tbuckley/cabot-search huggingface dataset:
Erratum. Maternal BMI and Glycemia Impact the Fetal Metabolome. Diabetes Care 2017;40:902–910
Authors: William L. Lowe, James R. Bain, Michael Nodzenski, Anna C. Reisetter, Michael J. Muehlbauer, Robert D. Stevens, Olga R. Ilkayeva, Lynn P. Lowe, Boyd E. Metzger, Christopher B. Newgard, Denise M. Scholtens
Journal: Diabetes Care (2018)

In the article cited above, the authors have requested that three sentences be corrected:

1.  In the research design and methods section of the abstract, the sentence was corrected to read: “Targeted metabolic assays were performed on cord blood plasma samples from European ancestry, Afro-Caribbean, Thai, and …
PD-L1 on host cells is essential for PD-L1 blockade–mediated tumor regression
Authors: Haidong Tang, Yong Liang, Robert A. Anders, Janis M. Taube, Xiangyan Qiu, Aditi Mulgaonkar, Xin Liu, Susan M. Harrington, Jingya Guo, Yangchun Xin, Yahong Xiong, Kien Nham, William Silvers, Guiyang Hao, Xiankai Sun, Mingyi Chen, Raquibul Hannan, Jian Qiao, Haidong Dong, Hua Peng, Yang-Xin Fu
Journal: Journal of Clinical Investigation (2018)

Programmed death–ligand 1 (PD-L1) expression on tumor cells is essential for T cell impairment, and PD-L1 blockade therapy has shown unprecedented durable responses in several clinical studies. Although higher expression of PD-L1 on tumor cells is associated with a better immune response after Ab blockade, some PD-L1–negative patients also respond to this therapy. In the current study, we explored whether PD-L1 on tumor or host cells was essential for anti–PD-L1–mediated therapy in 2 different murine tumor models. Using real-time imaging in whole tumor tissues, we found that anti–PD-L1 Ab accumulates in tumor tissues, regardless of the status of PD-L1 expression on tumor cells. We further observed that, while PD-L1 on tumor cells was largely dispensable for the response to checkpoint blockade, PD-L1 in host myeloid cells was essential for this response. Additionally, PD-L1 signaling in defined antigen-presenting cells (APCs) negatively regulated and inhibited T cell activation. PD-L1 blockade inside tumors was not sufficient to mediate regression, as limiting T cell trafficking reduced the efficacy of the blockade. Together, these findings demonstrate that PD-L1 expressed in APCs, rather than on tumor cells, plays an essential role in checkpoint blockade therapy, providing an insight into the mechanisms of this therapy.
Abstract #1310: An underlying mechanism of palindromic gene amplification in cancer
Authors: Hisashi Tanaka, Stephen Tapscott, Meng-Chao Yao
Journal: Cancer Research (2009)

The clinical importance of gene amplification in cancer has been well recognized, as it is often evident in patients with an unfavorable prognosis and resistance to therapy. Thus, delineating the molecular mechanisms at the beginning of gene amplification is necessary in order to achieve early detection and prevention of gene amplification. Gene amplification occurs as a result of structural aberrations of genomic regions. A DNA double strand break (DSB) is a dangerous lesion that leads to structural aberrations. However, how a DSB is processed to a structural aberration that establishes an amplified genomic region is still largely unknown. Using an induced chromosomal DSB in mammalian cell systems, we identified that a prevalent DNA rearrangement at the beginning of gene amplification is an inverted duplication (the formation of a large DNA palindrome) that increases the copy number from one to two. Importantly, the formation of palindrome is greatly facilitated by the presence of a short DNA inverted repeat next to the site of DSB. These data indicate that a beginning step of gene amplification is a DNA rearrangement between the repeated sequences near a DSB. In order to determine whether the formation of DNA palindromes is associated with gene amplification in cancer cells, we have developed a microarray-based approach Genome-wide Analysis of Palindrome Formation (GAPF). GAPF determines the location of DNA palindromes in the genome by hybridizing snap-back DNA, a pool of DNA that is enriched in DNA derived from palindromes on a microarray. Palindromic DNA can form double-stranded DNA by intra-strand annealing after de-naturation and quick re-naturation (snap-back), whereas non-palindromic DNA remains single-stranded after snap-back. Subsequent digestion of single-stranded DNA by nuclease S1 achieves the enrichment of palindromes. Based on the genome-wide locations of DNA palindromes and copy-number gain/loss in colon cancer cells, we show (1) that the location of DNA palindromes are more likely to be amplified, and (2) that DNA palindromes determine the boundaries of a highly amplified region. Consistent with our finding in cell culture model, a pre-existing 29 kb DNA inverted repeat is located at the boundary, strongly suggesting the DNA rearrangement between the repeated sequences as the underlying mechanism of palindrome formation. Therefore, we propose three important components for the underlying mechanism of gene amplification in cancer: DNA inverted repeats pre-existing in the genome, DNA palindromes at the beginning of gene amplification and highly amplified genomic regions.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1310.
Drug-induced urticaria (DIU) and angioedema in Latin American Countries
Authors: Edgardo J. Jares, Mario Sanchez-Borges, R. Maximiliano Gomez, Carlos D. Serrano, Luis Felipe C. Ensina, Ivan Cherrez- Ojeda, Jonathan A. Bernstein, Alicia Mabel De Falco, Mabel Noemi Cuello, Blanca Maria Del Refugio Morfin Maciel, Alfredo Arias Cruz, Ricardo Cardona Villa, Sandra Nora González- Diaz, Alejandra Macias-Weinmann, Silvana Beatriz Monsell, Galie E. Mimessi, Raul Adolfo Salvatierra, Andrea Zanacchi, Luis F. Ramirez Zuluaga, Norma Susana de Barayazarra, Juan F. Schuhl, Paola A. Toche Pinaud, Susana Diez, Miguel Angel Vinuesa, Mara Morelo Rocha Felix, Ada Del Castillo Mendez
Journal: Journal of Allergy and Clinical Immunology (2018)
Soluble Siglec-8 Levels Are Detectable In Subjects With Myeloid Variant Hypereosinophilic Syndromes, But Not In Those With D816V KIT + Systemic Mastocytosis
Authors: Fanny Legrand, Yun Cao, Dean D. Metcalfe, Paneez Khoury, Bruce S. Bochner, Amy D. Klion
Journal: Journal of Allergy and Clinical Immunology (2018)
Harm Minimization and Tobacco Control: Reframing Societal Views of Nicotine Use to Rapidly Save Lives
Authors: David B. Abrams, Allison M. Glasser, Jennifer L. Pearson, Andrea C. Villanti, Lauren K. Collins, Raymond S. Niaura
Journal: Annual Review of Public Health (2018)

Inhalation of the toxic smoke produced by combusting tobacco products, primarily cigarettes, is the overwhelming cause of tobacco-related disease and death in the United States and globally. A diverse class of alternative nicotine delivery systems (ANDS) has recently been developed that do not combust tobacco and are substantially less harmful than cigarettes. ANDS have the potential to disrupt the 120-year dominance of the cigarette and challenge the field on how the tobacco pandemic could be reversed if nicotine is decoupled from lethal inhaled smoke. ANDS may provide a means to compete with, and even replace, combusted cigarette use, saving more lives more rapidly than previously possible. On the basis of the scientific evidence on ANDS, we explore benefits and harms to public health to guide practice, policy, and regulation. A reframing of societal nicotine use through the lens of harm minimization is an extraordinary opportunity to enhance the impact of tobacco control efforts.
Letter by Chen and Shen Regarding Article, “Exosomal MicroRNA Transfer Into Macrophages Mediates Cellular Postconditioning”
Authors: Weiqian Chen, Zhenya Shen
Journal: Circulation (2018)

Recently, the article "Exosomal MicroRNA Transfer Into Macrophages Mediates Cellular Postconditioning" by de Couto et al 1 was published in Circulation.Cardiosphere-derived cell (CDC)-secreted exosomes (CDC exo ) recapitulate the cardioprotective role of CDCs in acute myocardial infarction.CDC exo markedly reduce CD68 + macrophage accumulation within an infarct border zone.They further demonstrated miR-181b/PKCδ axis as a critical mediator of macrophage polarization in vitro and cardioprotection in vivo.As nano-sized membrane vesicles, exosomes mediate local or remote cell-to-cell communication by transporting mRNAs, microRNAs, and proteins. 2Exosomes can be taken up by various cell types, including macrophages, endothelial cells, and fibroblasts.Of the cell types known to produce exosomes, mesenchymal stem cells (MSCs) are considered well suited for mass production of exosomes, which are ideal for drug delivery. 3First, human MSCs are well clinically tested.Second, immortalization of permanent MSC cell lines does not compromise the quality and quantity of exosome products.Finally, MSCs-derived exosomes (MSC exo ) are therapeutic and immunosuppressive.We have demonstrated that MSC exo significantly reduce infarct size and preserve cardiac function through both inhibiting inflammation infiltration and enhancing angiogenesis in a rat model with myocardial infarction. 4Nevertheless, mechanistic studies are still required to completely understand the immunosuppressive function of MSC exo .Considering the promising clinical prospect of MSC exo , it would be interesting to figure out the following questions: (1) Do MSC exo also modulate macrophage influx and polarization during acute myocardial infarction?(2) Is MSC exo more effective in modulating macrophage polarization?(3) Does the miR-181b/PKCδ axis still mediate this process?In summary, the work of de Couto et al 1 established the role of CDC exo in cardioprotection via regulating macrophage polarization.The precise mechanisms of how MSC exo modulates macrophage polarization and a comparison of cardioprotective efficiency between MSC exo and CDC exo are certainly warranted.These studies will pave the way to develop novel exosome-based therapies for clinical treatment of myocardial infarction.
Apples and oranges: comparing residency models in the UK and North America
Authors: Eugene Y H Yeung
Journal: BMJ (2018)

Baddeley mentions medical residency training in the US1; let me elaborate. Residents in North America do rotate because each hospital has its limitations, but their placements are usually in the same city. They have a wider variety of placements (four weeks), including many off-service rotations outside their specialties. This helps residents understand other teams and how to make reasonable referrals. A UK …
Rash on extensor surfaces of a child
Authors: Lyndon Wells, Satveer Mahil
Journal: BMJ (2018)

A 2 year old boy was referred to the emergency department by his general practitioner with a non-pruritic, erythematous, papular rash on his knees (fig 1), elbows, buttocks, and face for 10 days. He had experienced a recent viral upper respiratory tract infection, but was clinically well.



Fig 1 

What is the diagnosis and with which viral infections is it associated?

### Short answer

Gianotti-Crosti, also known as “infantile papular acrodermatitis,” is associated with several viral infections, including Epstein Barr …
Long-term benefits of airway clearance in bronchiectasis: a randomised placebo-controlled trial
Authors: Gerard Muñoz, Javier de Gracia, Maria Buxó, Antonio Alvarez, Montserrat Vendrell
Journal: European Respiratory Journal (2018)

Keeping airways clear of mucus by airway clearance techniques seems essential in bronchiectasis treatment, although no placebo-controlled trials or any studies lasting longer than 3 months have been conducted. We evaluate the efficacy of the ELTGOL (slow expiration with the glottis opened in the lateral posture) technique over a 1-year period in bronchiectasis patients with chronic expectoration in a randomised placebo-controlled trial. Patients were randomised to perform the ELTGOL technique (n=22) or placebo exercises (n=22) twice-daily (ClinicalTrials.gov, NCT01578681 ). The primary outcome was sputum volume during the first intervention and 24 h later. Secondary outcomes included sputum volume during the intervention and 24 h later at month 12, exacerbations, quality of life, sputum analyses, pulmonary function, exercise capacity, systemic inflammation, treatment adherence, and side effects. Sputum volume during intervention and 24 h later was higher in the ELTGOL group than in the placebo group both at the beginning and end of the study. Patients in the ELTGOL group had fewer exacerbations (p=0.042) and a clinically significant improvement in the St George's Respiratory Questionnaire score (p&lt;0.001) and the Leicester Cough Questionnaire score compared with the placebo group (p&lt;0.001). Twice-daily ELTGOL technique over 1 year in bronchiectasis patients facilitated secretion removal and was associated with fewer exacerbations, improved quality of life, and reduced cough impact.
Cross talk between the PI3K/Akt/mTOR pathway and the androgen receptor in hormone dependent prostate cancer and its implication in the progression to androgen independence
Authors: Adam Schayowitz, Gauri Sabnis, Vincent Njar, Angela Brodie
Journal: Cancer Research (2007)

2516  Prostate cancer is the most commonly diagnosed non-skin malignancy and the second leading cause of cancer related deaths in US men. The majority of patients present with localized hormone dependent disease. Following progression or in those presenting with regional or metastatic disease, androgen ablation is often temporally successful in preventing or delaying progression of disease. However, approximately 70% of patients’ eventually progress to hormone refractory prostate cancer (HRPC). Multiple mechanisms of progression to HRPC have been proposed including mutations in the androgen receptor (AR), over-expression of AR and promiscuous activation via growth factor signaling pathways. Previously presented data demonstrates the activation of both the PI3K/Akt/mTOR and AR pathways in a hormone dependent prostate cancer model (LNCaP cells). In the current studies, we have shown that HRPC models have significantly increased activation of the mTOR pathway compared to hormone dependent LNCaP models. We have also identified a compensatory signaling mechanism and cross-talk pathway between AR and PI3K/Akt/mTOR pathway using co-immunoprecipitation of Akt and AR. Inhibition of mTOR via Rapamycin and RAD-001 resulted in decreased p-mTOR (Ser2448) and a 40% increase of AR protein expression at 1 hour in treated cell lysates. RAD-001 has similar properties to rapamycin, though it is more potent (IC50=54pM) in hormone dependent prostate cancer cells. RAD-001 also significantly increased (4 fold) androgen regulated promoter activation compared to vehicle treated controls. Competitive binding studies have shown no significant changes in binding to the AR, confirming RAD-001 does not bind to the AR and is not agonistic. Combination treatment with VN/124-1, a novel anti-androgen synthesized in our lab, and RAD-001 demonstrated significant inhibition of cell proliferation in a HRPC model. Increased activation of p-mTOR in HRPC models as well as compensatory signaling and cross-talk mechanisms between the AR and mTOR pathways in hormone dependent prostate cancer models provide compelling evidence to implicate this pathway as a mechanism in the progression to HRPC. A better understanding of the mechanisms of disease progression will allow for the development of targeted treatments that may delay, re-sensitize or prevent HRPC.
Abstract 19271: Resting and Post Exercise Serum Brain Natriuretic Peptide Levels Do Not Help Differentiate Heart Failure With Normal Ejection Fraction From Respiratory Limitation and Deconditioning in Patients Aged Over 60 Years
Authors: Sathish Kumar Parasuraman, Satnam Singh, Konstantin Schwarz, Amelia Rudd, Dana Dawson, Michael P Frenneaux
Journal: Circulation (2016)

Introduction:  Although diagnosis of HFnEF based on elevated resting LV diastolic pressure necessarily results in associated elevation in plasma BNP, several groups have shown that resting LVEDP may be a poor indicator of patients with a cardiac cause for exercise limitation, because of the profoundly dynamic nature of diastolic function on exercise, wrongly diagnosing cardiac limitation in some and missing others. We therefore evaluated the use of both resting and exercise BNP in the prediction of the cause of exercise limitation breathlessness in a community population of patients aged over 60.   Hypothesis:  Exercise BNP would better distinguish patients with normal LVEF who had a cardiac vs non cardiac cause for exercise limitation.   Methods:  We measured bedside BNP levels before exercise, at peak exercise, and 15 minutes after a maximal cardio-pulmonary exercise test (CPEX), in 70 elderly (over 60 years) breathless subjects (NYHA ≥2b) and in 42 healthy and 28 hypertensive-but otherwise healthy subjects. All had prior echocardiogram showing LVEF >50% and no significant valve disease.   Results:  The breathless subjects were classified into HFnEF, respiratory limitation and deconditioning, based on CPEX. There was no statistically significant difference in BNP levels between the three groups at rest, peak exercise and 15 minute post exercise. Furthermore, ROC curves analysis showed while BNP levels could distinguish HFnEF and healthy subjects, there was no clear distinction between the HFnEF and hypertensive groups.   Conclusion:  Resting, peak-exercise or post-exercise BNP levels do not help identify the cause of breathlessness in an elderly population with normal ejection fraction.
Diplomatic impasse prevents cardiologists from attending conference in Qatar
Authors: Anthony Harwood
Journal: BMJ (2018)

Heart experts across the Gulf are being stopped from attending an international cardiology conference because of the Saudi Arabia led blockade of Qatar.

More than 1000 of the world’s leading cardiovascular experts are gathering in Doha on 11 January for the 14th Gulf Heart Association Conference.

But at least a dozen cardiologists from Saudi Arabia, the United Arab Emirates, and Bahrain will not be joining them because of a seven month long political row.

Last June, these countries launched a diplomatic and transport blockade of Qatar, accusing the country of “cosying up” to Iran, which they claim is …
Patterns of IgE sensitization to Dermatophagoides pteronyssinus in Persistent Allergic Rhinitis from subtropical Tenerife, Spain
Authors: Fernando Pineda, Ruperto Gonzalez-Perez, Paloma Poza-Guedes, Miriam Castillo, Inmaculada Sanchez-Machin, Victor Matheu
Journal: Journal of Allergy and Clinical Immunology (2018)
Medicare Spending and Potential Savings on Brand-Name Drugs With Available Generic Substitutes Excluded by 2 Large Pharmacy Benefit Managers, 2012 Through 2015
Authors: Alexander C. Egilman, Joshua D. Wallach, Joseph S. Ross, Sanket S. Dhruva
Journal: JAMA Internal Medicine (2018)

This study uses Medicare Part D drug utilization and spending data to estimate potential Part D program and beneficiary savings on brand-name medications excluded by pharmacy benefit managers for which generic substitutes are available.
Nuclear transport of EGFR is through the integral trafficking from the endoplasmic reticulum to the nuclear envelope
Authors: Ying-Nai Wang, Hirohito Yamaguchi, Yi Du, Longfei Huo, Jung-Mao Hsu, Hongmei Wang, Mien-Chie Hung
Journal: Cancer Research (2008)

3501   Accumulating evidence indicates that endocytosis plays an essential role in the nuclear translocation of the cell surface EGF receptor (EGFR). However, the central issue of the nuclear translocation of cell surface membrane receptors is how the receptors embedded in the endosome membrane pass through the nuclear pore complex. In this report, we propose a novel mechanism by which the membrane bound form of EGFR translocates into the nucleus. Digitonin permeabilization, which selectively release out soluble nuclear transporters in the cytoplasm, has no effects on EGFR nuclear transport, suggesting that the cytoplasmic-nuclear trafficking of EGFR depends on a membrane-bound environment. Confocal microscopy revealed that in response to EGF, a portion of EGFR redistributes to the endoplasmic reticulum (ER), where its NH 2 -terminus resides within the lumen. Furthermore, EGFR forms complex with Sec61-β, which is the component of ER translocon. Knockdown of Sec61-β prevents the EGF-dependent translocation of EGFR from the nuclear envelope to the nucleus. Together, these results suggest that upon EGF treatment, the membrane-bound EGFR translocates to the ER, then move into the nucleus through the interaction with the Sec61 translocon.
Allergy to Cynodon dactylon ( Cyn d ) pollen in seasonal rhinitis, comparison between skin tests and component-resolved diagnosis (CRD) in Bahía Blanca (Argentina)
Authors: German D. Ramon, Valentina Viego, Nadia Arango, Maria A. Long, Adrian Kahn, Laura B. Barrionuevo
Journal: Journal of Allergy and Clinical Immunology (2018)
Macrophage extracellular trap formation promoted by platelet activation is a key mediator of rhabdomyolysis-induced acute kidney injury
Authors: Koshu Okubo, Miho Kurosawa, Mako Kamiya, Yasuteru Urano, Akari Suzuki, Kazuhiko Yamamoto, Koji Hase, Koichiro Homma, Junichi Sasaki, Hiroaki Miyauchi, Tatsuo Hoshino, Matsuhiko Hayashi, Tanya N Mayadas, Junichi Hirahashi
Journal: Nature Medicine (2018)
Abstract 19007: Impact of Childhood Adversities on Blood Pressure Regulation in Real Life: Results From a 23-Year Longitudinal Study Through Childhood to Young Adulthood
Authors: Shaoyong Su, Guang Hao, Frank Treiber, Gregory Harshfield, Xiaoling Wang
Journal: Circulation (2016)

Background:  Adverse environments in early life have been consistently associated with the increased risk of hypertension in later life. Recently, we have shown that exposure to adverse childhood experiences (ACEs) was associated with a faster increase of blood pressure (BP) in adulthood, measured by the casual BP. Twenty-four-hour ambulatory blood pressure (24h ABP) is considered as a better predictor of organ damage and cardiovascular events, as it can assess not only the BP levels in nighttime, but also the BP variability (BPV) in real life. How childhood adversities influence BP regulation in real life during the transition period from childhood to adulthood is not clear.   Objective:  We aim to examine the impact of ACEs on ABP levels and BPV in 24 hours, as well as in daytime and nighttime, using longitudinal data obtained from a youth cohort followed up through childhood to young adulthood.   Methods:  Twenty-four-hour ABP was measured up to 15 times over a 23-year period in 373 subjects aged 7 to 38 years old. BPV was indexed by the weighted 24h (as well as daytime and nighttime) standard deviation of ABP recordings. ACEs were assessed in three categories: childhood maltreatment (abuse or neglect), household dysfunction, and low socioeconomic status, with a summary score (0-3) indicating the level of adverse environments in early life. Individual growth curve modeling within a multilevel framework was used to examine the relation of ACE scores with 24h, daytime and nighttime ABP levels, as well as BPV.   Results:  A positive association was found between ACE scores and DBP levels in nighttime (β=0.52, p=0.02), but not in daytime (β=0.34, p=0.23). Individuals with high ACE scores also showed increased SBP variability over 24-hour period (β=0.16, p=0.001) and in daytime (β=0.18, p=0.002), but not in nighttime (β=0.06, p=0.40). There was no interaction with age, suggesting that the patterns of ACEs in relation to BP regulation in daytime and nighttime are similar through childhood to young adulthood.   Conclusion:  Using the ABP data collected over 23 years, we found that individuals exposed to ACEs showed altered BP regulation in real life, with increased BPV in daytime and remained high BP levels during nighttime, and these impacts may occur through childhood to young adulthood.