tbuckley/cabot-search huggingface dataset:
Low-Dose Combination Blood Pressure Pharmacotherapy to Improve Treatment Effectiveness, Safety, and Efficiency
Authors: Mark D. Huffman, Gbenga Ogedegbe, Marc Jaffe
Journal: JAMA (2018)

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Abstract 15758: Relationship Between Physiological Coronary Artery Stenosis Severity Assessed by Fractional Flow Reserve and Optical Coherence Tomography Findings in Stable Angina Pectoris
Authors: Tetsumin Lee, Tadashi Murai, Yoshihisa Kanaji, Eisuke Usui, Makoto Araki, Takayuki Niida, Sadamitsu Ichijo, Tsunekazu Kakuta
Journal: Circulation (2015)

Backgrounds: The aim of the present study is to investigate the relationship between physiological coronary artery stenosis severity and lesion instability by Optical Coherence Tomography (OCT) in patients with stable angina pectoris (SAP). Methods and Results: We investigated 198 culprit lesions of 180 SAP patients who underwent OCT imaging and fractional flow reserve (FFR) measurement before PCI procedure. Physiological coronary stenosis severity was assessed by FFR analysis, and lesions were divided into two groups on the basis of FFR values; severe stenosis group (group S): FFR &lt;0.75 (n=78, 39%), moderate stenosis group (group M): FFR ≥0.75 (n=120, 61%) according to the previous study. Thin-capped fibroatheroma (TCFA) was defined as lipid-rich plaque (lipid arc ≥90°) with fibrous cap thickness &lt;70μm. The median FFR values in total lesions, group S, and group M were 0.77 (interquartile range [IQR]: 0.69—0.83), 0.65 (0.57—0.72), and 0.81 (0.78—0.87), respectively. There were no significant differences in patient characteristics expect for the frequency of previous myocardial infarction (S: 15%, M: 38%, P &lt;0.01) and previous PCI (S: 29%, M: 60%, P &lt;0.01). In angiographic analysis, there were significant differences in the frequency of culprit lesion location in LAD (S: 72%, M: 49%, P &lt;0.01), minimum lumen diameter (S: 1.07±0.36 mm, M: 1.35±0.32 mm, P &lt;0.01), % diameter stenosis (S: 58.9 % [53.1—70.8], M: 52.8 % [47.7—57.5], P &lt;0.01), and lesion length (S: 13.7 mm [10.6—17.5], M: 11.5 mm [9.2—14.5], P = 0.02) between the two groups. In OCT analysis, there were significant differences in the lipid arc (S: 200° [160—232], M: 168° [143—211], P &lt;0.01), CT (S: 110 μm [63—157], M: 140 μm [93—197], P &lt;0.01), and frequency of TCFA (S: 27%, M: 9%, P &lt;0.01) between the two groups. Subgroup analysis of LAD lesions showed similar results between the two groups. Conclusions: Lesions of physiologically severe coronary stenosis in SAP were associated with lesion instability assessed by OCT. These findings may challenge the concept that lesions responsible for acute coronary syndromes are mild in most cases provided that plaque rupture of TCFA evenly results in coronary events in the wide range of stenosis severity in patients with SAP.
Participation of Oxygen in the Local Control of Skeletal Muscle Microvasculature
Authors: PHILLIP M. HUTCHINS, ROBERT F. BOND, HAROLD D. GREEN
Journal: Circulation Research (1974)

The control of the local supply of oxygen to a skeletal muscle vascular bed was analyzed by: (1) determining if a relative oxygen lack causes vascular dilation, (2) ascertaining the vascular elements responsible for the dilation, and (3) attempting to elucidate the mechanism of the dilation. When the concentration of oxygen in the inspiratory air was reduced from that in room air to 18% without increasing the carbon dioxide concentration or inducing a fall in systemic arterial blood pressure, a dilation significant at the 5% level was observed in the terminal arterioles, the metarterioles, and the distribution arterioles of the cremaster muscle of the rat; all of these vessels were oriented transversely to the skeletal muscle fibers and had diameters of less than 40µ. The magnitude of the dilation, expressed as a percent of the control diameter, was inversely related to the vessel's average control diameter. No significant dilation was noted in the precapillary sphincters or the major arterioles with control diameters greater than 40µ. Intra-arterial injections of sodium cyanide produced responses that paralleled in relative magnitude those observed in similar vessels during hypoxia. The microcirculatory adjustments to mild systemic hypoxia were not altered by pharmacological blockade of sympathetic ganglia or α, β, γ, or histaminergic receptors.
Associations Between Oral Health Status and Diabetic Neuropathy in a Large Romanian Cohort of Patients With Diabetes
Authors: Anca Jivanescu, Cosmina I. Bondor, Rodica Pop-Busui, Ioan A. Veresiu, Diana I. Sima, Daniel-Tudor Cosma, Bogdan Florea, Norina A. Gavan
Journal: Diabetes Care (2018)

Diabetic neuropathy (DN) and periodontal disease (PD) (gingivitis/periodontitis) are two serious chronic complications of diabetes with shared pathogenetic mechanisms (1,2). This cross-sectional study evaluated the association between DN and self-reported oral health (OH) status in a large cohort of Romanian patients with diabetes initially phenotyped in 2012 (3). Among these, patients who agreed to participate were included in the follow-up. The protocol was approved by the Ethics Committee for Scientific Research of the “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania.

OH was assessed using a three-item self-reported questionnaire that included the following questions: “Do you have complete dentures?” (yes/no), “In the last 6 months, how often have you experienced gingival pain?” (never/rarely/often/very often), and “In the last 6 months, how often have you experienced gingival bleeding?” (never/rarely/often/very often). OH was defined as good (no symptoms), average (experienced symptoms rarely), poor (experienced symptoms often/very often), or very poor (complete dentures).

DN was assessed by trained diabetologists using the Michigan Neuropathy Screening Instrument (MNSI), comprising a questionnaire (MNSIq) and a clinical examination (MNSIe) (4,5). Clinical DN was defined as an MNSIe score of ≥2.5; symptomatic DN was defined as an MNSIq score of ≥4, or ≥2 for the reduced version of MNSIq (MNSIq4) (5).

Proportions of different OH categories in patients with and without DN were compared using the χ …
Novel KCNJ2 Mutation in Familial Periodic Paralysis With Ventricular Dysrhythmia
Authors: TomohikoAi, YuichiroFujiwara, KeikoTsuji, HideoOtani, ShozoNakano, YoshihiroKubo, MinoruHorie
Journal: Circulation (2002)

Background— Mutations in the KCNJ2 gene, which codes cardiac and skeletal inward rectifying K+ channels (Kir2.1), produce Andersen’s syndrome, which is characterized by periodic paralysis, cardiac arrhythmia, and dysmorphic features. Methods and Results— In 3 Japanese family members with periodic paralysis, ventricular arrhythmias, and marked QT prolongation, polymerase chain reaction/single-strand conformation polymorphism/DNA sequencing identified a novel, heterozygous, missense mutation in KCNJ2, Thr192Ala (T192A), which was located in the putative cytoplasmic chain after the second transmembrane region M2. Using the Xenopus oocyte expression system, we found that the T192A mutant was nonfunctional in the homomeric condition. Coinjection with the wild-type gene reduced the current amplitude, showing a weak dominant-negative effect. Conclusions— T192, which is located in the phosphatidylinositol-4,5-bisphosphate binding site and also the region necessary for Kir2.1 multimerization, is a highly conserved...
Plans to allow trusts to investigate patient safety incidents would “create mayhem”
Authors: Clare Dyer
Journal: BMJ (2018)

Controversial plans to accredit NHS trusts to use “safe spaces” to carry out investigations into patient safety incidents should be dropped from a government draft bill, a joint committee of MPs and peers has urged.1

Experts said that the plans would deny patients justice, “create mayhem,” and be “wholly misconceived.”

The draft Health Service Safety Investigations Bill sets up an independent body for England, with procedures modelled on the aircraft industry. The Health Service Safety Investigations Body (HSSIB) would create a safe space for its inquiries, giving staff the confidence to speak freely in the knowledge that the evidence it gathers is kept confidential. …
Aptamer-functionalized nanoscale metal-organic frameworks for targeted photodynamic therapy
Authors: Hong-Min Meng, Xiao-Xiao Hu, Ge-Zhi Kong, Chan Yang, Ting Fu, Zhao-Hui Li, Xiao-Bing Zhang
Journal: Theranostics (2018)

Photodynamic therapy (PDT) has been applied in clinical cancer treatment. Here we report an aptamer-functionalized nanoscale metal-organic framework for targeted PDT. Our nanosystem can be easily prepared and successfully used for targeted PDT with a significantly enhanced therapeutic efficacy in vitro and in vivo. Methods: By combining the strong binding ability between phosphate-terminated aptamers and Zr-based nanoscale metal-organic frameworks (Zr-NMOFs) and the intercalation of photosensitizer TMPyP4 within the G-quadruplex DNA structure, TMPyP4-G4-aptamer-NMOFs were prepared. The characteristics and photodynamic performance of TMPyP4-G4-aptamer-NMOFs were examined after preparation. Then, we studied their stability, specific recognition ability, and phototoxicity in vitro. For in vivo experiments, the nanosystem was intratumorally injected into a HeLa subcutaneous xenograft tumor mouse model. After irradiation on day 0, mice were further injected with the nanosystem on day 5 and were again subjected to laser irradiation for 30 min. Tumor volumes and body weights of all mice were measured by caliper every 2 days after the treatment. Results: The nanosystem induced 90% cell death of targeted cells. In contrast, the control cells maintained about 40% cell viability at the same concentration of nanosystem. For the in vivo experiments, the nanosystem-treated group maintained more than 76% inhibition within the entire experimental period. Conclusion: We have demonstrated that our smart TMPyP4-G4-sgc8-NMOFs nanosystem can be used for targeted cancer therapy with high efficiency.
Abstract P068: Obstructive Sleep Apnea is Associated with an Increase Risk of Osteoporosis
Authors: AnawinSanguankeo, SikarinUpala
Journal: Circulation (2015)

Background: Obstructive sleep apnea (OSA) is thought to be a systemic disease and has been associated with many disorders such as metabolic, endocrine, and especially cardiovascular diseases. One of the consequences of OSA is hypoxia, which can lead to a reduction in growth of osteoblast and a stimulation of osteoclast. Our meta-analysis was conducted to determine the risk of osteoporosis in patients with OSA compared to controls. Objectives: Eligible studies assessing the effects of obstructive sleep apnea on osteoporosis risk were comprehensively searched in PubMed/MEDLINE, EMBASE, and CENTRAL from their inception to September 2014. Two authors independently assessed article quality and extracted the data. Primary outcome were number of participants, prevalence, or risk ratio of osteoporosis in OSA and controls. Results: From 40 full-text articles, 3 studies involving 113,090 participants were included in the meta-analysis that were based on the random effects model. Compared with controls, participants...
Inhibition of Progression and Stabilization of Plaques by Postnatal Interferon-γ Function Blocking in ApoE-Knockout Mice
Authors: MitsuhisaKoga, HisashiKai, HideoYasukawa, TomokaYamamoto, YumikoKawai, SeiyaKato, KenKusaba, MamikoKai, KensukeEgashira, YasufumiKataoka, TsutomuImaizumi
Journal: Circulation Research (2007)

A role of interferon-γ is suggested in early development of atherosclerosis. However, the role of interferon-γ in progression and destabilization of advanced atherosclerotic plaques remains unknown. Thus, the aim of this study was to determine whether postnatal inhibition of interferon-γ signaling could inhibit progression of atherosclerotic plaques and stabilize the lipid- and macrophage-rich advanced plaques. Atherosclerotic plaques were induced in ApoE-knockout (KO) mice by feeding high-fat diet from 8 weeks old (w). Interferon-γ function was postnatally inhibited by repeated gene transfers of a soluble mutant of interferon-γ receptors (sIFNγR), an interferon-γ inhibitory protein, into the thigh muscle every 2 weeks. When sIFNγR treatment was started at 12 w (atherosclerotic stage), sIFNγR not only prevented plaque progression but also stabilized advanced plaques at 16 w: sIFNγR decreased accumulations of the lipid and macrophages and increased fibrotic area with more smooth muscle cells. Moreover, sIF...
Abstract 1126: Exploring the roles of Suppressor of Fused in the postnatal neurogenic niche and tumorigenesis
Authors: Jesse Garcia Castillo, Hector G. Gomez, David Aguilar, Samuel J. Pleasure, Odessa Yabut
Journal: Cancer Research (2018)

Abstract Isolated brain tumors consist of cells with stem cell features and a tissue microenvironment similar to the neurogenic niche, implying that tumors must require the same niche factors for tumor growth and progression. Thus, a better understanding of how neural stem cell (NSC) behavior is regulated can have significant therapeutic implications in brain cancers. To this end, we examined the roles of Suppressor of Fused (Sufu) in the postnatal neurogenic niche of the forebrain, the ventricular-subventricular zone (V-SVZ), a potential site of origin for forebrain tumors. Given that recent studies showed low expression of Sufu in gliomas, we wondered how conditional deletion of Sufu using the hGFAP-Cre driver (hGFAP-cre/+;Sufu-fl/fl) influences NSC behavior in the V-SVZ. We found that Sufu critically controls NSC proliferation, since loss of Sufu in the hGFAP-cre/+;Sufu-fl/fl mice resulted in abnormal expansion of the V-SVZ. These defects were due to the increased production of DCX+ Type A cells at the expense of transit amplifying Type C and oligodendrocyte precursor cells. Furthermore, many of these cells failed to migrate out of the V-SVZ, where they remained and continued to proliferate. Nevertheless, an increase in apoptotic cells was observed, which likely prevented the formation of brain tumors from loss of Sufu function alone. Indeed, our preliminary studies showed that the combined deletion of Sufu and the tumor suppressor p53 (hGFAP-Cre/+;Sufu-fl/fl;p53-fl/fl) resulted in a more severe and sustained cell expansion phenotype in the V-SVZ. We predict that these genetic conditions predispose NSCs within the V-SVZ to form tumors at later postnatal stages. We are now investigating this and the molecular mechanisms by which Sufu exerted this effect. Of particular focus is the role of Sufu as an inhibitor of the mitogenic Sonic hedgehog (Shh) signaling, which is highly active in various glioblastoma subtypes. Taken together, our findings point to a potential role for Sufu in preventing tumor development in the forebrain. Our studies also provide novel insights on how developmental and oncogenic signals converge to initiate tumorigenesis or tumor progression. We hope that these studies will lead to the identification of critical niche factors that may be targeted to treat brain cancers and improve patient outcome. Citation Format: Jesse Garcia Castillo, Hector G. Gomez, David Aguilar, Samuel J. Pleasure, Odessa Yabut. Exploring the roles of Suppressor of Fused in the postnatal neurogenic niche and tumorigenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1126.
Pertuzumab/Trastuzumab Breast Cancer Therapy Is Associated With Complex Hemodynamic Abnormalities
Authors: Srikanth Koneru, Kimi Sato, Adam Goldberg, Vedha Sanghi, Alberto Montero, Richard A. Grimm, L. Leonardo Rodriguez, Brian P. Griffin, G. Thomas Budd, Patrick C. Collier, Balaji Tamarappoo, Milind Y. Desai, Zoran B. Popović
Journal: JACC. Cardiovascular imaging (2018)
Abstract 13892: Incidence and Risk Factors of Restenosis, and Its Impact on Blood Pressure Control After Percutaneous Transluminal Renal Angioplasty in Patients With Renovascular Hypertension
Authors: Yoshio Iwashima, Tetsuya Fukuda, Fumiki Yoshihara, Hiroshi Kusunoki, Masatsugu Kishida, Shin-ichirou Hayashi, Satoko Nakamura, Kei Kamide, Takeshi Horio, Yuhei Kawano
Journal: Circulation (2015)

Background: Percutaneous transluminal renal angioplasty (PTRA) is one of the standard treatments for renal artery stenosis (RAS). Restenosis after PTRA may influence disease prognosis, but little is known about its frequency, risk factors, or impact on blood pressure control. Methods: This study included 175 renovascular hypertensive patients (mean age= 59.6 years; 33.7% women; 30.3% fibromuscular dysplasia [FMD]) with 207 treated renal arteries and were followed more than 12 months after PTRA. Data including blood pressure (BP), antihypertensive medication, and duplex ultrasonography (DUS) was collected before and 12 months, and then yearly after PTRA. Cure of hypertension was defines as a BP below 140/90mmHg without antihypertensive medication. Diagnosis of restenosis was based on DUS, by applying a renal aortic ratio &gt;3.5 in conjunction with a renal artery peak systolic velocity &gt; 250cm/s. Results: At 12 months after PTRA, the cumulative incidence of restenosis was 35 (20.0%). We divided the total patients into four groups on the basis of cause of RAS; FMD or atherosclerotic RAS (ARAS), and the absence/presence of restenosis, and found that the decrease in systolic BP (F=3.10, p&lt;0.05) as well as cure of hypertension (F=6.96, p&lt;0.01) were significantly different among the subgroups. Decrease in systolic BP (-31±19 vs -12±25mmHg, p&lt;0.05) as well as cure of hypertension (36.4 vs 5.0%, p&lt;0.01) were significantly greater in FMD patients without restenosis than those with restenosis; whereas no significant difference was found in patients with ARAS. During a median follow-up of 4.0 (IQR, 1.2-8.0) years, 56 patients (32.0%) developed restenosis. In multivariate Cox regression analysis, FMD was an independent predictor of restenosis (hazard ratio [HR] 2.65, p=0.02). We then divided total patients into two groups according to the cause of RAS, and found that statin use (HR 0.50) in FMD, and the presence of previous cardiovascular disease (HR 2.88) as well as severe RAS (≥90%) (HR 3.30) in ARAS were significant predictors of restenosis (p&lt;0.05, respectively). Conclusions: Incidence of restenosis after PTRA was higher in FMD than in ARAS among renovascular hypertensive patients. Assessment of restenosis is important for treatment success, especially for FMD.
Abstract 4239: Infection, inflammation and cancer: Understanding Alaska Native cancer health disparities
Authors: Holly Martinson, Steven Alberts, Matthew Olnes
Journal: Cancer Research (2018)

Abstract Gastric cancer is a leading cancer health disparity among the Alaska Native (AN) people, occurring at a 3-fold higher incidence and 4-fold higher mortality rate in comparison to U.S. Non-Hispanic whites (NHW). AN gastric cancer patients have significant differences in tumor location and appearance compared to NHW patients. In addition, AN patients are younger at the time of diagnosis, 60 versus 69 years and have a lower 5-year survival rate of 10% compared to 22% of NHW gastric cancer patients. The purpose of this research was to understand the role of gene mutations, inflammation, and infection as possible factors in the promotion of gastric cancer in the AN population. In this study, we examined previously obtained tissue samples from AN gastric cancer patients diagnosed between 2006-2014 at the Alaska Native Medical Center. Using next-generation sequencing, immunohistochemistry and in situ hybridization, we evaluated for 50 cancer related gene mutations, the presence of the virus, Epstein-Barr virus (EBV), the bacterium, Helicobacter pylori (H. pylori), and inflammatory factors. Cancer related gene mutations were observed in 69% of gastric tumors from AN patients. The most commonly mutated genes were TP53 (30%), PIK3CA (13%), STK11 (6%), KRAS (5%), and PTEN (5%). Of particular interest, gene mutations were associated with patients who were younger at time of diagnosis (less than 55 years old) and had a history of chronic gastritis. Additionally, EBV is associated with 23% of AN gastric cancers, which is significantly higher than the 10% of EBV associated gastric cancer cases observed in other populations. EBV associated AN gastric cancer patients were more likely to have a history of chronic gastritis, prior or current H. pylori infection, and tobacco use. Notably, aberrant overexpression of the inflammatory factor cyclooxygenase 2 (COX-2) and the glycoprotein Mucin 1 (MUC1) in gastric cancer cells was significantly associated with a poorer prognosis among AN gastric cancer patients. Collectively, these findings indicate infection and inflammation are potential driving factors in the pathogenesis of gastric cancer among the AN people, which may have important clinical implications. Citation Format: Holly Martinson, Steven Alberts, Matthew Olnes. Infection, inflammation and cancer: Understanding Alaska Native cancer health disparities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4239.
Abstract 19870: TRPV4 Channel Deletion Improves Cardiac Remodeling Following Pressure-Overload via Modulation of Mechanosensitive Rho/MRTF-A Pathway
Authors: Ravi kumar Adapala, Vahagn A Ohanyan, Holly C Cappelli, Anantha K Kanugula, Jordan Luli, Roslin J Thoppil, Sailaja Paruchuri, Gary J Meszaros, Charles K Thodeti
Journal: Circulation (2016)

Cardiac fibroblast (CF) differentiation is a critical event in the remodeling of the myocardium following cardiac injury. We have recently shown that mechanosensitive ion channel Transient Receptor Potential Vanilloid 4 (TRPV4) plays a key role in regulating CF differentiation by integrating soluble and mechanical signaling in rat cardiac fibroblasts. Here, we investigated the physiological significance of TRPV4 and the molecular mechanisms involved following pressure-overload. We induced pressure-overload using Trans Aortic Constriction (TAC) in wild type (WT) and TRPV4 knockout (KO) mice and monitored cardiac function for 28 days. We found that TRPV4KO mice exhibited decreased myocardial cross sectional area and left ventricular mass when compared with WT. Next, we analyzed cardiac function using 2D echocardiography, which revealed that TRPV4KO mice had preserved cardiac function (ejection fraction and fractional shortening) 28 days post-TAC. Histological analysis demonstrated that TRPV4KO mice displaye...