bluuebunny/crossref_metadata_2025_split huggingface dataset:
Landscape of Germline and Somatic Mitochondrial DNA Mutations in Pediatric Malignancies
Authors: Triska Petr , Kaneva Kristiyana , Merkurjev Daria , Sohail Noor , Falk Marni J. , Triche Timothy J. , Biegel Jaclyn A. , Gai Xiaowu 
Published: February 2019

Abstract

Little is known about the spectrum of mitochondrial DNA (mtDNA) mutations across pediatric malignancies. In this study, we analyzed matched tumor and normal whole genome sequencing data from 616 pediatric patients with hematopoietic malignancies, solid tumors, and brain tumors. We identified 391 mtDNA mutations in 284 tumors including 45 loss-of-function mutations, which clustered at four statistically significant hotspots in MT-COX3, MT-ND4, and MT-ND5, and at a mutation hotspot in MT-tRNA-MET. A skewed ratio (4.83) of nonsynonymous versus synonymous (dN/dS) mtDNA mutations with high statistical significance was identified on the basis of Monte Carlo simulations in the tumors. In comparison, opposite ratios of 0.44 and 0.93 were observed in 616 matched normal tissues and in 249 blood samples from children without cancer, respectively. mtDNA mutations varied by cancer type and mtDNA haplogroup. Collectively, these results suggest that deleterious mtDNA mutations play a role in the development and progression of pediatric cancers.

Significance:
This pan-cancer mtDNA study establishes the landscape of germline and tumor mtDNA mutations and identifies hotspots of tumor mtDNA mutations to pinpoint key mitochondrial functions in pediatric malignancies.
Revolutionizing Cancer Immunology: The Power of Next-Generation Sequencing Technologies
Authors: Singer Meromit , Anderson Ana C. 
Published: February 2019

Abstract
It has long been appreciated that tumors are diverse, varying in mutational status, composition of cellular infiltrate, and organizational architecture. For the most part, the information embedded in this diversity has gone untapped due to the limited resolution and dimensionality of assays for analyzing nucleic acid expression in cells. The advent of high-throughput, next-generation sequencing (NGS) technologies that measure nucleic acids, particularly at the single-cell level, is fueling the characterization of the many components that comprise the tumor microenvironment (TME), with a strong focus on immune composition. Understanding the immune and nonimmune components of the TME, how they interact, and how this shapes their functional properties requires the development of novel computational methods and, eventually, the application of systems-based approaches. The continued development and application of NGS technologies holds great promise for accelerating discovery in the cancer immunology field.
Early Unclamping Laparoscopic Partial Nephrectomy for Complex Renal Tumor: Data from a Chinese Cohort
Authors: Zhang Tao , Zhao Li , Ma Jiaxing , Min Jie , Yang Chao , Sun Xin , Qian Weiwei , Song Jin , Zhu Jinbo , Yu Dexin 
Published: February 2019

<b><i>Objective:</i></b> To evaluate the efficacy and safety of early unclamping laparoscopic partial nephrectomy (LPN) for complex renal tumor relative to the standard artery clamping technique (SCT). <b><i>Methods:</i></b> Sixty-one patients with complex renal tumor (RENAL score ≥7) underwent LPN at our institution from January 2013 to April 2017. LPN was performed via SCT in 32 patients and via the early unclamping technique (EUT) in 29 patients. Operation time, warm ischemia time (WIT), blood loss, bleeding requiring transfusion, tumor volume, excisional volume loss (EVL), complications, and renal function before and after operation of the affected kidney were compared between the groups. <b><i>Results:</i></b> All surgeries were successful without conversion to open or nephrectomy. EUT reduced the WIT (<i>p</i> &#x3c; 0.001) but did not increase the complication rate (<i>p</i> = 0.322). Although the tumor volume and EVL were larger in the EUT than in the SCT group (<i>p</i> = 0.011, <i>p</i> = 0.001), glomerular filtration rate (GFR) reduction in the affected kidney did not significantly differ between the groups (<i>p</i> = 0.120). <b><i>Conclusion:</i></b> Early unclamping LPN for complex renal tumor is safe and efficient. Additionally, the EUT could expand the application of LPN in complex renal tumors, and make this challenging surgery easier and safer.
A casa de Ulisses no labirinto de espelhos
Authors: Peixoto Gustavo Rocha 
Published: February 2019

O sonho de Telêmaco, entre morcegos melancólicos, dá início a uma odisseia noturna pelos labirintos espelhados da historiografia da arquitetura. O livro A coluna e o vulto, publicado em 2017, trata das“permutas de significados entre corpo e arquitetura.” O que deveria ser uma resenha daquele inovador ensaio de Mario Henrique d’Agostino, terminou por se converter em “mal disfarçado pretexto” para umaprofunda reflexão sobre os graus e direções da historiografia da arquitetura permeada por imaginação arquitetural e mitos literários de longa reverberação; por certezas e verdades; filologia e filosofia. Estãoconvocados para depor em juízo Homero e James Joyce; Manfredo Tafuri, Rudolf Wittkower, Joseph Rykwert, Giambattista Vico e Marco Lucchesi; Le Corbusier, Stanley Kubrick e Lewis Carroll.
Low Fluoroscopy Permanent His Bundle Pacing Using Electroanatomic Mapping
Authors: Sharma Parikshit S. , Huang Henry D. , Trohman Richard G. , Naperkowski Angela , Ellenbogen Kenneth A. , Vijayaraman Pugazhendhi 
Published: February 2019

Background:
Conventional permanent His Bundle pacing (PHBP) can be challenging and associated with high fluoroscopy exposure. The aim of this study was to assess the feasibility and safety of performing low fluoroscopy PHBP using 3-dimensional electroanatomic mapping and comparing outcomes with conventional fluoroscopy guided PHBP implants.

Methods:
PHBP was performed at 2 centers using electroanatomic mapping-guided low fluoroscopy implantation in 10 patients using a novel protocol (group 1) and conventional fluoroscopy guided implantation in 20 patients (group 2). The primary end point was feasibility of achieving PHBP with low/zero fluoroscopy and safety end points included total radiation exposure (fluoroscopy time and dose area product), procedure-related complications associated with lead implantation or need for lead revisions.

Results:

PHBP was successful in 9 of 10 patients (90%) in group 1 and 100% successful in the group 2 patients. The mean His lead fluoroscopy time was significantly lower in group 1 (0.2±0.2 minutes) compared with 8±7 minutes in group 2 (
P
=0.002) as was the total fluoroscopy time (0.8±0.3 versus 13±8 minutes,
P
=0.003) and the dose area product (96±83 versus 1531±923 microGy/m
2
,
P
=0.003). The HB capture threshold was lower in group 1 (0.7±0.4 at 1 ms) compared with patients in group 2 (1.15±0.7 at 1 ms)
P
=0.04. There were no procedure-related complications or lead dislodgements in either group. There was an increase in HB capture threshold in 1 patient (5%) in group 2 at 1-month follow-up.

Conclusions:
Electroanatomic mapping-guided PHBP is feasible can be performed safely and results in a significant reduction in fluoroscopy duration and exposure.
Five-Year Clinical and Echocardiographic Outcomes From the NOTION Randomized Clinical Trial in Patients at Lower Surgical Risk
Authors: Thyregod Hans Gustav Hørsted , Ihlemann Nikolaj , Jørgensen Troels Højsgaard , Nissen Henrik , Kjeldsen Bo Juel , Petursson Petur , Chang Yanping , Franzen Olaf Walter , Engstrøm Thomas , Clemmensen Peter , Hansen Peter Bo , Andersen Lars Willy , Steinbruüchel Daniel Andreas , Olsen Peter Skov , Søndergaard Lars 
Published: February 2019

Background:
The NOTION trial (Nordic Aortic Valve Intervention) was designed to compare transcatheter aortic valve replacement (TAVR) with surgical aortic valve replacement (SAVR) in patients ≥70 years old with isolated severe aortic valve stenosis. Clinical and echocardiographic outcomes are presented after 5 years.

Methods:
Patients were enrolled at 3 Nordic centers and randomized 1:1 to TAVR using the self-expanding CoreValve prosthesis (n=145) or SAVR using any stented bioprostheses (n=135). The primary composite outcome was the rate of all-cause mortality, stroke, or myocardial infarction at 1 year defined according to Valve Academic Research Consortium-2 criteria.

Results:

Baseline characteristics were similar. The mean age was 79.1±4.8 years and mean Society of Thoracic Surgeons Predicted Risk of Mortality score was 3.0%±1.7%. After 5 years, there were no differences between TAVR and SAVR in the composite outcome (Kaplan-Meier estimates 38.0% versus 36.3%, log-rank test
P
=0.86) or any of its components. TAVR patients had larger prosthetic valve area (1.7 cm
2
versus 1.2 cm
2
,
P
<0.001) with a lower mean transprosthetic gradient (8.2 mm Hg versus 13.7 mm Hg,
P
<0.001), both unchanged over time. More TAVR patients had moderate/severe total aortic regurgitation (8.2% versus 0.0%,
P
<0.001) and a new pacemaker (43.7% versus 8.7%,
P
<0.001). Four patients had prosthetic reintervention and no difference was found for functional outcomes.

Conclusions:
These are currently the longest follow-up data comparing TAVR and SAVR in lower risk patients, demonstrating no statistical difference for major clinical outcomes 5 years after TAVR with a self-expanding prosthesis compared to SAVR. Higher rates of prosthetic regurgitation and pacemaker implantation were seen after TAVR.

Clinical Trial Registration:

URL:
https://clinicaltrials.gov
. Unique identifier: NCT01057173.
Explicit Ensemble Prediction of Hail in 19 May 2013 Oklahoma City Thunderstorms and Analysis of Hail Growth Processes with Several Multimoment Microphysics Schemes
Authors: Labriola Jonathan , Snook Nathan , Jung Youngsun , Xue Ming 
Published: February 2019

AbstractHail forecast evaluations provide important insight into microphysical treatment of rimed ice. In this study we evaluate explicit 0–90-min EnKF-based storm-scale (500-m horizontal grid spacing) hail forecasts for a severe weather event that occurred in Oklahoma on 19 May 2013. Forecast ensembles are run using three different bulk microphysics (MP) schemes: the Milbrandt–Yau double-moment scheme (MY2), the Milbrandt–Yau triple-moment scheme (MY3), and the NSSL variable density-rimed ice double-moment scheme (NSSL). Output from a hydrometeor classification algorithm is used to verify surface hail size forecasts. All three schemes produce forecasts that predict the coverage of severe surface hail with moderate to high skill, but exhibit less skill at predicting significant severe hail coverage. A microphysical budget analysis is conducted to better understand hail growth processes in all three schemes. The NSSL scheme uses two-variable density-rimed ice categories to create large hailstones from dense, wet growth graupel particles; however, it is noted the scheme underestimates the coverage of significant severe hail. Both the MY2 and MY3 schemes produce many small hailstones aloft from unrimed, frozen raindrops; in the melting layer, hailstones become much larger than observations because of the excessive accretion of water. The results of this work highlight the importance of using a MP scheme that realistically models microphysical processes.
Timing of Anticoagulation in Atrial Fibrillation Status Post Cardioembolic Stroke
Authors: Core Ashley , Pinner Nathan , Bethea Brittany , Starr Jessica A. 
Published: February 2019

Background: Anticoagulation is the mainstay of secondary stroke prevention in patients with atrial fibrillation; however, few studies have assessed the optimal timing for initiation of anticoagulation post cardioembolic stroke. In the 2 weeks following an acute cardioembolic stroke, the risk of recurrent stroke is as high as 8%, but this risk must be balanced against the risk of hemorrhagic transformation with early initiation of anticoagulation. Purpose: This study described the time to initiation of anticoagulation and evaluated the in-hospital incidence of hemorrhagic and ischemic complications in 106 patients with atrial fibrillation post an acute cardioembolic stroke. Methods: A single-center retrospective cohort study was conducted to describe the time to initiation of therapeutic anticoagulation in patients with atrial fibrillation admitted to the hospital for an acute cardioembolic stroke. The primary outcome was the time to initiation of anticoagulation from the time of stroke onset. Secondary outcomes included the incidence of in-hospital hemorrhagic and ischemic complications. Results: The median time to initiation of anticoagulation was 59.5 hours after stroke onset for those who did not receive thrombolytic therapy and 82.6 hours for those who did received thrombolytic therapy. Out of 100 patients initiated on anticoagulation, no ischemic complications were observed. Four patients experienced a hemorrhagic conversion following initiation of anticoagulation. In 3 of these patients, anticoagulation was initiated within 48 hours of stroke onset. Conclusion: A small percentage of patients experienced an in-house hemorrhagic conversion when anticoagulation was initiated between 48 hours and 7 days.
Targeted advertisement of chlamydia screening on social media: A mixed-methods analysis
Authors: Nadarzynski Tom , Burton Jack , Henderson Kimberley , Zimmerman Deborah , Hill Orla , Graham Cynthia 
Published: February 2019

Objective Chlamydia is one of the most common sexually transmitted infections in teenagers and young adults. This study used a mixed-methods analysis to investigate targeted promotion of chlamydia home-testing on social media. Methods Our first study, in which face-to-face interviews with young women were conducted, sought to explore their attitudes and preferences towards social media-based health promotion. Our second study used Facebook and Google analytics to examine visits to a chlamydia testing page (where chlamydia testing kits could be ordered online), both before and after a targeted Facebook-based health promotion campaign was conducted. Results The interviews revealed Facebook to be the preferred choice of social media, with participants perceiving it to be a powerful and far-reaching platform for social interaction. Participants also highlighted several aspects of promotional content to be important at increasing engagement with the target population, including appropriate use of colour, level of interactivity, use of humour and anonymity. The website analysis showed a 277% increase in the direct entrance on the chlamydia testing kit page and a 41% increase in chlamydia test kit orders, in comparison with the baseline period prior to the intervention. Conclusions The findings support social media as an engaging medium for the online promotion of chlamydia self-testing and implicate Facebook advertising as a useful tool in addition to community-based chlamydia screening services. Future research needs to identify whether targeted social media-based health promotion could lead to higher chlamydia diagnosis rate in comparison to traditional communication channels.
Invariant phenotype and molecular association of biallelic TET2 mutant myeloid neoplasia
Authors: Awada Hassan , Nagata Yasunobu , Goyal Abhinav , Asad Mohammad F. , Patel Bhumika , Hirsch Cassandra M. , Kuzmanovic Teodora , Guan Yihong , Przychodzen Bartlomiej P. , Aly Mai , Adema Vera , Shen Wenyi , Williams Louis , Nazha Aziz , Abazeed Mohamed E. , Sekeres Mikkael A. , Radivoyevitch Tomas , Haferlach Torsten , Jha Babal K. , Visconte Valeria , Maciejewski Jaroslaw P. 
Published: February 2019

Abstract
Somatic TET2 mutations (TET2MT) are frequent in myeloid neoplasia (MN), particularly chronic myelomonocytic leukemia (CMML). TET2MT includes mostly loss-of-function/hypomorphic hits. Impaired TET2 activity skews differentiation of hematopoietic stem cells toward proliferating myeloid precursors. This study was prompted by the observation of frequent biallelic TET2 gene inactivations (biTET2i) in CMML. We speculated that biTET2i might be associated with distinct clinicohematological features. We analyzed TET2MT in 1045 patients with MN. Of 82 biTET2i cases, 66 were biTET2MT, 13 were hemizygous TET2MT, and 3 were homozygous TET2MT (uniparental disomy); the remaining patients (denoted biTET2− hereafter) were either monoallelic TET2MT (n = 96) or wild-type TET2 (n = 823). Truncation mutations were found in 83% of biTET2i vs 65% of biTET2− cases (P = .02). TET2 hits were founder lesions in 72% of biTET2i vs 38% of biTET2− cases (P &lt; .0001). In biTET2i, significantly concurrent hits included SRSF2MT (33%; P &lt; .0001) and KRAS/NRASMT (16%; P = .03) as compared with biTET2−. When the first TET2 hit was ancestral in biTET2i, the most common subsequent hits affected a second TET2MT, followed by SRSF2MT, ASXL1MT, RASMT, and DNMT3AMT. BiTET2i patients without any monocytosis showed an absence of SRSF2MT. BiTET2i patients were older and had monocytosis, CMML, normal karyotypes, and lower-risk disease compared with biTET2− patients. Hence, while a second TET2 hit occurred frequently, biTET2i did not portend faster progression but rather determined monocytic differentiation, consistent with its prevalence in CMML. Additionally, biTET2i showed lower odds of cytopenias and marrow blasts (≥5%) and higher odds of myeloid dysplasia and marrow hypercellularity. Thus, biTET2i might represent an auxiliary assessment tool in MN.
Pharmacological treatment of asthma in a cohort of adults during a 20-year period: results from the European Community Respiratory Health Survey I, II and III
Authors: Janson Christer , Accordini Simone , Cazzoletti Lucia , Cerveri Isa , Chanoine Sebastien , Corsico Angelo , Ferreira Diogenes Seraphim , Garcia-Aymerich Judith , Gislason David , Nielsen Rune , Johannessen Ane , Jogi Rain , Malinovschi Andrei , Martinez-Moratalla Rovira Jesús , Marcon Alessandro , Pin Isabelle , Quint Jennifer , Siroux Valerie , Almar Enrique , Bellisario Valeria , Franklin Karl A. , Gullón José A. , Holm Mathias , Heinrich Joachim , Nowak Dennis , Sánchez-Ramos José Luis , Weyler Joost J. , Jarvis Deborah 
Published: February 2019

Asthma often remains uncontrolled, despite the fact that the pharmacological treatment has undergone large changes. We studied changes in the treatment of asthma over a 20-year period and identified factors associated with the regular use of inhaled corticosteroid (ICS) treatment.Changes in the use of medication were determined in 4617 randomly selected subjects, while changes in adults with persistent asthma were analysed in 369 participants. The study compares data from three surveys in 24 centres in 11 countries.The use of ICSs increased from 1.7% to 5.9% in the general population and the regular use of ICSs increased from 19% to 34% among persistent asthmatic subjects. The proportion of asthmatic subjects reporting asthma attacks in the last 12 months decreased, while the proportion that had seen a doctor in the last 12 months remained unchanged (42%). Subjects with asthma who had experienced attacks or had seen a doctor were more likely to use ICSs on a regular basis.Although ICS use has increased, only one-third of subjects with persistent asthma take ICSs on a regular basis. Less than half had seen a doctor during the last year. This indicates that underuse of ICSs and lack of regular healthcare contacts remains a problem in the management of asthma.
A cadaveric and sonographic study of the morphology of the tibialis anterior tendon – a proposal for a new classification
Authors: Olewnik Łukasz , Podgórski Michał , Polguj Michał , Topol Mirosław 
Published: February 2019

AbstractBackgroundThe tibialis anterior tendon (TAT) presents little morphological variation. The tibialis anterior muscle originates at the lateral condyle of the tibia, the proximal one‐third to two‐thirds of the lateral surface of the tibia shaft, and the anterior surface of the interosseous membrane and inserts to the medial cuneiform bone and first metatarsal. The aim of our work is to classify types of TAT insertion by two complimentary methods ‐ anatomical dissection and ultrasound examination.MethodsIn the first part, classical anatomical dissection was performed on 100 lower limbs (50 right, 50 left) fixed in 10% formalin solution. The morphology of the insertion of the tendon was evaluated and the muscle was subjected to the appropriate morphometric measurements. In the second part, the morphology of the TAT insertion was evaluated in 50 volunteers with ultrasound.ResultsThe tibialis anterior muscle was present in all specimens. In the cadavers, five types of insertion were observed, the most common being Type V: a single band attaching to the medial cuneiform bone (32%). In the sonographic part, Type IV was not observed; however, an additional insertion type was recognised (Type VI), which was characterized by two identical bands attached only to the medial cuneiform bone. The most common type identified by ultrasound was Type II (35%).ConclusionThe tibialis anterior tendon presents high morphological variability that can be observed both in cadavers and in vivo by ultrasound examination.Level of evidenceII Prospective Comparative Study
Mechanisms of Osteoblastic Bone Metastasis in Prostate Cancer: Role of Prostatic Acid Phosphatase
Authors: Quiroz-Munoz Mariana , Izadmehr Sudeh , Arumugam Dushyanthy , Wong Beatrice , Kirschenbaum Alexander , Levine Alice C 
Published: February 2019

Abstract
Prostate cancer (PCa) preferentially metastasizes to bone, leading to complications including severe pain, fractures, spinal cord compression, bone marrow suppression, and a mortality of ∼70%. In spite of recent advances in chemo-, hormonal, and radiation therapies, bone-metastatic, castrate-resistant PCa is incurable. PCa is somewhat unique among the solid tumors in its tendency to produce osteoblastic lesions composed of hypermineralized bone with multiple layers of poorly organized type I collagen fibrils that have reduced mechanical strength. Many of the signaling pathways that control normal bone homeostasis are at play in pathologic PCa bone metastases, including the receptor activator of nuclear factor-κB/receptor activator of nuclear factor-κB ligand/osteoprotegerin system. A number of PCa-derived soluble factors have been shown to induce the dysfunctional osteoblastic phenotype. However, therapies directed at these osteoblastic-stimulating proteins have yielded disappointing clinical results to date. One of the soluble factors expressed by PCa cells, particularly in bone metastases, is prostatic acid phosphatase (PAP). Human PAP is a prostate epithelium-specific secretory protein that was the first tumor marker ever described. Biologically, PAP exhibits both phosphatase activity and ecto-5′-nucleotidase activity, generating extracellular phosphate and adenosine as the final products. Accumulating evidence indicates that PAP plays a causal role in the osteoblastic phenotype and aberrant bone mineralization seen in bone-metastatic, castrate-resistant PCa. Targeting PAP may represent a therapeutic approach to improve morbidity and mortality from PCa osteoblastic bone metastases.