bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatitis B Virus Capsids Have Diverse Structural Responses to Small-Molecule Ligands Bound to the Heteroaryldihydropyrimidine Pocket
Authors: Venkatakrishnan Balasubramanian , Katen Sarah P. , Francis Samson , Chirapu Srinivas , Finn M. G. , Zlotnick Adam 
Published: February 2016

ABSTRACT
Though the hepatitis B virus (HBV) core protein is an important participant in many aspects of the viral life cycle, its best-characterized activity is self-assembly into 240-monomer capsids. Small molecules that target core protein (core protein allosteric modulators [CpAMs]) represent a promising antiviral strategy. To better understand the structural basis of the CpAM mechanism, we determined the crystal structure of the HBV capsid in complex with HAP18. HAP18 accelerates assembly, increases protein-protein association more than 100-fold, and induces assembly of nonicosahedral macrostructures. In a preformed capsid, HAP18 is found at quasiequivalent subunit-subunit interfaces. In a detailed comparison to the two other extant CpAM structures, we find that the HAP18-capsid structure presents a paradox. Whereas the two other structures expanded the capsid diameter by up to 10 Å, HAP18 caused only minor changes in quaternary structure and actually decreased the capsid diameter by ∼3 Å. These results indicate that CpAMs do not have a single allosteric effect on capsid structure. We suggest that HBV capsids present an ensemble of states that can be trapped by CpAMs, indicating a more complex basis for antiviral drug design.

IMPORTANCE
Hepatitis B virus core protein has multiple roles in the viral life cycle—assembly, compartment for reverse transcription, intracellular trafficking, and nuclear functions—making it an attractive antiviral target. Core protein allosteric modulators (CpAMs) are an experimental class of antivirals that bind core protein. The most recognized CpAM activity is that they accelerate core protein assembly and strengthen interactions between subunits. In this study, we observe that the CpAM-binding pocket has multiple conformations. We compare structures of capsids cocrystallized with different CpAMs and find that they also affect quaternary structure in different ways. These results suggest that the capsid “breathes” and is trapped in different states by the drug and crystallization. Understanding that the capsid is a moving target will aid drug design and improve our understanding of HBV interaction with its environment.
αvβ3 Integrin Boosts the Innate Immune Response Elicited in Epithelial Cells through Plasma Membrane and Endosomal Toll-Like Receptors
Authors: Casiraghi Costanza , Gianni Tatiana , Campadelli-Fiume Gabriella 
Published: February 2016

ABSTRACT
We report that αvβ3 integrin strongly affects the innate immune response in epithelial cells. αvβ3 integrin greatly increased the response elicited via plasma membrane Toll-like receptors (TLRs) by herpes simplex virus or bacterial ligands. The endosomal TLR3, not the cytosolic sensor interferon gamma-inducible protein 16 (IFI16), was also boosted by αvβ3 integrin. The boosting was exerted specifically by αvβ3 integrin but not by αvβ6 or αvβ8 integrin. Current and previous work indicates that integrin-TLR cooperation occurs in epithelial and monocytic cells. The TLR response should be considered an integrin-TLR response.
Immediate Effects of Acupuncture on Tongue Pressure Including Swallowing Reflex Latency in Parkinson's Disease
Authors: Fukuda Shimpei , Kuriyama Nagato , Tsuru Hiroyuki , Egawa Masato 
Published: February 2016

Background It is important to evaluate tongue function in terms of its clinical implications for swallowing ability. Motor dysfunction and loss of coordination of the tongue are frequently seen, and this influences the oral and pharyngeal phases of swallowing. The purpose of this pilot study was to evaluate the effect of a single acupuncture treatment for tongue pressure in Parkinson's disease. Methods A total of 13 patients, aged 57– 84 years, were recruited. Tongue pressure was measured using a tongue pressure manometer. Furthermore, swallowing reflex latency was measured in 3 of the 13 patients. Results Significant changes were seen after acupuncture in mean tongue pressure, which increased from 23.1 to 26.7 kPa (p<0.01). Reductions were seen after acupuncture in mean swallowing reflex latency (from 5.2 to 4.6 s for first saliva swallow; from 19.9 to 15.7 s for second saliva swallow; and from 10.4 to 5.7 s for third saliva swallow(s)). Conclusions Our study's findings suggest that acupuncture may be useful for improving oral cavity function, but further controlled trials are needed.
Assessment of a non-invasive haemoglobin sensor NBM 200 among pregnant women in rural India
Authors: Ahankari A S , Fogarty A W , Tata L J , Dixit J V , Myles P R 
Published: February 2016

ObjectiveThis study aimed to assess a non-invasive haemoglobin (Hb) sensor NBM 200 in pregnant women in a rural Indian setting.MethodsThe study population consisted of women between 3 and 5 months of pregnancy, from 33 villages in Tuljapur and Lohara blocks of Osmanabad district, Maharashtra, between April 2014 and June 2015. Hb measurements obtained from the non-invasive sensor NBM 200 were compared with measurements obtained from an automated haematology analyser Sysmex XP-100, using the Bland Altman method and Spearman's Rank correlation coefficient. Interclass correlation coefficient (ICC), sensitivity and specificity values were used to assess the anaemia diagnostic accuracy of NBM 200 against the gold standard (Sysmex XP-100).ResultsData were obtained from 269 pregnant women (median age: 21 years, IQR: 19–23 years). Hb levels estimated by the Sysmex XP-100 analyser ranged from 5.5 g/dL to 14.1 g/dL (mean: 10.0 g/dL, SD: 1.28), while measurements obtained from NBM 200 ranged from 9.5 g/dL to 14.6 g/dL (mean: 11.9 g/dL, SD: 1.43). Spearman's test found a significant, moderately positive correlation between the two methods (rs=0.4, p<0.001), ICC was 0.22, and the Bland-Altman analysis showed a mean difference of −1.8 g/dL (95% CI −2.06 to −1.71), indicating a systematic overestimation of Hb using the NBM 200. The NBM 200 showed low sensitivity (33.7%; 95% CI 27.3% to 40.5%) but high specificity (91.8%; 95% CI 81.9% to 97.3%) for the diagnosis of anaemia.ConclusionsHb measurements obtained from the NBM 200 were higher with consequent underestimation of anaemia as compared with the gold standard reference method. This limits the use of the NBM 200 as an anaemia diagnostic test in our study population consisting of women during pregnancy.
Video training with peer feedback in real-time consultation: acceptability and feasibility in a general-practice setting
Authors: Eeckhout Thomas , Gerits Michiel , Bouquillon Dries , Schoenmakers Birgitte 
Published: February 2016

AbstractObjectiveSince many years, teaching and training in communication skills are cornerstones in the medical education curriculum. Although video recording in a real-time consultation is expected to positively contribute to the learning process, research on this topic is scarce. This study will focus on the feasibility and acceptability of video recording during real-time patient encounters performed by general practitioner (GP) trainees.MethodThe primary research question addressed the experiences (defined as feasibility and acceptability) of GP trainees in video-recorded vocational training in a general practice. The second research question addressed the appraisal of this training. The procedure of video-recorded training is developed, refined and validated by the Academic Teaching Practice of Leuven since 1974 (Faculty of Medicine of the University of Leuven). The study is set up as a cross-sectional survey without follow-up. Outcome measures were defined as ‘feasibility and acceptability’ (experiences of trainees) of the video-recorded training and were approached by a structured questionnaire with the opportunity to add free text comments. The studied sample consisted of all first-phase trainees of the GP Master 2011–2012 at the University of Leuven.ResultsAlmost 70% of the trainees were positive about recording consultations. Nevertheless, over 60% believed that patients felt uncomfortable during the video-recorded encounter. Almost 90% noticed an improvement of own communication skills through the observation and evaluation of. Most students (85%) experienced the logistical issues as major barrier to perform video consultations on a regular base.ConclusionsThis study lays the foundation stone for further exploration of the video training in real-time consultations. Both students and teachers on the field acknowledge that the power of imaging is underestimated in the training of communication and vocational skills. The development of supportive material and protocols will lower thresholds.Practice implicationsTime investment for teachers could be tempered by bringing up students to peer tutors and by an accurate scheduling of the video training. The development of supportive material and protocols will lower thresholds. Further research should finally focus on long-term efficacy and efficiency in terms of learning outcomes and on the facilitation of the technical process.
Failure of the Feynman R1 gauge for the standard model: An explicit example
Authors: Wu Tai Tsun , Wu Sau Lan 
Published: February 2016

The decay of the Higgs particle into two photons through a [Formula: see text] loop was calculated in a straightforward way four years ago on the basis of the standard model. This calculation was carried out in the unitary gauge. Nevertheless, all attempts to reproduce this correct answer using the Feynman rules in the [Formula: see text] gauge, or the more general [Formula: see text] gauge, have failed. In this paper, a detailed analysis is carried out to compare the unitary gauge with the [Formula: see text] gauge; through this comparison, the underlying reason is determined why the answer cannot be obtained using the Feynman rules in the [Formula: see text] gauge. This is the first example where the use of the Feynman rules in the [Formula: see text] gauge leads to an incorrect answer, and this incorrect answer cannot be ruled out by any simple argument such as gauge invariance. It means that great care must be exercised in using Feynman rules.
Of Mice and Melanoma: PDX System for Modeling Personalized Medicine
Authors: Hartsough Edward J. , Aplin Andrew E. 
Published: February 2016

Abstract
Targeted therapies have advanced the treatment options for cutaneous melanoma, but many patients will progress on drug. Patient-derived xenografts (PDX) can be used to recapitulate therapy-resistant tumors. Furthermore, PDX modeling can be utilized in combination with targeted sequencing and phosphoproteomic platforms, providing preclinical basis for second-line targeted inhibitor strategies. Clin Cancer Res; 22(7); 1550–2. ©2016 AACR.
See related article by Krepler et al., p. 1592
The MARINER trial of rivaroxaban after hospital discharge for medical patients at high risk of VTE
Authors: Spyropoulos Alex , Zrubek Julie , Ageno Walter , Albers Gregory , Elliott C. , Halperin Jonathan , Haskell Lloyd , Hiatt William , Maynard Gregory , Peters Gary , Spiro Theodore , Steg Philippe , Suh Eun , Weitz Jeffrey , Raskob Gary 
Published: February 2016

SummaryHospital-associated venous thromboembolism (VTE) is a leading cause of premature death and disability worldwide. Evidence-based guidelines recommend that anticoagulant thromboprophylaxis be given to hospitalised medical patients at risk of VTE, but suggest against routine use of thromboprophylaxis beyond the hospital stay. The MARINER study is a randomised, double-blind, placebo-controlled trial to evaluate the efficacy and safety of thromboprophylaxis using rivaroxaban, begun at hospital discharge and continued for 45 days, for preventing symptomatic VTE in high-risk medical patients. Eligible patients are identified using the International Medical Prevention Registry on Venous Thromboembolism (IMPROVE VTE) risk score, combined with a laboratory test, D-dimer. The rivaroxaban regimen is 10 mg once daily for patients with CrCl ≥ 50 ml/min, or 7.5 mg once daily for patients with CrCl ≥ 30 ml/min and < 50 ml/ min. The primary efficacy outcome is the composite of symptomatic VTE (lower extremity deep-vein thrombosis and non-fatal pulmonary embolism) and VTE-related death. The principal safety outcome is major bleeding. A blinded clinical events committee adjudicates all suspected outcome events. The sample size is event-driven with an estimated total of 8,000 patients to acquire 161 primary outcome events. Study design features that distinguish MARINER from previous and ongoing thromboprophylaxis trials in medically ill patients are: (i) use of a validated risk assessment model (IMPROVE VTE) and D-dimer determination for identifying eligible patients at high risk of VTE, (ii) randomisation at the time of hospital discharge, (iii) a 45-day treatment period and (iv) restriction of the primary efficacy outcome to symptomatic VTE events.
Introduction to “Artistic Awakening in Ankara,”
“The Artist and Politics,” and “The Burden of the
Intellectual” by Bülent Ecevit
Authors: Smith Sarah-Neel 
Published: February 2016

Abstract
This essay analyzes three polemic newspaper articles written in the early 1950s by the art critic, gallerist, and future Turkish prime minister Bülent Ecevit (1925–2006), “Artistic Awakening in Ankara” (1953), “The Artist and Politics” (1954), and “The Burden of the Intellectual” (1956). It argues that Ecevit's articles document a local intelligentsia's efforts to theorize the role of art in Turkish society at a crucial moment of political transformation. As Turkey abandoned its authoritarian past in order to conduct its inaugural experiment with multi-party democracy, Ecevit's columns took up two of the period's most pressing questions: the extent to which the state should control the local art world, and in what ways Turkey's newly enfranchised citizens might enact their individual rights within the realm of culture. The essay also demonstrates the importance of these three articles to Ecevit's subsequent political and intellectual trajectory: they were central to his lifelong efforts to continue the progressive social and political modernization project of the early Turkish Republic, while developing new forums for its critique, reinterpretation, and reinvigoration.
Decisions Made with Less Evidence Involve Higher Levels of Corticosubthalamic
Nucleus Theta Band Synchrony
Authors: Zavala Baltazar , Tan Huiling , Little Simon , Ashkan Keyoumars , Green Alexander L. , Aziz Tipu , Foltynie Thomas , Zrinzo Ludvic , Zaghloul Kareem , Brown Peter 
Published: February 2016

Abstract
The switch between automatic action selection and more controlled forms of decision-making is a dynamic process thought to involve both cortical and subcortical structures. During sensory conflict, medial pFC oscillations in the theta band (&lt;8 Hz) drive those of the subthalamic nucleus (STN), and this is thought to increase the threshold of evidence needed for one competing response to be selected over another. Here, we were interested in testing whether STN activity is also altered by the rate at which evidence is presented during a congruent dot motion task absent of any explicit sensory conflict. By having a series of randomly moving dots gradually transform to congruent motion at three different rates (slow, medium, fast), we were able to show that a slower rate increased the time it took participants to make a response but did not alter the total amount of evidence that was integrated before the response. Notably, this resulted in a decision being made with a lower amount of instantaneous evidence during the slow and medium trials. Consistent with the idea that medial pFC–STN activity is involved in executing cognitive control, the higher levels of ambiguity during these trials were associated with increased theta band synchrony between the cortex and the STN, with the cortical oscillations Granger-causal to those of the STN. These results further confirm the involvement of the STN in decision-making and suggest that the disruption of this network may underlie some of the unwanted cognitive deficits associated with STN deep brain stimulation.
A phylogeny of Dimerostemma (Asteraceae, Heliantheae, Ecliptinae) based on the ITS and ETS
Authors: MORAES MARTA D. , Panero Jose L. 
Published: February 2016

Bayesian phylogenetic analysis of nuclear ribosomal ITS and ETS confirms earlier results from chloroplast DNA phylogenetic analysis and morphology that support the recent synonymy under Dimerostemma of several species formerly recognized within the genus Angelphytum. The nine former Angelphytum species we sampled did not form a monophyletic group. Based on sampling 18 of 29 species Dimerostemma was found monophyletic and derived within Ecliptinae, although its position was not fully resolved among the accessions of 32 other genera of the subtribe. Our results add several new hypotheses of generic relationships in this group. Dimerostemma annuum, the only annual species of the genus, resolved sister to all other Dimerostemma. This with D. bishopii and D. retifolium formed a grade sister to two clades, each containing a combination of Angelphytum and Dimerostemma species. Species of Dimerostemma that have xylopodia do not form a monophyletic group. Montanoa of subtribe Montanoinae was sister to the Andean genera Idiopappus, Kingianthus and Monactis and collectively sister to a clade of Ecliptinae with seven subclades based on our sampling. The genera Kingianthus and Wedelia were not found to be monophyletic.
A taxonomic revision of the genus Primnoisis Studer [&amp; Wright], 1887 (Coelenterata: Octocorallia: Isididae) using morphological and molecular data
Authors: MOORE KIRRILY , ALDERSLADE PHILIP , MILLER KAREN 
Published: February 2016

A complete taxonomic revision of the genus Primnoisis (Isididae) is presented herein, based on original type material of all nominal species and additional specimens from deep-water surveys in sub-temperate and Antarctic waters. A multi-disciplinary approach was used combining morphological characteristics such as colonial branching patterns, polyp structure, sclerite form and arrangement, together with phylogenetic reconstructions using two mitochondrial gene regions (mtMutS and igr1–cox1). The genus Primnoisis is retained with 7 of the 8 nominal species validated (P. antarctica Wright & Studer, 1889, P. rigida Wright & Studer, 1889, P. ambigua Wright & Studer, 1889, P. delicatula Hickson, 1907, P. fragilis Kükenthal, 1912, P. formosa Gravier, 1913 and P. mimas Bayer & Stefani, 1987), with the eighth (P. sparsa Wright & Studer, 1889), synonymised with P. antarctica. In addition, the species Mopsea gracilis Gravier, 1913 is reassigned to Primnoisis and an additional five new species are described (P. chatham n. sp., P. erymna n. sp., P. millerae n. sp., P. niwa n. sp. and P. tasmani n. sp). Most of the species fell into two clear groups, defined both by morphology and genetic grouping, for which two new sub-genera are proposed (P. (Primnoisis) n. subg. and P. (Delicatisis) n. subg.). Three species, P. ambigua, P. mimas and P. tasmani, could not be placed reliably in either sub-genus due to distinctive morphological features or genetic dissimilarity. It was not possible to confirm the monophyly of the genus due to unresolved relationships with the closely related genus Notisis Gravier, 1913 and an undescribed genus of Mopseinae.
Southern Ocean Deep Circulation and Heat Uptake in a High-Resolution Climate Model
Authors: Newsom Emily R. , Bitz Cecilia M. , Bryan Frank O. , Abernathey Ryan , Gent Peter R. 
Published: February 2016

Abstract
The dynamics of the lower cell of the meridional overturning circulation (MOC) in the Southern Ocean are compared in two versions of a global climate model: one with high-resolution (0.1°) ocean and sea ice and the other a lower-resolution (1.0°) counterpart. In the high-resolution version, the lower cell circulation is stronger and extends farther northward into the abyssal ocean. Using the water-mass-transformation framework, it is shown that the differences in the lower cell circulation between resolutions are explained by greater rates of surface water-mass transformation within the higher-resolution Antarctic sea ice pack and by differences in diapycnal-mixing-induced transformation in the abyssal ocean.
While both surface and interior transformation processes work in tandem to sustain the lower cell in the control climate, the circulation is far more sensitive to changes in surface transformation in response to atmospheric warming from raising carbon dioxide levels. The substantial reduction in overturning is primarily attributed to reduced surface heat loss. At high resolution, the circulation slows more dramatically, with an anomaly that reaches deeper into the abyssal ocean and alters the distribution of Southern Ocean warming. The resolution dependence of associated heat uptake is particularly pronounced in the abyssal ocean (below 4000 m), where the higher-resolution version of the model warms 4.5 times more than its lower-resolution counterpart.
Internal Medicine Residents’ Beliefs, Attitudes, and Experiences Relating to Palliative Care: A Qualitative Study
Authors: Kawaguchi S. , Mirza R. , Nissim R. , Ridley J. 
Published: February 2016

Background: Internal medicine residents are frequently called upon to provide palliative care to hospitalized patients, but report feeling unprepared to do so effectively. Curricular development to enhance residents’ palliative care skills and competencies requires an understanding of current beliefs, attitudes and learning priorities. Methods: We conducted a qualitative study consisting of semi-structured interviews with ten internal medicine residents to explore their understanding of and experiences with palliative care. Results: All of the residents interviewed had a sound theoretical understanding of palliative care, but faced many challenges in being able to provide care in practice. The challenges described by residents were system-related, patient-related and provider-related. They identified several priority areas for further learning, and discussed ways in which their current education in palliative care could be enhanced. Conclusions: Our findings provide important insights to guide curricular development for internal medicine trainees. The top five learning priorities in palliative care that residents identified in our study were: 1) knowing how and when to initiate a palliative approach, 2) improving communication skills, 3) improving symptom management skills, 4) identifying available resources, and 5) understanding the importance of palliative care. Residents felt that their education in palliative care could be improved by having a mandatory rotation in palliative care, more frequent didactic teaching sessions, more case-based teaching from palliative care providers, opportunities to be directly observed, and increased support from palliative care providers after-hours.