bluuebunny/crossref_metadata_2025_split huggingface dataset:
Replication and Heritability of Prostate Cancer Risk Variants: Impact of Population-Specific Factors
Authors: Virlogeux Victor , Graff Rebecca E. , Hoffmann Thomas J. , Witte John S. 
Published: March 2015

Abstract
Background: Prostate cancer incidence and mortality rates vary across populations, with African American men exhibiting the highest rates. To date, genome-wide association studies have identified 104 SNPs independently associated with prostate cancer in men of European ancestry.
Methods: We investigated whether the ability to replicate findings for these 104 SNPs in African American, Asian, and Latino populations depends on variation in risk allele frequencies (RAF), strength of associations, and/or patterns of linkage disequilibrium (LD) at the associated loci. We extracted estimates of effect from the literature, and determined RAF and LD information across the populations from the 1000 Genomes Project.
Results: Risk variants were largely replicated across populations. Relative to Europeans, 83% had smaller effect sizes among African Americans and 73% demonstrated smaller effect sizes among Latinos. Among Asians, however, 56% showed larger effect sizes than among Europeans. The largest difference in RAFs was observed between European and African ancestry populations, but this difference did not impact our ability to replicate. The extent of LD within 250 kb of risk loci in Asian ancestry populations was suggestively lower for variants that did not replicate (P = 0.013).
Conclusions: Despite substantial overlap in prostate cancer risk SNPs across populations, the variation in prostate cancer incidence among different populations may still in part reflect unique underlying genetic architectures.
Impact: Studying different ancestral populations is crucial for deciphering the genetic basis of prostate cancer. Cancer Epidemiol Biomarkers Prev; 24(6); 938–43. ©2015 AACR.
Oral Human Papillomavirus Is Common in Individuals with Fanconi Anemia
Authors: Sauter Sharon L. , Wells Susanne I. , Zhang Xue , Hoskins Elizabeth E. , Davies Stella M. , Myers Kasiani C. , Mueller Robin , Panicker Gitika , Unger Elizabeth R. , Sivaprasad Umasundari , Brown Darron R. , Mehta Parinda A. , Butsch Kovacic Melinda 
Published: March 2015

Abstract
Background: Fanconi anemia is a rare genetic disorder resulting in a loss of function of the Fanconi anemia–related DNA repair pathway. Individuals with Fanconi anemia are predisposed to some cancers, including oropharyngeal and gynecologic cancers, with known associations with human papillomavirus (HPV) in the general population. As individuals with Fanconi anemia respond poorly to chemotherapy and radiation, prevention of cancer is critical.
Methods: To determine whether individuals with Fanconi anemia are particularly susceptible to oral HPV infection, we analyzed survey-based risk factor data and tested DNA isolated from oral rinses from 126 individuals with Fanconi anemia and 162 unaffected first-degree family members for 37 HPV types.
Results: Fourteen individuals (11.1%) with Fanconi anemia tested positive, significantly more (P = 0.003) than family members (2.5%). While HPV prevalence was even higher for sexually active individuals with Fanconi anemia (17.7% vs. 2.4% in family; P = 0.003), HPV positivity also tended to be higher in the sexually inactive (8.7% in Fanconi anemia vs. 2.9% in siblings). Indeed, having Fanconi anemia increased HPV positivity 4.9-fold (95% CI, 1.6–15.4) considering age and sexual experience, but did not differ by other potential risk factors.
Conclusion: Our studies suggest that oral HPV is more common in individuals with Fanconi anemia. It will be essential to continue to explore associations between risk factors and immune dysfunction on HPV incidence and persistence over time.
Impact: HPV vaccination should be emphasized in those with Fanconi anemia as a first step to prevent oropharyngeal cancers, although additional studies are needed to determine whether the level of protection it offers in this population is adequate. Cancer Epidemiol Biomarkers Prev; 24(5); 864–72. ©2015 AACR.
Genome-wide siRNA Screen Identifies the Radiosensitizing Effect of Downregulation of MASTL and FOXM1 in NSCLC
Authors: Nagel Remco , Stigter-van Walsum Marijke , Buijze Marijke , van den Berg Jaap , van der Meulen Ida H. , Hodzic Jasmina , Piersma Sander R. , Pham Thang V. , Jiménez Connie R. , van Beusechem Victor W. , Brakenhoff Ruud H. 
Published: March 2015

Abstract
Lung cancer is the most common cancer worldwide and on top of that has a very poor prognosis, which is reflected by a 5-year survival rate of 5% to 15%. Radiotherapy is an integral part of most treatment regimens for this type of tumor, often combined with radiosensitizing cytotoxic drugs. In this study, we identified many genes that could potentially be exploited for targeted radiosensitization using a genome-wide siRNA screen in non–small cell lung cancer (NSCLC) cells. The screen identified 433 siRNAs that potentially sensitize lung cancer cells to radiation. Validation experiments showed that knockdown of expression of Forkhead box M1 (FOXM1) or microtubule-associated serine/threonine kinase-like (MASTL) indeed causes radiosensitization in a panel of NSCLC cells. Strikingly, this effect was not observed in primary human fibroblasts, suggesting that the observed radiosensitization is specific for cancer cells. Phosphoproteomics analyses with and without irradiation showed that a number of cell-cycle–related proteins were significantly less phosphorylated after MASTL knockdown in comparison to the control, while there were no changes in the levels of phosphorylation of DNA damage response proteins. Subsequent analyses showed that MASTL knockdown cells respond differently to radiation, with a significantly shortened G2–M phase arrest and defects in cytokinesis, which are followed by a cell-cycle arrest. In summary, we have identified many potential therapeutic targets that could be used for radiosensitization of NSCLC cells, with MASTL being a very promising and druggable target to combine with radiotherapy. Mol Cancer Ther; 14(6); 1434–44. ©2015 AACR.
VTE primary prevention, including hospitalised medical and orthopaedic surgical patients
Authors: Granziera Serena , Cohen Alexander T. 
Published: March 2015

summaryPrimary prevention is the key to managing a significant proportion of the burden of venous thromboembolism (VTE), defined as deep venous thrombosis (DVT) or pulmonary embolism (PE). This is because VTE may lead to sudden death or are often misdiagnosed and therefore treatment is not feasible. Primary prevention usually commences in hospital as VTE following hospitalisation adds to the significant disease burden worldwide. Numerous medical, surgical and other risk factors have been recognised and studied as indications for prophylaxis. The risk of VTE continues following admission to hospital with a medical or surgical condition, usually long after discharge and therefore prolonged primary prophylaxis is often recommended. Clinical and observational studies in surgical patients show this risk extends for months and perhaps more than one year, for medical patients the risk extends for at least several weeks. For the specific groups of patients at higher risk of developing VTE primary prevention, either pharmaceutical or mechanical, is recommended. The aim of this review is to describe the population at risk, the main related risk factors and the approach to thromboprophylaxis in different populations.
Identification of the Vasoconstriction-Inhibiting Factor (VIF), a Potent Endogenous Cofactor of Angiotensin II Acting on the Angiotensin II Type 2 Receptor
Authors: Salem Silvia , Jankowski Vera , Asare Yaw , Liehn Elisa , Welker Pia , Raya-Bermudez Ana , Pineda-Martos Carmen , Rodriguez Mariano , Muñoz-Castañeda Juan Rafael , Bruck Heike , Marx Nikolaus , Machado Fernanda B. , Staudt Mareike , Heinze Georg , Zidek Walter , Jankowski Joachim 
Published: March 2015

Background—
The renin-angiotensin system and especially the angiotensin peptides play a central role in blood pressure regulation. Here, we hypothesize that an as-yet unknown peptide is involved in the action of angiotensin II modulating the vasoregulatory effects as a cofactor.

Methods and Results—
The peptide with vasodilatory properties was isolated from adrenal glands chromatographically. The effects of this peptide were evaluated in vitro and in vivo, and the receptor affinity was analyzed. The plasma concentration in humans was quantified in patients with chronic kidney disease, patients with heart failure, and healthy control subjects. The amino acid sequence of the peptide from bovine adrenal glands was HSSYEDELSEVL EKPNDQAE PKEVTEEVSSKDAAE, which is a degradation product of chromogranin A. The sequence of the peptide isolated from human plasma was HSGFEDELSEVLENQSSQAELKEAVEEPSSKDVME. Both peptides diminished significantly the vasoconstrictive effect of angiotensin II in vitro. Therefore, we named the peptide vasoconstriction-inhibiting factor (VIF). The vasoregulatory effects of VIF are mediated by the angiotensin II type 2 receptor. VIF impairs angiotensin II–induced phosphorylation of the p38 mitogen-activated protein kinase pathway but not of extracellular-regulated kinase 1/2. The vasodilatory effects were confirmed in vivo. The plasma concentration was significantly increased in renal patients and patients with heart failure.

Conclusions—
VIF is a vasoregulatory peptide that modulates the vasoconstrictive effects of angiotensin II by acting on the angiotensin II type 2 receptor. It is likely that the increase in VIF may serve as a counterregulatory effect to defend against hypertension. The identification of this target may help us to understand the pathophysiology of renal and heart failure and may form a basis for the development of new strategies for the prevention and treatment of cardiovascular disease.
Sequential Hybrid Procedure for Persistent Atrial Fibrillation
Authors: Bulava Alan , Mokracek Ales , Hanis Jiri , Kurfirst Vojtech , Eisenberger Martin , Pesl Ladislav 
Published: March 2015

Background
Catheter ablation of persistent atrial fibrillation yields an unsatisfactorily high number of failures. The hybrid approach has recently emerged as a technique that overcomes the limitations of both surgical and catheter procedures alone.

Methods and Results

We investigated the sequential (staged) hybrid method, which consists of a surgical thoracoscopic radiofrequency ablation procedure followed by radiofrequency catheter ablation 6 to 8 weeks later using the
CARTO
3 mapping system. Fifty consecutive patients (mean age 62±7 years, 32 males) with long‐standing persistent atrial fibrillation (41±34 months) and a dilated left atrium (>45 mm) were included and prospectively followed in an unblinded registry. During the electrophysiological part of the study, all 4 pulmonary veins were found to be isolated in 36 (72%) patients and a complete box‐lesion was confirmed in 14 (28%) patients. All gaps were successfully re‐ablated. Twelve months after the completed hybrid ablation, 47 patients (94%) were in normal sinus rhythm (4 patients with paroxysmal atrial fibrillation required propafenone and 1 patient underwent a redo catheter procedure). The majority of arrhythmias recurred during the first 3 months. Beyond 12 months, there were no arrhythmia recurrences detected. The surgical part of the procedure was complicated by 7 (13.7%) major complications, while no serious adverse events were recorded during the radiofrequency catheter part of the procedure.

Conclusions
The staged hybrid epicardial–endocardial treatment of long‐standing persistent atrial fibrillation seems to be extremely effective in maintenance of normal sinus rhythm compared to radiofrequency catheter or surgical ablation alone. Epicardial ablation alone cannot guarantee durable transmural lesions.

Clinical Trial Registration

URL:
www.ablace.cz
Unique identifier: cz‐060520121617
Basic Level Category Structure Emerges Gradually across Human Ventral Visual Cortex
Authors: Iordan Marius Cătălin , Greene Michelle R. , Beck Diane M. , Fei-Fei Li 
Published: March 2015

Abstract
Objects can be simultaneously categorized at multiple levels of specificity ranging from very broad (“natural object”) to very distinct (“Mr. Woof”), with a mid-level of generality (basic level: “dog”) often providing the most cognitively useful distinction between categories. It is unknown, however, how this hierarchical representation is achieved in the brain. Using multivoxel pattern analyses, we examined how well each taxonomic level (superordinate, basic, and subordinate) of real-world object categories is represented across occipitotemporal cortex. We found that, although in early visual cortex objects are best represented at the subordinate level (an effect mostly driven by low-level feature overlap between objects in the same category), this advantage diminishes compared to the basic level as we move up the visual hierarchy, disappearing in object-selective regions of occipitotemporal cortex. This pattern stems from a combined increase in within-category similarity (category cohesion) and between-category dissimilarity (category distinctiveness) of neural activity patterns at the basic level, relative to both subordinate and superordinate levels, suggesting that successive visual areas may be optimizing basic level representations.
Involvement of the TPJ Area in Processing of Novel Global Forms
Authors: Rennig Johannes , Himmelbach Marc , Huberle Elisabeth , Karnath Hans-Otto 
Published: March 2015

Abstract
The neuropsychological syndrome “simultanagnosia” is characterized by the inability to integrate local elements into a global entity. This deficit in Gestalt perception is mainly apparent for novel global structures administered in clinical tests or unfamiliar visual scenes. Recognition of familiar complex objects or well-known visual scenes is often unaffected. Recent neuroimaging studies and reports from simultanagnosia patients suggest a crucial involvement of temporoparietal brain areas in processing of hierarchically organized visual material. In this study, we investigated the specific role of the TPJ in Gestalt perception. On the basis of perceptual characteristics known from simultanagnosia, we hypothesized that TPJ is dominantly involved in processing of novel object arrangements. To answer this question, we performed a learning study with hierarchical stimuli and tested behavioral and neuronal characteristics of Gestalt perception pre- and posttraining. The study included 16 psychophysical training sessions and two neuroimaging sessions. Participants improved their behavioral performance for trained global stimuli and showed limited transfer to untrained global material. We found significant training dependent neuronal signal modulations in anterior right hemispheric TPJ regions. These activation changes were specific to trained global stimuli, whereas no systematic neuronal response changes were observed for recognition of untrained global stimuli, local elements and regular objects that served as control stimuli. In line with perceptual characteristics in simultanagnosia, the results argue for an involvement of TPJ in processing of novel global structures. We discuss the signal modulations in the context of a more efficient or different neuronal strategy to process familiar global stimuli.
The ENSO–Precipitation Teleconnection and Its Modulation by the Interdecadal Pacific Oscillation
Authors: Westra Seth , Renard Benjamin , Thyer Mark 
Published: March 2015

AbstractThis study evaluates the role of the interdecadal Pacific oscillation (IPO) in modulating the El Niño–Southern Oscillation (ENSO)–precipitation relationship. The standard IPO index is described together with several alternatives that were derived using a low-frequency ENSO filter, demonstrating that an equivalent IPO index can be obtained as a low-frequency version of ENSO. Several statistical artifacts that arise from using a combination of raw and smoothed ENSO indices in modeling the ENSO–precipitation teleconnection are then described. These artifacts include the potentially spurious identification of low-frequency variability in a response variable resulting from the use of smoothed predictors and the potentially spurious modulation of a predictor–response relationship by the low-frequency version of the predictor under model misspecification. The role of the IPO index in modulating the ENSO–precipitation relationship is evaluated using a global gridded precipitation dataset, based on three alternative statistical models: stratified, linear, and piecewise linear. In general, the information brought by the IPO index, beyond that already contained in the Niño-3.4 index, is limited and not statistically significant. An exception is in northeastern Australia using annual precipitation data, and only for the linear model. Stratification by the IPO index induces a nonlinear ENSO–precipitation relationship, suggesting that the apparent modulation by the IPO is likely to be spurious and attributable to the combination of sample stratification and model misspecification. Caution is therefore required when using smoothed climate indices to model or explain low-frequency variability in precipitation.
Changes in Intense Precipitation Events in Mexico City
Authors: Ochoa Carlos A. , Quintanar Arturo I. , Raga Graciela B. , Baumgardner Darrel 
Published: March 2015

AbstractThe authors analyzed an extensive precipitation dataset available for the Mexico City basin that included hourly precipitation in various sectors of the city from 1993 to 2007. Observations indicated that significant changes occurred in the timing and number of intense events (precipitation rate >20 mm h−1) over this time period. Alternative hypotheses that changes in the emission of aerosol pollutants or in the land use can result in the observed variations are tested. The Weather Research and Forecasting Model was used to simulate September precipitation from 2002 to 2011 at the peak of the wet season. Changes were introduced to the microphysical scheme as a proxy for differences in the aerosol population and the droplet activation spectra. Simulations were also performed with the land use of the urban areas set up to represent older and more current conditions. Results indicate that increased pollution (decreased urban area) led to an average precipitation decrease over the mountain areas of 20%–40% (10%–20%) and an increase of 20% (30%) to the east of Mexico City. The timing of intense precipitation shifts from 1900 to 1600 LT for the polluted and decreased urban area cases when compared to a control experiment. These results add valuable information about how precipitation is modified by complex terrain and surface exchange processes in large urban areas under wet conditions.
Medial Patellofemoral Ligament Tears in the Setting of Multiligament Knee Injuries Rarely Cause Patellar Instability
Authors: Allen Benjamin J. , Krych Aaron J. , Engasser William , Levy Bruce A. , Stuart Michael J. , Collins Mark S. , Dahm Diane L. 
Published: March 2015

Background: Multiligament knee injuries (MLKIs) can also involve the medial patellofemoral ligament (MPFL), but there is a paucity of information regarding prevalence and relevance of MPFL involvement in this setting. Purpose: (1) To identify the prevalence of MPFL injury in MLKIs, (2) to determine whether an MPFL tear results in symptomatic patellar instability, and (3) to report clinical and functional outcomes of patients with and without MPFL tears after MLKI surgical reconstruction. Study Design: Cohort study; Level of evidence, 3. Methods: The records of all patients who underwent surgical reconstruction of MLKI (defined as a grade 3 injury of ≥2 ligaments) at a single institution from 2007 to 2010 were reviewed. Age, sex, knee dislocation classification (according to Schenck), and MRI findings were documented. All preoperative MRI scans were reviewed by an experienced musculoskeletal radiologist to determine the presence or absence of MPFL involvement. If an MPFL tear was present, its anatomic location and severity as well as the presence of patellar or lateral femoral condyle bone bruises were documented. Inclusion criteria included (1) MLKI treated at a single institution, (2) presence of MPFL tear on preoperative MRI, and (3) minimum 2-year clinical follow-up. Patellar instability symptoms were assessed with the Kujala Knee Questionnaire. Functional outcomes were measured using the International Knee Documentation Committee (IKDC) score. IKDC scores were compared between patients who sustained MLKIs with and without MPFL tears. There were 21 patients in each group. Results: Over the 4-year study period, 30 of 51 patients (59%) treated surgically for a MLKI had MRI evidence of an MPFL tear. Nine were lost to follow-up, leaving 21 patients for review. There were 13 complete (62%), 5 high-grade partial (24%), and 3 partial (14%) MPFL tears. Sixteen of 21 tears (76%) occurred at the proximal third, with the remainder exhibiting diffuse signal abnormality consistent with tearing throughout the length of the MPFL. The superficial medial collateral ligament was involved in all patients. In no case was the MPFL repaired or reconstructed. At mean follow-up of 3.6 years (range, 2.0-5.7 years), only 1 of 21 patients (5%) complained of patellofemoral instability symptoms whereas 20 of 21 patients (95%) did not experience patellar subluxation or dislocation. No significant difference was found when IKDC scores were compared between patients with and without an MPFL tear (mean ± SD, 65.5 ± 22.9 vs 79.4 ± 16.1; P = .07). Conclusion: MPFL tears occur frequently in patients with MLKI but rarely cause instability. In the majority of cases, MPFL tears do not need to be addressed at the time of surgery.
Resection Arthroplasty for Resistant Ulcers Underlying the Hallux in Insensate Diabetics
Authors: Tamir Eran , Tamir Jeremy , Beer Yiftah , Kosashvili Yona , Finestone Aharon S. 
Published: March 2015

Background: Foot ulcers carry considerable morbidity in patients with peripheral neuropathy and frequently lead to foot amputation. The purpose of this study was to present our experience treating recalcitrant ulcers underlying the hallux interphalangeal joint in patients with diabetes mellitus (DM)–related neuropathy with a first metatarsophalangeal (MTPJ1) resection arthroplasty. Methods: We retrospectively reviewed the computerized medical files of patients with diabetic neuropathy treated with a MTPJ1 resection arthroplasty. We performed 28 arthroplasties on 20 patients with a mean age of 59 years. The patients had a diagnosis of DM for a mean of 10.7 years. Of the ulcers, 26 were grade 1A ulcers, and 2 were grade 2A ulcers (University of Texas score); the ulcer’s mean age was 5.4 months. The mean dorsiflexion of the hallux before surgery was 46 degrees. Results: The primary ulcer recovered in a mean of 3.1 weeks. Major complications (wound dehiscence and infection) occurred in 6 of 28 operations. Patients returned to normal activity 4 weeks after all procedures except in the 6 patients with dehiscence. In a subgroup of patients with follow-up longer than a year, the ulcer recurred after 4 of 18 arthroplasties (22%) between 3 and 12 months due to postoperative hallux rigidus. In the remaining 14 of 18 arthroplasties (78%), there was no recurrence during a mean follow-up of 26 months. Conclusion: MTPJ1 resection arthroplasty may be considered in a patient with resistant plantar hallux ulcerations, even in the absence of hallux rigidus. As with all operations on neuropathic feet in patients with DM, the surgeon and the patient should be aware that there is a significant likelihood of complications, but most are treatable. Level of Evidence: Level IV, case series.