tbuckley/cabot-search huggingface dataset:
Idiopathic normal pressure hydrocephalus
Authors: Aravindhan Baheerathan, Devkishan Chauhan, Louis Koizia, Hugh O’Neal
Journal: BMJ (2016)

#### What you need to know A 74 year old man describes problems with his balance and walking for a year. His family say he is increasingly forgetful, and he has had urinary incontinence recently. He is referred to neurology, where a computed tomography (CT) scan of the brain reveals ventriculomegaly in the absence of substantial sulcal atrophy, consistent with normal pressure hydrocephalus. A triad of gait and balance impairment, cognitive impairment, and urinary incontinence characterise idiopathic normal pressure hydrocephalus. The symptoms progress insidiously over at least three months. There is ventriculomegaly without marked elevation in cerebrospinal fluid pressure. Normal pressure hydrocephalus may be secondary to alternative pathologies, for example, subarachnoid haemorrhage, meningitis, or traumatic brain injury.1 The pathogenesis of idiopathic normal pressure hydrocephalus has been widely debated but no single theory has gained widespread acceptance. #### How common is idiopathic normal pressure hydrocephalus?
1-Year Outcomes With Intracoronary Abciximab in Diabetic Patients Undergoing Primary Percutaneous Coronary Intervention
Authors: Raffaele Piccolo, Ingo Eitel, Gennaro Galasso, Alberto Dominguez-Rodriguez, Allan Zeeberg Iversen, Pedro Abreu-Gonzalez, Stephan Windecker, Holger Thiele, Federico Piscione
Journal: Journal of the American College of Cardiology (2016)
Epigenomic and metabolic responses of hypothalamic POMC neurons to gestational nicotine exposure in adult offspring
Authors: Jose P. Silva, Guerline Lambert, Derek van Booven, Claes Wahlestedt
Journal: Genome Medicine (2016)

Epidemiological and animal studies have reported that prenatal nicotine exposure (PNE) leads to obesity and type-2 diabetes in offspring. Central leptin-melanocortin signaling via hypothalamic arcuate proopiomelanocortin (POMC) neurons is crucial for the regulation of energy and glucose balance. Furthermore, hypothalamic POMC neurons were recently found to mediate the anorectic effects of nicotine through activation of acetylcholine receptors. Here, we hypothesized that PNE impairs leptin-melanocortinergic regulation of energy balance in first-generation offspring by altering expression of long non-coding RNAs (lncRNAs) putatively regulating development and/or function of hypothalamic POMC neurons. C57BL/6J females were exposed ad libitum to nicotine through drinking water and crossed with C57BL/6J males. Nicotine exposure was sustained during pregnancy and discontinued at parturition. Offspring development was monitored from birth into adulthood. From the age of 8 weeks, central leptin-melanocortin signaling, diabetes, and obesity susceptibility were assessed in male offspring fed a low-fat or high-fat diet for 16 weeks. Nicotine-exposed and non-exposed C57BL/6J females were also crossed with C57BL/6J males expressing the enhanced green fluorescent protein specifically in POMC neurons. Transgenic male offspring were subjected to laser microdissections and RNA sequencing (RNA-seq) analysis of POMC neurons for determination of nicotine-induced gene expression changes and regulatory lncRNA/protein-coding gene interactions. Contrary to expectation based on previous studies, PNE did not impair but rather enhanced leptin-melanocortinergic regulation of energy and glucose balance via POMC neurons in offspring. RNA-seq of laser microdissected POMC neurons revealed only one consistent change, upregulation of Gm15851, a lncRNA of yet unidentified function, in nicotine-exposed offspring. RNA-seq further suggested 82 cis-regulatory lncRNA/protein-coding gene interactions, 19 of which involved coding genes regulating neural development and/or function, and revealed expression of several previously unidentified metabolic, neuroendocrine, and neurodevelopment pathways in POMC neurons. PNE does not result in obesity and type 2 diabetes but instead enhances leptin-melanocortinergic feeding and body weight regulation via POMC neurons in adult offspring. PNE leads to selective upregulation of Gm15851, a lncRNA, in adult offspring POMC neurons. POMC neurons express several lncRNAs and pathways possibly regulating POMC neuronal development and/or function.
GDF11 Protects against Endothelial Injury and Reduces Atherosclerotic Lesion Formation in Apolipoprotein E-Null Mice
Authors: Wen Mei, Guangda Xiang, Yixiang Li, Huan Li, Lingwei Xiang, Junyan Lu, Lin Xiang, Jing Dong, Min Liu
Journal: Molecular Therapy (2016)

Growth differentiation factor 11 (GDF11) reduces cardiac hypertrophy, improves cerebral vasculature and enhances neurogenesis in ageing mice. Higher growth differentiation factor 11/8 (GDF11/8) is associated with lower risk of cardiovascular events in humans. Here, we showed that adeno-associated viruses-GDF11 and recombinant GDF11 protein improve endothelial dysfunction, decrease endothelial apoptosis, and reduce inflammation, consequently decrease atherosclerotic plaques area in apolipoprotein E-/- mice. Moreover, adeno-associated viruses-GDF11 and recombinant GDF11 stabilize atherosclerotic plaques by selectively decreasing in macrophages and T lymphocytes, while increasing in collagen and vascular smooth muscle cells within plaques. In addition, GDF11 inhibit palmitic acid-induced endothelial apoptosis and ameliorate palmitic acid-induced inflammatory response in RAW264.7 macrophages in vitro. Mechanistically, GDF11 activates the TGF-β/Smad2/3, AMPK/endothelial nitricoxide synthase (eNOS) while suppresses JNK and NF-κB pathways. In humans, circulating GDF11/8 is positively associated with flow-mediated endothelium-dependent dilation in overweight subjects. We concluded that adeno-associated viruses-GDF11 and recombinant GDF11 protect against endothelial injury and reduce atherosclerosis in apolipoprotein E-/- mice, thus may be providing a novel approach to the treatment of atherosclerosis.
Frontal fibrosing alopecia: there is no statistically significant association with leave-on facial skin care products and sunscreens
Authors: S.D. Seegobin, C. Tziotzios, C.M. Stefanato, K. Bhargava, D.A. Fenton, J.A. McGrath
Journal: British Journal of Dermatology (2016)

We were interested to read the article Frontal Fibrosing Alopecia - Possible Association with Leave-on Facial Skin Care Products and Sunscreens; A Questionnaire Study by Aldoori et al1. The authors sought to identify possible causative environmental factors associated with frontal fibrosing alopecia (FFA). One conclusion was that the use of facial products containing sunscreens might be implicated.

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Does Previous Transradial Catheterization Preclude Use of the Radial Artery as a Conduit in Coronary Artery Bypass Surgery?
Authors: Craig A. Mounsey, Jamie A. Mawhinney, Raphael S. Werner, David P. Taggart
Journal: Circulation (2016)

The radial artery (RA) is a commonly used conduit for coronary artery bypass grafting, and recent studies have demonstrated that it provides superior long-term patency rates to the saphenous vein in most situations. In addition, the RA is also being used with increasing frequency as the access point for coronary angiography and percutaneous coronary interventions. However, there has been concern for many years that these transradial procedures may have a detrimental impact on the function of RA grafts used in coronary artery bypass grafting, and there is now comprehensive evidence that such interventions cause morphologic and functional damage to the artery in situ. Despite this, there remain remarkably few studies investigating the use of previously cannulated RAs as grafts in coronary artery bypass surgery, and there are no clear guidelines on the use of the RA in coronary artery bypass grafting after its catheterization. This article will review concisely the evidence that transradial procedures cause damage to the RA, and discuss the impact this could have on previously cannulated RAs used as coronary artery bypass grafting conduits. On the basis of the evidence assessed, we make a number of recommendations to both surgeons and cardiologists regarding use of the RA in cardiovascular procedures.
Clonal Heterogeneityand Evolutional Paths in Multiple Myeloma Revealed By QM-FISH in Single Cell of Sequential Analysis
Authors: Xiaoqi Qin, Gang An, Yu Qin, Yan Xu, Xiaoyan Feng, Meirong Zang, Weiwei Sui, Shuhui Deng, Shuhua Yi, Wen Zhou, Lugui Qiu
Journal: Blood (2014)
Exploration of candidate biomarkers for human psoriasis based on gas chromatography-mass spectrometry serum metabolomics
Authors: H. Kang, X. Li, Q. Zhou, C. Quan, F. Xue, J. Zheng, Y. Yu
Journal: British Journal of Dermatology (2016)

Recent studies have shown that dysregulated metabolic pathways are linked to psoriasis pathogenesis. However, an extensive, unbiased metabolic analysis in patients with psoriasis has not been completely explored. The metabolome represents the end products of proteomics or cellular processes that may be closely associated with the pathogenesis of psoriasis.To determine the differences in serum metabolomic profiles among patients with psoriasis and healthy controls with the goal of identifying potential biomarkers in patients with psoriasis.Serum metabolomic profiles from 29 subjects (14 patients with psoriasis and 15 sex- and age-matched healthy controls). The serum metabolites were analysed by gas chromatography-mass spectrometry based on a combined full scan and selected-ion monitoring mode.Multivariate statistical analysis of metabolomics data revealed altered serum metabolites between the patients with psoriasis and healthy individuals. Compared with healthy individuals, patients with psoriasis had higher levels of amino acids including asparagine, aspartic acid, isoleucine, phenylalanine, ornithine and proline; higher levels of lactic acid and urea; and lower levels of crotonic acid, azelaic acid, ethanolamine and cholesterol.It appears that the glycolysis pathway and amino acid metabolic activity are increased in patients with psoriasis. These metabolic perturbations may stem from increased demand for protein biosynthesis and keratinocyte hyperproliferation. Our findings may help to elucidate the pathogenesis of psoriasis and provide insights into early diagnosis and therapeutic intervention.
Maintenance rituximab for CNS lymphoma
Authors: D. E. Ney, L. E. Abrey
Journal: Journal of Clinical Oncology (2008)

2087 Background: Maintenance therapy with rituximab is being increasingly examined in patients with indolent non-Hodgkin's lymphoma (NHL) as a means of prolonging disease control. Patients with primary central nervous system lymphoma (PCNSL) and NHL with CNS involvement are at high risk for recurrence following response to initial or salvage therapy. The use of maintenance therapy in this patient population has not been rigorously studied. Methods: Following IRB approval, charts of patients with CD20+ CNS lymphoma receiving maintenance rituximab were retrospectively reviewed for demographics, treatment details, tumor progression and survival. Maintenance rituximab was defined as delivery of regularly scheduled rituximab following a radiographic CR to treatment for CNS lymphoma. All patients received 750mg/m2 on a monthly basis for at least one year. Results: 9 patients were identified; 6 with PCNSL and 3 with CNS relapse of systemic NHL. Median age was 59 years (range, 40–76) and median KPS was 80 (range, 70–90). Mean number of prior relapses was 2 (range, 0–6). All patients remain in CNS CR and continue on maintenance rituximab with a median duration of treatment of 15.9 months (range, 6.5–37.1). Treatment was well tolerated with one instance of grade 2 neutropenia. 7 patients received maintenance rituximab after successful salvage treatment for recurrent CNS lymphoma while two patients received maintenance rituximab after successful induction for PCNSL. These two patients were maintained on rituximab secondary to high risk of recurrence after initial treatment; one patient was unable to complete standard treatment due to methotrexate (8mg/m2) related toxicity, the other was an immunosuppressed multiorgan transplant recipient with PCNSL. All patients except for one received rituximab as part of initial or salvage therapy. One PCNSL patient developed lymphoma in his fibula (disease free until 36 months) which was irradiated, but continues on maintenance rituximab with CR in the brain. Among those 7 patients treated following relapse, 6 have exceeded their prior disease free interval (time from prior CR to relapse). Conclusions: Patients with PCNSL or NHL with CNS involvement are at high risk for recurrent disease. Maintenance rituximab is well tolerated and may improve disease control in this patient population. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech™ BioOncology Genentech™ BioOncology
Phase II trial of RAD001 (R) and bicalutamide (B) for castration-resistant prostrate cancer (CPRC).
Authors: G. C. Buckle, L. Werner, W. K. Oh, G. Bubley, J. H. Hayes, D. Weckstein, A. Elfiky, D. M. Sims, P. Kantoff, M. Taplin
Journal: Journal of Clinical Oncology (2010)

4660 Background: Treatments for CRPC are limited. CRPCs have activation of the PTEN-PI3K-AKT pathway increasing mTOR expression which drives cell proliferation. We hypothesize that combining the mTOR inhibitor R with the antiandrogen B in CRPC may improve response to second-line antiandrogens. We report a phase II trial of R/B in CRPC. Methods: Patients (pts) with progressive CRPC and < 24 months (m) of prior B were treated with R/B. Treatment consisted of R 10 mg qd and B 50 mg qd. Primary endpoint was composite of prostate-specific antigen (PSA), bone and CT responses by standard criteria. This single-stage trial was designed to enroll 36 eligible patients to distinguish a 40% vs. 20% response (as expected for B alone; alpha=0.10, power=0.90). Results: 36 pts had a median age of 68y (range 60-72). Median PSA was 22.2 ng/ml (range, 8.39-121.31). 30 pts (83%) had received prior B (median duration 7 m). 32 pts (89%) had metastastic disease; of these 30 (94%) had bone disease and 14 (44%) measurable disease. Any PSA decline was noted in 16/36 pts (44%). Maximum PSA declines of >30% and >50% were seen in 6 (17%) and 4 (11%) pts respectively. Median time to progression was 8w; 2 pts continue free of progression 32+ w. 33/36 pts have discontinued treatment: 24 progressed; 1 stopped for toxicity with stable disease (SD); 1 stopped due to intercurrent illness with SD; 7 stopped for other reasons prior to progression. Of the 24 pts that progressed: 17 (71%) had PSA progression; 7 (29%) measurable disease progression; 6 (25%) non-measurable progression. All 36 pts are evaluable for safety. Majority of adverse events were grade 1-2: mucositis 50%; rash 44%; fatigue 39%; diarrhea 25%; nausea 19%; CPK 14%. Most common grade 3 toxicities were hyperglycemia (n=3), fatigue (n=2), hemoglobin (n=2), hyponatremia (n=2), pain (n=2), and anal/perianal infection (n=2). No grade 4 toxicities were noted. 13 (36%) pts stopped for physician discretion or toxicity. Conclusions: Novel methods of androgen suppression are under investigation. Androgen receptor signaling and PTEN-PI3K-AKT are co-stimulating growth pathways. R/B had low activity in CRPC possibly due to up-stream activation of AKT. Toxicity was moderate and this combination will not be pursued further. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis
Bedside assessment of the effects of positive end-expiratory pressure on lung inflation and recruitment by the helium dilution technique and electrical impedance tomography
Authors: Tommaso Mauri, Nilde Eronia, Cecilia Turrini, Marta Battistini, Giacomo Grasselli, Roberto Rona, Carlo Alberto Volta, Giacomo Bellani, Antonio Pesenti
Journal: Intensive Care Medicine (2016)
Gout and Risk of Fracture in Women: A Prospective Cohort Study
Authors: Julie M. Paik, Seoyoung C. Kim, Diane Feskanich, Hyon K. Choi, Daniel H. Solomon, Gary C. Curhan
Journal: Arthritis & Rheumatology (2016)

Objective Uric acid may be linked to bone health through its antioxidant or prooxidant effects, thereby affecting bone resorption and formation, or through its dual inhibition of vitamin D activation and parathyroid hormone production. Results of prior studies on the relationship between uric acid and bone mineral density have been conflicting. This prospective study was undertaken to examine the relationship between gout, a disease characterized by hyperuricemia and inflammation, and risk of hip or wrist fracture in women. Methods We conducted a prospective observational study of gout and risk of incident wrist and hip fracture in women participating in the Nurses’ Health Study (n = 103,799 at baseline, with 14 years of follow‐up for the wrist fracture analysis and 22 years of follow‐up for the hip fracture analysis). Gout history and incident cases of wrist and hip fracture were assessed by biennial questionnaire. Cox proportional hazards models were used to simultaneously adjust for potential confounders. Results In this cohort, there were 3,769 incident wrist fractures (1990–2004) and 2,147 incident hip fractures (1990–2012), with 107 wrist fractures and 117 hip fractures occurring in participants with gout. In those women with a history of gout compared with women without gout, the multivariable‐adjusted relative risk of wrist fracture was 1.12 (95% confidence interval [95% CI] 0.92–1.36) and the multivariable‐adjusted relative risk of hip fracture was 1.38 (95% CI 1.14–1.68). Conclusion In women, a history of gout is associated with a modestly increased risk of hip fracture, but not significantly associated with a risk of wrist fracture.
Closed-Loop Insulin Delivery during Pregnancy in Women with Type 1 Diabetes
Authors: Zoe A. Stewart, Malgorzata E. Wilinska, Sara Hartnell, Rosemary C. Temple, Gerry Rayman, Katharine P. Stanley, David Simmons, Graham R. Law, Eleanor M. Scott, Roman Hovorka, Helen R. Murphy
Journal: New England Journal of Medicine (2016)

In patients with type 1 diabetes who are not pregnant, closed-loop (automated) insulin delivery can provide better glycemic control than sensor-augmented pump therapy, but data are lacking on the efficacy, safety, and feasibility of closed-loop therapy during pregnancy.
Characterization of Fusobacterium nucleatum ATCC 23726 adhesins involved in strain-specific attachment to Porphyromonas gingivalis
Authors: Jane Park, Bhumika Shokeen, Susan K Haake, Renate Lux
Journal: International Journal of Oral Science (2016)

Bacterial adherence is an essential virulence factor in pathogenesis and infection. Fusobacterium nucleatum has a central role in oral biofilm architecture by acting as a bridge between early Gram-positive and late Gram-negative colonizers that do not otherwise adhere to each other. In this study, we survey a key adherence interaction of F. nucleatum with Porphyromonas gingivalis, and present evidence that multiple fusobacterial adhesins have a role in the attachment of F. nucleatum ATCC 23726 to P. gingivalis in a highly strain-dependent manner. Interaction between these species displayed varying sensitivities to arginine, galactose and lactose. Arginine was found to hamper coaggregation by at least 62% and up to 89% with several P. gingivalis strains and galactose inhibition ranged from no inhibition up to 58% with the same P. gingivalis strains. Lactose consistently inhibited F. nucleatum interaction with these P. gingivalis strains ranging from 40% to 56% decrease in coaggregation. Among the adhesins involved are the previously described Fap2 and surprisingly, RadD, which was described in an earlier study for its function in attachment of F. nucleatum to Gram-positive species. We also provide evidence for the presence of at least one additional adhesin that is sensitive to arginine but unlike Fap2 and RadD, is not a member of the autotransporter family type of fusobacterial large outer membrane proteins. The strain-specific binding profile of multiple fusobacterial adhesins to P. gingivalis highlights the heterogeneity and complexity of interspecies interactions in the oral cavity. Different strains of pathogenic bacteria rely on distinct interactions to anchor themselves firmly into oral 'biofilm' communities. The microbe Fusobacterium nucleatum is a major component of these densely populated bacterial societies. This species is not harmful, but can mediate recruitment of disease-causing Porphyromonas gingivalis bacteria into biofilms. Renate Lux and colleagues at the University of California at Los Angeles have demonstrated that various strains of P. gingivalis apparently latch onto different proteins on the surface of F. nucleatum. Previous studiesidentified the protein Fap2 as a binding target for P. gingivalis, but Lux and colleagues found at least one strain that relies on a different protein and found evidence for other as yet unidentified protein 'anchors'. Identifying the proteins recognized by the most virulent P. gingivalis strains could lead to therapeutics that selectively block these interactions.
The Commission on Cancer Psychosocial Distress Screening Standard: The first year in review.
Authors: Nina S. Miller, Ryan M. McCabe, Allison Knutson
Journal: Journal of Clinical Oncology (2016)

198 Background: In response to recommendations from the 2007 Institute of Medicine report, Cancer Care for the Whole Patient, the American College of Surgeons’ Commission on Cancer developed a set of Continuum of Care standards, including a patient-centered standard regarding the delivery of psychosocial distress screening to all cancer patients. According to Cancer Program Standards 2012: Ensuring Patient-Centered Care, the accredited cancer program must implement a process to integrate and monitor on-site psychosocial distress screening and referral for the provision of psychosocial care. Patients experience psychological, social, financial, and behavioral issues that can interfere with their treatment plan and adversely affect outcomes. Screening processes result in the identification of distressed cancer patients and assessment and referral pathways to ensure appropriate psychosocial care provision can be obtained. The standard was established in 2012 with a 2015 implementation period allowing programs time to develop a screening, assessment, and referral process tailored to their patient population. Methods: Programs submit documentation to describe their process for delivery of care through an electronic activity report. Documentation of this standard includes the timing for delivery of the psychosocial distress screening tool; methodology; the specific tools selected with preference to validated and reliable screening tools; and a process for assessment, referral and documentation. This presentation will summarize the program submissions for 2015 and include an analysis of the details of the standard compliance as reported by accredited programs. Results: This analysis will include responses from all Commission on Cancer accredited programs reporting on this standard. The analysis will provide information about the trends in the timing, methods, and tools used by programs implementing a psychosocial distress screening process. Conclusions: This analysis will inform future decisions about standardization of a screening process and the feasibility of pooling data across centers.