tbuckley/cabot-search huggingface dataset:
Filaggrin mutations in relation to skin barrier and atopic dermatitis in early infancy*
Authors: A. Hoyer, E.M. Rehbinder, M. Färdig, S. Asad, K.C. Lødrup Carlsen, K.M.A. Endre, B. Granum, G. Haugen, G. Hedlin, C. Monceyron Jonassen, S. Katayama, J.R. Konradsen, L. Landrø, M. LeBlanc, C.A. Olsson Mägi, K. Rudi, H.O. Skjerven, A.C. Staff, R. Vettukattil, M. Bradley, B. Nordlund, C. Söderhäll
Journal: British Journal of Dermatology (2021)

Loss-of-function mutations in the skin barrier gene filaggrin (FLG) increase the risk of atopic dermatitis (AD), but their role in skin barrier function, dry skin and eczema in infancy is unclear.To determine the role of FLG mutations in impaired skin barrier function, dry skin, eczema and AD at 3 months of age and throughout infancy.FLG mutations were analysed in 1836 infants in the Scandinavian population-based PreventADALL study. Transepidermal water loss (TEWL), dry skin, eczema and AD were assessed at 3, 6 and 12 months of age.FLG mutations were observed in 166 (9%) infants. At 3 months, carrying FLG mutations was not associated with impaired skin barrier function (TEWL > 11·3 g m-2 h-1 ) or dry skin, but was associated with eczema [odds ratio (OR) 2·89, 95% confidence interval (CI) 1·95-4·28; P < 0·001]. At 6 months, mutation carriers had significantly higher TEWL than nonmutation carriers [mean 9·68 (95% CI 8·69-10·68) vs. 8·24 (95% CI 7·97-8·15), P < 0·01], and at 3 and 6 months mutation carriers had an increased risk of dry skin on the trunk (OR 1·87, 95% CI 1·25-2·80; P = 0·002 and OR 2·44, 95% CI 1·51-3·95; P < 0·001) or extensor limb surfaces (OR 1·52, 95% CI 1·04-2·22; P = 0·028 and OR 1·74, 95% CI 1·17-2·57; P = 0·005). FLG mutations were associated with eczema and AD in infancy.FLG mutations were not associated with impaired skin barrier function or dry skin in general at 3 months of age, but increased the risk for eczema, and for dry skin on the trunk and extensor limb surfaces at 3 and 6 months.
Influenza
Authors: Sam Ghebrehewet, Peter MacPherson, Antonia Ho
Journal: BMJ (2016)

The World Health Organisation estimates that approximately one billion people are infected and up to 500 000 people die from influenza each year. 1 The greatest burden of illness usually occurs among children, while the highest burden of severe disease (in terms of hospitalisation and death) occurs in those with underlying medical conditions, infants and young children, and elderly people. 2 Current circulating influenza strains in humans include influenza A(H1N1)pdm09, influenza A(H3N2), and both influenza B viruses (B/Victoria and B/Yamagata). 3 4 This article provides non-specialists with information on how to diagnose, manage, and prevent flu.
TCT-496 Development of Atrioventricular and Intraventricular Conduction Disturbances in Patients Undergoing Transcatheter Aortic Valve Replacement With New-Generation Self-Expanding Valves: A Real-World Multicenter Analysis
Authors: Luis Nombela-Franco, Alex Castro Mejía, Ignacio Amat-Santos, Raul Moreno, Jose Diaz, Alejandro Travieso, Pilar Jimenez, Sandra Santos-Martinez, Angela McInerney, Guillermo Galeote Garcia, Victor Alfonso Jimenez Diaz, Gabriela Tirado-Conte, Alejandro Barrero, Luis Alfonso Marroquin-Donday, Ivan Nuñez-Gil, Nieves Gonzalo, Antonio Fernandez-Ortiz, Javier Escaned
Journal: Journal of the American College of Cardiology (2021)
TCT-301 Diagnostic Accuracy of Angiography-Based Vessel Fractional Flow Reserve (vFFR) Virtual Stenting
Authors: Mariusz Tomaniak, Tara Neleman, Ibrahim Kucuk, Kaneshka Masdjedi, Laurens Zandvoort, Janusz Kochman, Wijnand Den Dekker, Jeroen Wilschut, Roberto Diletti, Isabella Kardys, Felix Zijlstra, Nicolas Van Mieghem, Joost Daemen
Journal: Journal of the American College of Cardiology (2021)
Resistance Testing for Management of HIV Virologic Failure in Sub-Saharan Africa
Authors: Mark J. Siedner, Mahomed-Yunus S. Moosa, Suzanne McCluskey, Rebecca F. Gilbert, Selvan Pillay, Isaac Aturinda, Kevin Ard, Winnie Muyindike, Nicholas Musinguzi, Godfrey Masette, Melendhran Pillay, Pravikrishnen Moodley, Jaysingh Brijkumar, Tamlyn Rautenberg, Gavin George, Rajesh T. Gandhi, Brent A. Johnson, Henry Sunpath, Mwebesa B. Bwana, Vincent C. Marconi
Journal: Annals of Internal Medicine (2021)

Virologic failure in HIV predicts the development of drug resistance and mortality. Genotypic resistance testing (GRT), which is the standard of care after virologic failure in high-income settings, is rarely implemented in sub-Saharan Africa.
Breast implants: US regulator issues “black box” warning and requires more patient information
Authors: Janice Hopkins Tanne
Journal: BMJ (2021)

The US Food and Drug Administration has placed a black box warning—its highest level of caution—on breast implant packaging, and it now requires manufacturers and surgeons to use a checklist to ensure that patients make informed decisions about using the devices.1

US doctors do about 400 000 implant operations every year, about three quarters for cosmetic reasons and the others for reconstruction after surgery to prevent or treat breast cancer. Breast implants marketed in the US are filled either with saline or with silicone gel with an outer silicone shell, which may be textured or smooth.

For several years women with breast implants have complained of a range of problems such as “brain fog,” fatigue, …
TCT-200 An Observational Study Assessing the Use of Sirolimus-Eluting Balloons for Side-Branch Treatment in the Provisional Stenting of Coronary Bifurcations
Authors: Johanna Jones, Kyriacos Mouyis, Angelos Tyrlis, Krishnaraj Rathod, Anthony Mathur, Andreas Baumbach, Daniel Jones
Journal: Journal of the American College of Cardiology (2021)
Neutrophil-to-lymphocyte ratio is associated with survival and sentinel lymph node positivity in invasive cutaneous squamous cell carcinoma: A retrospective study
Authors: Takuya Maeda, Azusa Hiura, Jiro Uehara, Rino Toyoshima, Tomoe Nakagawa, Koji Yoshino
Journal: Journal of the American Academy of Dermatology (2021)
Oscillospira - a candidate for the next-generation probiotics
Authors: Jingpeng Yang, Yanan Li, Zhiqiang Wen, Wenzheng Liu, Lingtong Meng, He Huang
Journal: Gut Microbes (2021)

Oscillospira is a class of organism that often appears in high-throughput sequencing data but has not been purely cultured and is widely present in the animal and human intestines. There is a strong association between variation in Oscillospira abundance and obesity, leanness, and human health. In addition, a growing body of studies has shown that Oscillospira is also implicated in other diseases, such as gallstones and chronic constipation, and has shown some correlation with the positive or negative changes in its course. Sequencing data combined with metabolic profiling indicate that Oscillospira is likely to be a genus capable of producing short-chain fatty acids (SCFAs) such as butyrate, which is an important reference indicator for screening "next-generation probiotics ". Considering the positive effects of Oscillospira in some specific diseases, such as obesity-related metabolic diseases, it has already been characterized as one of the next-generation probiotic candidates and therefore has great potential for development and application in the future food, health care, and biopharmaceutical products.
TCT-120 Optical Coherence Tomography Characterization of Shockwave Intravascular Lithotripsy for Treatment of Calcified Coronary Lesions: Patient-Level Pooled Analysis of the Disrupt CAD OCT Substudies
Authors: Ziad Ali, Jonathan Hill, Shigeru Saito, Nieves Gonzalo, Carlo Di Mario, Robert Riley, Benjamin Honton, Akiko Maehara, Mitsuaki Matsumura, Dean Kereiakes, Gregg Stone, Richard Shlofmitz
Journal: Journal of the American College of Cardiology (2021)
A non-internalised CD38-binding radiolabelled single-domain antibody fragment to monitor and treat multiple myeloma
Authors: Elodie Duray, Margaux Lejeune, Frederic Baron, Yves Beguin, Nick Devoogdt, Ahmet Krasniqi, Yoline Lauwers, Yong Juan Zhao, Matthias D’Huyvetter, Mireille Dumoulin, Jo Caers
Journal: Journal of Hematology & Oncology (2021)

Antibody-based therapies targeting CD38 are currently used as single agents as well as in combination regimens for multiple myeloma, a malignant plasma cell disorder. In this study, we aimed to develop anti-CD38 single-domain antibodies (sdAbs) that can be used to trace CD38+ tumour cells and subsequently used for targeted radionuclide therapy. SdAbs are derived from Camelidae heavy-chain antibodies and have emerged as promising theranostic agents due to their favourable pharmacological properties.Four different anti-CD38 sdAbs were produced, and their binding affinities and potential competition with the monoclonal antibody daratumumab were tested using biolayer interferometry. Their binding kinetics and potential cell internalisation were further studied after radiolabelling with the diagnostic radioisotope Indium-111. The resulting radiotracers were evaluated in vivo for their tumour-targeting potential and biodistribution through single-photon emission computed tomography (SPECT/CT) imaging and serial dissections. Finally, therapeutic efficacy of a lead anti-CD38 sdAb, radiolabelled with the therapeutic radioisotope Lutetium-177, was evaluated in a CD38+ MM xenograft model. RESULTS : We retained anti-CD38 sdAb #2F8 as lead based on its excellent affinity and superior stability, the absence of competition with daratumumab and the lack of receptor-mediated internalisation. When intravenously administered to tumour-xenografted mice, radiolabelled sdAb #2F8 revealed specific and sustained tumour retention with low accumulation in other tissues, except kidneys, resulting in high tumour-to-normal tissue ratios. In a therapeutic setting, myeloma-bearing mice received three consecutive intravenous administrations of a high (18.5 MBq) or a low radioactive dose (9.3 MBq) of 177Lu-DTPA-2F8 or an equal volume of vehicle solution. A dose-dependent tumour regression was observed, which translated into a prolonged median survival from 43 days for vehicle-treated mice, to 62 days (p = 0.027) in mice receiving the low and 65 days in mice receiving the high (p = 0.0007) radioactive dose regimen, respectively.These results highlight the theranostic potential of radiolabelled anti-CD38 sdAbs for the monitoring and treatment of multiple myeloma.
Dysregulated tumor-associated macrophages in carcinogenesis, progression and targeted therapy of gynecological and breast cancers
Authors: Tianhan Xu, Sihui Yu, Jiawen Zhang, Sufang Wu
Journal: Journal of Hematology & Oncology (2021)

Gynecological and breast cancers are a group of heterogeneous malignant tumors. Although existing treatment strategies have ameliorated the clinical outcomes of patients, the overall survival rate of advanced diseases remains unsatisfactory. Increasing evidence has indicated that the development and prognosis of tumors are closely related to the tumor microenvironment (TME), which restricts the immune response and provokes malignant progression. Tumor-associated macrophages (TAMs) are the main component of TME and act as a key regulator in tumor metastasis, immunosuppression and therapeutic resistance. Several preclinical trials have studied potential drugs that target TAMs to achieve potent anticancer therapy. This review focuses on the various functions of TAMs and how they influence the carcinogenesis of gynecological and breast cancers through regulating cancer cell proliferation, tumor angiogenesis and tumor-related immunosuppression. Besides, we also discuss the potential application of disabling TAMs signaling as a part of cancer therapeutic strategies, as well as CAR macrophages, TAMs-based vaccines and TAMs nanobiotechnology. These research advances support that targeting TAMs combined with conventional therapy might be used as effective therapeutics for gynecological and breast cancers in the future.
TCT-284 Long-Term Clinical Outcomes and Echocardiographic Hemodynamics Following Transcatheter Tricuspid Valve-in-Valve Implantation: 12-Year Single-Center Experience
Authors: Andrew Chatfield, Anthony Chuang, Mariama Akodad, Janarthanan Sathananthan, David Wood, Ali Alqadhi, David Meier, Anson Cheung, John Webb
Journal: Journal of the American College of Cardiology (2021)
TCT-168 Real-Time Optical Coherence Tomography and Angiographic Coregistration in Percutaneous Coronary Intervention—Impact on Treatment Strategy: One-Year Clinical Outcomes and Subgroup Analysis (iOPTICO Study)
Authors: Rony Mathew, Jabir Abdullakutty, Tejas Patel, Balbir Singh, Nagendra Chouhan, Fazila-Tun Nesa Malik, Sengottuvelu Gunasekaran, Samuel Mathew, Viveka Kumar, Vijayakumar Subban
Journal: Journal of the American College of Cardiology (2021)
Delivery of synthetic mRNAs for tissue regeneration
Authors: Heidrun Steinle, Josefin Weber, Sandra Stoppelkamp, Katharina Große-Berkenbusch, Sonia Golombek, Marbod Weber, Tuba Canak-Ipek, Sarah-Maria Trenz, Christian Schlensak, Meltem Avci-Adali
Journal: Advanced Drug Delivery Reviews (2021)
TCT-87 Clinical Outcomes of Optical Coherence Tomography-Guided Compared With Intravascular Ultrasound-Guided Percutaneous Coronary Intervention: A Meta-Analysis
Authors: Yehia Saleh, Abdullah Al-abcha, Ola Abdelkarim, Omar Abdelfattah, George Abela, Hayder Hashim, Sachin Goel, Neal Kleiman
Journal: Journal of the American College of Cardiology (2021)
RELATION BETWEEN DISEASE ACTIVITY INDICES AND THEIR INDIVIDUAL COMPONENTS AND RADIOGRAPHIC PROGRESSION IN RHEUMATOID ARTHRITIS: A SYSTEMATIC LITERATURE REVIEW
Authors: V. Navarro-Compan, A.M. Gherghe, J.S. Smolen, D. Aletaha, R. Landewe, D. van der Heijde
Journal: Annals of the Rheumatic Diseases (2014)
Dynamics of cell-cell junctions in squamous cell carcinoma
Authors: Miquella Chavez, Laurie Hudson
Journal: Cancer Research (2007)

2045  Squamous cell carcinoma (SCC) is the second most common type of skin cancer in humans, affecting over 200,000 people annually. Factors that lead to metastasis of SCC are as of yet unknown. Metastasis is facilitated by the breakdown of one or all of the three types of cell-cell contacts: adherens junctions (AJ), tight junctions and desmosomes. Remodeling of these junctions is observed during cell migration, wound repair, embryonic development and cancer metastasis. Loss of E-cadherin correlates with an invasive and metastatic phenotype in many cancer models, and additionally, a decrease in desmosomal proteins corresponds with metastasis in oral SCC tumors. Growth factors such as epidermal growth factor (EGF) initiate junctional remodeling both in vitro and in vivo. We find that activation of the EGF receptor (EGFR) disrupts two types of cell:cell contacts, adherens junctions and desmosomes. EGF treatment decreases total junctional cadherin protein levels (E-cadherin, desmoglein-2) as detected by immunoblot analysis. Using real time PCR, a transient decrease of desmoglein-2 mRNA levels is observed in response to EGF, whereas E-cadherin message remains unaltered. Differences in EGF-dependent cadherin internalization are also detected; endocytosis of desmosomal cadherins occurs before E-cadherin as determined by confocal microscopy. The importance of endogenous EGF receptor activation in junctional disruption and migration was demonstrated in in vitro wound healing assays. The EGFR inhibitor AG1478 delayed migration of keratinocytes in the absence of exogenous EGF. Redistribution of junctional components and cytoskeletal rearrangement were detected at the wound margins where EGFR levels are elevated, but not within the confluent cell monolayer. EGFR inhibition resulted in retention of the adherens junction component beta-catenin and the desmosomal component plakophilin at cell:cell junctions at the wound edge. Based on these findings, we propose that EGFR activation modulates both adherens junction and desmosomal junction components through multiple mechanisms. Downregulation of cell:cell junctions following EGFR activation may play an important role in the migratory and invasive capacity of SCC tumor cells.
TCT-371 Commissural Versus Coronary Optimized Alignment During Transcatheter Aortic Valve Replacement
Authors: Alfredo Redondo Dieguez, Carlos Baladron, Didier Tchetche, Sandra Santos-Martinez, Jose Raul Delgado Arana, Alejandro Barrero, Hipolito Gutierrez, Am Serrador, Cristina Ybarra Falcón, Mario Garcia-Gomez, Manuel Carrasco, Teresa Sevilla, Israel Sanchez Lite, Esther Sanz, Jose A. San Roman, Ignacio Amat-Santos
Journal: Journal of the American College of Cardiology (2021)
Association of race and health insurance in treatment disparities of colon cancer: A retrospective analysis utilizing a national population database in the United States
Authors: Scarlett Hao, Rebecca A. Snyder, William Irish, Alexander A. Parikh
Journal: PLoS Medicine (2021)

Both health insurance status and race independently impact colon cancer (CC) care delivery and outcomes. The relative importance of these factors in explaining racial and insurance disparities is less clear, however. This study aimed to determine the association and interaction of race and insurance with CC treatment disparities.Retrospective cohort review of a prospective hospital-based database.In this cross-sectional study, patients diagnosed with stage I to III CC in the United States were identified from the National Cancer Database (NCDB; 2006 to 2016). Multivariable regression with generalized estimating equations (GEEs) were performed to evaluate the association of insurance and race/ethnicity with odds of receipt of surgery (stage I to III) and adjuvant chemotherapy (stage III), with an additional 2-way interaction term to evaluate for effect modification. Confounders included sex, age, median income, rurality, comorbidity, and nodes and margin status for the model for chemotherapy. Of 353,998 patients included, 73.8% (n = 261,349) were non-Hispanic White (NHW) and 11.7% (n = 41,511) were non-Hispanic Black (NHB). NHB patients were less likely to undergo resection [odds ratio (OR) 0.66, 95% confidence interval [CI] 0.61 to 0.72, p < 0.001] or to receive adjuvant chemotherapy [OR 0.83, 95% CI 0.78 to 0.87, p < 0.001] compared to NHW patients. NHB patients with private or Medicare insurance were less likely to undergo resection [OR 0.76, 95% CI 0.63 to 0.91, p = 0.004 (private insurance); OR 0.59, 95% CI 0.53 to 0.66, p < 0.001 (Medicare)] and to receive adjuvant chemotherapy [0.77, 95% CI 0.68 to 0.87, p < 0.001 (private insurance); OR 0.86, 95% CI 0.80 to 0.91, p < 0.001 (Medicare)] compared to similarly insured NHW patients. Although Hispanic patients with private and Medicare insurance were also less likely to undergo surgical resection, this was not the case with adjuvant chemotherapy. This study is mainly limited by the retrospective nature and by the variables provided in the dataset; granular details such as continuity or disruption of insurance coverage or specific chemotherapy agents or dosing cannot be assessed within NCDB.This study suggests that racial disparities in receipt of treatment for CC persist even among patients with similar health insurance coverage and that different disparities exist for different racial/ethnic groups. Changes in health policy must therefore recognize that provision of insurance alone may not eliminate cancer treatment racial disparities.
Multisystem inflammatory syndrome in children and Kawasaki disease: a critical comparison
Authors: Chetan Sharma, Madhusudan Ganigara, Caroline Galeotti, Joseph Burns, Fernando M. Berganza, Denise A. Hayes, Davinder Singh-Grewal, Suman Bharath, Sujata Sajjan, Jagadeesh Bayry
Journal: Nature Reviews Rheumatology (2021)
Abstract 11562: Remote Ischemic Conditioning Attenuates the Effect of System Delay in STEMI Patients Treated With Primary Percutaneous Coronary Intervention
Authors: Kasper Pryds, Christian J Terkelsen, Astrid D Sloth, Kim Munk, Michael R Schmidt, Hans E Bøtker
Journal: Circulation (2014)

Purpose:  Remote ischemic conditioning (RIC) increases myocardial salvage, whereas extended system delay reduces myocardial salvage and increases infarct size in patients with ST-elevation myocardial infarction (STEMI). We investigated the influence of RIC on the effect of system delay in STEMI patients undergoing primary percutaneous coronary intervention (pPCI).   Methods:  In a prospective, single-blinded randomized controlled trial (n=251), we studied STEMI patients randomized to treatment with either pPCI alone or pPCI+RIC. RIC was performed during transport to hospital as 4 cycles of 5 min upper arm ischemia followed by 5 min of reperfusion. Area-at-risk, myocardial salvage index and final infarct size were assessed by single photon emission computerized tomography (SPECT). System delay was defined as time from emergency medical service call to pPCI-wire. Data were obtained from emergency medical service registries and files.   Results:  Data for final infarct size and system delay were available for 202 patients, and data for myocardial salvage index and system delay were available for 129 patients. Patients were equally distributed among treatment with pPCI alone or pPCI+RIC. Area-at-risk and system delay did not differ between patients treated with pPCI alone or pPCI+RIC (p=0.974 and p=0.909, respectively). While system delay in patients treated with pPCI alone was associated with significantly reduced myocardial salvage index (p=0.008) and increased final infarct size (p=0.043), these associations were attenuated in patients treated with pPCI+RIC (p=0.737 and p=0.628, respectively) with significantly different slopes (p=0.022) as shown for myocardial salvage index (figure).   Conclusion:  RIC attenuates the effect of extended system delay on myocardial salvage index and final infarct size in STEMI patients treated with pPCI, suggesting that the cardioprotective effect of RIC increases with extended duration of ischemia.
Lung function trajectory in progressive fibrosing interstitial lung disease
Authors: Justin M. Oldham, Cathryn T. Lee, Zhe Wu, Willis S. Bowman, Janelle Vu Pugashetti, Nam Dao, James Tonkin, Hasan Seede, Gabrielle Echt, Ayodeji Adegunsoye, Felix Chua, Toby M. Maher, Christine K. Garcia, Mary E. Strek, Chad A. Newton, Philip L. Molyneaux
Journal: European Respiratory Journal (2021)

Background Proposed criteria for progressive fibrosing interstitial lung disease (PF-ILD) have been linked to increased mortality risk, but lung function trajectory after satisfying individual criteria remains unknown. Because survival is rarely employed as the primary end-point in therapeutic trials, identifying PF-ILD criteria that best predict subsequent change in forced vital capacity (FVC) could improve clinical trial design. Methods A retrospective, multicentre longitudinal cohort analysis was performed in consecutive patients with fibrotic connective tissue disease-associated ILD (CTD-ILD), chronic hypersensitivity pneumonitis and idiopathic interstitial pneumonia at three US centres (test cohort) and one UK centre (validation cohort). 1-year change in FVC after satisfying proposed PF-ILD criteria was estimated using joint modelling. Subgroup analyses were performed to determine whether results varied across key subgroups. Results 1227 patients were included, with CTD-ILD predominating. Six out of nine PF-ILD criteria were associated with differential 1-year change in FVC, with radiological progression of fibrosis, alone and in combination with other features, associated with the largest subsequent decline in FVC. Findings varied significantly by ILD subtype, with CTD-ILD demonstrating little change in FVC after satisfying most PF-ILD criteria, while other ILDs showed significantly larger changes. Findings did not vary after stratification by radiological pattern or exposure to immunosuppressant therapy. Near-term change in FVC after satisfying proposed PF-ILD criteria was heterogeneous depending on the criterion assessed and was strongly influenced by ILD subtype. Conclusions These findings may inform future clinical trial design and suggest ILD subtype should be taken into consideration when applying PF-ILD criteria.