tbuckley/cabot-search huggingface dataset:
The Prognostic Significance of Translocation (1;19) in Adult Patients (Pts) with B-Cell Acute Lymphoblastic Leukemia (ALL)
Authors: Musa Yilmaz, Devendra Kc, Mary Abisola Akosile, Joseph David Khoury, Nicholas J Short, Jorge E. Cortes, Guillermo Garcia-Manero, Farhad Ravandi, Tapan Kadia, Koji Sasaki, Marina Konopleva, William G Wierda, Nitin Jain, Srdan Verstovsek, Zeev Estrov, Sherry Pierce, Susan M. O'Brien, Elias J. Jabbour, Hagop M. Kantarjian
Journal: Blood (2017)
Abstract 16024: Effect of Tadalafil on Exercise Parameters in Young Fontan Patients
Authors: Shaji C Menon, Richard V Willimas, Elizabeth Saarel, Amanda Grove, Cindy Weng, L.LuAnn Minich
Journal: Circulation (2013)

Aim: Sildenafil improves ventilatory efficiency during exercise in Fontan patients, but requires three times a day dosing. We sought to assess the effects of a long-acting phosphodiesterase-5 inhib...
Organization of Health Services
Journal: New England Journal of Medicine (1971)

In developing countries the most important preventive health measures in rural areas are health education immunization and the routine examinations of the antenatal and preschool clinics.   There are other preventive measures such as campaigns against specific diseases and legislation concerning such things as alcoholism building standards and accidents particularly burns.  Prevention and cure must be linked in rural health centers.  The biggest problem is planning these services to provide maximum human welfare from limited resources of money and skill.  Distance population finance and staff are the 4 main determinants of medical care.  Attendance at a clinic or hospital drops directly with the distance the patient must travel.  The further from home the patient is treated the greater the cost.  This is why a network of health centers dispensaries and aid posts is essential with a referral system to district hospitals for cases these outposts cannot handle.  In some areas it may pay to take the health services to the remote areas through traveling clinics.  This is because in Uganda the a verage number of outpatient attendances per person per year is cut 1/2 with every 2 miles for the hospital and the dispensary and every mile for the aid post.  In India attendance halves every 1/2 mile.  The cost and availability of various kinds of transport is a factor as well as the severity of the patients disease and the quality of care available.  The better the medicine the further people will go for it.  Population density is nearly as important a factor from the planning standpoint.  If a health center is to have an optimum output there must be sufficient people within reach of its services.  Population distribution is equally important.  A dense but uniformly distributed population will be harder to serve than a more sparse population clustered in villages.  In some instances a hospital appears to produce its own population.  A hospital that starts in a uniformly populated area may find 30 years later than within a radius of 5 miles the population is much denser than in the area beyond.  The logic of taking care to the people is shown when one calculates the costs of transport of many people to a health center plus the cost of lost wages while traveling.   In the case of a skilled Ugandan this hidden cost may be even more important than the transport cost.  Mobile services should be based on health centers must be provided by auxiliaries who must offer a wide range of skills and should be regular.  They should also take advantage of natural market gatherings.  In-patient care should be concentrated to make best use of expensive equipment.  Voluntary agencies can cooperate in these efforts.  To keep doctors in developing countries in government service it may be possible to ask the doctor to refund the amount the government spent on his education if he leaves for private practice.
Anxiety Cells in a Hippocampal-Hypothalamic Circuit
Authors: Jessica C. Jimenez, Katy Su, Alexander R. Goldberg, Victor M. Luna, Jeremy S. Biane, Gokhan Ordek, Pengcheng Zhou, Samantha K. Ong, Matthew A. Wright, Larry Zweifel, Liam Paninski, René Hen, Mazen A. Kheirbek
Journal: Neuron (2018)
Clonally expanded γδ T cells protect against Staphylococcus aureus skin reinfection
Authors: Carly A. Dillen, Bret L. Pinsker, Alina I. Marusina, Alexander A. Merleev, Orly N. Farber, Haiyun Liu, Nathan K. Archer, Da B. Lee, Yu Wang, Roger V. Ortines, Steven K. Lee, Mark C. Marchitto, Shuting S. Cai, Alyssa G. Ashbaugh, Larissa S. May, Steven M. Holland, Alexandra F. Freeman, Loren G. Miller, Michael R. Yeaman, Scott I. Simon, Joshua D. Milner, Emanual Maverakis, Lloyd S. Miller
Journal: Journal of Clinical Investigation (2018)

The mechanisms that mediate durable protection against Staphylococcus aureus skin reinfections are unclear, as recurrences are common despite high antibody titers and memory T cells. Here, we developed a mouse model of S. aureus skin reinfection to investigate protective memory responses. In contrast with WT mice, IL-1β-deficient mice exhibited poor neutrophil recruitment and bacterial clearance during primary infection that was rescued during secondary S. aureus challenge. The γδ T cells from skin-draining LNs utilized compensatory T cell-intrinsic TLR2/MyD88 signaling to mediate rescue by trafficking and producing TNF and IFN-γ, which restored neutrophil recruitment and promoted bacterial clearance. RNA-sequencing (RNA-seq) of the LNs revealed a clonotypic S. aureus-induced γδ T cell expansion with a complementarity-determining region 3 (CDR3) aa sequence identical to that of invariant Vγ5+ dendritic epidermal T cells. However, this T cell receptor γ (TRG) aa sequence of the dominant CDR3 sequence was generated from multiple gene rearrangements of TRGV5 and TRGV6, indicating clonotypic expansion. TNF- and IFN-γ-producing γδ T cells were also expanded in peripheral blood of IRAK4-deficient humans no longer predisposed to S. aureus skin infections. Thus, clonally expanded γδ T cells represent a mechanism for long-lasting immunity against recurrent S. aureus skin infections.
Response to: ‘Detection of myositis-specific antibodies’ by Vulsteke<i>et al</i>
Authors: Anna Tjärnlund, Johan Rönnelid, Matteo Bottai, Ingrid E Lundberg
Journal: Annals of the Rheumatic Diseases (2018)

It is with great interest we read the letter titled ‘Detection of myositis-specific antibodies’ by Dr Vulsteke et al 1 published in the Annals of the Rheumatic Diseases . The authors analysed the presence of myositis-specific autoantibodies in patients with idiopathic inflammatory myopathies (IIM) and in controls consisting of patients with other inflammatory conditions and blood donors. These analyses were performed using three different assays. In addition, the authors studied the association of autoantibody positivity from the different assays with specific clinical phenotypes in patients with IIM. In conclusion differences in specificities between assay manufacturers and between individual antibodies were found. The authors point to the fact that autoantibody data, namely anti-Jo-1 autoantibody positivity, were included in the 2017 European League Against Rheumatism/American …
Establishment of the nasal microbiota in the first 18 months of life: Correlation with early-onset rhinitis and wheezing
Authors: Le Duc Huy Ta, Gaik Chin Yap, Carina Jing Xuan Tay, Alicia Shi Min Lim, Chiung-Hui Huang, Collins Wenhan Chu, Paola Florez De Sessions, Lynette P. Shek, Anne Goh, Hugo P.S. Van Bever, Oon Hoe Teoh, Jian Yi Soh, Biju Thomas, Mahesh Babu Ramamurthy, Daniel Y.T. Goh, Christophe Lay, Shu-E Soh, Yiong Huak Chan, Seang-Mei Saw, Kenneth Kwek, Yap-Seng Chong, Keith M. Godfrey, Martin Lloyd Hibberd, Bee Wah Lee
Journal: Journal of Allergy and Clinical Immunology (2018)
Abstract 16623: Can We Predict Ventricular Arrhythmias in Familial Left Ventricular Non Compaction?
Authors: Riccardo Morgagni, Giovanni Battista Forleo, Francesco Romeo
Journal: Circulation (2015)

Introduction: Left Ventricular Non Compaction (LVNC) is an unclassified cardiomyopathy characterized by left ventricular hypertrabeculation and deep intertrabecular recesses in communication with the ventricular cavity. LVNC is often associated with other cardiomyopathies or with genetical disorders, and is familial at least in 25% of cases. The diagnosis is based on echocardiographic criteria (Chin et al. 1990; Jenni et al.2001; Stollberger et al. 1987-2002). Hypothesis: The aim of this study was to assess the value of echocardiographic parameters in predicting the occurrence of arrhythmic events in patients with familial LVNC. Methods: we studied 26 subjects, aged 39.9 ± 16.2 years, 11 males and 15 females, at a single institution, representing 7 families with LVNC. None had concomitant hypertension, diabetes mellitus or other significant cardiovascular disorder. Patients were evaluated at 3-month interval either clinically or with 12-Lead ECG, echocardiography and 24-hour Holter monitoring. The average duration of follow up was 36 ± 9 months. Echocardiographic parameters, ejection fraction (EF) and end-diastolic diameter (EDD), were matched with ventricular arrhythmias (VA) to assess their predictive value. The Kaplan-Meier method was used to calculate the probability of ventricular events. Results: Left Ventricular (LV) systolic function was depressed in 10 of 26 patients (38.5%), with a mean EF of 44 ± 3.2% at the first visit. Nine of 26 patients (34.6%) had LV dilatation (EDD ≥ 60 mm): among them only 5 patients (55.5%) had EF &lt; 45%. Six of 26 patients (23.1%) underwent episodes of ventricular tachycardia (VT) during follow up. All 6 patients (100%) had LV dilatation, among them only 3 patients (50%) had depressed EF. By Chi square test and Kaplan Meier analysis, the only echocardiographic predictor of VA was LV dilatation (p &lt; 0.001). Conclusions: In families with isolated LVNC, LV dilatation was the only echocardiographic predictor associated with subsequent development of ventricular arrhythmias. This finding might be helpful to optimally target preventive therapies in patients with familial LVNC.
Abstract MP74: Long Term Risk-Factor Profiles for Chronic Kidney Disease in the Framingham Heart Study
Authors: Gearoid M McMahon, Sarah R Preis, Shih-Jen Hwang, Caroline S Fox
Journal: Circulation (2013)

Background: Chronic Kidney Disease (CKD) is an important public health issue and is associated with an increased risk of cardiovascular disease. Risk factors for CKD are well established, but most are typically assessed at or near the time of CKD diagnosis. Our hypothesis was that risk factors for CKD are present earlier in the course of the disease. We compared the prevalence of risk factors between CKD cases and controls at time points up to 30 years prior to CKD diagnosis. Methods: Participants were drawn from the Framingham Heart Study Offspring cohort. CKD was defined as an estimated glomerular filtration rate of ≤60ml/min/1.73m2. Incident CKD cases occurring at examination cycles 6, 7, and 8 were age- and sex-matched 1:2 to controls. Risk factors including systolic blood pressure (SBP), hypertension, lipids, diabetes, smoking status, body mass index (BMI) and dipstick proteinuria were measured at the time of CKD diagnosis and 10, 20 and 30 years prior. Logistic regression models, adjusted for age, sex, and time period, were constructed to compare risk factor profiles at each time point between cases and controls Results: During follow-up, 441 new cases of CKD were identified and these were matched to 882 controls (mean age 69.2 years, 52.4% women). Up to 30 years prior to CKD diagnosis, those who ultimately developed CKD were more likely to have hypertension (OR 1.74, CI 1.21-2.49), be obese (OR 1.74, CI 1.15-2.63) and have higher triglycerides (OR 1.43, CI 1.12-1.84, p=0.005 per 1 standard deviation increase). Each 10mmHg increase in SBP was associated with an OR of 1.22 for future CKD (95% CI 1.10-1.35) Additionally, cases were more likely to have diabetes (OR 2.90, CI 1.59-5.29) and be on antihypertensive therapy (OR 1.65, CI 1.14-2.40, p=0.009) up to 20 years prior to diagnosis. Increasing HDLc was associated with a lower risk of CKD (OR 0.84, CI 0.81-0.97 per 10mg/dl). Conclusions: As many as 30 years prior to diagnosis, risk factors for CKD are identifiable. In particular, modifiable risk factors such as obesity, hypertension and dyslipidemia are present early in the course of the disease. These findings demonstrate the importance of early identification of risk factors in patients at risk of CKD through a life-course approach.
Paraoxonase-2 regulates coagulation activation through endothelial tissue factor
Authors: Julia Ebert, Petra Wilgenbus, John F. Teiber, Kerstin Jurk, Kathrin Schwierczek, Mareike Döhrmann, Ning Xia, Huige Li, Lisa Spiecker, Wolfram Ruf, Sven Horke
Journal: Blood (2018)
Bright Spots, physical activity investments that work: Choose to Move: scaling up a physical activity model for older adults
Authors: Heather A McKay, Lindsay Nettlefold, Christa Hoy, Adrian E Bauman, Joanie Sims-Gould
Journal: British Journal of Sports Medicine (2018)

### Programme card

#### Country/locality/coverage

#### Target population

#### What modes/types/domains of physical activity does the programme promote?

#### Which of the seven best investments does the programme address?

#### What sectors does it involve?

#### Estimated programme reach

#### What is special about this programme?

#### Key contacts

#### Programme website and Twitter handle

In Canada, there are now more older adults (≥65 years) than children (≤14 years).1 Mobility is ‘the best guarantee of retaining independence’,2 and limited mobility predicts …
Machine Learning Approaches for Clinical Psychology and Psychiatry
Authors: Dominic B. Dwyer, Peter Falkai, Nikolaos Koutsouleris
Journal: Annual Review of Clinical Psychology (2018)

Machine learning approaches for clinical psychology and psychiatry explicitly focus on learning statistical functions from multidimensional data sets to make generalizable predictions about individuals. The goal of this review is to provide an accessible understanding of why this approach is important for future practice given its potential to augment decisions associated with the diagnosis, prognosis, and treatment of people suffering from mental illness using clinical and biological data. To this end, the limitations of current statistical paradigms in mental health research are critiqued, and an introduction is provided to critical machine learning methods used in clinical studies. A selective literature review is then presented aiming to reinforce the usefulness of machine learning methods and provide evidence of their potential. In the context of promising initial results, the current limitations of machine learning approaches are addressed, and considerations for future clinical translation are outlined.
Avenues to molecular imaging of dying cells: Focus on cancer
Authors: Anna A. Rybczynska, Hendrikus H. Boersma, Steven de Jong, Jourik A. Gietema, Walter Noordzij, Rudi A. J. O. Dierckx, Philip H. Elsinga, Aren van Waarde
Journal: Medicinal Research Reviews (2018)

Abstract Successful treatment of cancer patients requires balancing of the dose, timing, and type of therapeutic regimen. Detection of increased cell death may serve as a predictor of the eventual therapeutic success. Imaging of cell death may thus lead to early identification of treatment responders and nonresponders, and to “patient‐tailored therapy.” Cell death in organs and tissues of the human body can be visualized, using positron emission tomography or single‐photon emission computed tomography, although unsolved problems remain concerning target selection, tracer pharmacokinetics, target‐to‐nontarget ratio, and spatial and temporal resolution of the scans. Phosphatidylserine exposure by dying cells has been the most extensively studied imaging target. However, visualization of this process with radiolabeled Annexin A5 has not become routine in the clinical setting. Classification of death modes is no longer based only on cell morphology but also on biochemistry, and apoptosis is no longer found to be the preponderant mechanism of cell death after antitumor therapy, as was earlier believed. These conceptual changes have affected radiochemical efforts. Novel probes targeting changes in membrane permeability, cytoplasmic pH, mitochondrial membrane potential, or caspase activation have recently been explored. In this review, we discuss molecular changes in tumors which can be targeted to visualize cell death and we propose promising biomarkers for future exploration.
Translational Implications of Platelets as Vascular First Responders
Authors: Richard C. Becker, Travis Sexton, Susan S. Smyth
Journal: Circulation Research (2018)

Platelets play a vital role in normal hemostasis to stem blood loss at sites of vascular injury by tethering and adhering to sites of injury, recruiting other platelets and blood cells to the developing clot, releasing vasoactive small molecules and proteins, and assembling and activating plasma coagulation proteins in a tightly regulated temporal and spatial manner. In synchrony with specific end products of coagulation, primarily cross-linked fibrin, a stable thrombus quickly forms. Far beyond physiological hemostasis and pathological thrombosis, emerging evidence supports platelets playing a pivotal role in vascular homeostasis, inflammation, cellular repair, regeneration, and wide range of autocrine and paracrine functions. In essence, platelets play both structural and functional roles as reporters, messengers, and active transporters surveying the vasculature for cues of environmental or developmental stimuli and participating as first responders.
Retrograde Signaling from Progranulin to Sort1 Counteracts Synapse Elimination in the Developing Cerebellum
Authors: Naofumi Uesaka, Manabu Abe, Kohtarou Konno, Maya Yamazaki, Kazuto Sakoori, Takaki Watanabe, Tzu-Huei Kao, Takayasu Mikuni, Masahiko Watanabe, Kenji Sakimura, Masanobu Kano
Journal: Neuron (2018)
Additional comment to: ‘Switching from the bio-originators to biosimilar: is it premature to recommend this procedure?’ by Scherlinger and Schaeverbeke
Authors: Fabrizio Cantini, Maurizio Benucci
Journal: Annals of the Rheumatic Diseases (2018)

We are grateful to Scherlinger and Schaeverbeke for their reply to our letter.1

We would like to remind that in our letter we raised several concerns regarding the low grade of evidence supporting recommendation 6 on the switching procedure, as reported in the recently published recommendations for the use of biosimilars in rheumatology practice.2 3 We believe that international recommendations should be based on solid bases, and, as underlined in our letter, by analysis of the existing literature, the evidence of such strategy in terms of efficacy, safety, retention rate and also economic advantages is poor. In particular, the colleagues focus their remarks on reduced bio-etanercept …
Paediatrician convicted of manslaughter must be erased from register, rules High Court
Authors: Clare Dyer
Journal: BMJ (2018)

A trainee paediatrician who was convicted of gross negligence manslaughter over the death of a 6 year old boy must be struck off the UK medical register to maintain public confidence in the profession, the High Court has ruled.1

A medical practitioners tribunal decided in June 2017 to suspend Hadiza Bawa-Garba for 12 months rather than erase her from the register, after taking account of system failures that contributed to Jack Adcock’s death.2

But two senior judges have substituted the sanction of erasure, after the General Medical Council appealed against the tribunal’s decision.

Mr Justice Ouseley, giving the leading judgment, said, “I have come firmly to the conclusion that the decision of the tribunal …
Strategic application of radiotherapy for hepatocellular carcinoma
Authors: Seo Hee Choi, Jinsil Seong
Journal: Clinical and Molecular Hepatology (2018)

With increasing clinical use, radiotherapy (RT) has been considered reliable and effective method for hepatocellular carcinoma (HCC) treatment, depending on extent of disease and patient characteristics. RT for HCC can improve therapeutic outcomes through excellent local control, downstaging, conversion from unresectable to resectable status, and treatments of unresectable HCCs with vessel invasion or multiple intrahepatic metastases. In addition, further development of modern RT technologies, including image-guided radiotherapy (IGRT), intensity-modulated radiotherapy (IMRT), and stereotactic body radiotherapy, has expanded the indication of RT. An essential feature of IGRT is that it allows image guidance therapy through in-room images obtained during radiation delivery. Compared with 3D-conformal RT, distinctions of IMRT are inverse treatment planning process and use of a large number of treatment fields or subfields, which provide high precision and exquisitely conformal dose distribution. These modern RT techniques allow more precise treatment by reducing inter- and intra-fractional errors resulting from daily changes and irradiated dose at surrounding normal tissues. More recently, particle therapy has been actively investigated to improve effectiveness of RT. This review discusses modern RT strategies for HCC, as well as optimal selection of RT in multimodal approach for HCC.
Transcriptional Profiles, Lineage Tracing with BRAF-V600E and HLA-DQB2 Expression Support a Model of Blood CD1c+ Cells As Precursors to LCH Lesion CD207+ Cells
Authors: Karen Phaik Har Lim, Paul Milne, Michael Poidinger, Kaibo Duan, Howard Lin, Harshal Abhyankar, Daniel Zinn, Olive S. Eckstein, Rikhia Chakraborty, Evan Newell, Miriam Merad, Kenneth L. McClain, Chris Tsz-Kwong Man, Florent Ginhoux, Matthew P. Collin, Carl E. Allen
Journal: Blood (2017)
Little Evidence for Usefulness of Biomarkers for Predicting Successful Dose Reduction or Discontinuation of a Biologic Agent in Rheumatoid Arthritis: A Systematic Review
Authors: Lieke Tweehuysen, Cornelia H. van den Ende, Fenna M. M. Beeren, Evelien M. J. Been, Frank H. J. van den Hoogen, Alfons A. den Broeder
Journal: Arthritis & Rheumatology (2016)

Objective To systematically review studies addressing prediction of successful dose reduction or discontinuation of a biologic agent in rheumatoid arthritis (RA). Methods PubMed, Embase, and Cochrane Library databases were searched for studies that examined the predictive value of biomarkers for successful dose reduction or discontinuation of a biologic agent in RA. Two reviewers independently selected studies, and extracted data and assessed the risk of bias. A biomarker was classified as a “potential predictor” if the univariate association was either strong (odds ratio or hazard ratio &gt;2.0 or &lt;0.5) or statistically significant. For biomarkers that were studied multiple times, qualitative best‐evidence synthesis was performed separately for the prediction of successful dose reduction and discontinuation. Biomarkers that were defined in ≥75% of the studies as potential predictors were regarded as “predictor” for the purposes of our study. Results Of 3,029 nonduplicate articles initially searched, 16 articles regarding 15 cohorts were included in the present study. Overall, 17 biomarkers were studied multiple times for the prediction of successful dose reduction, and 33 for the prediction of successful discontinuation of a biologic agent. Three predictors were identified: higher adalimumab trough level for successful dose reduction and lower Sharp/van der Heijde erosion score and shorter symptom duration at the start of a biologic agent for successful discontinuation. Conclusion The predictive value of a wide variety of biomarkers for successful dose reduction or discontinuation of biologic treatment in RA has been investigated. We identified only 3 biomarkers as predictors, in just 2 studies. The strength of the evidence is limited by the low quality of the included studies and the likelihood of reporting bias and multiple testing.