tbuckley/cabot-search huggingface dataset:
Abstract P186: Cardiovascular Outcomes Associated With Early- versus Late-onset Hypertension
Authors: Teemu Niiranen, Elizabeth McCabe, Martin Larson, Neal Lakdawala, Ramachandran Vasan, Susan Cheng
Journal: Circulation (2017)

Introduction: It is well known that hypertension confers substantial risk for developing cardiovascular disease (CVD) outcomes when present in either younger or older age. However, there are currently scant data to guide clinicians on the possible importance of distinguishing between the significance of hypertension that develops earlier versus later in life. We conducted an investigation in the original Framingham Heart Study cohort to assess the long-term CVD risks associated with developing early- versus late-onset hypertension over the adult life course. Methods: Assessment of hypertension onset was based on blood pressure (BP) data collected from serial biannual examinations performed from 1948 through 2005. We defined hypertension as BP ≥140/90 mmHg or use of antihypertensive medication on ≥2 consecutively attended examinations. We studied the relation of age-of-onset of hypertension with cause-specific mortality using a case (CVD deaths) versus control (non-CVD deaths) design. We used logistic regression to calculate case-versus-control odds ratios, adjusted for age at death, sex, smoking status, total cholesterol, and diabetes. Results: In 3614 decedents (1151 CVD deaths, including 630 coronary deaths), the odds of CVD death increased linearly with decreasing age of hypertension onset (Figure). Compared to non-hypertensives, hypertension onset at age &lt;45 conferred a 2.2-fold odds of CVD death and 2.3-fold odds of coronary death, whereas hypertension onset at age ≥65 conferred a lower-magnitude 1.5-fold odds of CVD death and 1.4-fold odds of coronary death ( P ≤.002 for differences in odds between hypertension onset at age &lt;45 and ≥65). Conclusions: Early- compared to late-onset hypertension was associated with greater odds of CVD and particularly coronary death. These findings suggest it may be important to distinguish between early- and late-onset hypertension as a specific type of BP trait when estimating risk for CVD outcomes in persons with established hypertension.
Abstract 14466: Volatile Benzene Exposure Induces Oxidative Stress, Inflammation and Insulin Resistance
Authors: Wesley Abplanalp, Daniel Conklin, Sanjay Srivastava, Aruni Bhatnagar, Timothy O'Toole
Journal: Circulation (2017)

Introduction: Benzene is a ubiquitous volatile pollutant and found in tobacco smoke, automobile exhaust, industrial emissions and all urban environments. Although benzene is well known as a leukemi...
Powder metallurgical Ti-Mg metal-metal composites facilitate osteoconduction and osseointegration for orthopedic application
Authors: Sihui Ouyang, Qianli Huang, Yong Liu, Zhengxiao Ouyang, Luxin Liang
Journal: Bioactive Materials (2018)

In this work, Ti-Mg metal-metal composites (MMCs) were successfully fabricated by spark plasma sintering (SPS). In vitro, the proliferation and differentiation of SaOS-2 cells in response to Ti-Mg metal-metal composites (MMCs) were investigated. In vivo, a rat model with femur condyle defect was employed, and Ti-Mg MMCs implants were embedded into the femur condyles. Results showed that Ti-Mg MMCs exhibited enhanced cytocompatibility to SaOS-2 cells than pure Ti. The micro-computed tomography (Micro-CT) results showed that the volume of bone trabecula was significantly more abundant around Ti-Mg implants than around Ti implants, indicating that more active new-bone formed around Ti-Mg MMCs implants. Hematoxylin-eosin (H&E) staining analysis revealed significantly greater osteointegration around Ti-Mg implants than that around Ti implants.
Inducible down-regulation of MHC class I results in natural killer cell tolerance
Authors: Michael D. Bern, Bijal A. Parikh, Liping Yang, Diana L. Beckman, Jennifer Poursine-Laurent, Wayne M. Yokoyama
Journal: The Journal of Experimental Medicine (2018)

Natural killer (NK) cells are innate lymphocytes that are thought to kill cells that down-regulate MHC class I (MHC-I) through "missing-self" recognition. NK cells from B2m-/- mice that lack surface MHC-I, however, are not autoreactive as predicted by the missing-self hypothesis. As a result, it is unclear if MHC-I down-regulation in vivo induces NK cell reactivity or tolerance to missing-self. Here, we generated a floxed B2m mouse to acutely down-regulate MHC-I in vivo in a host that normally expresses MHC-I. Global down-regulation of MHC-I induced NK cell hyporesponsiveness and tolerance to missing-self without overt missing-self reactivity. In contrast, down-regulation of MHC-I on a small fraction of hematopoietic cells triggered missing-self reactivity. Surprisingly, down-regulation of MHC-I only on CD4+ T cells predominately induced tolerance to missing-self without resetting NK cell responsiveness. In this setting, inflammation triggered substantial missing-self reactivity. These results show that MHC-I down-regulation can induce either NK cell tolerance or killing in vivo and that inflammation promotes missing-self reactivity.
Meta-theory rather than method fascism
Authors: Elke U. Weber
Journal: Behavioral and Brain Sciences (2001)

Three comments take issue with specifics of the target article. First, I argue for the development of meta-theory to deal with inconsistencies in experimental results. Second, I advocate the use of the compatibility between experiment and application to decide on the optimal design and procedure of experimental studies. Last, I support the explicit incorporation of motivation into models of decision making.
Abstract 15693: GSK-3β Mitigates Cardiac Hypertrophy by Phosphorylating Foxo1 During Pressure Overload
Authors: Yasuhiro Maejima, Narayani Nagarajan, Peiyong Zhai, Mitsuaki Isobe, Junichi Sadoshima
Journal: Circulation (2016)

Introduction: Both GSK-3β and FoxO1 negatively regulate cardiac hypertrophy. GSK-3β promotes nuclear translocation of FoxO1 and transcription of its targets by phosphorylating FoxO1 in cardiomyocytes (CMs) in vitro. Mice with knock-in of GSK-3β-S9A (S9A), a constitutively active form of GSK-3β, (β-KI) exhibit less severe cardiac hypertrophy in response to pressure overload (PO) than wild type (WT) mice. The role of FoxO1 in mediating the anti-hypertrophic effect of GSK-3β is currently unknown. Hypothesis: S9A alleviates PO-induced cardiac hypertrophy through phosphorylation of FoxO1 in vivo. Methods & Results: β-KI mice were crossed with cardiac-specific FoxO1-knockout (c-FoxO1-KO) mice. Mice were subjected to transverse aortic constriction (TAC). Cardiac hypertrophy in response to PO was significantly attenuated in β-KI mice compared to in wild type mice (WT), as indicated by LV weight (LVW) / tibial length (TL) (mg/mm, 6.8 ± 0.4 vs 7.4 ± 0.3, P < 0.05). S9A-induced suppression of cardiac hypertrophy was...
Extracellular Vesicle–Mimetic Ghost Nanovesicles for Delivering Anti‐Inflammatory Drugs to Mitigate Gram‐Negative Bacterial Outer Membrane Vesicle–Induced Systemic Inflammatory Response Syndrome
Authors: Gyeongyun Go, Jaewook Lee, Dong‐Sic Choi, Sang Soo Kim, Yong Song Gho
Journal: Advanced Healthcare Materials (2018)

Sepsis is one of the major causes of death in hospital patients and is represented by systemic inflammatory response syndrome (SIRS) associated with infection. Gram-negative bacteria including Escherichia coli can provoke sepsis by stimulating the immune systems. Outer membrane vesicles (OMVs), nanosized vesicular structures derived from Gram-negative bacteria, contain several pathogen-associated molecular patterns, and are demonstrated to mediate SIRS. Here, extracellular vesicle-mimetic ghost nanovesicles loaded with dexamethasone, an anti-inflammatory drug, are developed using alkaline solution, sonication, and buoyant density gradient ultracentrifugation. These ghost nanovesicles have comparable physical features with naturally released extracellular vesicles but have 200-fold higher production yields than extracellular vesicles. Importantly, these ghost nanovesicles are devoid of potentially unwanted luminal cargos, including cytosolic proteins and nucleic acids. By maintaining the same topology as the parental cells, these dexamethasone-loaded ghost nanovesicles derived from human U937 monocytes reduce the release of interleukin-8 from OMV-treated endothelial cells in vitro, and mitigate the symptoms of OMV-induced SIRS in vivo. This study sheds light on using extracellular vesicle-mimetic ghost nanovesicles to deliver therapeutics to treat diseases such as bacterial sepsis.
Treatment with a 5-day versus a 10-day schedule of decitabine in older patients with newly diagnosed acute myeloid leukaemia: a randomised phase 2 trial
Authors: Nicholas J Short, Hagop M Kantarjian, Sanam Loghavi, Xuelin Huang, Wei Qiao, Gautam Borthakur, Tapan M Kadia, Naval Daver, Maro Ohanian, Courtney D Dinardo, Zeev Estrov, Rashmi Kanagal-Shamanna, Abhishek Maiti, Christopher B Benton, Prithviraj Bose, Yesid Alvarado, Elias Jabbour, Steven M Kornblau, Naveen Pemmaraju, Nitin Jain, Yvonne Gasior, Mary Ann Richie, Sherry Pierce, Jorge Cortes, Marina Konopleva, Guillermo Garcia-Manero, Farhad Ravandi
Journal: The Lancet Haematology (2018)
Administration of BPX-501 Cells Following Αβ- T and B-Cell-Depleted HLA-Haploidentical HSCT in Children with Fanconi Anemia
Authors: Swati Naik, Susanne H.C. Baumeister, Victor Aquino, Annalisa Ruggeri, Daria Pagliara, Melissa Aldinger, Franco Locatelli
Journal: Blood (2018)
Maturing Clinical Profile of IMGN779, a Next-Generation CD33-Targeting Antibody-Drug Conjugate, in Patients with Relapsed or Refractory Acute Myeloid Leukemia
Authors: Jorge E. Cortes, Daniel J. DeAngelo, Harry P. Erba, Elie Traer, Nikolaos Papadantonakis, Cecilia Arana-Yi, William Blum, Callum M. Sloss, Kerry Culm-Merdek, Patrick A. Zweidler-McKay, Eunice S. Wang
Journal: Blood (2018)
Electrodissection for nevus lipomatosus cutaneous superficialis removal
Authors: Jesus Ancer-Arellano, Cesar Daniel Villarreal-Villarreal, Jesus Alberto Cardenas-de la Garza, Adrian Cuellar-Barboza, Osvaldo Vazquez-Martínez, Jorge Ocampo-Candiani
Journal: Journal of the American Academy of Dermatology (2018)
Biodegradable Gelatin Methacryloyl Microneedles for Transdermal Drug Delivery
Authors: Zhimin Luo, Wujin Sun, Jun Fang, KangJu Lee, Song Li, Zhen Gu, Mehmet R. Dokmeci, Ali Khademhosseini
Journal: Advanced Healthcare Materials (2018)

Abstract Biocompatible and bioresponsive microneedles (MNs) are emerging technology platforms for sustained drug release with a potential to be a key player in transdermal delivery of therapeutics. In this paper, an innovative biodegradable MNs patch for the sustained delivery of drugs using a polymer patch, which can adjust delivery rates based on its crosslinking degree, is reported. Gelatin methacryloyl (GelMA) is used as the base for engineering biodegradable MNs. The anticancer drug doxorubicin (DOX) is loaded into GelMA MNs using the one molding step. The GelMA MNs can efficiently penetrate the stratum corneum layer of a mouse cadaver skin. Mechanical properties and drug release behavior of the GelMA MNs can be adjusted by tuning the degree of crosslinking. The efficacy of the DOX released from the GelMA MNs is tested and the anticancer efficacy of the released drugs against melanoma cell line A375 is demonstrated. Since GelMA is a versatile material in engineering tissue scaffolds, it is expected that the GelMA MNs can be used as a platform for the delivery of various therapeutics.
Improvement of Legionnaires’ disease diagnosis using real-time PCR assay: a retrospective analysis, Italy, 2010 to 2015
Authors: Maria Luisa Ricci, Antonella Grottola, Giulia Fregni Serpini, Antonino Bella, Maria Cristina Rota, Francesca Frascaro, Emanuela Pegoraro, Marisa Meacci, Anna Fabio, Elena Vecchi, Antonietta Girolamo, Fabio Rumpianesi, Monica Pecorari, Maria Scaturro
Journal: Eurosurveillance (2018)

Aim To evaluate real-time PCR as a diagnostic method for Legionnaires’ disease (LD). Detection of Legionella DNA is among the laboratory criteria of a probable LD case, according to the European Centre for Disease Prevention and Control, although the utility and advantages, as compared to culture, are widely recognised. Methods Two independent laboratories, one using an in-house and the other a commercial real-time PCR assay, analysed 354 respiratory samples from 311 patients hospitalised with pneumonia between 2010–15. The real-time PCR reliability was compared with that of culture and urinary antigen tests (UAT). Concordance, specificity, sensitivity and positive and negative predictive values (PPV and NPV, respectively) were calculated. Results Overall PCR detected eight additional LD cases, six of which were due to Legionella pneumophila (Lp) non-serogroup 1. The two real-time PCR assays were concordant in 99.4% of the samples. Considering in-house real-time PCR as the reference method, specificity of culture and UAT was 100% and 97.9% (95% CI: 96.2–99.6), while the sensitivity was 63.6% (95%CI: 58.6–68.6) and 77.8% (95% CI: 72.9–82.7). PPV and NPV for culture were 100% and 93.7% (95% CI: 91.2-96.3). PPV and NPV for UAT were 87.5% (95% CI: 83.6-91.4) and 95.8% (95% CI: 93.5-98.2). Conclusion Regardless of the real-time PCR assay used, it was possible to diagnose LD cases with higher sensitivity than using culture or UAT. These data encourage the adoption of PCR as routine laboratory testing to diagnose LD and such methods should be eligible to define a confirmed LD case.
Independent panel calls for head of UNAIDS to be fired
Authors: Jacqui Wise
Journal: BMJ (2018)

A damning independent report has called for a change of leadership at the United Nations Joint Programme on HIV/AIDS (UNAIDS) and accused its executive director, Michel Sidibe, of creating a patriarchal culture tolerant of harassment and bullying.1

The report from an independent expert panel said that Sidibe had built up a “cult of personality” and that his senior management staff was a “boys’ club” that did not effectively prevent or properly respond to allegations of sexual harassment, bullying, and abuse of power.

It said that the failure of the leadership to meet its responsibilities was reflected in repeated examples of favouritism, preferment, and ethical blindness. The UNAIDS secretariat was in crisis, and the evidence of a broken organisational culture was overwhelming, it concluded.

> The UNAIDS secretariat was in crisis, and the evidence of a broken organisational culture was overwhelming

The report said …
SPEG Controls Calcium Reuptake Into the Sarcoplasmic Reticulum Through Regulating SERCA2a by Its Second Kinase-Domain
Authors: Chao Quan, Min Li, Qian Du, Qiaoli Chen, Hong Wang, David Campbell, Lei Fang, Bin Xue, Carol MacKintosh, Xiang Gao, Kunfu Ouyang, Hong Yu Wang, Shuai Chen
Journal: Circulation Research (2018)

SPEG (Striated muscle preferentially expressed protein kinase) has 2 kinase-domains and is critical for cardiac development and function. However, it is not clear how these 2 kinase-domains function to maintain cardiac performance.To determine the molecular functions of the 2 kinase-domains of SPEG.A proteomics approach identified SERCA2a (sarcoplasmic/endoplasmic reticulum calcium ATPase 2a) as a protein interacting with the second kinase-domain but not the first kinase-domain of SPEG. Furthermore, the second kinase-domain of SPEG could phosphorylate Thr484 on SERCA2a, promote its oligomerization and increase calcium reuptake into the sarcoplasmic/endoplasmic reticulum in culture cells and primary neonatal rat cardiomyocytes. Phosphorylation of SERCA2a by SPEG enhanced its calcium-transporting activity without affecting its ATPase activity. Depletion of Speg in neonatal rat cardiomyocytes inhibited SERCA2a-Thr484 phosphorylation and sarcoplasmic reticulum calcium reuptake. Moreover, overexpression of SERCA2aThr484Ala mutant protein also slowed sarcoplasmic reticulum calcium reuptake in neonatal rat cardiomyocytes. In contrast, domain mapping and phosphorylation analysis revealed that the first kinase-domain of SPEG interacted and phosphorylated its recently identified substrate JPH2 (junctophilin-2). An inducible heart-specific Speg knockout mouse model was generated to further study this SPEG-SERCA2a signal nexus in vivo. Inducible deletion of Speg decreased SERCA2a-Thr484 phosphorylation and its oligomerization in the heart. Importantly, inducible deletion of Speg inhibited SERCA2a calcium-transporting activity and impaired calcium reuptake into the sarcoplasmic reticulum in cardiomyocytes, which preceded morphological and functional alterations of the heart and eventually led to heart failure in adult mice.Our data demonstrate that the 2 kinase-domains of SPEG may play distinct roles to regulate cardiac function. The second kinase-domain of SPEG is a critical regulator for SERCA2a. Our findings suggest that SPEG may serve as a new target to modulate SERCA2a activation for treatment of heart diseases with impaired calcium homeostasis.
Ultrasound findings in palindromic rheumatism
Authors: Raimon Sanmarti, Julio Ramírez, Raul Castellanos-Moreira, Sonia Raquel Cabrera-Villalba, Virginia Ruiz-Esquide, Georgina Salvador
Journal: Annals of the Rheumatic Diseases (2018)

We read the article by Mankia et al on the distinct ultrasound (US) imaging phenotype in palindromic rheumatism (PR) with great interest.1 The authors found characteristic US findings in PR during flares that differ from those observed in patients with early rheumatoid arthritis (RA) or anti-cyclic citrullinated peptide (CCP)+ arthralgia. US extracapsular inflammation (periarticular inflammation, subcutaneous or peritendinous oedema), in most cases without joint synovitis, is the most frequent US finding in PR. These findings disappeared after acute attacks. The authors concluded that this imaging phenotype of extracapsular inflammation is specific for PR and may be distinguished from that observed in RA or persistent arthritis. They also suggest that true US intrasynovial inflammation may predict future RA in these patients. …
Large-scale, multiethnic genome-wide association study identifies novel loci contributing to asthma susceptibility in adults
Authors: Amber Dahlin, Joanne E. Sordillo, John Ziniti, Carlos Iribarren, Meng Lu, Scott T. Weiss, Kelan G. Tantisira, Quan Lu, Mengyuan Kan, Blanca E. Himes, Eric Jorgenson, Ann Chen Wu
Journal: Journal of Allergy and Clinical Immunology (2018)
Bronchus-associated lymphoid tissue–resident Foxp3+ T lymphocytes prevent antibody-mediated lung rejection
Authors: Wenjun Li, Jason M. Gauthier, Ryuji Higashikubo, Hsi-Min Hsiao, Satona Tanaka, Linh Vuong, Jon H. Ritter, Alice Y. Tong, Brian W. Wong, Ramsey R. Hachem, Varun Puri, Ankit Bharat, Alexander S. Krupnick, Chyi S. Hsieh, William M. Baldwin, Francine L. Kelly, Scott M. Palmer, Andrew E. Gelman, Daniel Kreisel
Journal: Journal of Clinical Investigation (2018)

Antibody-mediated rejection (AMR) is a principal cause of acute and chronic failure of lung allografts. However, mechanisms mediating this oftentimes fatal complication are poorly understood. Here, we show that Foxp3+ T cells formed aggregates in rejection-free human lung grafts and accumulated within induced bronchus-associated lymphoid tissue (BALT) of tolerant mouse lungs. Using a retransplantation model, we show that selective depletion of graft-resident Foxp3+ T lymphocytes resulted in the generation of donor-specific antibodies (DSA) and AMR, which was associated with complement deposition and destruction of airway epithelium. AMR was dependent on graft infiltration by B and T cells. Depletion of graft-resident Foxp3+ T lymphocytes resulted in prolonged interactions between B and CD4+ T cells within transplanted lungs, which was dependent on CXCR5-CXCL13. Blockade of CXCL13 as well as inhibition of the CD40 ligand and the ICOS ligand suppressed DSA production and prevented AMR. Thus, we have shown that regulatory Foxp3+ T cells residing within BALT of tolerant pulmonary allografts function to suppress B cell activation, a finding that challenges the prevailing view that regulation of humoral responses occurs peripherally. As pulmonary AMR is largely refractory to current immunosuppression, our findings provide a platform for developing therapies that target local immune responses.
New era of surgery promises safer and tailored treatments but will require new methods of learning, says report
Authors: Greta McLachlan
Journal: BMJ (2018)

Surgery is about to undergo a massive transformation, an independent review has predicted, because a wave of new technologies and better understanding of human biology will change the way all types of surgery are provided and how surgeons are trained.

These innovations will mean safer, less invasive, and more personalised treatment for patients, as well as more predictable outcomes and faster recovery, said the Future of Surgery report,1 from a commission established by the Royal College of Surgeons.

Surgical training must adapt for the future to allow surgeons to evaluate and embrace change, the report said, including distant and virtual learning.

The role of some surgeons is likely to become increasingly wide ranging and collaborative. Surgeons will need to understand the language of genetics, surgery, radiotherapy, and bioengineering, said the report, and in the future they may be the first healthcare professionals to discuss genetic analysis with patients.

The commission comprises some of the …
“Migratory” Pattern of Corticosteroid-Related Multifocal Bone Infarction on Bone Scintigraphy
Authors: Michael A. Roarke, Ba D. Nguyen, Ming Yang, Michael C. Roarke
Journal: Clinical Nuclear Medicine (2018)

We present serial bone scintigraphy examinations in a 38-year-old woman who presented with posterior left rib pain in the setting of adrenal insufficiency secondary to pituitary damage as a result of radiation treatment for orbital sarcoma.
Abstract P144: Red Meat Consumption and Risk of Nonfatal Acute Myocardial Infarction: Results From a Population-based Case-control Study in Costa Rica
Authors: Dongqing Wang, Hannia Campos, Ana Baylin
Journal: Circulation (2016)

Background: Red meat consumption has been found positively associated with cardiovascular disease (CVD) incidence and mortality in the United States and some European countries, but not in Asian countries where red meat consumption is low. The association is still unknown in Hispanic American populations which have relatively low red meat consumption but are undergoing nutrition transition towards Western dietary patterns. Objective: We aimed to estimate the association between total, processed, and unprocessed red meat consumption and nonfatal acute myocardial infarction (AMI) in the Costa Rican population. We also assessed potential mediators, effect modifiers, and the association of substituting other alternative healthy foods for red meat. Design: We recruited cases (n=1785) with a first nonfatal AMI and population-based controls (n=1785) living in Costa Rica, matched for age, sex, and area of residence. Dietary intake was assessed with a validated food frequency questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariate conditional logistic regression. Results: After adjusting for non-dietary and dietary confounders, the OR and 95% CI of nonfatal AMI was 1.12 (1.00-1.24) for 1-serving/day increase of total red meat. After further mutual adjustments between processed and unprocessed red meat, the OR and 95% CI was 1.16 (1.01-1.34) for 1-serving/day increase of processed red meat, and 1.03 (0.85-1.25) for 1-serving/day increase of unprocessed red meat. The associations were slightly modified after additionally adjusting for potential mediators including cholesterol, saturated fat, heme iron, and sodium. Substituting alternative healthier foods such as nuts, legumes, dairy, whole grains, fish, and chicken without skin or fat for red meat was associated with lower risk (ORs vary between 0.52 and 0.97). Conclusions: Increased red meat consumption as a result of the nutrition transition towards Western dietary patterns might partially explain the increased CVD rates in Costa Rica and other Hispanic American countries.