bluuebunny/crossref_metadata_2025_split huggingface dataset:
Necessity of transnasal gastroscopy in routine diagnostics: a patient-centred requirement analysis
Authors: Schuldt Anna-Livia , Kirsten Holger , Tuennemann Jan , Heindl Mario , van Bommel Florian , Feisthammel Juergen , Hollenbach Marcus , Hoffmeister Albrecht 
Published: April 2019

IntroductionNumerous indications require regular upper gastrointestinal endoscopy (oesophagogastroduodenoscopy; EGD) in outpatients. In most cases, peroral gastroscopy is performed. The aim of this study was to evaluate the need of transnasal gastroscopy (nEGD) in outpatients.MethodsA questionnaire was used to assess patients’ preferred choice of method, previous experience with EGD, psychological aspects and sociodemographic data. Furthermore, patient satisfaction with and potentially perceived discomfort during the examination as well as preference for a method in regard to future examinations was evaluated.ResultsFrom September 2016 to March 2017, a total of 283 outpatients at endoscopy of the University Hospital of Leipzig were approached to participate in the study. 196 patients were eligible, of whom 116 (60%) chose nEGD. For 87 patients (87/283, 31%) nEGD had to be excluded for medical reasons. The average age in the total sample was 53 (±17) years. 147 (77%) have had previous experience with peroral EGD (oEGD). Of the nEGD examined patients 83% were fairly up to extremely satisfied with the procedure. Satisfaction significantly predicted the choice of future EGD examinations. Nasal pain experienced during nEGDs was associated with rejection of nEGD in further EGD examinations (p<0.01). Patients who did choose a specific procedure were more likely to select the same procedure as their future preference (χ²= 73.6, df=1, p<0.001); this preference was unaffected by the procedure that had been chosen previously (reselecting nEGD: 84%, oEGD: 89%, p=0.874).ConclusionnEGD without sedation is a viable alternative. Patient satisfaction with nEGD is high, and reselection rate for nEGD is similar to that for oEGD. As a result of this study nEGD is now offered as a routine procedure at the University of Leipzig.Trial registration numberNCT03663491.
Is the elimination of ‘sleeping sickness’ affordable? Who will pay the price? Assessing the financial burden for the elimination of human African trypanosomiasisTrypanosoma brucei gambiensein sub-Saharan Africa
Authors: Sutherland C Simone , Tediosi Fabrizio 
Published: April 2019

IntroductionProgramme to eliminate neglected tropical diseases (NTDs) have gained global recognition, and may allow for improvements to universal health coverage and poverty alleviation. It is hoped that elimination of human African trypanosomiasis (HAT)Trypanosoma brucei gambiense (Tbg) would assist in this goal, but the financial costs are still unknown. The objective of this analysis was to forecast the financial burden of direct costs of HATTbgto funders and society.MethodsIn order to estimate the total costs to health services and individuals: (1) potential elimination programmes were defined; (2) the direct costs of programmes were calculated; (3) the per case out-of-pocket payments (OOPs) by programme and financial risk protection indicators were estimated. The total estimated costs for control and elimination programme were reported up till 2020 in international dollars. The mean results for both direct programme costs and OOPs were calculated and reported along with 95% CIs.ResultsAcross sub-Saharan Africa, HATTbgmaintaining ‘Control’ would lead to a decline in cases and cost US$630.6 million. In comparison, the cost of ‘Elimination’ programme ranged from US$410.9 million to US$1.2 billion. Maintaining ‘Control’ would continue to cause impoverishment and financial hardship to households; while all ‘Elimination’ programme would lead to significant reductions in poverty.ConclusionOverall, the total costs of either control or elimination programme would be near US$1 billion in the next decade. However, only elimination programme will reduce the number of cases and improve financial risk protection for households who are impacted by HATTbg.
International normative data for paediatric foot posture assessment: a cross-sectional investigation
Authors: Gijon-Nogueron Gabriel , Martinez-Nova Alfonso , Alfageme-Garcia Pilar , Montes-Alguacil Jesus , Evans Angela Margaret 
Published: April 2019

ObjectivesThe foot posture index (FPI) is an observational tool designed to measure the position of the foot. The objective of this study was to establish international reference data for foot posture across childhood, and influence of body mass index (BMI) on paediatric foot posture.DesignCross-sectional study.Setting and participantsThe dataset comprised 3217 healthy children, aged from 3 to 15 years. Contributing data were acquired from Spain, UK and Australia.InterventionsFoot posture was described by means and z-score of the FPI and the height and weight of each subject was measured and the BMI was calculated.ResultsThe foot posture of 3217 children were reviewed. A pronated (FPI ≥+6) foot posture was found in 960 (29.8%) children, a normal (FPI 0 to +6) foot posture in 1776 (55.2%) and a highly pronated (FPI +10) foot posture was found in 127 children (3.9%) (range −4 to +12 FPI). Less than 11% were found to have a supinated foot type (n=354). Approximately 20% of children were overweight/obese, but correlation between BMI and FPI was weak and inverse (r=−0.066, p<0.01), refuting the relationship between increased body mass and flatfeet.ConclusionsThis study confirms that the ‘flat’ or pronated foot is the common foot posture of childhood, with FPI score of +4 (3) the average finding. Trend indicated a less flatfoot with age, although non-linear. A wide normal range of foot posture across childhood is confirmed.
Involving the general practitioner during curative cancer treatment: a systematic review of health care interventions
Authors: Perfors Ietje A A , May Anne M , Boeijen Josi A , de Wit Niek J , van der Wall Elsken , Helsper Charles W 
Published: April 2019

ObjectiveThe role of primary care providers (PCP) in the cancer care continuum is expanding. In the post-treatment phase, this role is increasingly recognised by policy makers and healthcare professionals. During treatment, however, the role of PCP remains largely undefined. This systematic review aims to map the content and effect of interventions aiming to actively involve the general practitioner (GP) during cancer treatment with a curative intent.Study designSystematic review.ParticipantsPatients with cancer treated with curative intent.Data sourcesRandomised controlled trials (RCTs), controlled clinical trials (CCT), controlled before and after studies and interrupted time series focusing on interventions designed to involve the GP during curative cancer treatment were systematically identified from PubMed and EMBASE and were subsequently reviewed. Risk of bias was scored according to the Effective Practice and Organisation of Care Group risk of bias criteria.ResultsFive RCTs and one CCT were included. Interventions and effects were heterogeneous across studies. Four studies implemented interventions focussing on information transfer to the GP and two RCTs implemented patient-tailored GP interventions. The studies have a low–medium risk of bias. Three studies show a low uptake of the intervention. A positive effect on patient satisfaction with care was found in three studies. Subgroup analysis suggests a reduction of healthcare use in elderly patients and reduction of clinical anxiety in those with higher mental distress. No effects are reported on patients’ quality of life (QoL).ConclusionInterventions designed to actively involve the GP during curative cancer treatment are scarce and diverse. Even though uptake of interventions is low, results suggest a positive effect of GP involvement on patient satisfaction with care, but not on QoL. Additional effects for vulnerable subgroups were found. More robust evidence for tailored interventions is needed to enable the efficient and effective involvement of the GP during curative cancer treatment.PROSPERO registration numberCRD42018102253.
Implementing a digital clinical decision support tool for side effects of antipsychotics: a focus group study
Authors: Henshall Catherine , Cipriani Andrea , Ruvolo David , Macdonald Orla , Wolters Leona , Koychev Ivan 
Published: April 2019

BackgroundIn medicine, algorithms can inform treatment decisions by combining the most up-to-date evidence about side effect profiles of medications, which are comparable in efficacy. Their use provides opportunities for improved shared clinician–patient decision-making when initiating therapy. We designed a decision support tool (DST) that incorporated the latest evidence regarding antipsychotic side effects. The tool allowed patients to select one side effect commonly associated with antipsychotics that they wished to avoid; the tool then provided a list of suggested medications and ones to avoid.ObjectiveTo explore qualitatively the acceptability and usefulness of the DST from the perspectives of patients and psychiatrists.MethodsThis qualitative study took place at a mental health and community hospital in Oxford, UK, in 2018. Four patients/carers and four psychiatrists were recruited to two focus groups to explore their perceptions of the tool. Data were thematically analysed.FindingsFindings demonstrated a high degree of acceptability and potential usability of the DST for patients and psychiatrists. The main themes to emerge relating to the DST were ‘prescribing preferences and practices’, ‘consideration and awareness of side effects’, ‘app content, layout and accessibility’, ‘influence on clinical practice’ and ‘role in decision-making’.ConclusionsA proof-of-concept clinical study will incorporate the recommendations produced from the findings into the tool’s design.Clinical implicationsDigital DSTs provide opportunities for the most up-to-date information on medication side effects to be used as the basis for shared clinician–patient decision-making. This tool has the potential to improve adherence to psychiatric medication, with benefits to clinical outcomes and healthcare resourcing.
Biophysical Techniques in Structural Biology
Authors: Dobson Christopher M. 
Published: April 2019

Over the past six decades, steadily increasing progress in the application of the principles and techniques of the physical sciences to the study of biological systems has led to remarkable insights into the molecular basis of life. Of particular significance has been the way in which the determination of the structures and dynamical properties of proteins and nucleic acids has so often led directly to a profound understanding of the nature and mechanism of their functional roles. The increasing number and power of experimental and theoretical techniques that can be applied successfully to living systems is now ushering in a new era of structural biology that is leading to fundamentally new information about the maintenance of health, the origins of disease, and the development of effective strategies for therapeutic intervention. This article provides a brief overview of some of the most powerful biophysical methods in use today, along with references that provide more detailed information about recent applications of each of them. In addition, this article acts as an introduction to four authoritative reviews in this volume. The first shows the ways that a multiplicity of biophysical methods can be combined with computational techniques to define the architectures of complex biological systems, such as those involving weak interactions within ensembles of molecular components. The second illustrates one aspect of this general approach by describing how recent advances in mass spectrometry, particularly in combination with other techniques, can generate fundamentally new insights into the properties of membrane proteins and their functional interactions with lipid molecules. The third reviewdemonstrates the increasing power of rapidly evolving diffraction techniques, employing the very short bursts of X-rays of extremely high intensity that are now accessible as a result of the construction of free-electron lasers, in particular to carry out time-resolved studies of biochemical reactions. The fourth describes in detail the application of such approaches to probe the mechanism of the light-induced changes associated with bacteriorhodopsin's ability to convert light energy into chemical energy.
The Impact of Reservoir Fluctuations on Reactivated Large Landslides: A Case Study
Authors: Iqbal Javed , Tu Xinbin , Gao Wei 
Published: April 2019

Filling of Xiangjiaba Reservoir Lake in the Southwest China triggered and reactivated numerous landslides due to water fluctuation. In order to understand the relationship between reservoirs and slope instability, a typical reservoir landslide (Dasha landslide) at the right bank of Jinsha River was selected as a case study for in-depth investigations. The detailed field investigations were carried out to identify the landslide with respect to its surroundings and to find out the slip surface. Boreholes were drilled to find out the subsurface lithology and the depth of failure of Dasha landslide. The in situ geotechnical tests were performed, and the soil samples from exposed slip surface were retrieved for geotechnical laboratory analysis. Finally, stability analysis was done using the 3D strength reduction method under different conditions of reservoir water level fluctuations and rainfall conditions. The in-depth investigations show that the Dasha landslide is a bedding rockslide which was once activated in 1986. The topography of Dasha landslide is relatively flat, while the back scarp and local terrain is relatively steep. The total volume of landslides is about 580×104 m3 with an average thickness of 20 m. Bedrock in the landslide area is composed of Suining Formation of the Jurassic age. The main rock type is silty mudstone with sandstone, and the bedding orientation is 300~310° ∠ 7~22°. The factor of safety (FOS) of Dasha landslide obtained by 3D strength reduction cannot meet the minimum safety requirement under the working condition of reservoir level fluctuation as designed, with effect of rainfall and rapid drawdown.
DR4-Ser424O-GlcNAcylation Promotes Sensitization of TRAIL-Tolerant Persisters and TRAIL-Resistant Cancer Cells to Death
Authors: Lee Hyeonjeong , Oh Yumin , Jeon Young-Jun , Lee Song-Yi , Kim Hyunjoo , Lee Ho-June , Jung Yong-Keun 
Published: April 2019

AbstractTNF-related apoptosis-inducing ligand (TRAIL) resistance, including nongenetically acquired tolerance in cancer persister cells, is a major obstacle to translating TRAIL therapy into patients with cancer. However, the underlying mechanisms remain to be elucidated. Here, we show that DR4/TRAIL-R1 is O-GlcNAcylated at Ser424 in its death domain to mediate both apoptosis and necrosis upon TRAIL ligation. We found that DR4–Ser424 mutations, identified from our cell-based functional screen using a cancer patient–derived cDNA expression library and from The Cancer Genome Atlas, caused TRAIL resistance in various human cancer cell lines. Using O-GlcNAc transferase knockdown cells, DR4-preferred versus DR5-preferred cancer cells, and a DR5-neutralizing antibody, we evaluated the essential role of DR4-specific O-GlcNAc modification in TRAIL cytotoxicity. In contrast to DR4, DR5 was not O-GlcNAcylated by TRAIL treatment, discriminating DR4 from DR5-mediated signaling. Apart from genetic changes in DR4-Ser424, we further classified various cancer cell lines originated from stomach, colon, lung, and glioblastoma according to their sensitivity to and receptor preference upon TRAIL death signaling and generated TRAIL-tolerant persister-derived DLD-1PER cells. Among these, we discovered that DR4 was not modified by O-GlcNAc in most of the TRAIL-resistant cancer cells and DLD-1PER cells. Interestingly, promoting DR4 O-GlcNAcylation intentionally using 2-deoxy-d-glucose or a high concentration of glucose sensitized those resistant cancer cells to TRAIL. The O-GlcNAcylation–defective DR4 failed to form DISC/necrosome and could not translocate to aggregated platforms for receptor clustering. Our findings demonstrate that DR4 O-GlcNAcylation is crucial for TRAIL death signaling, providing new opportunities for TRAIL therapy overcoming TRAIL resistance in cancers.Significance:This study reports that a novel posttranslational modification by O-GlcNAcylation of one of the two human TRAIL receptors with a death domain, TRAIL-R1 (DR4), plays a crucial role in enabling both apoptotic and necroptotic cell death induction by TRAIL.
Inhibition of Ataxia-Telangiectasia Mutated and RAD3-Related (ATR) Overcomes Oxaliplatin Resistance and Promotes Antitumor Immunity in Colorectal Cancer
Authors: Combès Eve , Andrade Augusto F. , Tosi Diego , Michaud Henri-Alexandre , Coquel Flavie , Garambois Veronique , Desigaud Delphine , Jarlier Marta , Coquelle Arnaud , Pasero Philippe , Bonnefoy Nathalie , Moreaux Jerome , Martineau Pierre , Del Rio Maguy , Beijersbergen Roderick L. , Vezzio-Vie Nadia , Gongora Celine 
Published: April 2019

Abstract

Although many patients with colorectal cancer initially respond to the chemotherapeutic agent oxaliplatin, acquired resistance to this treatment remains a major challenge to the long-term management of this disease. To identify molecular targets of oxaliplatin resistance in colorectal cancer, we performed an shRNA-based loss-of-function genetic screen using a kinome library. We found that silencing of ataxia-telangiectasia mutated and RAD3-related (ATR), a serine/threonine protein kinase involved in the response to DNA stress, restored oxaliplatin sensitivity in a cellular model of oxaliplatin resistance. Combined application of the ATR inhibitor VE-822 and oxaliplatin resulted in strong synergistic effects in six different colorectal cancer cell lines and their oxaliplatin-resistant subclones, promoted DNA single- and double-strand break formation, growth arrest, and apoptosis. This treatment also increased replicative stress, cytoplasmic DNA, and signals related to immunogenic cell death such as calreticulin exposure and HMGB1 and ATP release. In a syngeneic colorectal cancer mouse model, combined administration of VE-822 and oxaliplatin significantly increased survival by promoting antitumor T-cell responses. Finally, a DNA repair gene signature discriminated sensitive from drug-resistant patients with colorectal cancer. Overall, our results highlight the potential of ATR inhibition combined with oxaliplatin to sensitize cells to chemotherapy as a therapeutic option for patients with colorectal cancer.

Significance:
These findings demonstrate that resistance to oxaliplatin in colorectal cancer cells can be overcome with inhibitors of ATR and that combined treatment with both agents exerts synergistic antitumor effects.
When Failure Is Worse Than Giving Up: The Case of CTL
Authors: Colombo Mario Paolo , Lecis Daniele 
Published: April 2019

Abstract
Although much emphasis is given to the use of immune checkpoint inhibitors to restore the functionality of exhausted lymphocytes, very little is known about the fate of cancer cells that escape from the cytotoxic activity of T cells. In a previous issue of Cancer Research, Stein and colleagues investigated the response of cancer cells to CD8+ T cells disarmed of their killing activity. Spared cancer cells acquired stem cell–like features and displayed an enhanced capacity to form tumors and metastasize. These increased tumorigenic properties could represent the other side of the coin of T-cell surveillance seen in wound healing in which recognition of damaged tissue as “self” gives the green light for healing process.
See related article by Stein and colleagues; Cancer Res 79(7):1507–19
Association of N-Terminal Pro Brain Natriuretic Peptide and Long-Term Outcome in Patients With Pulmonary Arterial Hypertension
Authors: Chin Kelly M. , Rubin Lewis J. , Channick Richard , Di Scala Lilla , Gaine Sean , Galiè Nazzareno , Ghofrani Hossein-Ardeschir , Hoeper Marius M. , Lang Irene M. , McLaughlin Vallerie V. , Preiss Ralph , Simonneau Gérald , Sitbon Olivier , Tapson Victor F. 
Published: April 2019

Background:

NT-proBNP (N-terminal pro brain natriuretic peptide) levels are included in the multiparametric risk assessment approach for pulmonary arterial hypertension (PAH) outlined in PAH guidelines. However, data supporting the use of NT-proBNP risk thresholds in assessing prognosis in PAH are limited. The GRIPHON trial (Prostacyclin [PGI
2
] Receptor Agonist In Pulmonary Arterial Hypertension) provides an opportunity to assess the prognostic value of NT-proBNP thresholds in a controlled clinical trial and to evaluate the response to selexipag according to these thresholds.

Methods:
The event-driven GRIPHON trial randomly assigned patients to selexipag or placebo. NT-proBNP was measured at regular intervals in GRIPHON. Here, patients were categorized post hoc into low, medium, and high NT-proBNP subgroups according to 2 independent sets of thresholds: (1) baseline tertiles: <271 ng/L; 271 to 1165 ng/L; >1165 ng/L; and (2) 2015 European Society of Cardiology/European Respiratory Society guidelines cutoffs: <300 ng/L; 300 to 1400 ng/L; >1400 ng/L. Hazard ratios (selexipag versus placebo) with 95% CIs were calculated for the primary end point (composite morbidity/mortality events) by NT-proBNP category at baseline using Cox proportional-hazards models, and at any time during the exposure period using a time-dependent Cox model.

Results:

With both thresholds, baseline and follow-up NT-proBNP categories were highly prognostic for future morbidity/mortality events during the study (
P
<0.0001). In the time-dependent analysis, the risk of experiencing a morbidity/mortality event was 92% and 83% lower in selexipag-treated patients with a low and medium NT-proBNP level, and 90% and 56% lower in placebo-treated patients with a low and medium NT-proBNP level, in comparison with patients with a high NT-proBNP level. Selexipag reduced the risk of morbidity/mortality events across all 3 NT-proBNP categories in both the baseline and time-dependent analyses, with a more pronounced treatment benefit of selexipag seen in the medium and low NT-proBNP subgroups (interaction
P
values 0.20 and 0.007 in the baseline and time-dependent analyses).

Conclusions:
These analyses further establish the prognostic relevance of NT-proBNP levels in PAH and provide first evidence for the association of NT-proBNP level and treatment response. Using 2 similar sets of thresholds, these analyses support the relevance of the low, medium, and high NT-proBNP categories as part of the multiparametric risk assessment approach outlined in the European Society of Cardiology/European Respiratory Society guidelines for the management of PAH patients.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT01106014.