bluuebunny/crossref_metadata_2025_split huggingface dataset:
Foundation year one and year two doctors’ prescribing errors: a comparison of their causes
Authors: Lewis Penny J , Seston Elizabeth , Tully Mary P 
Published: January 2019

AbstractObjectiveJunior doctors have the highest rates of prescribing errors, yet no study has set out to understand the differences between completely novice prescribers (Foundation year one (FY1) doctors) and those who have gained some experience (Foundation year two (FY2) doctors). The objective of this study was to uncover the causes of prescribing errors made by FY2 doctors and compare them with previously collected data of the causes of errors made by FY1 doctors.DesignQualitative interviews, using the critical incident technique, conducted with 19 FY2 doctors on the causes of their prescribing errors and compared with interviews previously conducted with 30 FY1 doctors. Data were analysed using a constant comparison approach after categorisation of the data using Reason’s model of accident causation and the London protocol.ResultsCommon contributory factors in both FY1 and FY2 doctors’ prescribing errors included working on call, tiredness and complex patients. Yet, important differences were revealed in terms of application of prescribing knowledge, with FY1 doctors lacking knowledge and FY2 misplacing their knowledge. Due to the rotation of foundation doctors, both groups are faced with novel prescribing contexts, yet the previous experience that FY2 doctors gained led to misplaced confidence when caution would have been expedient.ConclusionsDifferences in the contributory factors of prescribing errors should be taken into account when designing interventions to improve the prescribing of foundation doctors. Furthermore, careful consideration should be taken when inferring expertise in FY2 doctors, who are likely to prescribe in contexts in which their experience is little different to an FY1 doctor.
Vitamin D to prevent exacerbations of COPD: systematic review and meta-analysis of individual participant data from randomised controlled trials
Authors: Jolliffe David A , Greenberg Lauren , Hooper Richard L , Mathyssen Carolien , Rafiq Rachida , de Jongh Renate T , Camargo Carlos A , Griffiths Christopher J , Janssens Wim , Martineau Adrian R 
Published: January 2019

BackgroundRandomised controlled trials (RCTs) of vitamin D to prevent COPD exacerbations have yielded conflicting results.Individual participant data meta-analysis could identify factors that explain this variation.MethodsPubMed, Embase, the Cochrane Central Register of Controlled Trials and Web of Science were searched from inception up to and including 5 October 2017 to identify RCTs of vitamin D supplementation in patients with COPD that reported incidence of acute exacerbations. Individual participant data meta-analysis was performed using fixed effects models adjusting for age, sex, Global Initiative for Chronic Obstructive Lung Disease spirometric grade and trial.ResultsFour eligible RCTs (total 560 participants) were identified; individual participant data were obtained for 469/472 (99.4%) participants in three RCTs. Supplementation did not influence overall rate of moderate/severe COPD exacerbations (adjusted incidence rate ratio (aIRR) 0.94, 95% CI 0.78 to 1.13). Prespecified subgroup analysis revealed that protective effects were seen in participants with baseline 25-hydroxyvitamin D levels <25 nmol/L (aIRR 0.55, 95% CI 0.36 to 0.84) but not in those with baseline 25-hydroxyvitamin D levels ≥25 nmol/L (aIRR 1.04, 95% CI 0.85 to 1.27; p for interaction=0.015). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (adjusted OR 1.16, 95% CI 0.76 to 1.75).ConclusionsVitamin D supplementation safely and substantially reduced the rate of moderate/severe COPD exacerbations in patients with baseline 25-hydroxyvitamin D levels <25 nmol/L but not in those with higher levels.Trial registration numberCRD42014013953.
Exosomes from Nischarin-Expressing Cells Reduce Breast Cancer Cell Motility and Tumor Growth
Authors: Maziveyi Mazvita , Dong Shengli , Baranwal Somesh , Mehrnezhad Ali , Rathinam Rajamani , Huckaba Thomas M. , Mercante Donald E. , Park Kidong , Alahari Suresh K. 
Published: January 2019

Abstract

Exosomes are small extracellular microvesicles that are secreted by cells when intracellular multivesicular bodies fuse with the plasma membrane. We have previously demonstrated that Nischarin inhibits focal adhesion formation, cell migration, and invasion, leading to reduced activation of focal adhesion kinase. In this study, we propose that the tumor suppressor Nischarin regulates the release of exosomes. When cocultured on exosomes from Nischarin-positive cells, breast cancer cells exhibited reduced survival, migration, adhesion, and spreading. The same cocultures formed xenograft tumors of significantly reduced volume following injection into mice. Exosomes secreted by Nischarin-expressing tumors inhibited tumor growth. Expression of only one allele of Nischarin increased secretion of exosomes, and Rab14 activity modulated exosome secretions and cell growth. Taken together, this study reveals a novel role for Nischarin in preventing cancer cell motility, which contributes to our understanding of exosome biology.

Significance:
Regulation of Nischarin-mediated exosome secretion by Rab14 seems to play an important role in controlling tumor growth and migration.
See related commentary by McAndrews and Kalluri, p. 2099
WNT/β-catenin Pathway Activation Correlates with Immune Exclusion across Human Cancers
Authors: Luke Jason J. , Bao Riyue , Sweis Randy F. , Spranger Stefani , Gajewski Thomas F. 
Published: January 2019

Abstract

Purpose:
The T-cell-inflamed phenotype correlates with efficacy of immune-checkpoint blockade, whereas non-T-cell-inflamed tumors infrequently benefit. Tumor-intrinsic WNT/β-catenin signaling mediates immune exclusion in melanoma, but association with the non-T-cell-inflamed tumor microenvironment in other tumor types is not well understood.

Experimental Design:
Using The Cancer Genome Atlas (TCGA), a T-cell-inflamed gene expression signature segregated samples within tumor types. Activation of WNT/β-catenin signaling was inferred using three approaches: somatic mutations or somatic copy number alterations (SCNA) in β-catenin signaling elements including CTNNB1, APC, APC2, AXIN1, and AXIN2; pathway prediction from RNA-sequencing gene expression; and inverse correlation of β-catenin protein levels with the T-cell-inflamed gene expression signature.

Results:
Across TCGA, 3,137/9,244 (33.9%) tumors were non-T-cell-inflamed, whereas 3,161/9,244 (34.2%) were T-cell-inflamed. Non-T-cell-inflamed tumors demonstrated significantly lower expression of T-cell inflammation genes relative to matched normal tissue, arguing for loss of a natural immune phenotype. Mutations of β-catenin signaling molecules in non-T-cell-inflamed tumors were enriched three-fold relative to T-cell-inflamed tumors. Across 31 tumors, 28 (90%) demonstrated activated β-catenin signaling in the non-T-cell-inflamed subset by at least one method. This included target molecule expression from somatic mutations and/or SCNAs of β-catenin signaling elements (19 tumors, 61%), pathway analysis (14 tumors, 45%), and increased β-catenin protein levels (20 tumors, 65%).

Conclusions:
Activation of tumor-intrinsic WNT/β-catenin signaling is enriched in non-T-cell-inflamed tumors. These data provide a strong rationale for development of pharmacologic inhibitors of this pathway with the aim of restoring immune cell infiltration and augmenting immunotherapy.
See related commentary by Dangaj et al., p. 2943
PRMT5-mediated H4R3sme2 Confers Cell Differentiation in Pediatric B-cell Precursor Acute Lymphoblastic Leukemia
Authors: Mei Mei , Zhang Ruidong , Zhou Zhong-Wei , Ying Zhengzhou , Wang Jincheng , Zhang Han , Zheng Huyong , Bao Shilai 
Published: January 2019

Abstract

Purpose:
Little is known about the function of histone arginine methylation in acute lymphoblastic leukemia (ALL). The objective was to evaluate whether protein arginine methyltransferase 5 (PRMT5) plays a role in pediatric ALL and to determine the possible mechanism of epigenetic regulation.

Experimental Design:
We used bone marrow samples from patients with pediatric ALL, the Nalm6 cell line, mature B-cell lines, and mouse xenograft models to evaluate the function of PRMT5 in ALL tumorigenesis.

Results:
This study showed that PRMT5 and the symmetric dimethylation of H4R3 (H4R3sme2) were upregulated in most initially diagnosed (n = 15; 100%) and relapsed (n = 4; 75%) bone marrow leukemia cells from patients with pediatric B-cell precursor ALL (BCP-ALL) and were decreased when the disease was in remission (n = 15; 6.7%). Downregulation of H4R3sme2 by PRMT5 silencing induced BCP-ALL cell differentiation from the pre-B to immature B stage, whereas overexpressed PRMT5 with enhanced H4R3sme2 promoted human mature B cells to dedifferentiate back to the pre-B II/immature B stages in vitro. High PRMT5 expression enhanced the proportion of CD43+/B220+/sIgM− B leukocytes in recipient mice. CLC and CTSB were identified as potential target genes of PRMT5 in BCP-ALL cells and were inhibited by H4R3sme2 in gene promoters.

Conclusions:
We demonstrate that enhanced PRMT5 promotes BCP-ALL leukemogenesis partially by the dysregulation of B-cell lineage differentiation. H4R3sme2 and PRMT5 may serve as potential sensitive biomarkers of pediatric BCP-ALL. Suppression of the activation of PRMT5 may offer a promising therapeutic strategy against pediatric BCP-ALL.
Gamma Drop Size Distribution Assumptions in Bulk Model Parameterizations and Radar Polarimetry and Their Impact on Polarimetric Radar Moments
Authors: Schinagl Katharina , Friederichs Petra , Trömel Silke , Simmer Clemens 
Published: January 2019

AbstractA suitable formulation of the rain drop size distribution (DSD) is a prerequisite for a successful assimilation of radar polarimetric information on rain into a numerical weather prediction model. Popular DSD parameterizations in two-moment bulk microphysics schemes use relations between the so-called mean-mass diameter and the DSD shape parameter μ, in order to prevent overly strong size sorting in the models. In radar polarimetry constrained-gamma DSDs with empirical relations between the shape and scale parameter are commonly used. This study compares the different DSD formulations and highlights the differences. Synthetic polarimetric radar observations for X band (9.39 GHz) and S band (3 GHz) were calculated from the different DSDs using the T-matrix method. Depending on the constraint that is assumed for the DSDs, the polarimetric moments exhibit quite different dependencies on the mean diameter, which are particularly striking for differential reflectivity ZDR. To successfully assimilate observed polarimetric moments into atmospheric models, formulations—possibly more flexible than those investigated in this study—have to be found that sufficiently represent microphysical processes and at the same time are consistent with empirical relations derived from disdrometer and radar polarimetric measurements.
Defining the Northeast Monsoon of India
Authors: Misra Vasubandhu , Bhardwaj Amit 
Published: January 2019

AbstractThis study introduces an objective definition for onset and demise of the northeast Indian monsoon (NEM). The definition is based on the land surface temperature analysis over the Indian subcontinent. It is diagnosed from the inflection points in the daily anomaly cumulative curve of the area-averaged surface temperature over the provinces of Andhra Pradesh, Rayalseema, and Tamil Nadu located in the southeastern part of India. Per this definition, the climatological onset and demise dates of the NEM season are 6 November and 13 March, respectively. The composite evolution of the seasonal cycle of 850-hPa winds, surface wind stress, surface ocean currents, and upper-ocean heat content suggest a seasonal shift around the time of the diagnosed onset and demise dates of the NEM season. The interannual variations indicate onset date variations have a larger impact than demise date variations on the seasonal length, seasonal anomalies of rainfall, and surface temperature of the NEM. Furthermore, it is shown that warm El Niño–Southern Oscillation (ENSO) episodes are associated with excess seasonal rainfall, warm seasonal land surface temperature anomalies, and reduced lengths of the NEM season. Likewise, cold ENSO episodes are likely to be related to seasonal deficit rainfall anomalies, cold land surface temperature anomalies, and increased lengths of the NEM season.
Factors predictive for early and late mortality after surgical repair for Stanford A acute aortic dissection
Authors: Merkle Julia , Sabashnikov Anton , Liebig Lisa , Weber Carolyn , Eghbalzadeh Kaveh , Liakopoulos Oliver , Zeriouh Mohamed , Kuhn-Régnier Ferdinand , Wahlers Thorsten 
Published: January 2019

Objectives: The aim of this study was to evaluate independent risk factors predictive for mortality of patients with Stanford A acute aortic dissection. Methods: From January 2006 to March 2015, a total of 240 consecutive patients diagnosed with acute Stanford A acute aortic dissection underwent surgical aortic repair in our center. After analysis of pre- and perioperative variables, univariate logistic and multivariate logistic regression analyses were performed for mortality of patients. Subsequently, Kaplan–Meier estimation analysis of short- and long-term survival of these variables was carried out. Results: Primary entry tear in descending aorta (odds ratio = 4.71, p = 0.021), preoperative international normalized ratio higher than 1.2 (odds ratio = 7.36, p = 0.001), additional coronary artery bypass grafting (odds ratio = 3.39, p = 0.003), cannulation in ascending aorta (odds ratio = 3.22, p = 0.005), preoperative neurological coma (odds ratio = 3.30, p = 0.003), and reduced perfusion (odds ratio = 2.91, p = 0.006) as well as prolonged reperfusion time (odds ratio = 3.36, p = 0.002) showed to be independent predictors for early mortality as well as for late mortality (hazard ratio of all variables p < 0.05). Kaplan–Meier survival estimation analysis with up to 9-year-follow-up in terms of these risk factors showed significantly poorer short- and long-term survival (log-rank and Breslow test all p < 0.05). Conclusion: Our study revealed that early and late mortality of patients with Stanford A acute aortic dissection surgery was significantly influenced by preoperative and perioperative variables as independent predictors especially of variables displaying coronary, cerebral, and visceral malperfusion. Also, short- and long-term survival of patients was significantly poorer in terms of these risk factors.
Application of continuous epidural anesthesia in transforaminal lumbar endoscopic surgery: a prospective randomized controlled trial
Authors: Xu Tiantong , Tian Rong , Qiao Pan , Han Zhihua , Shen Qingfeng , Jia Yutao 
Published: January 2019

Objective This study aimed to compare intraoperative lower back pain and leg pain, surgical time, and intraoperative X-ray dose in patients offered local infiltration anesthesia or continuous epidural anesthesia for transforaminal endoscopic spine system (TESSYS) surgery. Methods A total of 98 patients who received TESSYS treatment for single-segmental lumbar disc herniation were included, and were randomly divided into two groups: group A (49 cases; local infiltration anesthesia) and group B (49 cases; continuous epidural anesthesia). Surgical duration, intraoperative X-ray dose, and visual analog scale (VAS) scores of lower back pain and leg pain before surgery, during surgery, and 48 h after surgery were recorded and compared. Results After surgery, the VAS scores of both lower back pain and leg pain decreased in group A, and similar findings were found in group B. Group B had a shorter surgical duration, lower intraoperative X-ray dose, and lower intraoperative VAS scores of lower back pain and leg pain compared with group A. Conclusion Compared with local infiltration anesthesia, continuous epidural anesthesia was more effective for pain relief during TESSYS for single-segmental lumbar disc herniation, and also contributed to a shorter surgical duration and lower X-ray exposure.
East goes West — West goes East: border crossing and development
Authors: Seidler Christoph 
Published: January 2019

In the aftermath of the Nazi era and the Second World War the ‘Bloodlands’ of Eastern Europe including Germany were left with a pervasive and significant loss of empathy. Robi Friedman speaks of the ‘Soldier’s Matrix’ (2015), in which dehumanizing dissociation increases, and empathy, guilt and shame disappear. In the GDR (German Democratic Republic)—under totalitarian and authoritarian conditions—this state of emotional deficit persisted for longer than in the Federal Republic (BRD). Gradually, but only after reunification, could change in the whole of Germany become possible. In the following text I will review the fragmented state of psychoanalysis in the battered city of Berlin after the Second World War. I describe the predicament of psychoanalysts, who are hopelessly entangled in adaptation processes, fearing the new rulers and dreading their own conscience. Despite their weakened sense of courage, they were however able to create space for freedom of thought. I intend to convey the trajectory of that process. The GDR history, despite the experience of confinement, is also a story of opening. Specific developments within the borders enabled the preservation as well as the transportation of psychoanalytic thought: some examples can be seen in inpatient forms of psychotherapy, individual psychodynamic therapy and especially the Intended Dynamic Group Psychotherapy (IDG). The opening of the ‘Wall’ made profound psychoanalytic post-qualification possible, but it came at a cost to the specific developments of the health system in the East. Within this system group therapists took their own particular path. After several years of cautious rapprochement the founding of BIG (Berlin Institute for Group Analysis) could be negotiated and established in 2003, supported by all Institutes of Berlin belonging to the umbrella organization of the DGPT (German Society for Psychoanalyse, Psychotherapy, Psychosomatic). Nine years later the Deutsche Gesellschaft für Gruppenanalyse und Gruppenpsychotherapie (D3G) consolidated in the merger of several individual groups resulting in a continuous and refreshingly pluralistic cooperation today. This article will therefore describe a series of societal shifts, transitions, internal and external attempts to heal, that are well reflected within the parallel process visible in the development of group analysis and its practitioners. One example to consider would be the asymmetry between psychoanalytic ‘teachers’ (West) and ‘students’ (East) and the dynamics experienced during professional encounters, which were very particular and rather complicated. However, that is a chapter in itself and will be considered separately.
It is safe to use minimal restrictions following posterior approach total hip arthroplasty: results from a large cohort study
Authors: van der Weegen Walter , Kornuijt Anke , Das Dirk , Vos Rein , Sijbesma Thea 
Published: January 2019

Background: To prevent early postoperative dislocation following a total hip arthroplasty (THA) procedure, patients must adhere to restrictions. Restrictive protocols are common if THA surgery is performed using the posterior approach, but scientific evidence form larger studies that supports these restrictions are scarce. In this large cohort study we compare the <90-days dislocation rate between patients receiving posterior approach THA managed with minimal versus extensive restrictions. Methods: Prospective cohort ( n = 1049) of consecutive elective primary hip replacement surgery procedures (September 2014–July 2017) managed with minimal postoperative restrictions. Hospital charts were prospectively reviewed for patient demographics, risk factors and any hip dislocation. Control ( n = 1102) consecutive primary elective THAs (January 2011–August 2014) managed with a traditional restrictive protocol. A posterior surgical approach was used in all procedures. Results: Minimal restrictions group: 17 dislocations <90 days (1.6%); Restricted group: 28 (2.5%), chi-square p = 0.1. Testing the hypothesis of inferiority by a minimum of 1% increase in ⩽90 days dislocation risk: p = 0.14 (test for difference) and p < 0.001 (non-inferiority test), allowing us to discard the null hypothesis (absolute increase in risk of ⩾1% with minimal restrictions). The proportion of surgeries performed with a femoral head size ⩾32 mm was higher in the minimal restrictions group. Conclusions: Patients can be managed safely with minimal restrictions following posterior approach THA if combined with frequent use of larger femoral heads.
In vitro gene expression and detergent-free reconstitution of active proteorhodopsin in lipid vesicles
Authors: Fracasso Giorgio , Körner Yvonne , Gonzales David Thomas T , Dora Tang T-Y. 
Published: January 2019

In situ generation of proton gradients across membranes is a key component for energy generation within cells and is therefore an important feature for the design of energy converting artificial cells. Here, we establish a stepwise method for the in vitro expression and detergent-free reconstitution of proteorhodopsin into the membrane of lipid vesicles. This represents a novel technique towards the bottom-up synthesis of energy-generating artificial cells. Impact statement Our results offer the potential for straightforward, additive-free, and molecularly simple routes to building complex bioreactors based on in vitro transcription–translation systems and lipid vesicles.
Association Between Olfactory and Gustatory Dysfunction and Cognition in Older Adults
Authors: Churnin Ian , Qazi Jamiluddin , Fermin Cyrelle R. , Wilson James H. , Payne Spencer C. , Mattos Jose L. 
Published: January 2019

Background The association between olfactory dysfunction (OD) and cognitive decline is becoming apparent in the emerging literature. However, the literature demonstrating a similar effect between gustatory dysfunction (GD) and cognition is not well established. Objective To determine whether OD and GD are independently associated with cognitive impairment. Methods The 2013–2014 National Health and Nutrition Examination Survey was queried for 1376 older adults, corresponding to a weighted population sample of 50 816 529, to assess olfactory and gustatory status and cognition using univariate and multivariate regression analyses. OD and GD were determined using objective measurements with validated protocols. Participants were stratified as normal or abnormal cognition status using accepted cutoff values as indicated for the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) neuropsychological test, Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). Results OD was associated with both mild cognitive impairment (odds ratio [OR] 1.809, P = .004) and dementia (OR 3.173, P < .001) with CERAD testing, abnormal AFT (OR 2.424, P < .001), and abnormal DSST (OR 4.028, P < .001). GD based on 1M NaCl whole mouth taste testing was associated with dementia on CERAD testing (OR 2.217, P = .004). When smell and taste parameters were included together in the regression model, both OD and GD remained significant independent predictors of dementia status based on CERAD testing (OR 3.133, P < .001, OR 1.904, P = .015). Conclusions OD and severe GD represent independent predictors of cognitive impairment in a nationally representative sample of older adults.