bluuebunny/crossref_metadata_2025_split huggingface dataset:
Joint linkage and association mapping of complex traits in shrub willow (Salix purpurea L.)
Authors: Carlson Craig H , Gouker Fred E , Crowell Chase R , Evans Luke , DiFazio Stephen P , Smart Christine D , Smart Lawrence B 
Published: March 2019

AbstractBackground and AimsIncreasing energy demands and the necessity to reduce greenhouse gas emissions are key motivating factors driving the development of lignocellulosic crops as an alternative to non-renewable energy sources. The effects of global climate change will require a better understanding of the genetic basis of complex adaptive traits to breed more resilient bioenergy feedstocks, like willow (Salix spp.). Shrub willow is a sustainable and dedicated bioenergy crop, bred to be fast-growing and high-yielding on marginal land without competing with food crops. In a rapidly changing climate, genomic advances will be vital for the sustained improvement of willow and other non-model bioenergy crops. Here, joint genetic mapping was used to exploit genetic variation garnered from both recent and historical recombination events in S. purpurea.MethodsA panel of North American naturalized S. purpurea accessions and full-sib F2S. purpurea population were genotyped and phenotyped for a suite of morphological, physiological, pest and disease resistance, and wood chemical composition traits, collected from multi-environment and multi-year replicated field trials. Controlling for population stratification and kinship in the association panel and spatial variation in the F2, a comprehensive mixed model analysis was used to dissect the complex genetic architecture and plasticity of these important traits.Key ResultsIndividually, genome-wide association (GWAS) models differed in terms of power, but the combined approach, which corrects for yearly and environmental co-factors across datasets, improved the overall detection and resolution of associated loci. Although there were few significant GWAS hits located within support intervals of QTL for corresponding traits in the F2, many large-effect QTL were identified, as well as QTL hotspots.ConclusionsThis study provides the first comparison of linkage analysis and linkage disequilibrium mapping approaches in Salix, and highlights the complementarity and limits of these two methods for elucidating the genetic architecture of complex bioenergy-related traits of a woody perennial breeding programme.
Disruption of the Prefrontal Cortex Improves Implicit Contextual Memory-Guided Attention: Combined Behavioral and Electrophysiological Evidence
Authors: Rosero Pahi Mario , Cavalli Juliana , Nees Frauke , Flor Herta , Andoh Jamila 
Published: March 2019

Abstract
Many studies have shown that the dorsolateral prefrontal cortex (DLPFC) plays an important role in top-down cognitive control over intentional and deliberate behavior. However, recent studies have reported that DLPFC-mediated top-down control interferes with implicit forms of learning. Here we used continuous theta-burst stimulation (cTBS) combined with electroencephalography to investigate the causal role of DLPFC in implicit contextual memory-guided attention. We aimed to test whether transient disruption of the DLPFC would interfere with implicit learning performance and related electrical brain activity. We applied neuronavigation-guided cTBS to the DLPFC or to the vertex as a control region prior to the performance of an implicit contextual learning task. We found that cTBS applied over the DLPFC significantly improved performance during implicit contextual learning. We also noted that beta-band (13–19 Hz) oscillatory power was reduced at fronto-central channels about 140 to 370 ms after visual stimulus onset in cTBS DLPFC compared with cTBS vertex. Taken together, our results provide evidence that DLPFC-mediated top-down control interferes with contextual memory-guided attention and beta-band oscillatory activity.
Pre-test probability prediction in patients with a low to intermediate probability of coronary artery disease: a prospective study with a fractional flow reserve endpoint
Authors: Winther Simon , Nissen Louise , Westra Jelmer , Schmidt Samuel Emil , Bouteldja Nadia , Knudsen Lars Lyhne , Madsen Lene Helleskov , Frost Lars , Urbonaviciene Grazina , Holm Niels Ramsing , Christiansen Evald Høj , Bøtker Hans Erik , Bøttcher Morten 
Published: March 2019

Abstract

Aims
European and North American guidelines currently recommend pre-test probability (PTP) stratification based on simple probability models in patients with suspected coronary artery disease (CAD). However, no unequivocal recommendation has yet been established. We aimed to compare the ability of risk factors and different PTP stratification models to predict haemodynamically obstructive CAD with fractional flow reserve (FFR) as reference in low to intermediate probability patients.

Methods and results
We prospectively included 1675 patients with low to intermediate risk who had been referred to coronary computed tomography angiography (CTA). Patients with coronary stenosis were subsequently investigated by invasive coronary angiography (ICA) with FFR measurement if indicated. Discrimination and calibration were assessed for four models: the updated Diamond–Forrester (UDF), the CAD Consortium Basic, the Clinical, and the Clinical + Coronary artery calcium score (CACS). At coronary CTA, 24% of patients were diagnosed with a suspected stenosis and 10% had haemodynamically obstructive CAD at the ICA. Calibration for all CAD Consortium models increased compared with the UDF score. However, all models overestimated the probability of haemodynamically obstructive CAD. Discrimination increased by area under the receiver operating curve from 67% to 86% for UDF vs. CAD Consortium Clinical + CACS. The proportion of low-probability patients (pre-test score < 15%) was for the UDF, CAD Consortium Basic, Clinical, and Clinical + CACS: 14%, 58%, 51%, and 66%, respectively. The corresponding negative predictive values were 97%, 94%, 95%, and 98%, respectively.

Conclusion
CAD Consortium models improve PTP stratification compared with the UDF score, mainly due to superior calibration in low to intermediate probability patients. Adding the coronary calcium score to the models substantially increases discrimination.

Clinical Trials. gov identifier
NCT02264717.
Adjuvanted influenza vaccine for the Italian elderly in the 2018/19 season: an updated health technology assessment
Authors: de Waure Chiara , Boccalini Sara , Bonanni Paolo , Amicizia Daniela , Poscia Andrea , Bechini Angela , Barbieri Marco , Capri Stefano , Specchia Maria Lucia , Di Pietro Maria Luisa , Arata Lucia , Cacciatore Pasquale , Panatto Doanatella , Gasparini Roberto 
Published: March 2019

Abstract

Background
The elderly, defined here as subjects aged ≥ 65 years, are among at-risk subjects for whom annual influenza vaccination is recommended. For the 2018/19 season, three vaccine types are available for the elderly in Italy: trivalent inactivated vaccine (TIV), adjuvanted TIV (aTIV) and quadrivalent inactivated vaccines (QIV). No health technology assessment (HTA) of seasonal influenza vaccination in the elderly has previously been conducted in Italy.

Methods
An HTA was conducted in 2017 to analyze the burden of influenza illness, the characteristics, efficacy, safety and cost-effectiveness of available vaccines and the related organizational and ethical implications. This was then contextualized to the 2018/19 influenza season. Comprehensive literature reviews/analyses were performed and a static mathematical model developed in order to address the above issues.

Results
In Italy, influenza is usually less common in the elderly than in other age-classes, but the burden of disease is the highest; >10% of infected elderly subjects develop complications, and about 90% of all influenza-related deaths occur in this age-class. All available vaccines are effective, safe and acceptable from an ethical standpoint. However, aTIV has proved more immunogenic and effective in the elderly. Furthermore, from the third payer’s perspective, aTIV is highly cost-effective and cost-saving in comparison with TIV and QIV, respectively. Nevertheless, vaccination coverage needs to be improved.

Conclusions
According to this HTA, aTIV appeared the vaccine of choice in the elderly. HTA should be reapplied whenever new relevant data become available.
Constructing a general competency model for Chinese public health physicians: a qualitative and quantitative study
Authors: Shi Lei , Fan Lihua , Xiao Hai , Chen Zhenkang , Tong Xinfa , Liu Ming , Cao Depin 
Published: March 2019

Abstract

Background
The purpose of the study was to construct a general model of the competencies required by Chinese public health physicians. This study is intended to lay the foundation for promoting reform of public health education in China, and may help perfect the testing and grading system of public health courses.

Methods
The behavioral event interviews were used to collect data on knowledge, skills and performance characteristics of public health physicians for coping with public health events. A random stratified sampling survey was used to select public health professionals and workers from different public health institutions in 14 provinces (municipalities or autonomous regions) of China. We then purposively selected 150 senior public health professionals from various agencies and 85 senior public health educators at colleges and universities to take part in the checklist survey. Finally, three times expert consultations were performed to determine the dimensions and elements of the general competency model for Chinese public health physicians.

Results
The age range of the 3245 participants was 18–65 years old. When comparing public health professionals and public health education specialists, we found significant differences in the perceived importance of the core competencies between these groups. The model was revised several times and finalized through the expert consultations, and comprised seven competency dimensions.

Conclusion
The final public health practitioner competency model comprised seven competency dimensions: basic knowledge of medicine, public health knowledge, health management and health promotion, specialized skills, research and development, comprehensive abilities and professionalism.
Affine Orlicz Pólya–Szegö Principles and Their Equality Cases
Authors: Lin Youjiang , Xi Dongmeng 
Published: March 2019

AbstractThe conjecture about the Orlicz Pólya–Szegö principle posed in [42] is proved. The cases of equality are characterized in the affine Orlicz Pólya–Szegö principle with respect to Steiner symmetrization and Schwarz spherical symmetrization.
Towards the elimination of mother-to-child transmission of HIV in Nigeria: a health system perspective of the achievements and challenges
Authors: Olakunde Babayemi O , Adeyinka Daniel A , Olawepo John O , Pharr Jennifer R , Ozigbu Chamberline E , Wakdok Sabastine , Oladele Tolu , Ezeanolue Echezona E 
Published: March 2019

Abstract
Despite its scaled-up response for prevention of mother-to-child transmission of HIV (PMTCT), Nigeria still contributes the greatest number of infants infected with HIV worldwide. Drawing on our knowledge, and review of policy documents and research papers, we explored the achievements and challenges in the elimination of mother-to-child transmission of HIV in Nigeria using the WHO’s health systems framework. We found that Nigeria has increased the number of PMTCT sites, decentralized and integrated PMTCT care for expanded service delivery, adopted task-shifting to address the shortage of skilled healthcare providers, explored alternative sources of domestic funding to bridge the funding gap and harmonized the health management information system to improve data quality. Some of the challenges we identified included: difficulty in identifying HIV-infected pregnant women because of low uptake of antenatal care; interrupted supplies of medical commodities; knowledge gaps among healthcare workers; and lack of a national unique identifying system to enhance data quality. While there have been some achievements in the PMTCT program, gaps still exist in the different blocks of the health system. Elimination of mother-to-child transmission of HIV in Nigeria will require the implementation of feasible, culturally acceptable and sustainable interventions to address the health system-related challenges.
Characterization and functional analysis of novel circulating NK cell sub-populations
Authors: Khummuang Saichit , Chuensirikulchai Kantinan , Pata Supansa , Laopajon Witida , Chruewkamlow Nuttapol , Mahasongkram Kodchakorn , Sugiura Nobuo , Watanabe Hideto , Tateno Hiroaki , Kamuthachad Ludthawun , Wongratanacheewin Surasakdi , Takheaw Nuchjira , Kasinrerk Watchara 
Published: March 2019

AbstractNatural killer (NK) cells are innate lymphoid cells having potent cytolytic function that provide host defense against microbial infections and tumors. Using our generated monoclonal antibody (mAb), named FE-1H10, new NK cell sub-populations in peripheral blood were identified. The molecules recognized by mAb FE-1H10 were expressed on a sub-population of CD3−CD56dim NK cells. The epitope recognized by mAb FE-1H10 was demonstrated to be N-glycan and proven to be different from CD57. Upon K562 stimulation, the CD56dimFE-1H10+ NK cell sub-population exhibited significantly lower cytolytic function with low ability to degranulate and release cytolytic granules compared to the CD56dimFE-1H10− NK cell sub-population. Moreover, the CD56dimFE-1H10+ NK cells produced less IFN-γ and TNF-α than the CD56dimFE-1H10− NK cells. We demonstrated here that mAb FE-1H10 could identify two sub-populations of circulating CD56dim NK cells with different functions. Our discovery of new sub-populations of NK cells improves our understanding of NK cell biology and may lead to the development of new approaches for NK cell therapy.
Count me in: using a patient portal to minimize implicit bias in clinical research recruitment
Authors: Kannan Vaishnavi , Wilkinson Kathleen E , Varghese Mereeja , Lynch-Medick Sarah , Willett Duwayne L , Bosler Teresa A , Chu Ling , Gates Samantha I , Holbein M E Blair , Willett Mallory M , Reimold Sharon C , Toto Robert D 
Published: March 2019

Abstract

Objective
Determine whether women and men differ in volunteering to join a Research Recruitment Registry when invited to participate via an electronic patient portal without human bias.

Materials and Methods
Under-representation of women and other demographic groups in clinical research studies could be due either to invitation bias (explicit or implicit) during screening and recruitment or by lower rates of deciding to participate when offered. By making an invitation to participate in a Research Recruitment Registry available to all patients accessing our patient portal, regardless of demographics, we sought to remove implicit bias in offering participation and thus independently assess agreement rates.

Results
Women were represented in the Research Recruitment Registry slightly more than their proportion of all portal users (n = 194 775). Controlling for age, race, ethnicity, portal use, chronic disease burden, and other questionnaire use, women were statistically more likely to agree to join the Registry than men (odds ratio 1.17, 95% CI, 1.12–1.21). In contrast, Black males, Hispanics (of both sexes), and particularly Asians (both sexes) had low participation-to-population ratios; this under-representation persisted in the multivariable regression model.

Discussion
This supports the view that historical under-representation of women in clinical studies is likely due, at least in part, to implicit bias in offering participation. Distinguishing the mechanism for under-representation could help in designing strategies to improve study representation, leading to more effective evidence-based recommendations.

Conclusion
Patient portals offer an attractive option for minimizing bias and encouraging broader, more representative participation in clinical research.
Distinct Clinicopathological and Prognostic Features of Thin Nodular Primary Melanomas: An International Study from 17 Centers
Authors: Dessinioti Clio , Dimou Niki , Geller Alan C , Stergiopoulou Aravella , Lo Serigne , Keim Ulrike , Gershenwald Jeffrey E , Haydu Lauren E , Ribero Simone , Quaglino Pietro , Puig Susana , Malvehy Josep , Kandolf-Sekulovic Lidija , Radevic Tatjana , Kaufmann Roland , Meister Laura , Nagore Eduardo , Traves Victor , Champsas Grigorios G , Plaka Mihaela , Dreno Brigitte , Varey Emilie , Ramirez David Moreno , Dummer Reinhard , Mangana Joanna , Hauschild Axel , Egberts Friederike , Peris Ketty , del Regno Laura , Forsea Ana-Maria , Zurac Sabina A , Vieira Ricardo , Brinca Ana , Zalaudek Iris , Deinlein Teresa , Linos Eleni , Evangelou Evangelos , Thompson John F , Scolyer Richard A , Garbe Claus , Stratigos Alexander J 
Published: March 2019

AbstractBackgroundNodular melanoma (NM) is more likely to be fatal compared with other melanoma subtypes, an effect attributed to its greater Breslow thickness.MethodsClinicopathological features of NM and superficial spreading melanoma (SSM) diagnosed in 17 centers in Europe (n = 15), the United States, and Australia between 2006 and 2015, were analyzed by multivariable logistic regression analysis, with emphasis on thin (T1 ≤ 1.0 mm) melanomas. Cox analysis assessed melanoma-specific survival. All statistical tests were two sided.ResultsIn all, 20 132 melanomas (NM: 5062, SSM: 15 070) were included. Compared with T1 SSM, T1 NM was less likely to have regression (odds ratio [OR] = 0.46, 95% confidence interval [CI] = 0.29 to 0.72) or nevus remnants histologically (OR = 0.60, 95% CI = 0.42 to 0.85), and more likely to have mitoses (OR = 1.97, 95% CI = 1.33 to 2.93) and regional metastasis (OR = 1.77, 95% CI = 1.02 to 3.05). T1 NM had a higher mitotic rate than T1 SSM (adjusted geometric mean = 2.2, 95% CI = 1.9 to 2.5 vs 1.6, 95% CI = 1.5 to 1.7 per mm2, P &lt; .001). Cox multivariable analysis showed a higher risk for melanoma-specific death for NM compared with SSM for T1 (HR = 2.10, 95% CI = 1.24 to 3.56) and T2 melanomas (HR = 1.30, 95% CI = 1.01 to 1.68), and after accounting for center heterogeneity, the difference was statistically significant only for T1 (HR = 2.20, 95% CI = 1.28 to 3.78). The NM subtype did not confer increased risk within each stratum (among localized tumors or cases with regional metastasis).ConclusionsT1 NM (compared with T1 SSM) was associated with a constellation of aggressive characteristics that may confer a worse prognosis. Our results indicate NM is a high-risk melanoma subtype that should be considered for inclusion in future prognostic classifications of melanoma.
STAT3 Modulation of Regulatory T Cells in Response to Radiation Therapy in Head and Neck Cancer
Authors: Oweida Ayman J , Darragh Laurel , Phan Andy , Binder David , Bhatia Shilpa , Mueller Adam , Court Benjamin Van , Milner Dallin , Raben David , Woessner Richard , Heasley Lynn , Nemenoff Raphael , Clambey Eric , Karam Sana D 
Published: March 2019

AbstractBackgroundRadioresistance represents a major problem in the treatment of head and neck cancer (HNC) patients. To improve response, understanding tumor microenvironmental factors that contribute to radiation resistance is important. Regulatory T cells (Tregs) are enriched in numerous cancers and can dampen the response to radiation by creating an immune-inhibitory microenvironment. The purpose of this study was to investigate mechanisms of Treg modulation by radiation in HNC.MethodsWe utilized an orthotopic mouse model of HNC. Anti-CD25 was used for Treg depletion. Image-guided radiation was delivered to a dose of 10 Gy. Flow cytometry was used to analyze abundance and function of intratumoral immune cells. Enzyme-linked immunosorbent assay was performed to assess secreted factors. For immune-modulating therapies, anti–PD-L1, anti-CTLA-4, and STAT3 antisense oligonucleotide (ASO) were used. All statistical tests were two-sided.ResultsTreatment with anti-CD25 and radiation led to tumor eradication (57.1%, n = 4 of 7 mice), enhanced T-cell cytotoxicity compared with RT alone (CD4 effector T cells [Teff]: RT group mean = 5.37 [ 0.58] vs RT + αCD25 group mean =10.71 [0.67], P = .005; CD8 Teff: RT group mean = 9.98 [0.81] vs RT + αCD25 group mean =16.88 [2.49], P = .01) and induced tumor antigen-specific memory response (100.0%, n = 4 mice). In contrast, radiation alone or when combined with anti-CTLA4 did not lead to durable tumor control (0.0%, n = 7 mice). STAT3 inhibition in combination with radiation, but not as a single agent, improved tumor growth delay, decreased Tregs, myeloid-derived suppressor cells, and M2 macrophages and enhanced effector T cells and M1 macrophages. Experiments in nude mice inhibited the benefit of STAT3 ASO and radiation.ConclusionWe propose that STAT3 inhibition is a viable and potent therapeutic target against Tregs. Our data support the design of clinical trials integrating STAT3 ASO in the standard of care for cancer patients receiving radiation.
Family Frames as Exile Photography
Authors: Kosh-Zohar Talila 
Published: March 2019

Abstract
This article examines five family photographs. The first of these family frames was taken in Czechoslovakia during the early 1930s and was found after the Holocaust, the one and only surviving photograph of my father’s exterminated family. The other four are family frames taken in Israel, the land of rebirth, where the survivors tried to start over from scratch, forget the past, and create a new family. All five frames are discussed as ‘exile photographs’—images of absence, alienation, and nostalgia; images of emotions like anxiety, sadness, and loneliness, all of which are inherent to the condition of exile. The article argues that the new family frames, which are supposed to represent new (personal and national) beginnings, continue to authenticate the traumatic past. Their testimony bears witness not to revival and reconstruction, but to forced exile from one’s birthplace, a devastated home and family, a condition of terminal loss.