the literature
Authors: Han Gao-hua , Huang Jun-Xing 
Published: April 2014

Background Capecitabine is a tumor-activated oral fluoropyrimidine used in breast and colorectal cancer. Hypertriglyceridemia associated with this drug has rarely been reported in the literature. Methods Two patients with colorectal carcinoma who developed capecitabine-induced hypertriglyceridemia (including a patient who developed hyperglycemia concurrently) were described, treatment modalities were discussed, and the literatures were reviewed. Results The first patient, a 43-year-old man, developed hyperlipidemia and hyperglycemia after two cycles of XELOX regimen chemotherapy for colorectal cancer. His triglyceride was 2.47 mmol/L (normal range 0.34–1.7 mmol/L) and total cholesterol was 6.93 mmol/L (normal range 3.12–5.9 mmol/L), while blood glucose was abnormal (fasting blood glucose was 10.58–11.9 mmol/L and 2 h postprandial glucose was 14.5–17.2 mmol/L) and glucose was positive in the urine(3+). The second patient, a 47-year-old woman, developed abnormalities in the lipid profile after the sixth cycle of XELOX regimen chemotherapy for colorectal cancer. Her serum triglyceride was 2.41 mmol/L (normal range 0.34–1.7 mmol/L), while the cholesterol level was 7.73 mmol/L (normal range 3.12–5.9 mmol/L). The profile of lipid improved gradually with reduced doses of capecitabine and was well restored after chemotherapy without any lipid-lowering agents. The Naranjo score for capecitabine-induced hypertriglyceridemia was 9 (definite). An analysis of the underlying pathogenic mechanisms was provided. Conclusion It is important of physicians and pharmacists to be aware of the possibility of dyslipidemia, particularly hypertriglyceridemia induced by capecitabine.
Surgical Management of Rib Fractures: Strategies and Literature Review
Authors: de Jong M. B. , Kokke M. C. , Hietbrink F. , Leenen L. P. H. 
Published: April 2014

Background and Aims: Rib fractures can cause significant problems in trauma patients, often resulting in pain and difficulty with respiration. To prevent pulmonary complications and decrease the morbidity and mortality rates of patients with rib fractures, currently there is a trend to provide surgical management of patients with flail chest. However, the indications for rib fracture fixation require further specification. Material and Methods: Past and current strategies are described according to a review of the medical literature. A systematic review was performed including current indications for rib fracture fixation. MEDLINE (2000–2013) was searched, as well as Embase (2000–2013) and Cochrane Databases, using the keywords rib, fracture, fixation, plate, repair, and surgery. Results: Three retrospective studies were found that described different techniques for rib fracture fixation. The results demonstrated a reduced number of ventilation days, decreased long-term morbidity and pain, and satisfactory rehabilitation after surgical treatment. In addition to flail chest, age, Injury Severity Score, and the number of rib fractures were important predictive factors for morbidity and mortality. Conclusion: Surgical rib fracture fixation might be indicated in a broader range of cases than is currently performed. Prospective randomized trials are needed for further confirmation.
Studying medicine – a cross-sectional questionnaire-based analysis of the motivational factors which influence graduate and undergraduate entrants in Ireland
Authors: Sulong Saadah , McGrath Deirdre , Finucane Paul , Horgan Mary , O’Flynn Siún , O’Tuathaigh Colm 
Published: April 2014

Summary Objectives The number of places available in Ireland for graduate entry to medical school has steadily increased since 2006. Few studies have, however, characterized the motivational factors underlying decision to study medicine via this route. We compared the factors motivating graduate entrants versus undergraduate entry (UGE) students to choose medicine as a course of study. Design The present study was a quantitative cross-sectional questionnaire-based investigation. Setting The study was conducted in University College Cork and University of Limerick, Ireland. Participants It involved 185 graduate entry (GE) and 120 UGE students. Outcome measures Questionnaires were distributed to students addressing the following areas: demographic/academic characteristics; factors influencing the selection of academic institution and motivation to study medicine; and the role of career guidance in choice of study. Results When asked to list reasons for selecting medicine, both groups listed a wish to help and work with people, and a desire to prevent and cure disease. UGE students were significantly more motivated by intellectual satisfaction, encouragement by family/friends, financial reasons, and professional independence. Approximately half of GE students selected their first degree with a view to potentially studying medicine in the future. GE and UGE students differed significantly with respect to sources consulted for career guidance and source of study information. Conclusions This study is the first systematic examination of study and career motivation in GE medical students since the programme was offered by Irish universities and provides insight into the reasons why graduate entrants in Ireland choose to study medicine via this route.
TBLR1 fuses to retinoid acid receptor α in a variant t(3;17)(q26;q21) translocation of acute promyelocytic leukemia
Authors: Chen Yirui , Li Shouyun , Zhou Chunlin , Li Chengwen , Ru Kun , Rao Qing , Xing Haiyan , Tian Zheng , Tang Kejing , Mi Yingchang , Wang Baohong , Wang Min , Wang Jianxiang 
Published: April 2014

Key Points
A novel RARα fusion gene, TBLR1-RARα, was found in rare cases of APL with t(3;17) chromosomal translocation. TBLR1-RARα exhibited diminished transcriptional activity by recruiting more corepressors compared with RARα.
CD28-mediated pro-survival signaling induces chemotherapeutic resistance in multiple myeloma
Authors: Murray Megan E. , Gavile Catherine M. , Nair Jayakumar R. , Koorella Chandana , Carlson Louise M. , Buac Daniela , Utley Adam , Chesi Marta , Bergsagel P. Leif , Boise Lawrence H. , Lee Kelvin P. 
Published: April 2014

Key PointsCD28 delivers a pro-survival signal to MM cells via regulation of PI3K/Akt, FoxO3a, and Bim. Blockade of CD28:CD80/CD86 in vivo resensitizes MM cells to chemotherapy and significantly reduces tumor burden.
Closely related T-memory stem cells correlate with in vivo expansion of CAR.CD19-T cells and are preserved by IL-7 and IL-15
Authors: Xu Yang , Zhang Ming , Ramos Carlos A. , Durett April , Liu Enli , Dakhova Olga , Liu Hao , Creighton Chad J. , Gee Adrian P. , Heslop Helen E. , Rooney Cliona M. , Savoldo Barbara , Dotti Gianpietro 
Published: April 2014

Key PointsThe frequency of CD8+CD45RA+CCR7+ cells, a subset closest to T-memory stem cells, correlates with CAR–T-cell expansion in lymphoma patients. IL-7 and IL-15 increase the frequency of CD8+CD45RA+CCR7+ cells during the ex vivo expansion of CAR+ T cells.
Fabrication of porous silicon nanowires by MACE method in HF/H2O2/AgNO3 system at room temperature
Authors: Li Shaoyuan , Ma Wenhui , Zhou Yang , Chen Xiuhua , Xiao Yongyin , Ma Mingyu , Zhu Wenjie , Wei Feng 
Published: April 2014

Abstract
In this paper, the moderately and lightly doped porous silicon nanowires (PSiNWs) were fabricated by the ‘one-pot procedure’ metal-assisted chemical etching (MACE) method in the HF/H2O2/AgNO3 system at room temperature. The effects of H2O2 concentration on the nanostructure of silicon nanowires (SiNWs) were investigated. The experimental results indicate that porous structure can be introduced by the addition of H2O2 and the pore structure could be controlled by adjusting the concentration of H2O2. The H2O2 species replaces Ag+ as the oxidant and the Ag nanoparticles work as catalyst during the etching. And the concentration of H2O2 influences the nucleation and motility of Ag particles, which leads to formation of different porous structure within the nanowires. A mechanism based on the lateral etching which is catalyzed by Ag particles under the motivation by H2O2 reduction is proposed to explain the PSiNWs formation.
Synovial phenotypes in rheumatoid arthritis correlate with response to biologic therapeutics
Authors: Dennis Glynn , Holweg Cécile TJ , Kummerfeld Sarah K , Choy David F , Setiadi A Francesca , Hackney Jason A , Haverty Peter M , Gilbert Houston , Lin Wei Yu , Diehl Lauri , Fischer S , Song An , Musselman David , Klearman Micki , Gabay Cem , Kavanaugh Arthur , Endres Judith , Fox David A , Martin Flavius , Townsend Michael J 
Published: April 2014

Abstract
Introduction
Rheumatoid arthritis (RA) is a complex and clinically heterogeneous autoimmune disease. Currently, the relationship between pathogenic molecular drivers of disease in RA and therapeutic response is poorly understood.

Methods
We analyzed synovial tissue samples from two RA cohorts of 49 and 20 patients using a combination of global gene expression, histologic and cellular analyses, and analysis of gene expression data from two further publicly available RA cohorts. To identify candidate serum biomarkers that correspond to differential synovial biology and clinical response to targeted therapies, we performed pre-treatment biomarker analysis compared with therapeutic outcome at week 24 in serum samples from 198 patients from the ADACTA (ADalimumab ACTemrA) phase 4 trial of tocilizumab (anti-IL-6R) monotherapy versus adalimumab (anti-TNFα) monotherapy.

Results
We documented evidence for four major phenotypes of RA synovium – lymphoid, myeloid, low inflammatory, and fibroid - each with distinct underlying gene expression signatures. We observed that baseline synovial myeloid, but not lymphoid, gene signature expression was higher in patients with good compared with poor European league against rheumatism (EULAR) clinical response to anti-TNFα therapy at week 16 (P =0.011). We observed that high baseline serum soluble intercellular adhesion molecule 1 (sICAM1), associated with the myeloid phenotype, and high serum C-X-C motif chemokine 13 (CXCL13), associated with the lymphoid phenotype, had differential relationships with clinical response to anti-TNFα compared with anti-IL6R treatment. sICAM1-high/CXCL13-low patients showed the highest week 24 American College of Rheumatology (ACR) 50 response rate to anti-TNFα treatment as compared with sICAM1-low/CXCL13-high patients (42% versus 13%, respectively, P =0.05) while anti-IL-6R patients showed the opposite relationship with these biomarker subgroups (ACR50 20% versus 69%, P =0.004).

Conclusions
These data demonstrate that underlying molecular and cellular heterogeneity in RA impacts clinical outcome to therapies targeting different biological pathways, with patients with the myeloid phenotype exhibiting the most robust response to anti-TNFα. These data suggest a path to identify and validate serum biomarkers that predict response to targeted therapies in rheumatoid arthritis and possibly other autoimmune diseases.

Trial registration
ClinicalTrials.gov NCT01119859
Predicting targeted drug combinations based on Pareto optimal patterns of coexpression network connectivity
Authors: Penrod Nadia M , Greene Casey S , Moore Jason H 
Published: April 2014

Abstract
Background
Molecularly targeted drugs promise a safer and more effective treatment modality than conventional chemotherapy for cancer patients. However, tumors are dynamic systems that readily adapt to these agents activating alternative survival pathways as they evolve resistant phenotypes. Combination therapies can overcome resistance but finding the optimal combinations efficiently presents a formidable challenge. Here we introduce a new paradigm for the design of combination therapy treatment strategies that exploits the tumor adaptive process to identify context-dependent essential genes as druggable targets.

Methods
We have developed a framework to mine high-throughput transcriptomic data, based on differential coexpression and Pareto optimization, to investigate drug-induced tumor adaptation. We use this approach to identify tumor-essential genes as druggable candidates. We apply our method to a set of ER+ breast tumor samples, collected before (n = 58) and after (n = 60) neoadjuvant treatment with the aromatase inhibitor letrozole, to prioritize genes as targets for combination therapy with letrozole treatment. We validate letrozole-induced tumor adaptation through coexpression and pathway analyses in an independent data set (n = 18).

Results
We find pervasive differential coexpression between the untreated and letrozole-treated tumor samples as evidence of letrozole-induced tumor adaptation. Based on patterns of coexpression, we identify ten genes as potential candidates for combination therapy with letrozole including EPCAM, a letrozole-induced essential gene and a target to which drugs have already been developed as cancer therapeutics. Through replication, we validate six letrozole-induced coexpression relationships and confirm the epithelial-to-mesenchymal transition as a process that is upregulated in the residual tumor samples following letrozole treatment.

Conclusions
To derive the greatest benefit from molecularly targeted drugs it is critical to design combination treatment strategies rationally. Incorporating knowledge of the tumor adaptation process into the design provides an opportunity to match targeted drugs to the evolving tumor phenotype and surmount resistance.