tbuckley/cabot-search huggingface dataset:
Association of Sensorineural Hearing Loss in Patients With Alopecia Areata
Authors: Sheng-Hsiang Ma, Ying-Hsuan Tai, Ying-Xiu Dai, Yun-Ting Chang, Tzeng-Ji Chen, Mu-Hong Chen
Journal: JAMA Dermatology (2020)

Alopecia areata (AA) is a common autoimmune disease, leading to chronic and relapsing hair loss. 1 Current evidence suggests that follicular melanocytes may be an important target in the autoimmune process of AA. 2 In addition to their presence in the skin, melanocytes are also present as intermediate cells in the stria vascularis of the cochlea, which are critical for normal hearing.In patients with Vogt-Koyanagi-Harada disease, a rare autoimmune disorder that targets melanocytes, sensorineural hearing loss (HL) is a common complication in late-stage disease.Few studies have found audiological abnormalities in patients with AA 3,4 ; however, existing studies are limited by their cross-sectional designs and small sample sizes.This nationwide population-based cohort study was conducted to investigate the risk of HL in patients with AA using claims data from the National Health Insurance Research Database in Taiwan.Methods | This study was approved by the Institutional Review Board of Taipei Veterans General Hospital (2018-07-016AC).The institutional review board waived the requirement to obtain informed consent owing to the use of deidentified data (VGHIRB No.: 2018-07-016AC).We identified patients with AA diagnosed by dermatologists between January 1, 1998, and December 31, 2011.The diagnosis of AA was established according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 704.01.For each patient with AA, 10 controls were selected after matching for age, sex, monthly premium, and residence.The primary outcome assessed was new-onset HL, which was identified by ICD-9-CM code 389.The diagnosis of HL was established by otorhinolaryngologists and was classified into conductive HL (ICD-9-CM code 389.0), sensorineural HL (ICD-9-CM code 389.1), mixed HL (ICD-9-CM code 389.2), and others (ICD-9-CM codes 389.7, 389.8, and 389.9).Participants were observed until a diagnosis of HL, death, or December 31, 2013.Cox regression model was used to calculate adjusted hazard ratios with 95% CIs.Two-sided P values <.05 were considered statistically significant.Data management and analyses were performed using the Statistical Analysis System (SAS) software, version 9.
Ethyl 4-hydroxybenzoate toxicity towards human SK-MEL-28 melanoma cell line involves mitochondrial toxicity, intracellular GSH depletion, quinone and reactive oxygen species formation
Authors: Nikhil Vad, Imam Shaik, Reza Mehvar, Majid Moridani
Journal: Cancer Research (2007)

3968  In search of a novel drug for melanoma therapy, we set to investigate the biochemical basis of ethyl 4-hydroxybenzoate (4-EHB) toxicity against human SK-MEL-28 melanoma cells. 4-EHB was investigated for its metabolism by tyrosinase, an abundant enzyme found in melanoma, and rat liver microsomal P450 enzymes. The extent of GSH depletion was used as a surrogate marker for 4-EHB metabolism by these enzymes. A number of biochemical modulators were used to investigate the mechanism of the 4-EHB toxicity towards human SK-MEL-28 melanoma cells using thiazolyl blue tetrazolium bromide (MTT) assay. The reactive oxygen species (ROS) formation was measured using 2’,7’-dichlorofluorescein diacetate assay. The intracellular GSH was investigated. 4-EHB was metabolized 60% by tyrosinase/O2 at 2 h. The extent of 4-EHB metabolism by CYP2E1 induced rat liver microsomes/NADPH/O2 was 26% at 2h. 4-Hydroxyanisole (4-HA), an analogue of 4-EHB, was metabolized by tyrosinase/O2 and microsomes/NADPH/O2 for 100% and 88%, respectively. The LD50s (day 2) of 4-EHB and 4-HA towards SK-MEL-28 human melanoma cells were 75 and 50 μM, respectively. It was found that dicoumarol, a diaphorase inhibitor, and 1-bromoheptane, a GSH reactant and intracellular GSH depletory agent, increased 4-EHB toxicity towards SK-MEL-28 melanoma cells indicating that quinone formation played an important role in 4-EHB’s mechanism of toxicity towards melanoma cells. Cyclosporin A, an inhibitor of mitochondrial permeability transition pore (MPTP) protein, was significantly potent in inhibiting 4-EHB toxicity towards melanoma cells. In addition, trifluoperazine was equally effective at inhibiting MPTP opening in melanoma cells. 4-EHB also led to ROS formation when it was incubated with melanoma cells. Dicoumarol and 1-bromoheptane increased the extent of ROS formation when co-incubated with 4-EHB whereas trifluperazine and cyclosporin A significantly inhibited the ROS formation by 4-EHB. We also showed that 4-EHB (75 μM) significantly depleted the intracellular GSH without a significant change in viability after 2 h incubation, indicating that the GSH depletion precedes 4-EHB cytotoxicity. In summary, the mechanisms of 4-EHB toxicity towards melanoma cells were found to be due to quinone reactive intermediate formation, ROS formation, intracellular GSH depletion and induced mitochondrial toxicity.
Replacement and Parallel Simplification of Nonhomologous Proteinases Maintain Venom Phenotypes in Rear-Fanged Snakes
Authors: Juan David Bayona-Serrano, Vincent Louis Viala, Rhett M Rautsaw, Tristan D Schramer, Gesiele A Barros-Carvalho, Milton Yutaka Nishiyama, Luciana A Freitas-de-Sousa, Ana Maria Moura-da-Silva, Christopher L Parkinson, Felipe Gobbi Grazziotin, Inácio L M Junqueira-de-Azevedo
Journal: Molecular Biology and Evolution (2020)

Novel phenotypes are commonly associated with gene duplications and neofunctionalization, less documented are the cases of phenotypic maintenance through the recruitment of novel genes. Proteolysis is the primary toxic character of many snake venoms, and ADAM metalloproteinases, named snake venom metalloproteinases (SVMPs), are largely recognized as the major effectors of this phenotype. However, by investigating original transcriptomes from 58 species of advanced snakes (Caenophidia) across their phylogeny, we discovered that a different enzyme, matrix metalloproteinase (MMP), is actually the dominant venom component in three tribes (Tachymenini, Xenodontini, and Conophiini) of rear-fanged snakes (Dipsadidae). Proteomic and functional analyses of these venoms further indicate that MMPs are likely playing an "SVMP-like" function in the proteolytic phenotype. A detailed look into the venom-specific sequences revealed a new highly expressed MMP subtype, named snake venom MMP (svMMP), which originated independently on at least three occasions from an endogenous MMP-9. We further show that by losing ancillary noncatalytic domains present in its ancestors, svMMPs followed an evolutionary path toward a simplified structure during their expansion in the genomes, thus paralleling what has been proposed for the evolution of their Viperidae counterparts, the SVMPs. Moreover, we inferred an inverse relationship between the expression of svMMPs and SVMPs along the evolutionary history of Xenodontinae, pointing out that one type of enzyme may be substituting for the other, whereas the general (metallo)proteolytic phenotype is maintained. These results provide rare evidence on how relevant phenotypic traits can be optimized via natural selection on nonhomologous genes, yielding alternate biochemical components.
Prognostic Value of Cardiac Magnetic Resonance Estimates of Ventriculoarterial Coupling in Pulmonary Hypertension
Authors: Carlos González Lengua, Chirag Agarwal, Aalap Chokshi, Lindsay Elbaum, Pirkash Kumar, Richard Amara, Maria Giovanna Trivieri, Ana García Álvarez, Javier Sanz
Journal: JACC. Cardiovascular imaging (2020)
THU0087 THE RELATIONSHIP BETWEEN THE LEVEL OF FETUIN-A, THE PRESENCE OF OSTEOPOROSIS AND OSTEOPORETIC FRACTURES IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: I. Zborovskaya, В. Zavodovsky, Y. Akhverdyan, E. Papichev, P. J, S. L
Journal: Annals of the Rheumatic Diseases (2020)

Background: According to the literature, a number of markers (irisin, adiponectin, visfatin, and others) have a positive correlation with the frequency of osteoporosis, osteoporotic fractures and inflammatory response in patients with rheumatoid arthritis. Objectives: to study the relationship between the level of fetuin-A (FA), the presence of osteoporosis (OP) and osteoporetic fractures in patients with rheumatoid arthritis (RA). Methods: We examined 110 patients with a reliable diagnosis of RA, verified on the basis of the ACR / EULAR 2010 criteria. The age of the examined was from 18 to 69 years, all patients were female. The comparison group consisted of 30 conditionally healthy women. Patients in both groups was determined by the level of FA using a commercial kit ELISA BioVendor, bone mineral density was assessed using dual energy X-ray absorptiometry method DEXA (Lunar DPX-NT GE). The diagnosis of OP was made on the basis of WHO criteria (for women over 50 in the postmenopausal period) and the Recommendations of the International Society of Clinical Densitometry (for women in the premenopausal period). Results: The average level of FA in patients with RA was 765.67±120.66 μg/ml, which was significantly lower than in healthy individuals - 812.95±76.21 μg/ml (p=0.0437). OP was detected in 52 (47.2%) patients with RA. The level of FA in serum in patients with OP was 733.65±135.84 μg/ml, which is also lower than that of healthy individuals (p=0.002). We divided all patients with RA into 2 groups, depending on the presence of osteoporetic fractures. The average level of FA in the group of patients with osteoporetic fractures (n=24) was 694.79±110.47 μg/ml, which is significantly lower than the level of the group without fractures (n=86) - 785.45±116.43 μg/ml (p=0.00091). Conclusion: The average level of FA in patients with RA is significantly lower than in healthy individuals. In addition, in patients with the presence of OP and osteoporetic fractures, the level of FA in the blood serum is also lower than in patients without OP and fractures. Thus, a decreased level of FA in the blood serum of patients with RA may indicate the presence of OP and an increased risk of osteoporetic fractures. References: [1]D. Lavrova et al. Decreased irisin level as risk factor of pathological fractures in rheumatoid arthritis patients // Ann Rheum Dis, volume 77, supplement Suppl, year 2018, page A1227 (10.1136/annrheumdis-2018-eular.4463) [2]Akhverdyan, Y. et al. Laboratory markers of inflammation and serum nicotinamide phosphoribosyltransferase level in rheumatoid arthritis patients. Annals of the Rheumatic Diseases. 2015. Т. 74. № S2. С. 372. Annals of the Rheumatic Diseases. 2017. Т. 76. № S2. С. 1149. Disclosure of Interests: None declared
Abstract 167: Assessing Laryngoscope Blade Positioning During Pediatric Intubation by Video Review
Authors: Priyanka Kharayat, Aaron Donoghue, Akira Nishisaki, Elizabeth Laverriere
Journal: Circulation (2018)

Introduction: Classical teaching in laryngoscopy advocates the use of Miller (Straight) blades to be placed underneath the epiglottis and lift it, whereas for Macintosh (Curved) blades the tip is positioned in the vallecula. Published studies in anesthesia suggest that straight blade positioning in the vallecula may be a satisfactory technique for small children. However, there is no clear evidence of consistent implementation of this methodology in practice and associated intubation success. Objectives: To assess laryngoscope blade tip position during pediatric tracheal intubation in the emergency department (ED) and its association with intubation success and time of laryngoscopy. Methods: Single center retrospective observational cohort study. Children undergoing tracheal intubation in a tertiary pediatric ED under video-recorded conditions were eligible for inclusion. A CMAC video laryngoscope was used as first line device with the video feed recorded for review. Videos were reviewed and the blade tip position during intubation recorded by study personnel. Blade tip position was categorized as ‘Correct’ if the curved blade was in the vallecula or straight blade was lifting the epiglottis; otherwise the position was categorized as ‘Incorrect’. Time of laryngoscopy was defined as time from blade insertion to removal. Univariate analysis between covariates was done by Fisher’s exact testing for intubation success and by nonparametric methods for laryngoscopy time. Results: A total of 17 complete videos were included in the study. Mac blade was used correctly in 8/10 cases (80%); Miller was used correctly in 1/7 cases (14%). Among infants (≤ 12 months), the Miller was used incorrectly in 3/4 cases (75%). Intubation was successful in 9/9 cases (100%) with correct blade position and in 5/8 cases (63%) with incorrect position (p=0.04). There was no significant difference in mean calculated laryngoscopy time for correct versus incorrect blade tip position (37.90 ± 26.80 sec vs. 44.33± 15.22 sec, p=0.12) Conclusion: Correct position of the laryngoscope blade tip is associated with higher intubation success. There was no significant difference in the laryngoscopy time for both correct and incorrect blade position.
Severe clinical outcomes of COVID-19 associated with proton pump inhibitors: a nationwide cohort study with propensity score matching
Authors: Seung Won Lee, Eun Kyo Ha, Abdullah Özgür Yeniova, Sung Yong Moon, So Young Kim, Hyun Yong Koh, Jee Myung Yang, Su Jin Jeong, Sun Joon Moon, Joo Young Cho, In Kyung Yoo, Dong Keon Yon
Journal: Gut (2020)

The adverse effects of proton pump inhibitors (PPIs) have been documented for pneumonia; however, there is no consensus regarding whether the use of PPIs might be harmful regarding the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this regard, we aimed to measure the potential associations of the current use of PPIs with the infection rates of COVID-19 among patients who underwent SARS-CoV-2 testing.
Talocalcaneal Coalition With Os Sustentaculum
Authors: Sharjeel Usmani, Samreen Muzaffar, Fareeda Al Kandari, Najeeb Ahmed, Uzma Rehman
Journal: Clinical Nuclear Medicine (2020)

Abstract Os sustentaculi is a rare accessory bone of the foot located along the posterior end of sustentaculum tali. It is a component type of extra-articular talocalcaneal coalition. We report the case of a 17-year-old boy with symptomatic os sustentaculum with talocalcaneal coalition diagnosed on 99m Tc-HDP SPECT/CT. We wish to emphasize on the use of SPECT/CT in not only characterizing the ossicle morphologically, but also for evaluation of this anatomical variant as an active source of pain in the absence of a more common cause of pain in young physically active patients.
MDM2-Mediated Ubiquitination of Angiotensin-Converting Enzyme 2 Contributes to the Development of Pulmonary Arterial Hypertension
Authors: Hui Shen, Jiao Zhang, Chen Wang, Pritesh P. Jain, Mingmei Xiong, Xinxing Shi, Yuyang Lei, Shanshan Chen, Qian Yin, Patricia A. Thistlethwaite, Jian Wang, Kaizheng Gong, Zu-Yi Yuan, Jason X.-J. Yuan, John Y.-J. Shyy
Journal: Circulation (2020)

Angiotensin-converting enzyme 2 (ACE2) converts angiotensin II, a potent vasoconstrictor, to angiotensin-(1-7) and is also a membrane protein that enables coronavirus disease 2019 (COVID-19) infectivity. AMP-activated protein kinase (AMPK) phosphorylation of ACE2 enhances ACE2 stability. This mode of posttranslational modification of ACE2 in vascular endothelial cells is causative of a pulmonary hypertension (PH)-protective phenotype. The oncoprotein MDM2 (murine double minute 2) is an E3 ligase that ubiquitinates its substrates to cause their degradation. In this study, we investigated whether MDM2 is involved in the posttranslational modification of ACE2 through its ubiquitination of ACE2, and whether an AMPK and MDM2 crosstalk regulates the pathogenesis of PH.Bioinformatic analyses were used to explore E3 ligase that ubiquitinates ACE2. Cultured endothelial cells, mouse models, and specimens from patients with idiopathic pulmonary arterial hypertension were used to investigate the crosstalk between AMPK and MDM2 in regulating ACE2 phosphorylation and ubiquitination in the context of PH.Levels of MDM2 were increased and those of ACE2 decreased in lung tissues or pulmonary arterial endothelial cells from patients with idiopathic pulmonary arterial hypertension and rodent models of experimental PH. MDM2 inhibition by JNJ-165 reversed the SU5416/hypoxia-induced PH in C57BL/6 mice. ACE2-S680L mice (dephosphorylation at S680) showed PH susceptibility, and ectopic expression of ACE2-S680L/K788R (deubiquitination at K788) reduced experimental PH. Moreover, ACE2-K788R overexpression in mice with endothelial cell-specific AMPKα2 knockout mitigated PH.Maladapted posttranslational modification (phosphorylation and ubiquitination) of ACE2 at Ser-680 and Lys-788 is involved in the pathogenesis of pulmonary arterial hypertension and experimental PH. Thus, a combined intervention of AMPK and MDM2 in the pulmonary endothelium might be therapeutically effective in PH treatment.
Prevention of Multidrug-Resistant Tuberculosis in Close Contacts. Back to the Future?
Authors: Neil W. Schluger
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

The author focuses on data from patients who were exposed with tuberculosis (TB) treated with isoniazid (INH) according to Peruvian national guidelines in Peru  Topics discussed include vaccine candidates in phase trials after cases of coronavirus disease (COVID-19), clinical trials examining treatment for latent TB and infectious disease challenge in hospitals
The DaBlaCa-13 Study: Short-term, Intensive Chemoresection Versus Standard Adjuvant Intravesical Instillations in Non–muscle-invasive Bladder Cancer—A Randomised Controlled Trial
Authors: Maria S. Lindgren, Peter Bue, Nessn Azawi, Linea Blichert-Refsgaard, Maria O. Sundelin, Lars Dyrskjøt, Jørgen B. Jensen
Journal: European Urology (2020)
Functional metabolomics reveal the role of AHR/GPR35 mediated kynurenic acid gradient sensing in chemotherapy-induced intestinal damage
Authors: Di Wang, Danting Li, Yuxin Zhang, Jie Chen, Ying Zhang, Chuyao Liao, Siyuan Qin, Yuan Tian, Zunjian Zhang, Fengguo Xu
Journal: Acta Pharmaceutica Sinica B (2020)

Intestinal toxicity induced by chemotherapeutics has become an important reason for the interruption of therapy and withdrawal of approved agents. In this study, we demonstrated that chemotherapeutics-induced intestinal damage were commonly characterized by the sharp upregulation of tryptophan (Trp)−kynurenine (KYN)−kynurenic acid (KA) axis metabolism. Mechanistically, chemotherapy-induced intestinal damage triggered the formation of an interleukin-6 (IL-6)−indoleamine 2,3-dioxygenase 1 (IDO1)−aryl hydrocarbon receptor (AHR) positive feedback loop, which accelerated kynurenine pathway metabolism in gut. Besides, AHR and G protein-coupled receptor 35 (GPR35) negative feedback regulates intestinal damage and inflammation to maintain intestinal integrity and homeostasis through gradually sensing kynurenic acid level in gut and macrophage, respectively. Moreover, based on virtual screening and biological verification, vardenafil and linagliptin as GPR35 and AHR agonists respectively were discovered from 2388 approved drugs. Importantly, the results that vardenafil and linagliptin significantly alleviated chemotherapy-induced intestinal toxicity in vivo suggests that chemotherapeutics combined with the two could be a promising therapeutic strategy for cancer patients in clinic. This work highlights GPR35 and AHR as the guardian of kynurenine pathway metabolism and core component of defense responses against intestinal damage.
Assessment of Eculizumab and C5 Levels in PNH Treatment: Molar Ratio of Eculizumab to C5 Level Effectively Predicts Ongoing Dosage Changes in a Cohort of 50 Patients Treated with Eculizumab
Authors: Darren J Newton, Claire E McKinley, Alonso Ricardo, Michelle D Hoarty, Louise Arnold, Kathryn Riley, Nicola Copeland, Talha Munir, Morag Griffin, Anita Hill, Peter Hillmen
Journal: Blood (2017)
Abstract 17112: Racial And Gender Disparities In Shift To Outpatient Revascularization Among Medicare Fee-for-service Beneficiaries
Authors: Samuel Savitz, Kristine M Falk, Sally C Stearns, Jason Fines, Lexie Grove, Joseph Rossi
Journal: Circulation (2019)

Background: There has been a significant shift from inpatient to outpatient percutaneous coronary intervention (PCI) over the last decade. However, the shift to outpatient PCI may differ for patien...
Abstract 15738: Cyclooxygenase-2 and Heart Failure With Preserved Ejection Fraction
Authors: Emanuela Ricciotti, Philip G Haines, Manu Beerens, Uri Kartoun, Nicholas F Lahens, Tao Wang, Stanley Y Shaw, Calum A MacRae, Garret A Fitzgerald
Journal: Circulation (2019)

Nonsteroidal anti-inflammatory drugs (NSAIDs), which inhibit the activity of cyclooxygenase (COX)-1 and COX-2, are used to relieve pain and inflammation. Their use is associated with an increased r...
The Myc and Ras Partnership in Cancer: Indistinguishable Alliance or Contextual Relationship?
Authors: Wadie D. Mahauad-Fernandez, Dean W. Felsher
Journal: Cancer Research (2020)

Myc and Ras are two of the most commonly activated oncogenes in tumorigenesis. Together and independently they regulate many cancer hallmarks including proliferation, apoptosis, and self-renewal. Recently, they were shown to cooperate to regulate host tumor microenvironment programs including host immune responses. But, is their partnership always cooperative or do they have distinguishable functions? Here, we provide one perspective that Myc and Ras cooperation depends on the genetic evolution of a particular cancer. This in turn, dictates when they cooperate via overlapping and identifiably distinct cellular- and host immune-dependent mechanisms that are cancer type specific.
Abstract 12029: Nuclear IP3 Receptor Knockdown Reveals a Key Role of IP3 Receptor Upregulation in Disrupted Nuclear Calcium-Dependent Signaling in Atrial Fibrillation
Authors: Xiaoyan Qi, Jiening Xiao, Feng Xiong, Yoshihiro Sobue, Louis R Villeneuve, Senka Ljubojevic, Donald M Bers, Dobromir Dobrev, Stanley Nattel
Journal: Circulation (2018)

Introduction: Nucleoplasmic (Nuc) Ca2+ regulates gene expression; nuclear Ca2+ changes in AF are poorly understood. Hypothesis: AF modulates atrial cardiomyocyte (ACM) nuclear Ca2+ handling via IP3...
Annals Graphic Medicine - The Weekly Road to Burnout in Primary Care
Authors: Julie Caplow
Journal: Annals of Internal Medicine (2020)

Web Exclusives4 August 2020Annals Graphic Medicine - The Weekly Road to Burnout in Primary CareFREEJulie Caplow, MDJulie Caplow, MDNorthern Navajo Medical Center, Shiprock, New Mexico (J.C.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/G19-0087 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Northern Navajo Medical Center, Shiprock, New Mexico (J.C.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G19-0087.Author/Illustrator Information: Julie Caplow, MD (e-mail, [email protected]com).This article was published at Annals.org on 28 July 2020. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 4 August 2020Volume 173, Issue 3Page: W55-W56KeywordsConflicts of interestDisclosureHealth care ePublished: 28 July 2020 Issue Published: 4 August 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...