bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced CD160 Expression Contributes to Impaired NK-cell Function and Poor Clinical Outcomes in Patients with HCC
Authors: Sun Haoyu , Xu Jing , Huang Qiang , Huang Mei , Li Kun , Qu Kun , Wen Hao , Lin Renyong , Zheng Meijuan , Wei Haiming , Xiao Weihua , Sun Rui , Tian Zhigang , Sun Cheng 
Published: September 2018

AbstractWe previously reported that deficiencies in natural killer (NK)–cell number and function play an important role in the progression of hepatocellular carcinoma (HCC). However, the mechanisms underlying this phenomenon remain obscure. In this study, we analyzed the expression of CD160 on intrahepatic NK cells by evaluating peritumoral and intratumoral tissues of 279 patients with HCC and 20 healthy livers. We observed reduced expression of CD160 on intratumoral NK cells, and patients with lower CD160 cell densities within tumors exhibited worse disease and a higher recurrence rate. High-resolution microarray and gene set enrichment analysis of flow cytometry–sorted primary intrahepatic CD160+ and CD160− NK cells of healthy livers indicated that human CD160+ NK cells exhibited functional activation, high IFNγ production, and NK-mediated immunity. In addition, global transcriptomic analysis of sorted peritumoral and intratumoral CD160+ NK cells revealed that intratumoral CD160+ NK cells are more exhausted than peritumoral CD160+ NK cells and produce less IFNγ. High levels of TGFβ1 interfered with production of IFNγ by CD160+ NK cells, blocking of which specifically restored IFNγ production in CD160+ NK cells to normal levels. These findings indicate that reduced numbers of CD160+ NK cells, together with the functional impairment of CD160+ NK cells by TGFβ1, contribute to tumor immune escape. In addition, restoring the expression of CD160 and blocking TGFβ1 appear a promising therapeutic strategy against liver cancer.Significance:These findings show that reduced number and function of CD160+ NK cells in the tumor microenvironment contributes to immune escape of HCC; blocking TGFβ1 restores IFNγ production of CD160+ NK cells.
CANCERTOOL: A Visualization and Representation Interface to Exploit Cancer Datasets
Authors: Cortazar Ana R. , Torrano Veronica , Martín-Martín Natalia , Caro-Maldonado Alfredo , Camacho Laura , Hermanova Ivana , Guruceaga Elizabeth , Lorenzo-Martín Luis F. , Caloto Ruben , Gomis Roger R. , Apaolaza Iñigo , Quesada Victor , Trka Jan , Gomez-Muñoz Antonio , Vincent Silvestre , Bustelo Xose R. , Planes Francisco J. , Aransay Ana M. , Carracedo Arkaitz 
Published: September 2018

AbstractWith the advent of OMICs technologies, both individual research groups and consortia have spear-headed the characterization of human samples of multiple pathophysiologic origins, resulting in thousands of archived genomes and transcriptomes. Although a variety of web tools are now available to extract information from OMICs data, their utility has been limited by the capacity of nonbioinformatician researchers to exploit the information. To address this problem, we have developed CANCERTOOL, a web-based interface that aims to overcome the major limitations of public transcriptomics dataset analysis for highly prevalent types of cancer (breast, prostate, lung, and colorectal). CANCERTOOL provides rapid and comprehensive visualization of gene expression data for the gene(s) of interest in well-annotated cancer datasets. This visualization is accompanied by generation of reports customized to the interest of the researcher (e.g., editable figures, detailed statistical analyses, and access to raw data for reanalysis). It also carries out gene-to-gene correlations in multiple datasets at the same time or using preset patient groups. Finally, this new tool solves the time-consuming task of performing functional enrichment analysis with gene sets of interest using up to 11 different databases at the same time. Collectively, CANCERTOOL represents a simple and freely accessible interface to interrogate well-annotated datasets and obtain publishable representations that can contribute to refinement and guidance of cancer-related investigations at all levels of hypotheses and design.Significance: In order to facilitate access of research groups without bioinformatics support to public transcriptomics data, we have developed a free online tool with an easy-to-use interface that allows researchers to obtain quality information in a readily publishable format. Cancer Res; 78(21); 6320–8. ©2018 AACR.
A Phase II Trial of the Aurora Kinase A Inhibitor Alisertib for Patients with Castration-resistant and Neuroendocrine Prostate Cancer: Efficacy and Biomarkers
Authors: Beltran Himisha , Oromendia Clara , Danila Daniel C. , Montgomery Bruce , Hoimes Christopher , Szmulewitz Russell Z. , Vaishampayan Ulka , Armstrong Andrew J. , Stein Mark , Pinski Jacek , Mosquera Juan M. , Sailer Verena , Bareja Rohan , Romanel Alessandro , Gumpeni Naveen , Sboner Andrea , Dardenne Etienne , Puca Loredana , Prandi Davide , Rubin Mark A. , Scher Howard I. , Rickman David S. , Demichelis Francesca , Nanus David M. , Ballman Karla V. , Tagawa Scott T. 
Published: September 2018

Abstract

Purpose:
Neuroendocrine prostate cancer (NEPC) is an aggressive variant of prostate cancer that may develop de novo or as a mechanism of treatment resistance. N-myc is capable of driving NEPC progression. Alisertib inhibits the interaction between N-myc and its stabilizing factor Aurora-A, inhibiting N-myc signaling, and suppressing tumor growth.

Patients and Methods:
Sixty men were treated with alisertib 50 mg twice daily for 7 days every 21 days. Eligibility included metastatic prostate cancer and at least one: small-cell neuroendocrine morphology; ≥50% neuroendocrine marker expression; new liver metastases without PSA progression; or elevated serum neuroendocrine markers. The primary endpoint was 6-month radiographic progression-free survival (rPFS). Pretreatment biopsies were evaluated by whole exome and RNA-seq and patient-derived organoids were developed.

Results:
Median PSA was 1.13 ng/mL (0.01–514.2), number of prior therapies was 3, and 68% had visceral metastases. Genomic alterations involved RB1 (55%), TP53 (46%), PTEN (29%), BRCA2 (29%), and AR (27%), and there was a range of androgen receptor signaling and NEPC marker expression. Six-month rPFS was 13.4% and median overall survival was 9.5 months (7.3–13). Exceptional responders were identified, including complete resolution of liver metastases and prolonged stable disease, with tumors suggestive of N-myc and Aurora-A overactivity. Patient organoids exhibited concordant responses to alisertib and allowed for the dynamic testing of Aurora–N-myc complex disruption.

Conclusions:
Although the study did not meet its primary endpoint, a subset of patients with advanced prostate cancer and molecular features supporting Aurora-A and N-myc activation achieved significant clinical benefit from single-agent alisertib.
Precipitation Sensitivity to Local Variations in Tropical Sea Surface Temperature
Authors: He Jie , Johnson Nathaniel C. , Vecchi Gabriel A. , Kirtman Ben , Wittenberg Andrew T. , Sturm Stephan 
Published: September 2018

AbstractThe driving of tropical precipitation by the variability of the underlying sea surface temperature (SST) plays a critical role in the atmospheric general circulation. To assess the precipitation sensitivity to SST variability, it is necessary to observe and understand the relationship between precipitation and SST. However, the precipitation–SST relationships from any coupled atmosphere–ocean system can be difficult to interpret given the challenge of disentangling the SST-forced atmospheric response and the atmospheric intrinsic variability. This study demonstrates that the two components can be isolated using uncoupled atmosphere-only simulations, which extract the former when driven by time-varying SSTs and the latter when driven by climatological SSTs. With a simple framework that linearly combines the two types of uncoupled simulations, the coupled precipitation–SST relationships are successfully reproduced. Such a framework can be a useful tool for quantitatively diagnosing tropical air–sea interactions. The precipitation sensitivity to SST variability is investigated with the use of uncoupled simulations with prescribed SST anomalies, where the influence of atmospheric intrinsic variability on SST is deactivated. Through a focus on local precipitation–SST relationships, the precipitation sensitivity to local SST variability is determined to be predominantly controlled by the local background SST. In addition, the strength of the precipitation response increases monotonically with the local background SST, with a very sharp growth at high SSTs. These findings are supported by basic principles of moist static stability, from which a simple formula for precipitation sensitivity to local SST variability is derived.
Occupational and Take-home Lead Exposure Among Lead Oxide Manufacturing Employees, North Carolina, 2016
Authors: Rinsky Jessica L. , Higgins Sheila , Angelon-Gaetz Kim , Hogan Doris , Lauffer Pierre , Davies Megan , Fleischauer Aaron , Musolin Kristin , Gibbins John , MacFarquhar Jennifer , Moore Zack 
Published: September 2018

Objective: In 2016, North Carolina blood lead level (BLL) surveillance activities identified elevated BLLs among 3 children exposed to take-home lead by household members employed at a lead oxide manufacturing facility. We characterized BLLs among employees and associated children and identified risk factors for occupational and take-home lead exposure. Methods: We reviewed BLL surveillance data for 2012-2016 to identify facility employees and associated children. We considered a BLL ≥5 μg/dL elevated for adults and children and compared adult BLLs with regulatory limits and recommended health-based thresholds. We also conducted an environmental investigation and interviewed current employees about exposure controls and cleanup procedures. Results: During 2012-2016, 5 children associated with facility employees had a confirmed BLL ≥5 μg/dL. Among 77 people employed during 2012-2016, median BLLs increased from 22 μg/dL (range, 4-45 μg/dL) in 2012 to 37 μg/dL (range, 16-54 μg/dL) in 2016. All employee BLLs were <60 μg/dL, the national regulatory threshold for immediate medical removal from lead exposure; however, 55 (71%) had a BLL ≥20 μg/dL, a recommended health-based threshold for removal from lead exposure. Because of inadequate controls in the facility, areas considered clean were visibly contaminated with lead dust. Employees reported bringing personal items to work and then into their cars and homes, resulting in take-home lead exposure. Conclusions: Integration of child and adult BLL surveillance activities identified an occupational source of lead exposure among workers and associated children. Our findings support recent recommendations that implementation of updated lead standards will support better control of lead in the workplace and prevent lead from being carried home.
Desirable leadership attributes are preferentially associated with women: A quantitative study of gender and leadership roles in the Australian workforce
Authors: Griffiths Oren , Roberts Lynette , Price Josh 
Published: September 2018

Women are under-represented globally in leadership roles. One theory suggests that this imbalance is due to a mismatch between the qualities women are perceived to have, and the qualities desired in business leaders. Yet, little is known about whether this incongruence remains prevalent in the Australian business environment. To this end, this study investigated gender stereotypes and desired leadership attributes in 1885 participants from 25 companies using a priopietary measure developed by a local diversity consulting company. Participants ranked the attributes that they believed were most important for leadership and rated the degree to which each attribute was associated with men or women. Men were more strongly associated with some agentic traits, whereas women were more strongly associated with a diverse range of both agentic and communal traits. Desired leadership qualities included both agentic and communal qualities, but generally favoured traits associated with women. JEL Classification: J16, M12
The optical coherence tomography angiography findings of rheumatoid arthritis patients taking hydroxychloroquine
Authors: Ozek Dilay , Onen Mehmet , Karaca Emine Esra , Omma Ahmet , Kemer Ozlem Evren , Coskun Cigdem 
Published: September 2018

Purpose: The aim of this study is to measure retinal vessel density and thickness of the macula by optical coherence tomography angiography in patients with rheumatoid arthritis taking hydroxychloroquine. Methods: The study included 40 patients with rheumatoid arthritis taking hydroxychloroquine and 20 age-, gender-, and axial length-matched control subjects. Patients were divided into two groups according to the duration of hydroxychloroquine use. Twenty four of the patients were taking hydroxychloroquine for more than 5 years (Group 1), and the rest of 16 were taking hydroxychloroquine for less than 5 years (Group 2). A total of 20 age- and gender-matched volunteers with similar axial length were selected as Group 3. All of the patients underwent optical coherence tomography angiography, and 3 mm × 3 mm scanning mode was chosen for analyzing vascular density and morphological characteristics on the choriocapillaris layer. In addition, Humphrey visual field 10–2 was evaluated in each subject. Results: The temporal deep vascular density was measured as 48.13% ± 8.5% in Group 1, 54.42% ± 10.3% in Group 2, and 60.35% ± 13.1% in Group 3. Deep temporal and deep hemi-inferior vascular density was significantly lower in Group 1 in comparison with Group 3 (p = 0.041 and p = 0.046, respectively). Visual field testing was normal in all patients. Conclusion: The optical coherence tomography angiography findings showed that the parafoveal deep temporal and deep hemi-inferior vascular plexus density was reduced in patients taking hydroxychloroquine for more than 5 years despite having normal perimetry. This observation, which can be obtained only through optical coherence tomography angiography, may be relevant to the early findings of hydroxychloroquine toxicity.
Comparative study of the efficacy of selective laser trabeculoplasty as initial or adjunctive treatment for primary open-angle glaucoma
Authors: Gračner Tomaž 
Published: September 2018

Aim: The aim of this study is to compare the efficacy of selective laser trabeculoplasty as initial or adjunctive treatment for primary open-angle glaucoma in a retrospective chart review. Methods: 28 eyes of 28 patients with newly diagnosed primary open-angle glaucoma, who formed the initial selective laser trabeculoplasty group, and 31 eyes of 31 patients suffering from medical uncontrolled primary open-angle glaucoma, who formed the adjunctive selective laser trabeculoplasty group, were treated with 180° selective laser trabeculoplasty. Patients were evaluated 1, 3, 6, 12, 18 and 24 months after treatment. Success was defined as an intraocular pressure lowering exceeding 20% of pretreatment intraocular pressure. Results: The mean follow-up time was 20.25 months (standard deviation = 8.1) for the initial selective laser trabeculoplasty group and 18.87 months (standard deviation = 8.8) for the adjunctive selective laser trabeculoplasty group (p = 0.538). No significant difference was found between the two groups for mean pretreatment intraocular pressure (21.43 mmHg (standard deviation = 3.2) vs 21.97 mmHg (standard deviation = 2.6); p = 0.766), for mean intraocular pressures and mean intraocular pressure reductions during whole follow-up period. At all follow-up visits, the mean percent intraocular pressure reduction was smaller in the adjunctive selective laser trabeculoplasty group than in the initial selective laser trabeculoplasty group, and such a difference was significant at 1 month (21.55% vs 26.79%; p = 0.039) and 24 months (24.82% vs 28.10%; p = 0.041). According to the Kaplan–Meier survival analysis, the 24-month success rate was 71.4% in the initial selective laser trabeculoplasty group and 71% in the adjunctive selective laser trabeculoplasty group, with no differences between the groups (p = 0.913). Conclusion: Selective laser trabeculoplasty is equally efficient in reducing intraocular pressure as initial or adjunctive treatment for primary open-angle glaucoma over 24 months.
Symptomatology and symptomatic treatment in multiple sclerosis: Results from a nationwide MS registry
Authors: Rommer Paulus Stefan , Eichstädt Kerstin , Ellenberger David , Flachenecker Peter , Friede Tim , Haas Judith , Kleinschnitz Christoph , Pöhlau Dieter , Rienhoff Otto , Stahmann Alexander , Zettl Uwe Klaus 
Published: September 2018

Background: Multiple sclerosis (MS) is a neuroinflammatory and neurodegenerative disease. Over time, symptoms accumulate leading to increased disability of patients. Objective: The objective of this article is to analyze the prevalence of symptoms and symptomatic treatment patterns in a nationwide MS registry. Methods: Data sets from 35,755 patients were analyzed. Results: More than two-thirds of patients were women with a mean age of 46.1 (±12.8) years. Median Expanded Disability Status Score (EDSS) was 3.0. The most frequently reported symptoms were fatigue, spasticity, and voiding disorders. In patients with short disease duration, fatigue was reported most frequently. Symptomatic treatment was most common for spasticity and depression, whereas fatigue was treated only in a third of affected patients. Almost a fifth of patients with EDSS ⩽ 3.5 and neuropsychological symptoms had retired from work. Conclusion: Whereas treatment for spasticity and depression is common in our cohort, sexual dysfunction, dysphagia, cognitive dysfunction, and fatigue are treated to a far lesser extent. The need for psychological support, physical, and occupational therapy has to be recognized as neuropsychological symptoms have a great impact on retirement at an early stage. Overall symptomatic treatment rates for the most common symptoms have increased over the last years ( p < 0.001).
Ivory arthroplasty for trapeziometacarpal osteoarthritis: 10-year follow-up
Authors: Vissers Gino , Goorens Chul Ki , Vanmierlo Bert , Bonte Francis , Mermuys Koen , Fils Jean-François , Goubau Jean F. 
Published: September 2018

This prospective study investigates long-term functional outcome after total trapeziometacarpal joint replacement with the Ivory arthroplasty for trapeziometacarpal joint osteoarthritis. Clinical outcome, overall function, pain, and radiologic outcome after a minimum of 10 years were evaluated for 26 Ivory arthroplasty in 24 patients. Two patients had bilateral arthroplasties. The female to male ratio was 22:2, and the mean age was 71 years (range 57–83). The mean follow-up period was 130 months (range 120–142). Overall functioning as defined by the QuickDASH score and visual analogue pain score improved by 50% and 81%, respectively, when compared with the preoperative status. However, these outcomes deteriorated beyond 5 years after surgery. Long-term results suggest the Ivory arthroplasty to be a reliable treatment for trapeziometacarpal osteoarthritis since it improves overall function and reduces pain up to 10 years postoperatively. However, revision within 10 years after surgery was needed in four of 26 cases. Level of evidence: II
Teaching Residents Frontal Sinus Anatomy Using a Novel 3-Dimensional Conceptualization Planning Software-Based Module
Authors: Chen Philip G. , Bassiouni Ahmed , Taylor Christine B. , Psaltis Alkis J. , Alrasheed Abdulaziz , Wrobel Bozena , Tewfik Marc A. , McMains K. Christopher 
Published: September 2018

Background The Frontal Sinus Masterclass (FSMC) is an effective method for teaching frontal sinus anatomy. A third party developed new software using the same 3-dimensional building block concept. The authors sought to determine whether the use of the software for the educational module yielded similar results to the original FSMC, which used wooden blocks. Methods The study was performed at a sinus course for residents. A precourse test assessed the ability to decipher frontal sinus anatomy prior to the course. Computed tomography (CT) scans of the sinuses were evaluated in triplanar view, and participants attempted to reconstruct the anatomy using the new software. Subsequently, the course instructor explained the anatomy and showed a short corresponding surgical video of the frontal sinusotomy. Cases progressed in anatomical difficulty and inflammatory load. A postcourse test determined knowledge after the course. Results In sum, 50 residents completed the pre- and postcourse tests. Overall scores increased from 60.5% to 65.2% ( P = .004). Subanalysis also demonstrated improved ability to locate the frontal drainage pathway from 32.5% to 46% ( P = .011) and label the frontal recess cell structures from 64% to 67.6% ( P = .045). Conclusion There is minimal literature on proven methods for teaching frontal sinus anatomy. Objectively, participants of the modified FSMC simulation training using new software improved their ability to recognize cells of the frontal recess on CT scans. They especially exhibited better localization of the frontal sinus drainage pathway. Subjectively, participants reported benefit from the course and felt they would be better surgeons.
Family physicians’ knowledge, attitudes, and behaviors regarding the weight effects of added sugar
Authors: Mackey Christian , Plegue Melissa A , Deames Marian , Kittle Matthew , Sonneville Kendrin R , Chang Tammy 
Published: September 2018

Background and objectives: Added sugar consumption is a major risk factor for negative health outcomes and family physicians play an important role in educating patients regarding nutrition behaviors, such as consumption of added dietary sugar. The aim of this study was to describe the knowledge, attitudes, and behaviors of family physicians regarding added dietary sugar. Methods: An online questionnaire was administered to family physician members of the Council of Academic Family Medicine organizations, which support teaching physicians that train family physicians throughout the United States. Survey items underwent rigorous pilot and cognitive testing prior to administration. Descriptive statistics and Pearson’s chi-square test were performed to evaluate physician’s dietary counseling for patients with overweight and obesity. Results: Among practicing family physician members (n = 1196), 72% reported providing dietary counseling to the majority (⩾50%) of their patients with overweight and obesity. Most (90%) believed that their counseling was ineffective for the majority of patients. Frequency of counseling was significantly associated with beliefs about counseling effectiveness (p-value < 0.001). Nearly all physicians (97%) advised against consuming sugary beverages, while advising patients to limit foods with added sugar was less common (82%). Discussion: Dietary counseling is often, but not always, provided to patients with overweight and obesity by family physicians in our sample, though most physicians believed their counseling is ineffective. National attention to added sugar as a risk for poor health should serve as a catalyst for renewed efforts from primary care educators and clinicians to engage in innovative practices to empower at-risk patients to improve their nutrition.