bluuebunny/crossref_metadata_2025_split huggingface dataset:
TeamSTEPPS online simulation: expanding access to teamwork training for medical students
Authors: Burns Rebekah , Gray Megan , Peralta Dana , Scheets Andrew , Umoren Rachel 
Published: January 2021

BackgroundThe Team Strategies and Tools to Enhance Performance and Patient Safety (TeamSTEPPS) programme is an evidence-based approach to teamwork training. In-person education is not always feasible for medical student education. The aim of this study was to evaluate the impact of online, interactive TeamSTEPPS simulation versus an in-person simulation on medical students’ TeamSTEPPS knowledge and attitudes.MethodsFourth-year medical students self-selected into an in-person or online training designed to teach and evaluate teamwork skills. In-person participants received didactic sessions, team-based medical simulations and facilitated debriefing sessions. The online group received an equivalent online didactic session and participated in an interactive software-based simulation with immediate, personalised performance-based feedback and scripted debriefing. Both trainings used three iterations of a case of septic shock, each with increasing medical complexity. Participants completed a demographic survey, a preintervention/postintervention TeamSTEPPS Benchmarks test and a retrospective preintervention/postintervention TeamSTEPPS teamwork attitudes questionnaire. Data were analysed using descriptive statistics and repeated measures analysis of variance.ResultsThirty-one students (18 in-person, 13 online) completed preintervention/postintervention surveys, tests and questionnaires. Gender, age and exposure to interprofessional education, teamwork training and games were similar between groups. There were no statistical differences in preintervention knowledge or teamwork attitude scores between in-person and online groups. Postintervention knowledge scores increased significantly from baseline (+2.0% p=0.047), and these gains did not differ significantly based on whether participants received in-person versus online training (+1.5% vs +2.9%; p=0.49). Teamwork attitudes scores also showed a statistically significant increase with training (+0.9, p<0.01) with no difference in the effect of training by group (+0.8 vs +1.0; p=0.64).ConclusionsGraduating medical students who received in-person and online teamwork training showed similar increases in TeamSTEPPS knowledge and attitudes. Online simulations may be used to teach and reinforce team communication skills when in-person, interprofessional simulations are not feasible.
Opioid prescribing attitudes of palliative care physicians versus other specialists: a questionnaire-based survey
Authors: Dzierzanowski Tomasz , Kozlowski Michael 
Published: January 2021

AbstractPurpose of the studyWhile opioid overuse is a public health crisis in the USA, opioid analgesics are used suboptimally in Central and Eastern Europe, causing many pain cases to remain untreated or undertreated.Study designThis questionnaire study aimed to identify the prevalent prescribing patterns and attitudes and the possible internal impediments to optimal opioid use among palliative care physicians and other specialists in Poland.ResultsTramadol was the most commonly preferred opioid. While palliative care physicians (n=81) used various strong opioids, other physicians (n=87) prescribed mostly buprenorphine, accessible with standard prescription forms. Neither internal prejudices and beliefs nor administrative regulations impede prescribing opioids by palliative care physicians, unlike specialists other than palliative medicine. Special prescription forms for psychoactive medications, fear of drug addiction of their patients and penalties for possible errors on prescriptions affect the latter's optimal prescribing. They also revealed significant gaps in the knowledge of prescribing opioids and would take part in additional training. Palliative care physicians appeared optimally prepared for cancer pain management and report fewer internal barriers than other specialists.ConclusionsContinuous medical education on cancer pain treatment should be provided to all specialists to ensure optimal opioid pharmacotherapy and avoid overprescribing or underprescribing opioids. Administrative restrictions are the main barrier to optimal pain treatment.
Surgical training in the UK: is cost a barrier to entry?
Authors: Vinnicombe Zak , Little Max , Super Jonathan , Anakwe Raymond 
Published: January 2021

AbstractBackgroundThere is good quality evidence linking socioeconomic background and the likelihood of a surgical career. Additionally, training in surgery is more expensive than in other specialties. Our aim was to assess the awareness and perceptions of trainees and medical students of the relative costs of surgical training and to determine whether perceptions of cost deter potential surgical trainees.MethodsMedical students, foundation doctors and core trainees in England were surveyed over a 2-week period. χ2 tests of independence were used to assess statistically significant associations between measured variablesMain findingsA total of 284 responses were received. More than half of respondents (54%) were not previously aware of the high costs of surgical training. More than a quarter of respondents (27%) did not take out a student loan. There was a significant association (p=0.003) between familial income and being less likely to consider a surgical career due to the costs. Respondents who reported receipt of a student loan were also significantly less likely to consider a surgical career due to the costs (p=0.033).ConclusionOur study demonstrates an important relationship between perceived costs of surgical training and future career aspirations. This suggests that access to surgical training may still be difficult for many. This study also highlights a general lack of awareness of high surgical training costs. It is important that surgical training is accessible. Financial status should not be a significant disincentive and widening access to surgical training can only serve to enrich and advance the specialty.
Breathomics for the clinician: the use of volatile organic compounds in respiratory diseases
Authors: Ibrahim Wadah , Carr Liesl , Cordell Rebecca , Wilde Michael J , Salman Dahlia , Monks Paul S , Thomas Paul , Brightling Chris E , Siddiqui Salman , Greening Neil J 
Published: January 2021

Exhaled breath analysis has the potential to provide valuable insight on the status of various metabolic pathways taking place in the lungs locally and other vital organs, via systemic circulation. For years, volatile organic compounds (VOCs) have been proposed as feasible alternative diagnostic and prognostic biomarkers for different respiratory pathologies.
We reviewed the currently published literature on the discovery of exhaled breath VOCs and their utilisation in various respiratory diseases
Key barriers in the development of clinical breath tests include the lack of unified consensus for breath collection and analysis and the complexity of understanding the relationship between the exhaled VOCs and the underlying metabolic pathways. We present a comprehensive overview, in light of published literature and our experience from coordinating a national breathomics centre, of the progress made to date and some of the key challenges in the field and ways to overcome them. We particularly focus on the relevance of breathomics to clinicians and the valuable insights it adds to diagnostics and disease monitoring.
Breathomics holds great promise and our findings merit further large-scale multicentre diagnostic studies using standardised protocols to help position this novel technology at the centre of respiratory disease diagnostics.
Smokeless tobacco products, supply chain and retailers’ practices in England: a multimethods study to inform policy
Authors: Siddiqui Faraz , Khan Talib , Readshaw Anne , Croucher Ray , Dockrell Martin , Jackson Cath , Kanaan Mona , McCambridge Jim , McNeill Ann , Parrott Steve , Sheikh Aziz , Siddiqi Kamran 
Published: January 2021

BackgroundIn England, many people of South Asian origin consume smokeless tobacco (ST). ST use can lead to oral cancer, which is disproportionately high in South Asians. Our aims were to assess the compliance of ST product retailers with statutory regulations and to explore the supply chain of ST.MethodsWe undertook a multimethods study between August 2017 and July 2019 in five English boroughs with a high proportion of ethnic South Asians. We purchased ST products and conducted field surveys with ST retailers at point of sale. Qualitative interviews were conducted with ST retailers and suppliers. ST packs were assessed for regulatory compliance, while quantitative and qualitative data triangulated information on retailers’ practices and the ST supply chain.ResultsWe collected 41 unique ST products, which included dry snuff, naswar, gutka, chewing tobacco and zarda. ST products were not registered, and demonstrated low compliance with health warning (14.6%) and packaging (56.1%) requirements. ST availability in surveyed boroughs was high (38.2%–69.7%); dry snuff, naswar and zarda were most commonly available. ST retailers demonstrated limited knowledge of regulations, and one-third were found to advertise ST at point of sale. Qualitative insights revealed illicit supply and distribution networks, as well as ST production in discreet locations.ConclusionST products are widely available in England, yet non-compliant with statutory regulations. In order to safeguard consumers, in particular ethnic South Asians, stronger efforts are needed to regulate the supply chain of ST at both national and international levels.
Challenges when identifying migration from geo-located Twitter data
Authors: Armstrong Caitrin , Poorthuis Ate , Zook Matthew , Ruths Derek , Soehl Thomas 
Published: January 2021

AbstractGiven the challenges in collecting up-to-date, comparable data on migrant populations the potential of digital trace data to study migration and migrants has sparked considerable interest among researchers and policy makers. In this paper we assess the reliability of one such data source that is heavily used within the research community: geolocated tweets. We assess strategies used in previous work to identify migrants based on their geolocation histories. We apply these approaches to infer the travel history of a set of Twitter users who regularly posted geolocated tweets between July 2012 and June 2015. In a second step we hand-code the entire tweet histories of a subset of the accounts identified as migrants by these methods. Upon close inspection very few of the accounts that are classified as migrants appear to be migrants in any conventional sense or international students. Rather we find these approaches identify other highly mobile populations such as frequent business or leisure travellers, or people who might best be described as “transnationals”. For demographic research that draws on this kind of data to generate estimates of migration flows this high mis-classification rate implies that findings are likely sensitive to the adjustment model used. For most research trying to use these data to study migrant populations, the data will be of limited utility. We suspect that increasing the correct classification rate substantially will not be easy and may introduce other biases.
Privacy preserving data visualizations
Authors: Avraam Demetris , Wilson Rebecca , Butters Oliver , Burton Thomas , Nicolaides Christos , Jones Elinor , Boyd Andy , Burton Paul 
Published: January 2021

AbstractData visualizations are a valuable tool used during both statistical analysis and the interpretation of results as they graphically reveal useful information about the structure, properties and relationships between variables, which may otherwise be concealed in tabulated data. In disciplines like medicine and the social sciences, where collected data include sensitive information about study participants, the sharing and publication of individual-level records is controlled by data protection laws and ethico-legal norms. Thus, as data visualizations – such as graphs and plots – may be linked to other released information and used to identify study participants and their personal attributes, their creation is often prohibited by the terms of data use. These restrictions are enforced to reduce the risk of breaching data subject confidentiality, however they limit analysts from displaying useful descriptive plots for their research features and findings.Here we propose the use of anonymization techniques to generate privacy-preserving visualizations that retain the statistical properties of the underlying data while still adhering to strict data disclosure rules. We demonstrate the use of (i) the well-known k-anonymization process which preserves privacy by reducing the granularity of the data using suppression and generalization, (ii) a novel deterministic approach that replaces individual-level observations with the centroids of each k nearest neighbours, and (iii) a probabilistic procedure that perturbs individual attributes with the addition of random stochastic noise. We apply the proposed methods to generate privacy-preserving data visualizations for exploratory data analysis and inferential regression plot diagnostics, and we discuss their strengths and limitations.
Targeting ACSS2 with a Transition-State Mimetic Inhibits Triple-Negative Breast Cancer Growth
Authors: Miller Katelyn D. , Pniewski Katherine , Perry Caroline E. , Papp Sara B. , Shaffer Joshua D. , Velasco-Silva Jesse N. , Casciano Jessica C. , Aramburu Tomas M. , Srikanth Yellamelli V.V. , Cassel Joel , Skordalakes Emmanuel , Kossenkov Andrew V. , Salvino Joseph M. , Schug Zachary T. 
Published: January 2021

Abstract

Acetyl-CoA is a vitally important and versatile metabolite used for many cellular processes including fatty acid synthesis, ATP production, and protein acetylation. Recent studies have shown that cancer cells upregulate acetyl-CoA synthetase 2 (ACSS2), an enzyme that converts acetate to acetyl-CoA, in response to stresses such as low nutrient availability and hypoxia. Stressed cancer cells use ACSS2 as a means to exploit acetate as an alternative nutrient source. Genetic depletion of ACSS2 in tumors inhibits the growth of a wide variety of cancers. However, there are no studies on the use of an ACSS2 inhibitor to block tumor growth. In this study, we synthesized a small-molecule inhibitor that acts as a transition-state mimetic to block ACSS2 activity in vitro and in vivo. Pharmacologic inhibition of ACSS2 as a single agent impaired breast tumor growth. Collectively, our findings suggest that targeting ACSS2 may be an effective therapeutic approach for the treatment of patients with breast cancer.

Significance:
These findings suggest that targeting acetate metabolism through ACSS2 inhibitors has the potential to safely and effectively treat a wide range of patients with cancer.
Targeting Leukemia-Initiating Cells in Acute Lymphoblastic Leukemia
Authors: Tamiro Francesco , Weng Andrew P. , Giambra Vincenzo 
Published: January 2021

Abstract
The concept that different leukemias are developmentally distinct and, like in normal hematopoiesis, generated by restricted populations of cells named leukemia-initiating cells (LIC), is becoming more established. These cancer stem-like cells have been assumed to have unique properties, including the capability of self-renewing and giving rise to “differentiated” or non-LICs that make up the whole tumor. Cell populations enriched with LIC activity have been characterized in different hematopoietic malignancies, including human acute lymphoblastic leukemia (ALL). Related studies have also demonstrated that LICs are functionally distinct from bulk cells and modulated by distinct molecular signaling pathways and epigenetic mechanisms. Here we review several biological and clinical aspects related to LICs in ALL, including (i) immunophenotypic characterization of LIC-enriched subsets in human and mouse models of ALL, (ii) emerging therapeutics against regulatory signaling pathways involved in LIC progression and maintenance in T- and B-cell leukemias, (iii) novel epigenetic and age-related mechanisms of LIC propagation, and (iv) ongoing efforts in immunotherapy to eradicate LIC-enriched cell subsets in relapsed and refractory ALL cases. Current conventional treatments do not efficiently eliminate LICs. Therefore, innovative therapeutics that exclusively target LICs hold great promise for developing an effective cure for ALL.
BRCA2, ATM, and CDK12 Defects Differentially Shape Prostate Tumor Driver Genomics and Clinical Aggression
Authors: Warner Evan , Herberts Cameron , Fu Simon , Yip Steven , Wong Amanda , Wang Gang , Ritch Elie , Murtha Andrew J. , Vandekerkhove Gillian , Fonseca Nicolette M. , Angeles Arkhjamil , Beigi Arshia , Schönlau Elena , Beja Kevin , Annala Matti , Khalaf Daniel , Chi Kim N. , Wyatt Alexander W. 
Published: January 2021

Abstract

Purpose:
DNA damage repair (DDR) defects are common across cancer types and can indicate therapeutic vulnerability. Optimal exploitation of DDR defects in prostate cancer requires new diagnostic strategies and a better understanding of associated clinical genomic features.

Experimental Design:
We performed targeted sequencing of 1,615 plasma cell-free DNA samples from 879 patients with metastatic prostate cancer. Depth-based copy-number calls and heterozygous SNP imbalance were leveraged to expose DDR-mutant allelic configuration and categorize mechanisms of biallelic loss. We used split-read structural variation analysis to characterize tumor suppressor rearrangements. Patient-matched archival primary tissue was analyzed identically.

Results:
BRCA2, ATM, and CDK12 were the most frequently disrupted DDR genes in circulating tumor DNA (ctDNA), collectively mutated in 15% of evaluable cases. Biallelic gene disruption via second somatic alteration or mutant allele–specific imbalance was identified in 79% of patients. A further 2% exhibited homozygous BRCA2 deletions. Tumor suppressors TP53, RB1, and PTEN were controlled via disruptive chromosomal rearrangements in BRCA2-defective samples, but via oncogene amplification in context of CDK12 defects. TP53 mutations were rare in cases with ATM defects. DDR mutations were re-detected across 94% of serial ctDNA samples and in all available archival primary tissues, indicating they arose prior to metastatic progression. Loss of BRCA2 and CDK12, but not ATM, was associated with poor clinical outcomes.

Conclusions:
BRCA2, ATM, and CDK12 defects are each linked to distinct prostate cancer driver genomics and aggression. The consistency of DDR status in longitudinal samples and resolution of allelic status underscores the potential for ctDNA as a diagnostic tool.
Molecular Characterization and Therapeutic Targeting of Colorectal Cancers Harboring Receptor Tyrosine Kinase Fusions
Authors: Singh Harshabad , Li Yvonne Y. , Spurr Liam F. , Shinagare Atul B. , Abhyankar Ritika , Reilly Emma , Brais Lauren K. , Nag Anwesha , Ducar Matthew D. , Thorner Aaron R. , Shapiro Geoffrey I. , Keller Rachel B. , Siletti Cheta , Clark Jeffrey W. , Farago Anna F. , Lin Jessica J. , Demetri George D. , Gujrathi Rahul , Kulke Matthew H. , MacConaill Laura E. , Ligon Azra H. , Sicinska Ewa , Meyerson Matthew L. , Meyerhardt Jeffrey A. , Cherniack Andrew D. , Wolpin Brian M. , Ng Kimmie , Giannakis Marios , Hornick Jason L. , Cleary James M. 
Published: January 2021

AbstractPurpose:Receptor tyrosine kinase fusions in colorectal cancers are rare, but potentially therapeutically relevant. We describe clinical, molecular, and pathologic attributes of RTK fusion–associated colorectal cancer.Experimental Design:We identified all cases with RTK fusions in patients with colorectal cancer seen at Dana-Farber Cancer Institute (Boston, MA) who underwent OncoPanel testing between 2013 and 2018. Clinical, histologic, and molecular features were extracted from the patient charts and molecular testing results.Results:We identified 12 driver oncogenic fusions in various RTKs. These fusions occurred exclusively in BRAF and RAS wild-type tumors and were enriched in right-sided and mismatch repair–deficient (MMR-D) colorectal cancers. All of the MMR-D colorectal cancers with RTK fusions were found in tumors with acquired MMR-D due to MLH1 promoter hypermethylation and one was associated with a sessile serrated polyp. Molecular profiles of MMR-D colorectal cancer with RTK fusions largely resembled BRAF V600E–mutated MMR-D colorectal cancer, rather than those secondary to Lynch syndrome. We describe two patients with fusion-associated microsatellite stable (MSS) colorectal cancer who derived clinical benefit from therapeutic targeting of their translocation. The first harbored an ALK-CAD fusion and received sequential crizotinib and alectinib therapy for a total of 7.5 months until developing an ALK L1196Q gatekeeper mutation. The second patient, whose tumor contained an ROS1-GOPC fusion, continues to benefit from entrectinib after 9 months of therapy.Conclusions:RTK fusions in colorectal cancer are a rare, but important disease subgroup that occurs in RAS and BRAF wild-type tumors. Despite enrichment in acquired MMR-D tumors, RTK fusions also occur in MSS colorectal cancer and provide an important therapeutic target.
The State of Melanoma: Emergent Challenges and Opportunities
Authors: Atkins Michael B. , Curiel-Lewandrowski Clara , Fisher David E. , Swetter Susan M. , Tsao Hensin , Aguirre-Ghiso Julio A. , Soengas Maria S. , Weeraratna Ashani T. , Flaherty Keith T. , Herlyn Meenhard , Sosman Jeffrey A. , Tawbi Hussein A. , Pavlick Anna C. , Cassidy Pamela B. , Chandra Sunandana , Chapman Paul B. , Daud Adil , Eroglu Zeynep , Ferris Laura K. , Fox Bernard A. , Gershenwald Jeffrey E. , Gibney Geoffrey T. , Grossman Douglas , Hanks Brent A. , Hanniford Douglas , Hernando Eva , Jeter Joanne M. , Johnson Douglas B. , Khleif Samir N. , Kirkwood John M. , Leachman Sancy A. , Mays Darren , Nelson Kelly C. , Sondak Vernon K. , Sullivan Ryan J. , Merlino Glenn 
Published: January 2021

Abstract
Five years ago, the Melanoma Research Foundation (MRF) conducted an assessment of the challenges and opportunities facing the melanoma research community and patients with melanoma. Since then, remarkable progress has been made on both the basic and clinical research fronts. However, the incidence, recurrence, and death rates for melanoma remain unacceptably high and significant challenges remain. Hence, the MRF Scientific Advisory Council and Breakthrough Consortium, a group that includes clinicians and scientists, reconvened to facilitate intensive discussions on thematic areas essential to melanoma researchers and patients alike, prevention, detection, diagnosis, metastatic dormancy and progression, response and resistance to targeted and immune-based therapy, and the clinical consequences of COVID-19 for patients with melanoma and providers. These extensive discussions helped to crystalize our understanding of the challenges and opportunities facing the broader melanoma community today. In this report, we discuss the progress made since the last MRF assessment, comment on what remains to be overcome, and offer recommendations for the best path forward.