bluuebunny/crossref_metadata_2025_split huggingface dataset:
C9orf72 expansion differentially affects males with spinal onset amyotrophic lateral sclerosis
Authors: Rooney James , Fogh Isabella , Westeneng Henk-Jan , Vajda Alice , McLaughlin Russell , Heverin Mark , Jones Ashley , van Eijk Ruben , Calvo Andrea , Mazzini Letizia , Shaw Christopher , Morrison Karen , Shaw Pamela J , Robberecht Wim , Van Damme Phillip , Al-Chalabi Ammar , van den Berg Leonard , Chiò Adriano , Veldink Jan , Hardiman Orla 
Published: September 2016

IntroductionTheC9orf72repeat expansion has been reported as a negative prognostic factor in amyotrophic lateral sclerosis (ALS). We have examined the prognostic impact of theC9orf72repeat expansion in European subgroups based on gender and site of onset.MethodsC9orf72status and demographic/clinical data from 4925 patients with ALS drawn from 3 prospective ALS registers (Ireland, Italy and the Netherlands), and clinical data sets in the UK and Belgium. Flexible parametric survival models were built including known prognostic factors (age, diagnostic delay and site of onset), gender and the presence of an expanded repeat inC9orf72.These were used to explore the effects ofC9orf72on survival by gender and site of onset. Individual patient data (IPD) meta-analysis was used to estimate HRs for results of particular importance.Results457 (8.95%) of 4925 ALS cases carried theC9orf72repeat expansion. A meta-analysis ofC9orf72estimated a survival HR of 1.36 (1.18 to 1.57) for those carrying the expansion. Models evaluating interaction between gender andC9orf72repeat expansions demonstrated that the reduced survival due toC9orf72expansion was being driven by spinal onset males (HR 1.56 (95% CI 1.25 to 1.96).ConclusionsThis study represents the largest combined analysis of the prognostic characteristics of theC9orf72expansion. We have shown for the first time that the negative prognostic implication of this variant is driven by males with spinal onset disease, indicating a hitherto unrecognised gender-mediated effect of the variant that requires further exploration.
Co-clinical Assessment of Tumor Cellularity in Pancreatic Cancer
Authors: Heid Irina , Steiger Katja , Trajkovic-Arsic Marija , Settles Marcus , Eßwein Manuela R. , Erkan Mert , Kleeff Jörg , Jäger Carsten , Friess Helmut , Haller Bernhard , Steingötter Andreas , Schmid Roland M. , Schwaiger Markus , Rummeny Ernst J. , Esposito Irene , Siveke Jens T. , Braren Rickmer F. 
Published: September 2016

Abstract
Purpose: Tumor heterogeneity is a hallmark of pancreatic ductal adenocarcinoma (PDAC). It determines tumor biology including tumor cellularity (i.e., amount of neoplastic cells and arrangement into clusters), which is related to the proliferative capacity and differentiation and the degree of desmoplasia among others. Given the close relation of tumor differentiation with differences in progression and therapy response or, e.g., the recently reported protective role of tumor stroma, we aimed at the noninvasive detection of PDAC groups, relevant for future personalized approaches. We hypothesized that histologic differences in PDAC tissue composition are detectable by the noninvasive diffusion weighted- (DW-) MRI-derived apparent diffusion coefficient (ADC) parameter.
Experimental design: PDAC cellularity was quantified histologically and correlated with the ADC parameter and survival in genetically engineered mouse models and human patients.
Results: Histologic analysis showed an inverse relationship of tumor cellularity and stroma content. Low tumor cellularity correlated with a significantly prolonged mean survival time (PDAClow = 21.93 months vs. PDACmed = 12.7 months; log-rank P &lt; 0.001; HR = 2.23; CI, 1.41–3.53). Multivariate analysis using the Cox regression method confirmed tumor cellularity as an independent prognostic marker (P = 0.034; HR = 1.73; CI, 1.04–2.89). Tumor cellularity showed a strong negative correlation with the ADC parameter in murine (r = −0.84; CI, −0.90– −0.75) and human (r = −0.79; CI, −0.90 to −0.56) PDAC and high preoperative ADC values correlated with prolonged survival (ADChigh = 41.7 months; ADClow = 14.77 months; log rank, P = 0.040) in PDAC patients.
Conclusions: This study identifies high tumor cellularity as a negative prognostic factor in PDAC and supports the ADC parameter for the noninvasive identification of PDAC groups. Clin Cancer Res; 23(6); 1461–70. ©2016 AACR.
Platinum-Based Chemotherapy Induces Methylation Changes in Blood DNA Associated with Overall Survival in Patients with Ovarian Cancer
Authors: Flanagan James M. , Wilson Angela , Koo Chail , Masrour Nahal , Gallon John , Loomis Erick , Flower Kirsty , Wilhelm-Benartzi Charlotte , Hergovich Alexander , Cunnea Paula , Gabra Hani , Braicu Elena Ioana , Sehouli Jalid , Darb-Esfahani Silvia , Vanderstichele Adriaan , Vergote Ignace , Kreuzinger Caroline , Castillo-Tong Dan Cacsire , Wisman G. Bea A. , Berns Els MJJ , Siddiqui Nadeem , Paul James , Brown Robert 
Published: September 2016

Abstract
Purpose: DNA damage repair can lead to epigenetic changes. DNA mismatch repair proteins bind to platinum DNA adducts and at sites of DNA damage can recruit the DNA methylating enzyme DNMT1, resulting in aberrant methylation. We hypothesised that DNA damage repair during platinum-based chemotherapy may cause aberrant DNA methylation in normal tissues of patients such as blood.
Experimental Design: We used Illumina 450k methylation arrays and bisulphite pyrosequencing to investigate methylation at presentation and relapse in blood DNA from patients with ovarian cancer enrolled in the SCOTROC1 trial (n = 247) and in a cohort of ovarian tumor DNA samples collected at first relapse (n = 46). We used an ovarian cancer cell line model to investigate the role of the DNA mismatch repair gene MLH1 in platinum-induced methylation changes.
Results: Specific CpG methylation changes in blood at relapse are observed following platinum-based chemotherapy and are associated with patient survival, independent of other clinical factors [hazard ratio, 3.7; 95% confidence interval, 1.8–7.6, P = 2.8 × 10−4]. Similar changes occur in ovarian tumors at relapse, also associated with patient survival (hazard ratio, 2.6; 95% confidence interval, 1.0–6.8, P = 0.048). Using an ovarian cancer cell line model, we demonstrate that functional mismatch repair increases the frequency of platinum-induced methylation.
Conclusions: DNA methylation in blood at relapse following chemotherapy, and not at presentation, is informative regarding survival of patients with ovarian cancer. Functional DNA mismatch repair increases the frequency of DNA methylation changes induced by platinum. DNA methylation in blood following chemotherapy could provide a noninvasive means of monitoring patients' epigenetic responses to treatment without requiring a tumor biopsy. Clin Cancer Res; 23(9); 2213–22. ©2016 AACR.
Role of KEAP1/NRF2 and TP53 Mutations in Lung Squamous Cell Carcinoma Development and Radiation Resistance
Authors: Jeong Youngtae , Hoang Ngoc T. , Lovejoy Alexander , Stehr Henning , Newman Aaron M. , Gentles Andrew J. , Kong William , Truong Diana , Martin Shanique , Chaudhuri Aadel , Heiser Diane , Zhou Li , Say Carmen , Carter Justin N. , Hiniker Susan M. , Loo Billy W. , West Robert B. , Beachy Philip , Alizadeh Ash A. , Diehn Maximilian 
Published: September 2016

Abstract
Lung squamous cell carcinoma (LSCC) pathogenesis remains incompletely understood, and biomarkers predicting treatment response remain lacking. Here, we describe novel murine LSCC models driven by loss of Trp53 and Keap1, both of which are frequently mutated in human LSCCs. Homozygous inactivation of Keap1 or Trp53 promoted airway basal stem cell (ABSC) self-renewal, suggesting that mutations in these genes lead to expansion of mutant stem cell clones. Deletion of Trp53 and Keap1 in ABSCs, but not more differentiated tracheal cells, produced tumors recapitulating histologic and molecular features of human LSCCs, indicating that they represent the likely cell of origin in this model. Deletion of Keap1 promoted tumor aggressiveness, metastasis, and resistance to oxidative stress and radiotherapy (RT). KEAP1/NRF2 mutation status predicted risk of local recurrence after RT in patients with non–small lung cancer (NSCLC) and could be noninvasively identified in circulating tumor DNA. Thus, KEAP1/NRF2 mutations could serve as predictive biomarkers for personalization of therapeutic strategies for NSCLCs.
Significance: We developed an LSCC mouse model involving Trp53 and Keap1, which are frequently mutated in human LSCCs. In this model, ABSCs are the cell of origin of these tumors. KEAP1/NRF2 mutations increase radioresistance and predict local tumor recurrence in radiotherapy patients. Our findings are of potential clinical relevance and could lead to personalized treatment strategies for tumors with KEAP1/NRF2 mutations. Cancer Discov; 7(1); 86–101. ©2016 AACR.
This article is highlighted in the In This Issue feature, p. 1
Challenges and Outcomes of Posterior Wall Isolation for Ablation of Atrial Fibrillation
Authors: Kumar Prabhat , Bamimore Ayotunde M. , Schwartz Jennifer D. , Chung Eugene H. , Gehi Anil K. , Kiser Andy C. , Hummel James P. , Mounsey J. Paul 
Published: September 2016

Background

The left atrial posterior wall (
PW
) often contains sites required for maintenance of atrial fibrillation (
AF
). Electrical isolation of the PW is an important feature of all open surgeries for AF. This study assessed the ability of current ablation techniques to achieve PW isolation (
PWI
) and its effect on recurrent
AF
.

Methods and Results

Fifty‐seven consecutive patients with persistent or high‐burden paroxysmal
AF
underwent catheter ablation, which was performed using an endocardial‐only (30) or a hybrid endocardial–epicardial procedure (27). The catheter ablation lesion set included pulmonary vein antral isolation and a box lesion on the
PW
(roof and posterior lines). Success in creating the box lesion was assessed as electrical silence of the PW (voltage <0.1 mV) and exit block in the
PW
with electrical capture. Cox proportional hazards models were used for analysis of
AF
recurrence.
PWI
was achieved in 21 patients (36.8%), more often in patients undergoing hybrid ablation than endocardial ablation alone (51.9% versus 23.3%,
P
=0.05). Twelve patients underwent redo ablation. Five of 12 had a successful procedural
PWI
, but all had
PW
reconnection at the redo procedure. Over a median follow‐up of 302 days, 56.1% of the patients were free of atrial arrhythmias. No parameter including procedural
PWI
was a statistically significant predictor of recurrent atrial arrhythmias.

Conclusions

PWI
during catheter ablation for AF is difficult to achieve, especially with endocardial ablation alone. Procedural achievement of
PWI
in this group of patients was not associated with a reduction in recurrent atrial arrhythmias, but reconnection of the
PW
was common.
Assessment of the effectiveness and practical feasibility of glass solar chimney walls by open frame in Thailand
Authors: Ratanachotinun Jaran , Pairojn Pithan 
Published: September 2016

This research will assess the effectiveness of glass solar chimney wall by open frame (GSCW-O) and compare it with one-layer glass wall (OLGW) in Thailand. The results showed that the use of a GSCW-O can reduce the inside temperature compared with that of OLGW by around 2–4℃ annually, providing heat transfer to the outside, as well as limiting the relative humidity (RH) to 60%, which protects against the occurrence of fungi that cause allergies. The research also found that GSCW-O results in 10–20% less energy consumption when compared to OLGW. In addition being five times cheaper than insulation glass, the payback period for GSCW-O is only 5–6 years. The questionnaire results were satisfactory and proved GSCW-O is very good in practice, pleasing in design, and providing significant energy savings. Testing of hydroponic cultivation in a GSCW house also showed satisfactory growth with a lack of pests, resulting from controlled temperature, humidity, and protection from the elements. For a tropical climate such as Thailand’s, GSCW-O is a suitable design for the reduction in energy consumption and for sustainable architecture. Practical application This research provides helpful information on glass solar chimney wall by open frame for both the owners and developers by adopting an energy efficient building for sustainable energy conservation. For tropical country like Thailand, glass solar chimney wall by open frame is a suitable design and the best alternative for saving energy and global environmental conservation in the building industry.
Patients With a History of Idiopathic Deep Venous Thrombosis Have Long-Term Increased Levels of Inflammatory Markers and Markers of Endothelial Damage
Authors: Jezovnik Mateja Kaja , Fareed Jawed , Poredos Pavel 
Published: September 2016

Introduction: Although the role of inflammation in DVT has been investigated in different studies, there is no definite answer as to whether increased systemic inflammation is the cause or the consequence of DVT. Aim: To follow inflammatory parameters in a cohort of patients with idiopathic DVT. Methods: Out of 49 patients with an acute idiopathic DVT, which were investigated four months after an acute episode (DEVTA 1), 43 patients were included in the follow-up study investigating inflammatory markers and hemostatic markers of endothelial damage five years after an acute DVT (DEVTA 2). A control group consisted of 43 sex and age matched healthy subjects (CONTROLS). Results: The levels of inflammatory markers were significantly higher in DEVTA 2 in comparison to CONTROLS: tumor necrosis factor alpha 2.0 pg/mL (1.1-2.3) vs 1.3 pg/mL (0.8-1.9), p < .001, high sensitivity C-reactive protein 3.2 mg/L (1.5-5.2) vs 1.7 mg/L (0.9-3.0), p = .008, interleukin-6 (IL-6) 2.7 pg/mL (2.0-3.5) vs 2.1 pg/mL (1.5-2.6), p = .025, IL-8 5.0 pg/mL (3.6-7.3) vs 2.4 pg/mL (1.8-2.8), p < .001. IL-10 was significantly decreased (0.9 pg/mL (0.7-1.8) vs 1.8 (1.5-2.2), p < .001. Most of the proinflammatory markers remained elevated in the DEVTA 2 in comparison to DEVTA 1. Markers of endothelial damage were higher in DEVTA 2 in comparison to CONTROLS and higher than in DEVTA 1. Conclusion: Patients with idiopathic DVT have long-term increased inflammatory markers and markers of endothelial damage. These findings favor the hypothesis that inflammation is a cause and not merely a consequence of acute DVT.
Single-Stage Bipedicle Local Tissue Transfer and Skin Graft for Achilles Tendon Surgery Wound Complications
Authors: Dekker Travis J. , Avashia Yash , Mithani Suhail K. , Matson Andrew P. , Lampley Alexander J. , Adams Samuel B. 
Published: September 2016

Introduction. Achilles tendon and posterior heel wound complications are difficult to treat. These typically require soft tissue coverage via microvascular free tissue transfer at a tertiary referral center. Here, we describe coverage of a series of posterior heel and Achilles wounds via simple, local tissue transfer, called a bipedicle fasciocutaneous flap. This flap can be performed by an orthopaedic foot and ankle surgeon, without resources of tertiary/specialized care or microvascular support. Methods. Three patients with separate pathologies were treated with a single-stage bipedicle fasciocutaneous local tissue transfer. Case 1 was a patient with insertional wound breakdown after Achilles debridement and repair to the calcaneus. Case 2 was a heel venous stasis ulcer with calcaneal exposure in a diabetic patient with vasculopathy. Case 3 was a patient with wound breakdown following midsubstance Achilles tendon repair. All three cases were treated with a single-stage bipedicle local tissue transfer for posterior ankle and heel wound complications. Results. All 3 patients demonstrated complete healing of the posterior defect, lateral ankle skin graft recipient site, and the skin graft donor site after surgery. Case 3 had a subsequent recurrent ulceration after initial healing. This was superficial and healed with local wound care. All patients regained full preoperative range of motion and were able to ambulate independently without modified footwear. Conclusions. The bipedicled fasciocutaneous flap described here offers a predictable single stage procedure that can be accomplished by an orthopaedic foot and ankle surgeon without resources of a tertiary care center for posterior foot and ankle defects. This flap can be performed with short operative times and can be customized to facilitate defect coverage. The flap is durable to withstand local tissue stresses required for early ambulation. Despite its reliability, patients require careful follow-up to manage underlying comorbid conditions that may complicate wound healing. Levels of Evidence: Level IV: Case series
Association of glutathione S-transferase GSTM1 and GSTT1 deletion polymorphisms with obesity and their relationship with body mass index, lipoprotein and hypertension among young age Saudis
Authors: Almoshabek Hamoud A , Mustafa Md , Al-Asmari Mohammed M , Alajmi Tahani K , Al-Asmari Abdulrahman K 
Published: September 2016

Objectives Persistent oxidative stress is one of the several risk factors that may be associated with the etiology of obesity. The present study is aimed to investigate association between GSTM1 and GSTT1 polymorphisms with obesity and their relationship with plasma lipoproteins, body mass index (BMI) and hypertension. Design The GSTM1 and GSTT1 deletion polymorphisms were analyzed by multiplex polymerase chain reaction. The lipoproteins were measured in plasma using commercially available kit and the weight, height, systolic (SBP) and diastolic (DBP) blood pressures by standard procedure of measurements. Setting Prince Sultan Military Medical City, Riyadh Saudi Arabia. Participants A total of 420 overweight/obese cases and 234 normal weight controls belong to young age Saudis. Main outcomes measures GSTM1/ GSTT1 polymorphisms may be associated with obesity. Results Weight, BMI, low-density lipoprotein (LDL) and SBP were significantly higher while high-density lipoprotein (HDL) was significantly lower in cases in comparison to controls. Frequency of GSTM1+/ GSTT1− (OR = 2.70, 95% CI = 1.52–4.81, p = <0.001) and GSTM1−/ GSTT1− (OR = 2.43, 95% CI = 1.15–5.15, p = 0.018) was significantly higher in cases as compared to controls. BMI and weight were significantly higher in GSTM1+/ GSTT1− and GSTM1−/ GSTT1− genotypes, and LDL, DBP and SBP significantly higher in GSTM1−/ GSTT1− null genotype while HDL was significantly lower in GSTM1−/ GSTT1+ and GSTM1−/ GSTT1− genotypes in comparison to GSTM1+/ GSTT1+ genotype. Conclusions The GSTM1+/ GSTT1− and GSTM1−/ GSTT1− null genotypes were significantly associated with obesity and have shown relationship with obesity risk factors in cases. Hence, these genes may be associative genetic risk factor for obesity among young age Saudis.
Abortion, substance abuse and mental health in early adulthood: Thirteen-year longitudinal evidence from the United States
Authors: Sullins Donald Paul 
Published: September 2016

Objective: To examine the links between pregnancy outcomes (birth, abortion, or involuntary pregnancy loss) and mental health outcomes for US women during the transition into adulthood to determine the extent of increased risk, if any, associated with exposure to induced abortion. Method: Panel data on pregnancy history and mental health history for a nationally representative cohort of 8005 women at (average) ages 15, 22, and 28 years from the National Longitudinal Study of Adolescent to Adult Health were examined for risk of depression, anxiety, suicidal ideation, alcohol abuse, drug abuse, cannabis abuse, and nicotine dependence by pregnancy outcome (birth, abortion, and involuntary pregnancy loss). Risk ratios were estimated for time-dynamic outcomes from population-averaged longitudinal logistic and Poisson regression models. Results: After extensive adjustment for confounding, other pregnancy outcomes, and sociodemographic differences, abortion was consistently associated with increased risk of mental health disorder. Overall risk was elevated 45% (risk ratio, 1.45; 95% confidence interval, 1.30–1.62; p < 0.0001). Risk of mental health disorder with pregnancy loss was mixed, but also elevated 24% (risk ratio, 1.24; 95% confidence interval, 1.13–1.37; p < 0.0001) overall. Birth was weakly associated with reduced mental disorders. One-eleventh (8.7%; 95% confidence interval, 6.0–11.3) of the prevalence of mental disorders examined over the period were attributable to abortion. Conclusion: Evidence from the United States confirms previous findings from Norway and New Zealand that, unlike other pregnancy outcomes, abortion is consistently associated with a moderate increase in risk of mental health disorders during late adolescence and early adulthood.
Opioid use disorder patients’ perceptions of healthcare delivery platforms
Authors: Rakita Uros , Giacobbe Peter , Cavacuiti Chris 
Published: September 2016

Objectives: To assess the acceptability and quality of web-based videoconferencing telemedicine consultation platform in the treatment of opioid use disorder at TrueNorth Medical Centre. Methods: We conducted an interview based quality improvement initiative using an investigator-designed questionnaire. The questionnaire consisted of 17 Agree/Disagree questions, measured on a 7-point Likert scale and 2 questions where patients had the ability to elaborate qualitatively on their perceptions and experiences with their telemedicine service. Content-style analysis was performed on qualitative responses. Results: The majority of patients (n=14; 47%) preferred face-to-face over telemedicine consultations. The number of patients that preferred telemedicine consultations over face-to-face consultations was lower (n=6; 20%). A notable number of patients (n=10; 33%) indicated no specific preference for either telemedicine or face-to-face consultations. Patients preferring face-to-face consultations rated their clinical outcome and patient-physician relationship following telemedicine consultations similarly as those who preferred telemedicine consultations. Patients preferring telemedicine rated their experience and overall perceptions of the service significantly higher than those preferring face-to-face consultations. Patients who preferred telemedicine consultations identified the efficient and timesaving nature of telemedicine consultations as primary advantages whereas those preferring face-to-face consultations reported lower levels of empathy from their physician during telemedicine consultations as a major disadvantage. Conclusions: The majority of patients at TrueNorth Medical Centre viewed telemedicine consultations as an acceptable treatment modality. Patients preferring telemedicine consultations and those preferring face-to-face consultations evaluated the majority of the measured indices of care in a similar fashion.