tbuckley/cabot-search huggingface dataset:
Associations of Socioeconomic Deprivation and Preterm Birth With Speech, Language, and Communication Concerns Among Children Aged 27 to 30 Months
Authors: Daniela Ene, Geoff Der, Sue Fletcher-Watson, Sinéad O’Carroll, Graham MacKenzie, Martin Higgins, James P. Boardman
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Successful acquisition of language is foundational for health and well-being across the life course and is patterned by medical and social determinants that operate in early life. <h3>Objective</h3> To investigate the associations of neighborhood disadvantage, gestational age, and English as first language with speech, language, and communication concerns among children aged 27 to 30 months. <h3>Design, Setting, and Participants</h3> This cohort study used birth data from the National Health Service maternity electronic medical record linked to the Child Health Surveillance Programme for preschool children. The cohort included 28 634 children in the United Kingdom (NHS Lothian, Scotland) born between January 2011 and December 2014 who were eligible for a health review at age 27 to 30 months between April 2013 and April 2016. Data analysis was conducted between January 2018 and February 2019. <h3>Exposures</h3> The associations of neighborhood deprivation (using the Scottish Index of Multiple Deprivation 2016 quintiles), gestational age, and whether English was the first language spoken in the home with preschool language function were investigated using mutually adjusted logistic regression models. <h3>Main Outcomes and Measures</h3> Speech, language, and communication (SLC) concern ascertained at age 27 to 30 months. <h3>Results</h3> Records of 28 634 children (14 695 [51.3%] boys) with a mean (SD) age of 27.7 (2.2) months were matched. After excluding records with missing data, there were 26 341 records. The prevalence of SLC concern was 13.0% (3501 of 26 963 children with SLC data). In fully adjusted analyses, each 1-week increase in gestational age from 23 to 36 weeks was associated with an 8.8% decrease in the odds of a child having an SLC concern reported at 27 months (odds ratio, 0.92; 95% CI, 0.90-0.93). The odds of a child for whom English is not the first language of having SLC concern at age 27 to 30 months were 2.1-fold higher than those for a child whose first language is English (OR, 2.09; 95% CI, 1.66-2.64). The odds ratio for having an SLC concern among children living in the most deprived neighborhoods, compared with the least deprived neighborhoods, was 3.15 (95% CI, 2.79-3.56). The estimated probabilities for preterm children having an SLC concern were highest for those living in the most deprived areas. <h3>Conclusions and Relevance</h3> This study found that SLC concerns at age 27 to 30 months are common and independently associated with increasing levels of neighborhood deprivation and lower gestational age. Policies that reduce childhood deprivation could be associated with improved preschool language ability and potentially avoid propagation of disadvantage across the life course, including for children born preterm.
Abdominal Aortic Aneurysm Repair in England and the United States
Authors: Kosmas I Paraskevas, Dimitri P Mikhailidis
Journal: New England Journal of Medicine (2017)

The authors reply: The standard regimen choices in the KEYNOTE-024 trial did not include bevacizumab or nab-paclitaxel.The permitted combinations represent a standard of care in patients with advanced NSCLC worldwide.We do not believe that the addition of bevacizumab or nab-paclitaxel would affect the outcomes because of several factors.First, a very small number of patients received a paclitaxel combination (17 of 150 patients randomly assigned to chemotherapy).Second, although a carboplatin-nabpaclitaxel regimen has shown a higher rate of response than carboplatin-paclitaxel, it did not result in longer survival, even among patients with squamous-cell carcinoma (hazard ratio for death, 0.89; 95% confidence interval, 0.72 to 1.10; P = 0.28). 1 Third, the introduction of bevacizumab in combination with carboplatin-paclitaxel would have required the introduction of an additional selection factor related to the restricted eligibility criteria for bevacizumab use.Decisions regarding which contemporary standard therapies to include in lung-cancer trials have become more complex.Issues arise particularly when there are differences with regard to preferred standard therapy across the globe.In this trial, patterns of care show that pemetrexedbased therapy remains a preferred standard for non-squamous-cell histologic type NSCLC and gemcitabine-based therapy remains preferred for squamous-cell histologic type NSCLC.
Development of an “Art of Oncology” curriculum to mitigate burnout and foster solidarity among hematology/oncology fellows.
Authors: Daniel R. Richardson, Gary Winzelberg, Donald Lee Rosenstein, Frances A. Collichio
Journal: Journal of Clinical Oncology (2019)

10507 Background: Oncologists and fellows in Hematology/Oncology (HO) training programs report high levels of burnout. The ACGME requires accredited programs to have a mechanism to foster “well-being” and “ethical behavior” among fellows. A loss of solidarity among oncology professionals may contribute to known causes of burnout, such as heavy workload and severity of patient illness, that may in turn negatively impact patient outcomes. Methods: Through a multidisciplinary process involving fellows and faculty from psychiatry, palliative care, and hematology/oncology, a 3-year longitudinal “Art of Oncology” (AOO) curriculum was created for HO fellows at our institution to foster solidarity and mitigate burnout. The curriculum principally involved monthly hour-long sessions intended to promote reflection on oncologists’ shared experiences and the humanistic aspects of caring for patients with cancer. Facilitated by topic experts utilizing personal and published narratives, sessions foster group discussion. Fellows are also invited to write a personal narrative reflecting on their role as an oncologist. Topics include death and dying, caring for patients after treatment failure, cultivating resilience, religion/spirituality, the moral responsibility of oncologists, and oncology as a calling. Cancer patients and spouses were invited to facilitate a session to emphasize the patient experience. Burnout and preparedness for covered topic areas were measured prior to curriculum initiation and will be re-assessed annually. Results: The curriculum began in 2018. Of current fellows, 94.7% (18/19) completed the initial survey. A greater proportion of HO fellows participated in the AOO sessions than non-AOO didactic lectures (mean attendance, 59.2% v. 42.7%, p = 0.037). At curriculum initiation, most fellows reported burnout a few times or more a month (all fellows = 75%, 1st year = 85.7%, 2nd year = 80%, and higher = 62.5%). Conclusions: The implementation of a dedicated curriculum to foster solidarity among HO fellows through narrative medicine and group discussion of the humanistic aspects of oncology is feasible. A substantial degree of burnout exists among HO fellows, even incoming fellows. Further research to assess whether this curriculum mitigates burnout is needed. Because burnout is already a problem for incoming fellows, further work should investigate interventions aimed at ameliorating burnout among both residents and fellows.
Research in Cystic Fibrosis
Authors: Paul A. Di Sant'Agnese, Pamela B. Davis
Journal: New England Journal of Medicine (1976)

Autonomic Nervous SystemMost of the clinical features of cystic fibrosis are due to malfunction of exocrine glands, which are intimately associated with autonomic nerve fibers. Therefore, dysfunction of this system has always been an attractive explanation for this generalized exocrinopathy. However, the studies performed in the past have resulted in either negative or controversial findings.1 More recently, in 1973, a careful ultrastructure and histochemical study of autonomic nerve fibers in labial salivary glands from patients with cystic fibrosis failed to identify any differences from normal.143Conversely, experimental studies using animal models have been more fruitful. . . .
Phospholipid methylation regulates muscle metabolic rate through Ca2+ transport efficiency
Authors: Anthony R. P. Verkerke, Patrick J. Ferrara, Chien-Te Lin, Jordan M. Johnson, Terence E. Ryan, J. Alan Maschek, Hiroaki Eshima, Christopher W. Paran, Brenton T. Laing, Piyarat Siripoksup, Trevor S. Tippetts, Edward J. Wentzler, Hu Huang, Espen E. Spangenburg, Jeffrey J. Brault, Claudio J. Villanueva, Scott A. Summers, William L. Holland, James E. Cox, Dennis E. Vance, P. Darrell Neufer, Katsuhiko Funai
Journal: Nature Metabolism (2019)
REGγ controls Th17 cell differentiation and autoimmune inflammation by regulating dendritic cells
Authors: Lei Zhou, Liangfang Yao, Qing Zhang, Wei Xie, Xiaoshuang Wang, Huihui Zhang, Jinjin Xu, Qingxia Lin, Qing Li, Yang Xuan, Lei Ji, Lu Wang, Weicang Wang, Weichao Wang, Tingting Shi, Lei Fang, Biao Zheng, Lei Li, Shuang Liu, Bianhong Zhang, Xiaotao Li
Journal: Cellular and Molecular Immunology (2019)
Cell-type-specific profiling of brain mitochondria reveals functional and molecular diversity
Authors: Caroline Fecher, Laura Trovò, Stephan A. Müller, Nicolas Snaidero, Jennifer Wettmarshausen, Sylvia Heink, Oskar Ortiz, Ingrid Wagner, Ralf Kühn, Jana Hartmann, Rosa Maria Karl, Arthur Konnerth, Thomas Korn, Wolfgang Wurst, Doron Merkler, Stefan F. Lichtenthaler, Fabiana Perocchi, Thomas Misgeld
Journal: Nature Neuroscience (2019)
Serious Illness Treatment Preferences for Older Adults with Advanced CKD
Authors: Nicolas Awad Baddour, Edward D. Siew, Cassianne Robinson-Cohen, Huzaifah Salat, Olivia J. Mason, Thomas G. Stewart, Mohana Karlekar, Maie H. El-Sourady, Loren Lipworth, Khaled Abdel-Kader
Journal: Journal of the American Society of Nephrology (2019)

Significance Statement Effective advance care planning is a national priority for nephrologists. Yet, multiple barriers stymie patient–provider communication about treatment goals and patient preferences, including limited provider time and reluctance to initiate these conversations. This study examined a single-item measure eliciting patients’ treatment preference when confronted with a serious illness. This simple measure associated with two validated tools measuring health outcome priorities as well as acceptability of hypothetical end-of-life scenarios, including chronic dialysis. These results suggest that the serious illness treatment preference question is an efficient measure that can serve as an important point of entry for initiating goals-of-care communication and discussing the trade-offs of aggressive treatments ( e.g. , dialysis) with respect to patients’ overarching goals. Background Patient-centered care for older adults with CKD requires communication about patient’s values, goals of care, and treatment preferences. Eliciting this information requires tools that patients understand and that enable effective communication about their care preferences. Methods Nephrology clinic patients age ≥60 years with stage 4 or 5 nondialysis-dependent CKD selected one of four responses to the question, “If you had a serious illness, what would be important to you?” Condensed versions of the options were, “Live as long as possible;” “Try treatments, but do not suffer;” “Focus on comfort;” or “Unsure.” Patients also completed a validated health outcome prioritization tool and an instrument determining the acceptability of end-of-life scenarios. Patient responses to the three tools were compared. Results Of the 382 participants, 35% ( n =134) selected “Try treatments, but do not suffer;” 33% ( n =126) chose “Focus on comfort;” 20% ( n =75) opted for “Live as long as possible;” and 12% ( n =47) selected “Unsure.” Answers were associated with patients’ first health outcome priority and acceptability of end-of-life scenarios. One third of patients with a preference to “Focus on comfort” reported that a life on dialysis would not be worth living compared with 5% of those who chose “Live as long as possible” ( P &lt;0.001). About 90% of patients agreed to share their preferences with their providers. Conclusions Older adults with advanced CKD have diverse treatment preferences and want to share them. A single treatment preference question correlated well with longer, validated health preference tools and may provide a point of entry for discussions about patient’s treatment goals.
Risk factors for the development of epilepsy in patients with brain metastases
Authors: Fabian Wolpert, Anna Lareida, Robert Terziev, Bettina Grossenbacher, Marian C Neidert, Patrick Roth, Rositsa Poryazova, Lukas L Imbach, Emilie Le Rhun, Michael Weller
Journal: Neuro-Oncology (2019)

Abstract Background Current guidelines do not recommend primary prophylactic anti-epileptic drug (AED) therapy for patients with brain metastases (BM). Yet, subgroups of patients at high seizure risk might still benefit from prophylaxis. Methods We identified 799 patients diagnosed with BM by retrospective screening of our electronic chart system. Candidate risk factors for the development of epilepsy were tested by univariate and multivariate Cox regression models. Results Epilepsy was diagnosed in 226 of 799 patients (28%). Risk factors for epilepsy in non-operated patients were single BM (P = 0.002, hazard ratio [HR] 3.2, 95% CI: 1.5–6.6) and detection of tumoral hemorrhage (P = 0.008, HR 2.5, 95% CI: 1.3–4.9). Preoperative seizures occurred predominantly in patients with supratentorial BM (P = 0.003, HR 20.78, 95% CI: 2.8–153.4) and lung cancer (P = 0.022; HR 2.0, 95% CI: 1.1–3.6). Postoperative seizures were associated with supratentorial localization (P = 0.017, HR 5.8, 95% CI: 1.4–24.3), incomplete resection (P = 0.005, HR 4.6, 95% CI: 1.6–13.1), and by trend for multiple brain surgeries (P = 0.095, HR 1.9, 95% CI: 0.9–4.0). These risk factors were integrated into a predictive score model for postoperative epilepsy (score sum 0–8). A gradual increase of seizure rates along with higher sum score was confirmed post hoc (score 0 = no seizures; score 8 = 48% seizures). Receiver operating characteristic analysis supported diagnostic accuracy (P = 0.00001, area under the curve = 0.75). Conclusions Here we have defined risk profiles for the development of BM-related epilepsy and derived a score which might help to estimate the risk of postoperative seizures and identify individuals at risk who might benefit from primary prophylactic AED therapy.
ERCP assessment tool: evidence of validity and competency development during training
Authors: Keith Siau, Paul Dunckley, Mark Feeney, Gavin Johnson
Journal: Endoscopy (2019)

Abstract Background The endoscopic retrograde cholangiopancreatography (ERCP) direct observation of procedural skills (DOPS) is a 27-item competency assessment tool that was developed to support UK ERCP training. We evaluated validity of ERCP DOPS and competency development during training. Methods This prospective study analyzed ERCP DOPS performed in the UK between July 2016 and October 2018. Reliability was measured using Cronbach’s alpha, and DOPS scores were benchmarked using the contrasting groups method. The percentage of competent scores was averaged for each item, domain, and overall rating, and stratified by lifetime procedure count to evaluate learning curves. Multivariable analyses were performed to identify predictors of DOPS competence. Results 818 DOPS (109 trainees, 80 UK centers) were analyzed. Overall Cronbach’s alpha was 0.961. Attaining competency in 87 % of assessed DOPS items provided the optimal competency benchmark. This was achieved in the domain sequence of: pre-procedure, post-procedure management, endoscopic non-technical skills, cannulation &amp; imaging, and execution of selected therapy, and across all items after 200 – 249 procedures (89 %). After 300 procedures, the benchmark was reached for selective cannulation (89 %), but not for stenting (plastic 73 %; metal 70 %), sphincterotomy (80 %), and sphincteroplasty (56 %). On multivariable analysis, lifetime procedure count (P = 0.002), easier case difficulty (P &lt; 0.001), trainee grade (P = 0.03), and higher lifetime DOPS count (P = 0.01) were predictors of DOPS competence. Conclusion This study provides novel validity, reliability, and learning curve data for ERCP DOPS. Trainees should have a minimum of 300 hands-on ERCP procedures before undertaking summative assessment for independent practice.
High-dependency units play a key role in the treatment of a Chinese military patient who developed liver failure while abroad
Authors: Chen Li, Hai-Bin Su, Xiao-Yan Liu, Li-Na Zhang, Jin-Hua Hu
Journal: Military Medical Research (2019)

Abstract High-dependency units (HDUs) provide high-level care to patients who suffer from single organ failure, with the exception of respiratory failure requiring mechanical ventilation; HDUs serve as an intermediary between general wards and Intensive Care Units. Due to military and civilian needs, our hospital has established a unique HDU for patients with liver disease in China. A Chinese military officer in the United Nations Peacekeeping Forces in South Sudan was transferred to our HDU for liver failure treatment in 2018. The patient’s disease status, nutrition, sleep habits, and psychological behaviour were monitored on different scales. The patient was provided with vascular monitoring, telemetry, pulse oximetry, drug treatment, nutritional support, sleep intervention, psychological intervention, and humanistic care by a multidisciplinary treatment team. After treatment, the patient recovered and avoided liver transplantation. Based on the experience with this HDU, this new model may create an efficient treatment process for military and civilian patients with severe liver disease at home or abroad.
Tinkering with cognitive gadgets: Cultural evolutionary psychology meets active inference
Authors: Paul Benjamin Badcock, Axel Constant, Maxwell James Désormeau Ramstead
Journal: Behavioral and Brain Sciences (2019)

Cognitive Gadgets offers a new, convincing perspective on the origins of our distinctive cognitive faculties, coupled with a clear, innovative research program. Although we broadly endorse Heyes' ideas, we raise some concerns about her characterisation of evolutionary psychology and the relationship between biology and culture, before discussing the potential fruits of examining cognitive gadgets through the lens of active inference.
Potential role of iron in repair of inflammatory demyelinating lesions
Authors: Nathanael J. Lee, Seung-Kwon Ha, Pascal Sati, Martina Absinta, Govind Nair, Nicholas J. Luciano, Emily C. Leibovitch, Cecil C. Yen, Tracey A. Rouault, Afonso C. Silva, Steven Jacobson, Daniel S. Reich
Journal: Journal of Clinical Investigation (2019)

Inflammatory destruction of iron-rich myelin is characteristic of multiple sclerosis (MS). Although iron is needed for oligodendrocytes to produce myelin during development, its deposition has also been linked to neurodegeneration and inflammation, including in MS. We report perivascular iron deposition in multiple sclerosis lesions that was mirrored in 72 lesions from 13 marmosets with experimental autoimmune encephalomyelitis. Iron accumulated mainly inside microglia/macrophages from 6 weeks after demyelination. Consistently, expression of transferrin receptor, the brain's main iron-influx protein, increased as lesions aged. Iron was uncorrelated with inflammation and postdated initial demyelination, suggesting that iron is not directly pathogenic. Iron homeostasis was at least partially restored in remyelinated, but not persistently demyelinated, lesions. Taken together, our results suggest that iron accumulation in the weeks after inflammatory demyelination may contribute to lesion repair rather than inflammatory demyelination per se.
The Association between Supraphysiologic Arterial Oxygen Levels and Mortality in Critically Ill Patients. A Multicenter Observational Cohort Study
Authors: Edward Palmer, Benjamin Post, Roman Klapaukh, Giampiero Marra, Niall S. MacCallum, David Brealey, Ari Ercole, Andrew Jones, Simon Ashworth, Peter Watkinson, Richard Beale, Stephen J. Brett, J. Duncan Young, Claire Black, Aasiyah Rashan, Daniel Martin, Mervyn Singer, Steve Harris
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Rationale: There is conflicting evidence on harm related to exposure to supraphysiologic PaO2 (hyperoxemia) in critically ill patients.Objectives: To examine the association between longitudinal exposure to hyperoxemia and mortality in patients admitted to ICUs in five United Kingdom university hospitals.Methods: A retrospective cohort of ICU admissions between January 31, 2014, and December 31, 2018, from the National Institute of Health Research Critical Care Health Informatics Collaborative was studied. Multivariable logistic regression modeled death in ICU by exposure to hyperoxemia.Measurements and Main Results: Subsets with oxygen exposure windows of 0 to 1, 0 to 3, 0 to 5, and 0 to 7 days were evaluated, capturing 19,515, 10,525, 6,360, and 4,296 patients, respectively. Hyperoxemia dose was defined as the area between the PaO2 time curve and a boundary of 13.3 kPa (100 mm Hg) divided by the hours of potential exposure (24, 72, 120, or 168 h). An association was found between exposure to hyperoxemia and ICU mortality for exposure windows of 0 to 1 days (odds ratio [OR], 1.15; 95% compatibility interval [CI], 0.95–1.38; P = 0.15), 0 to 3 days (OR 1.35; 95% CI, 1.04–1.74; P = 0.02), 0 to 5 days (OR, 1.5; 95% CI, 1.07–2.13; P = 0.02), and 0 to 7 days (OR, 1.74; 95% CI, 1.11–2.72; P = 0.02). However, a dose–response relationship was not observed. There was no evidence to support a differential effect between hyperoxemia and either a respiratory diagnosis or mechanical ventilation.Conclusions: An association between hyperoxemia and mortality was observed in our large, unselected multicenter cohort. The absence of a dose–response relationship weakens causal interpretation. Further experimental research is warranted to elucidate this important question.
Identification of SETBP1 As an Epigenetic Hub Protein That Induces the Transcription of a Network of Development-Related Genes
Authors: Rocco Piazza, Vera Magistroni, Sara Redaelli, Mario Mauri, Luca Massimino, Alessandro Sessa, Marco Peronaci, Maciej Lalowski, Rabah Soliymani, Caterina Mezzatesta, Alessandra Pirola, Federica Banfi, Alicia Rubio, Delphine Rea, Fabio Stagno, Emilio Usala, Bruno Martino, Leonardo Campiotti, Michele Merli, Francesco Passamonti, Francesco Onida, Alessandro Morotti, Francesca Pavesi, Marco Bregni, Vania Broccoli, Marc Baumann, Carlo Gambacorti-Passerini
Journal: Blood (2017)
A neuronal circuit for activating descending modulation of neuropathic pain
Authors: Junting Huang, Vinicius M. Gadotti, Lina Chen, Ivana A. Souza, Shuo Huang, Decheng Wang, Charu Ramakrishnan, Karl Deisseroth, Zizhen Zhang, Gerald W. Zamponi
Journal: Nature Neuroscience (2019)