bluuebunny/crossref_metadata_2025_split huggingface dataset:
A non-hierarchical organization of tumorigenic NG2 cells in glioblastoma promoted by EGFR
Authors: Al-Mayhani Talal F , Heywood Richard M , Vemireddy Vamsidhara , Lathia Justin D , Piccirillo Sara G M , Watts Colin 
Published: December 2018

Abstract

Background
Expression of neuron-glial antigen 2 (NG2) identifies an aggressive malignant phenotype in glioblastoma (GBM). Mouse models have implicated NG2 in the genesis, evolution, and maintenance of glial cancers and have highlighted potential interactions between NG2 and epidermal growth factor receptor (EGFR). However, it is unknown whether the lineage relationship of NG2+ and NG2− cells follows a hierarchical or stochastic mode of growth. Furthermore, the interaction between NG2 and EGFR signaling in human GBM is also unclear.

Methods
Single GBM NG2+ and NG2− cells were studied longitudinally to assess lineage relationships. Short hairpin RNA knockdown of NG2 was used to assess the mechanistic role of NG2 in human GBM cells. NG2+ and NG2− cells and NG2 knockdown (NG2-KD) and wild type (NG2-WT) cells were analyzed for differential effects on EGFR signaling.

Results
Expression of NG2 endows an aggressive phenotype both at single cell and population levels. Progeny derived from single GBM NG2− or GBM NG2+ cells consistently establish phenotypic equilibrium, indicating the absence of a cellular hierarchy. NG2 knockdown reduces proliferation, and mice grafted with NG2-KD survive longer than controls. Finally, NG2 promotes EGFR signaling and is associated with EGFR expression.

Conclusions
These data support a dynamic evolution in which a bidirectional relationship exists between GBM NG2+ and GBM NG2− cells. Such findings have implications for understanding phenotypic heterogeneity, the emergence of resistant disease, and developing novel therapeutics.
Pneumocystis jirovecii prophylaxis in patients treated for high-grade gliomas: a survey among neuro-oncologists
Authors: Skorupan Nebojša , Ranjan Surabhi , Mehta Seema , Yankulina Olga , Nenortas Nathan , Grossman Stuart , Ye Xiaobu , Holdhoff Matthias 
Published: December 2018

Abstract

Background
Pneumocystis jirovecii pneumonia (PJP) is a known complication in patients with high-grade gliomas (HGGs) who are treated with radiation and chemotherapy. PJP prophylaxis is commonly recommended, but there are currently no clear guidelines regarding duration of treatment and choice of drugs. This study aimed to assess current practice patterns of PJP prophylaxis among neuro-oncologists.

Methods
An online survey of 14 multiple choice questions was sent to 207 neuro-oncologists and medical oncologists treating brain cancers at all National Cancer Institute-designated cancer centers in the United States. Recipients were identified via a search of the cancer centers’ websites.

Results
Sixty-one invited experts completed the survey (response rate 29%; of these, 72% were neuro-oncologists, 18% were medical oncologists, and 10% were pediatric neuro- or medical oncologists). Seventy percent of respondents stated that they routinely prescribe PJP prophylaxis, while 7% do not provide prophylaxis. Eighty-one percent of respondents use absolute lymphocyte count (ALC) to assess lymphopenia and 13% also monitor CD4 lymphocyte counts during prophylaxis. The most commonly used first-line agent is trimethoprim-sulfamethoxazole (88% of respondents), followed by pentamidine (6%). Discontinuation of PJP prophylaxis is determined by the following: count recovery (33% by ALC; 18% by CD4 lymphocyte counts), radiation completion (23%), and chemotherapy completion (7%). Glucose-6-phosphate dehydrogenase levels were routinely checked by only 13% of respondents.

Conclusions
PJP prophylaxis is commonly used in HGG patients, but there are large variations in practice patterns, including the duration of prophylaxis. As consideration for PJP prophylaxis affects all patients with HGG, standardization of prophylaxis should be formally addressed.
Comparative Effectiveness of Group-Delivered Acceptance and Commitment Therapy versus Cognitive Behavioral Therapy for Smoking Cessation: A Randomized Controlled Trial
Authors: McClure Jennifer B , Bricker Jonathan , Mull Kristin , Heffner Jaimee L 
Published: December 2018

AbstractIntroductionPreliminary trial data suggest group-delivered acceptance and commitment therapy (ACT) might be effective for smoking cessation. If so, this could offer a viable alternative to mainstream behavioral therapies, such as those grounded in cognitive behavioral therapy (CBT). The goal of the current study was to compare the effectiveness of group-delivered ACT versus group-delivered CBT in a rigorous randomized trial design with long-term follow-up.MethodsParticipants (n = 450) were recruited from the Kaiser Permanente Washington health care system and randomized to either ACT-based group counseling or an attention-matched CBT-based group program. All were prescribed an 8-week course of nicotine patches. The primary outcome was self-reported 30-day point prevalence abstinence at 12 months post-randomization assessed with missing values imputed as smoking. Sensitivity analyses using multiple imputation and complete cases were examined, as were biochemically confirmed and 6-month outcomes.ResultsThirty-day point prevalence abstinence rates at the 12-month follow-up did not differ between study arms in the primary analysis (13.8% ACT vs. 18.1% CBT, adjusted odds ratio = 0.68 [95% CI = 0.35 to 1.27], p = .23) or the sensitivity analyses.ConclusionsGroup-based ACT and CBT had similar long-term quit rates in this methodologically rigorous randomized trial. Group-based ACT is a reasonable alternative to group-based CBT for smoking cessation.ImplicationsThis study compared the effectiveness of group-based ACT with group-based CBT for smoking cessation using a rigorous, large-scale, attention-matched, randomized trial with 1-year follow-up. One-year cessation rates did not differ between group-based ACT and CBT, suggesting ACT-based intervention is a reasonable alternative to CBT-based counseling for smoking cessation. The results add to the nascent but growing literature assessing ACT and other mindfulness-based treatments for smoking cessation.
No Impact of Probiotics to Reduce Clostridium difficile Infection in Hospitalized Patients: A Real-world Experience
Authors: Box Maggie J , Ortwine Kristine N , Goicoechea Miguel ,   Scripps Antimicrobial Stewardship Program (SASP)
Published: December 2018

Abstract
We assessed the effectiveness of a Lactobacillus probiotic on rates of health care facility–onset Clostridium difficile infection (HO-CDI) in patients receiving antibiotics. A total of 1576 patients were evaluated. There was no difference in the HO-CDI incidence between those who received probiotics and those who did not (1.8% vs 0.9%; P = .16).
Impact of Diabetes Mellitus on the Presentation and Response to Treatment of Adults With Pulmonary Tuberculosis in Qatar
Authors: Dousa Khalid M , Hamad Abdelrahman , Albirair Mohamed , Al Soub Hussam , Elzouki Abdel-Naser , Alwakeel Mahmoud I , Thiel Bonnie A , Johnson John L 
Published: December 2018

AbstractBackgroundPersons with diabetes mellitus (DM) have a 3-fold increased risk of tuberculosis (TB). Atypical radiographic findings and differences in bacteriologic response during anti-TB treatment have been reported in earlier studies; however, the findings have varied. We evaluated the effect of DM on manifestations and response to treatment in adults with pulmonary TB in Qatar.MethodsThe impact of DM on the clinical and radiographic presentations of pulmonary TB and bacteriologic response during anti-TB treatment was evaluated between January 2007 and December 2011, comparing patients with and without DM. This is a retrospective unmatched case-control study conducted at a large national hospital. Cases and controls were randomly selected from patients diagnosed with pulmonary TB over a 5-year period. Sputum culture conversion was assessed after 2 months of anti-TB treatment.ResultsClinical symptoms were similar between patients with and without DM. Patients with DM had a higher initial sputum acid-fast bacillus (AFB) smear grade and were less likely to have cavitary lesions on initial chest radiographs than patients without DM. Of 134 adults with DM and TB, 71 (53%) remained sputum culture positive after 2 months of anti-TB treatment, compared with 36 (27%) patients without DM.ConclusionsDM was associated with atypical radiographic findings and delayed sputum culture conversion at 2 months in adults with pulmonary TB in Qatar. Increased health education of patients with DM about symptoms of TB, low thresholds for evaluation for active TB, and close monitoring of bacteriologic response to treatment among patients with TB and DM are warranted.
Randomized Controlled Pilot Study of Antiretrovirals and a Behavioral Intervention for Persons With Acute HIV Infection: Opportunity for Interrupting Transmission
Authors: Miller William C , Rutstein Sarah E , Phiri Sam , Kamanga Gift , Nsona Dominic , Pasquale Dana K , Rucinski Katherine B , Chen Jane S , Golin Carol E , Powers Kimberly A , Dennis Ann M , Hosseinipour Mina C , Eron Joseph J , Chege Wairimu , Hoffman Irving F , Pettifor Audrey E 
Published: December 2018

AbstractBackgroundPersons with acute HIV infection (AHI) have heightened transmission risk. We evaluated potential transmission reduction using behavioral and biomedical interventions in a randomized controlled pilot study in Malawi.MethodsPersons were randomized 1:2:2 to standard counseling (SC), 5-session behavioral intervention (BI), or behavioral intervention plus 12 weeks of antiretrovirals (ARVs; BIA). All were followed for 26–52 weeks and, regardless of arm, referred for treatment according to Malawi-ARV guidelines. Participants were asked to refer partners for testing.ResultsAmong 46 persons (9 SC, 18 BI, 19 BIA), the average age was 28; 61% were male. The median viral load (VL) was 5.9 log copies/mL at enrollment. 67% (10/15) of BIA participants were suppressed (&lt;1000 copies/mL) at week 12 vs 25% BI and 50% SC (P = .07). Although the mean number of reported condomless sexual acts in the past week decreased from baseline across all arms (1.5 vs 0.3 acts), 36% experienced incident sexually transmitted infection by 52 weeks (12% SC, 28% BI, 18% BIA). Forty-one percent (19/46) of participants referred partners (44% SC, 44% BI, 37% BIA); 15 of the partners were HIV-infected.ConclusionsDiagnosis of AHI facilitates behavioral and biomedical risk reduction strategies during a high-transmission period that begins years before people are typically identified and started on ARVs. Sexually transmitted infection incidence in this cohort suggests ongoing risk behaviors, reinforcing the importance of early intervention with ARVs to reduce transmission. Early diagnosis coupled with standard AHI counseling and early ARV referral quickly suppresses viremia, may effectively change behavior, and could have tremendous public health benefit in reducing onward transmission.
Clinical, Virologic, and Immunologic Characteristics of Zika Virus Infection in a Cohort of US Patients: Prolonged RNA Detection in Whole Blood
Authors: El Sahly Hana M , Gorchakov Rodion , Lai Lilin , Natrajan Muktha S , Patel Shital M , Atmar Robert L , Keitel Wendy A , Hoft Daniel F , Barrett Jill , Bailey Jason , Edupuganti Srilatha , Raabe Vanessa , Wu Henry M , Fairley Jessica , Rouphael Nadine , Murray Kristy O , Mulligan Mark J 
Published: December 2018

Abstract

Background
Clinical, virologic, and immunologic characteristics of Zika virus (ZIKV) infections in US patients are poorly defined.

Methods
US subjects with suspected ZIKV infection were enrolled. Clinical data and specimens were prospectively collected for ZIKV RNA detection and serologic and cellular assays. Confirmed ZIKV infection (cases) and ZIKV-negative (controls) subjects were compared. Dengue-experienced and dengue-naïve cases were also compared.

Results
We enrolled 45 cases and 14 controls. Commonly reported symptoms among cases and controls were maculopapular rash (97.8% and 81.8%), fatigue (86.7% and 81.8%), and arthralgia (82.2% and 54.5%), respectively. The sensitivity (94%) and duration of infection detection (80% positivity at 65–79 days after disease onset) by polymerase chain reaction were highest in whole-blood specimens. ZIKV-neutralizing antibodies had a half-life of 105 days and were significantly higher in dengue virus–experienced cases than naïve ones (P = .046). In intracellular cytokine staining assays, the ZIKV proteins targeted most often by peripheral blood mononuclear cells from cases were structural proteins C and E for CD4+ T cells and nonstructural proteins NS3, NS5, and NS4B for CD8+ T cells.

Conclusions
ZIKV RNA detection was more frequent and prolonged in whole-blood specimens. Immunoglobulin G (IgG) and neutralizing antibodies, but not IgM, were influenced by prior dengue infection. Robust cellular responses to E and nonstructural proteins have potential vaccine development implications.
Expanded Endoscopic Endonasal Approach for Resection of Intradural Chordoma: Surgical and Anatomic Nuances: 2-Dimensional Operative Video
Authors: Marigil Miguel , Almeida Joao Paulo , Karekezi Claire , de Almeida John R , Gentili Fred 
Published: December 2018

Abstract
The expanded endoscopic endonasal approach (EEA) has been growing as a surgical alternative for the treatment of clival chordomas because of their frequent midline location and bone erosion. The endoscopic transclival approach provides with a safer and more direct anatomic route for tumors located predominantly in the midline contributing to minimize postoperative comorbidities. In this video, we demonstrate the step-by-step technique for resection of such challenging clival pathology.
This is an operative video of an extended endoscopic resection of a clival chordoma with stepwise description of the surgical technique.
We present the case of a 49-yr-old man in whom, incidentally in the context of low testosterone level, a clival lesion with purely midline location with intradural extension into the ventral brainstem and occupation of the left cerebellopontine angle was discovered. The patient was submitted to an expanded endoscopic transclival approach and a macroscopic gross total resection was successfully achieved. The final pathology was compatible with a conventional chordoma. This video details the surgical anatomy of the clival region to facilitate the identification of surgical landmarks and anatomic boundaries with the goal of avoiding injury to the neurovascular structures involved in this approach.
Extended endoscopic transclival surgery is a useful and safer option for the management of midline chordomas because it provides with a dissection corridor free of major neurovascular structures. Endoscopic techniques are associated with good outcomes in terms of macroscopic gross total resection and low surgical risks in these selected tumors.
Adaptation of an Ultrasound-Guided Technique for Pulsed Radiofrequency on Axillary and Suprascapular Nerves in the Treatment of Shoulder Pain
Authors: Esparza-Miñana José Miguel , Mazzinari Guido 
Published: December 2018

Abstract

Background
It has been estimated that 20% of the general population will suffer shoulder pain throughout their lives, with a prevalence that can reach up to 50%. The suprascapular nerve (SSN) provides sensation for the posterior and superior regions of the glenohumeral joint, whereas the anterior and inferior zones and the skin are innervated mostly by the axillary nerve. Pulsed radiofrequency on the SSN has been proposed as a therapeutic option in chronic shoulder pain. Axillary nerve block has been proposed in the context of surgical analgesia as an adjuvant to SSN block.

Interventions
Ultrasound (US)-guided techniques target the nerve selectively, minimizing patients’ and physicians’ exposure to harmful radiation while increasing success rates by better needle placement. We perform both US-guided techniques with the patient in a lateral decubitus position with the affected shoulder on the upper side.

Objective
The aim of this report is to describe the adaptation of a US-guided technique that targets both the suprascapular and axillary nerves for the treatment of painful shoulder syndrome. The simultaneous pulsed radiofrequency on the suprascapular and axillary nerves for the treatment of the chronic condition of shoulder pain has been scarcely studied, with very few references in the literature.

Conclusions
By adapting an approach developed in acute pain management, we can safely deliver pulsed radiofrequency to the suprascapular and axillary nerves for the treatment of shoulder pain.
SIMULATION OF OSL AND TLD DOSEMETER RESPONSE FOR THE DEVELOPMENT OF NEW EXTREMITY DOSEMETERS
Authors: Hoedlmoser H , Brönner J , Bandalo V , Wahl F , Greiter M B 
Published: December 2018

Abstract
The individual monitoring service at the Helmholtz Zentrum München is currently developing a new eye lens dosemeter to be integrated in radiation protection glasses and a new ring dosemeter using a new BeOSL detector element for extremity dosimetry developed by Dosimetrics. In the design process for the new eye lens dosemeter, MCNP6 Monte Carlo simulations were used to model the energy and angular response of new dosemeters before ordering the expensive tools for injection molding. This study describes the simulation of the dosemeter and detector, and the involved calculations do obtain the response in terms of the radiation protection quantity Hp(3). Simulations were carried out also for existing whole body dosemeters and TLD rings in order to verify the MC tools. With the final dosemeter prototypes becoming available earlier this year, all MC models could be verified and show very good agreement with experimental data.
Macropinosomes as units of signal transduction
Authors: Swanson Joel A. , Yoshida Sei 
Published: December 2018

Macropinosome formation occurs as a localized sequence of biochemical activities and associated morphological changes, which may be considered a form of signal transduction leading to the construction of an organelle. Macropinocytosis may also convey information about the availability of extracellular nutrients to intracellular regulators of metabolism. Consistent with this idea, activation of the metabolic regulator mechanistic target of rapamycin complex-1 (mTORC1) in response to acute stimulation by growth factors and extracellular amino acids requires internalization of amino acids by macropinocytosis. This suggests that macropinocytosis is necessary for mTORC1-dependent growth of metazoan cells, both as a route for delivery of amino acids to sensors associated with lysosomes and as a platform for growth factor-dependent signalling to mTORC1 via phosphatidylinositol 3-kinase (PI3K) and the Akt pathway. Because the biochemical signals required for the construction of macropinosomes are also required for cell growth, and inhibition of macropinocytosis inhibits growth factor signalling to mTORC1, we propose that signalling by growth factor receptors is organized into stochastic, structure-dependent cascades of chemical reactions that both build a macropinosome and stimulate mTORC1. More generally, as discrete units of signal transduction, macropinosomes may be subject to feedback regulation by metabolism and cell dimensions.This article is part of the Theo Murphy meeting issue ‘Macropinocytosis’.
Successful exome capture and sequencing in lemurs using human baits
Authors: Webster Timothy H. , Guevara Elaine E. , Lawler Richard R. , Bradley Brenda J. 
Published: December 2018

ABSTRACTObjectivesWe assessed the efficacy of exome capture in lemurs using commercially available human baits.Materials and MethodsWe used two human kits (Nimblegen SeqCap EZ Exome Probes v2.0; IDT xGen Exome Research Panel v1.0) to capture and sequence the exomes of wild Verreaux’s sifakas (Propithecus verreauxi,n = 8), a lemur species distantly related to humans. For comparison, we also captured exomes of a primate species more closely related to humans (Macaca mulatta,n= 4). We mapped reads to both the human reference assembly and the most closely related reference for each species before calling variants. We used measures of mapping quality and read coverage to compare capture success.ResultsWe observed high and comparable mapping qualities for both species when mapped to their respective nearest-relative reference genomes. When investigating breadth of coverage, we found greater capture success in macaques than sifakas using both nearest-relative and human assemblies. Exome capture in sifakas was still highly successful with more than 90% of annotated coding sequence in the sifaka reference genome captured, and 80% sequenced to a depth greater than 7x using Nimblegen baits. However, this success depended on probe design: the use of IDT probes resulted in substantially less callable sequence at low-to-moderate depths.DiscussionOverall, we demonstrate successful exome capture in lemurs using human baits, though success differed between kits tested. These results indicate that exome capture is an effective and economical genomic method of broad utility to evolutionary primatologists working across the entire primate order.
iScore: A novel graph kernel-based function for scoring protein-protein docking models
Authors: Geng Cunliang , Jung Yong , Renaud Nicolas , Honavar Vasant , Bonvin Alexandre M.J.J. , Xue Li C. 
Published: December 2018

ABSTRACTProtein complexes play a central role in many aspects of biological function. Knowledge of the three-dimensional (3D) structures of protein complexes is critical for gaining insights into the structural basis of interactions and their roles in the biomolecular pathways that orchestrate key cellular processes. Because of the expense and effort associated with experimental determination of 3D structures of protein complexes, computational docking has evolved as a valuable tool to predict the 3D structures of biomolecular complexes. Despite recent progress, reliably distinguishing near-native docking conformations from a large number of candidate conformations, the so-called scoring problem, remains a major challenge. Here we present iScore, a novel approach to scoring docked conformations that combines HADDOCK energy terms with a score obtained using a graph representation of the protein-protein interfaces and a measure of evolutionary conservation. It achieves a scoring performance competitive with, or superior to that of the state-of-the-art scoring functions on independent data sets consisting docking software-specific data sets and the CAPRI score set built from a wide variety of docking approaches. iScore ranks among the top scoring approaches on the CAPRI score set (13 targets) when compared with the 37 scoring groups in CAPRI. The results demonstrate the utility of combining evolutionary and topological, and physicochemical information for scoring docked conformations. This work represents the first successful demonstration of graph kernel to protein interfaces for effective discrimination of near-native and non-native conformations of protein complexes. It paves the way for the further development of computational methods for predicting the structure of protein complexes.