tbuckley/cabot-search huggingface dataset:
Tinea Pseudoimbricata
Authors: Gilles Absil, Murielle Sabatiello, Arjen Nikkels
Journal: JAMA Dermatology (2022)

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Targeting ligand-dependent wnt pathway dysregulation in gastrointestinal cancers through porcupine inhibition
Authors: Dustin J. Flanagan, Simon A. Woodcock, Caroline Phillips, Catherine Eagle, Owen J. Sansom
Journal: Pharmacology & Therapeutics (2022)

Gastrointestinal cancers are responsible for more cancer deaths than any other system of the body. This review summarises how Wnt pathway dysregulation contributes to the development of the most common gastrointestinal cancers, with a particular focus on the nature and frequency of upstream pathway aberrations. Tumors with upstream aberrations maintain a dependency on the presence of functional Wnt ligand, and are predicted to be tractable to inhibitors of Porcupine, an enzyme that plays a key role in Wnt secretion. We summarise available pre-clinical efficacy data from Porcupine inhibitors in vitro and in vivo, as well as potential toxicities and the data from early phase clinical trials. We appraise the rationale for biomarker-defined targeted approaches, as well as outlining future opportunities for combination with other therapeutics.
Pros and cons of causative association between periodontitis and rheumatoid arthritis
Authors: Joanna Koziel, Jan Potempa
Journal: Periodontology 2000 (2022)

Research in recent decades has brought significant advancements in understanding of the molecular basis of the etiology of autoimmune diseases, including rheumatoid arthritis, a common systemic disease in which an inappropriate or inadequate immune response to environmental challenges leads to joint destruction. Recent studies have indicated that the classical viewpoint of the immunological processes underpinning the pathobiology of rheumatoid arthritis is restricted and needs to be expanded to include a more holistic and interdisciplinary approach incorporating bacteria-induced inflammatory reactions as an important pathway in rheumatoid arthritis etiology. Here, we discuss in detail data showing the clinical and molecular association of rheumatoid arthritis development with periodontal diseases. We also describe the unique role of periopathogens, which have been proposed to be crucial in the initiation and progression of this autoimmune pathological disorder.
MALE SEX, HLA-C*04:01 AND COVID-19: A RISKY CONSTELLATION
Authors: Phillip Suwalski, Dimitri Patriki, Claudia Quedenau, Tatiana Borodina, Juerg H. Beer, Benedikt Wiggli, Toumy Guettouche, Ulf Landmesser, Bettina Heidecker
Journal: Journal of the American College of Cardiology (2022)
Adjuvant Versus Early Salvage Radiation Therapy After Radical Prostatectomy for pN1 Prostate Cancer and the Risk of Death
Authors: Derya Tilki, Ming-Hui Chen, Jing Wu, Hartwig Huland, Markus Graefen, Anthony V. D'Amico
Journal: Journal of Clinical Oncology (2022)

PURPOSE An association with a reduction in the risk of all-cause mortality (ACM) and the use of adjuvant as compared with early postradical prostatectomy salvage radiation therapy (sRT) in men with pN1 prostate cancer (PC) has been observed. Yet, whether this finding applies irrespective of the number of positive lymph nodes (LNs) after adjusting for the time-dependent use and duration of androgen deprivation therapy is unknown and is addressed in the current study. METHODS Univariable and multivariable Cox regression was used to evaluate whether the ACM risk ratio for time-dependent use of adjuvant versus early sRT per unit increase in positive pelvic LNs was significantly reduced. Adjusted ACM estimates were calculated among men who received adjuvant, early salvage, or no RT stratified by one to three or four or more positive pelvic LNs. RESULTS After a median follow-up of 7.02 years, 986 (5.50%) men died, with 223 (22.62%) of PC. Adjuvant compared with early sRT was associated with a significantly lower ACM risk per unit increase in positive pelvic LNs (adjusted hazard ratio: 0.92; 95% CI, 0.85 to 0.99; P = .03). A significant difference in the 7-year adjusted ACM estimates favoring aRT versus early sRT was observed in men with four or more positive LNs (7.74% v 23.36%) in that the 95% CI for the 15.62% difference (5.90 to 25.35) excluded 0.00, but this was not true for men with 1-3 positive LNs (14.27% v 13.89%; 95% CI for the 0.38% difference [–7.02 to 7.79]). CONCLUSION Adjuvant compared with early sRT in men with pN1 PC was associated with a decreased ACM risk, and this reduction increased with each additional positive pelvic LN.
Tom Nolan’s research reviews—31 March 2022
Authors: Tom Nolan
Journal: BMJ (2022)

Variant varianceMass vaccination against covid-19 means we're in a very different place to two years ago.Where once GPs received no positive covid tests (because you weren't allowed one unless you were admitted to hospital) but plenty of calls from frightened breathless patients unsure if they were allowed to go to hospital, we now have positive test results coming in by the hour, but thankfully few people becoming severely unwell.
ECHOCARDIOGRAPHIC ASSESSMENT OF THE RIGHT HEART BEFORE AND AFTER PERCUTANEOUS PULMONIC BALLOON VALVULOPLASTY IN A PATIENT WITH CARCINOID PULMONIC STENOSIS AND A BIOPROSTHETIC TRICUSPID VALVE
Authors: Ramon Miguel Rivera, Regine Elena M. Bisnar, Bryan Rene Fortich Toledano, Edwin Tucay
Journal: Journal of the American College of Cardiology (2022)
Ectopic Gallbladder in the Left Upper Abdomen Shown on Hepatobiliary Scintigraphy
Authors: Xia Bai, Hongming Zhuang
Journal: Clinical Nuclear Medicine (2022)

Abstract The gallbladder is normally located in the right upper abdomen below the undersurface of the liver. We reported an ectopically located gallbladder, which was located in the left upper abdomen on hepatobiliary scintigraphy in an 18-year-old woman.
Antibiotics for lower respiratory tract infection in children presenting in primary care (ARTIC-PC): the predictive value of molecular testing
Authors: Paul Little, Robert C. Read, Taeko Becque, Nick A. Francis, Alastair D. Hay, Beth Stuart, Gilly O'Reilly, Natalie Thompson, Kerenza Hood, Saul Faust, Kay Wang, Michael Moore, Theo Verheij
Journal: Clinical Microbiology and Infection (2022)

This study aimed to assess whether the presence of bacteria or viruses in the upper airway of children presenting with uncomplicated lower respiratory tract infection (LRTI) predicts the benefit of antibiotics.Children between 6 months and 12 years presenting to UK general practices with an acute LRTI were randomized to receive amoxicillin 50 mg/kg/d for 7 days or placebo. Children not randomized (ineligible or clinician/parental choice) could participate in a parallel observational study. The primary outcome was the duration of symptoms rated moderately bad or worse. Throat swabs were taken and analyzed for the presence of bacteria and viruses by multiplex PCR.Swab results were available for most participants in the trial (306 of 432; 71%) and in the observational (182 of 326; 59%) studies. Bacterial pathogens potentially sensitive to amoxicillin (Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae) were detected among 51% of the trial placebo group and 49% of the trial antibiotic group. The median difference in the duration of symptoms rated moderately bad or worse between antibiotic and placebo was similar when potentially antibiotic-susceptible bacteria were present (median: -1 day; 99% CI, -12.3 to 10.3) or not present (median: -1 day; 99% CI, -4.5 to 2.5). Furthermore, bacterial genome copy number did not predict benefit. There were similar findings for all secondary outcomes and when including the data from the observational study.There was no clear evidence that antibiotics improved clinical outcomes conditional on the presence or concentration of bacteria or viruses in the upper airway. Before deploying microbiologic point-of-care tests for children with uncomplicated LRTI in primary care, rigorous validating trials are needed.
Residual ctDNA after treatment predicts early relapse in patients with early-stage non-small cell lung cancer
Authors: D. Gale, K. Heider, A. Ruiz-Valdepenas, S. Hackinger, M. Perry, G. Marsico, V. Rundell, J. Wulff, G. Sharma, H. Knock, J. Castedo, W. Cooper, H. Zhao, C.G. Smith, S. Garg, S. Anand, K. Howarth, D. Gilligan, S.V. Harden, D.M. Rassl, R.C. Rintoul, N. Rosenfeld
Journal: Annals of Oncology (2022)

Identification of residual disease in patients with localized non-small cell lung cancer (NSCLC) following treatment with curative intent holds promise to identify patients at risk of relapse. New methods can detect circulating tumour DNA (ctDNA) in plasma to fractional concentrations as low as a few parts per million, and clinical evidence is required to inform their use.
2D ECHOCARDIOGRAPHY IS SENSITIVE BUT NOT SPECIFIC FOR LEFT VENTRICULAR HYPERTROPHY IN HFPEF: COMPARISON WITH 3D ECHOCARDIOGRAPHY
Authors: Viral Desai, Apurv Agarwal, Gaurang N. Vaidya, Mohammad Mathbout, Marcus F. Stoddard
Journal: Journal of the American College of Cardiology (2022)
CRLF3 plays a key role in the final stage of platelet genesis and is a potential therapeutic target for thrombocythemia
Authors: Cavan Bennett, Moyra Lawrence, Jose A. Guerrero, Simon Stritt, Amie K. Waller, Yahui Yan, Richard W. Mifsud, Jose Ballester-Beltrán, Ayesha Baig, Annett Mueller, Louisa Mayer, James Warland, Christopher J. Penkett, Parsa Akbari, Thomas Moreau, Amanda L. Evans, Souradip Mookerjee, Gary J. Hoffman, Kourosh Saeb-Parsy, David J. Adams, Amber L. Couzens, Markus Bender, Wendy N. Erber, Bernhard Nieswandt, Randy J. Read, Cedric Ghevaert
Journal: Blood (2022)

The process of platelet production has so far been understood to be a 2-stage process: megakaryocyte maturation from hematopoietic stem cells followed by proplatelet formation, with each phase regulating the peripheral blood platelet count. Proplatelet formation releases into the bloodstream beads-on-a-string preplatelets, which undergo fission into mature platelets. For the first time, we show that preplatelet maturation is a third, tightly regulated, critical process akin to cytokinesis that regulates platelet count. We show that deficiency in cytokine receptor-like factor 3 (CRLF3) in mice leads to an isolated and sustained 25% to 48% reduction in the platelet count without any effect on other blood cell lineages. We show that Crlf3-/- preplatelets have increased microtubule stability, possibly because of increased microtubule glutamylation via the interaction of CRLF3 with key members of the Hippo pathway. Using a mouse model of JAK2 V617F essential thrombocythemia, we show that a lack of CRLF3 leads to long-term lineage-specific normalization of the platelet count. We thereby postulate that targeting CRLF3 has therapeutic potential for treatment of thrombocythemia.
IN-HOSPITAL CARDIAC ARREST COMPLICATING ACUTE MYOCARDIAL INFARCTION: TEMPORAL TRENDS AND OUTCOMES BASED ON MANAGEMENT STRATEGY
Authors: Dhiran Verghese, Anusha Bhat, Sri Harsha Patlolla, Charles R. McKay, Quang T. Bui, Matthew J. Budoff, Saraschandra Vallabhajosyula
Journal: Journal of the American College of Cardiology (2022)
HIGH-DOSE STATIN GIVEN AS LOADING DOSE PRIOR TO PCI REDUCES NO-REFLOW PHENOMENON IN ACUTE CORONARY SYNDROME: A META-ANALYSIS OF 4829 PROCEDURES
Authors: Sonali Sachdeva, Udita Gupta, Jenish Bhandari, Avilash Mondal, Abdulrahman Hashem, Mahnoor Sukaina, Harshwardhan Khandait, Farah Yasmin, Rupak Desai, Akhil Jain, Hasnan M. Ijaz, Ankit Vyas
Journal: Journal of the American College of Cardiology (2022)
CLO22-068: An Assessment of Extended Pembrolizumab Dosing and Outcomes in Advanced Non-Small Cell Lung Cancer Patients During the COVID-19 Pandemic
Authors: Gordon Taylor Moffat, Lilian Hanna, Wilma Hopman, Andrea S. Fung, Pierre-Olivier Gaudreau
Journal: Journal of the National Comprehensive Cancer Network (2022)

"CLO22-068: An Assessment of Extended Pembrolizumab Dosing and Outcomes in Advanced Non-Small Cell Lung Cancer Patients During the COVID-19 Pandemic" published on 31 Mar 2022 by National Comprehensive Cancer Network.
Results of <scp>ARI</scp>‐0001 <scp>CART19</scp> cell therapy in patients with relapsed/refractory <scp>CD19</scp>‐positive acute lymphoblastic leukemia with isolated extramedullary disease
Authors: Valentín Ortiz‐Maldonado, Anna Alonso‐Saladrigues, Marta Español‐Rego, Nuria Martínez‐Cibrián, Anna Faura, Laura Magnano, Albert Català, Daniel Benítez‐Ribas, Eva Giné, Marina Díaz‐Beyá, Juan Gonzalo Correa, Montserrat Rovira, Mercedes Montoro‐Lorite, Alexandra Martínez‐Roca, Luis Gerardo Rodríguez‐Lobato, Raquel Cabezón, Joan Cid, Miquel Lozano, Enric Garcia‐Rey, Nuria Conde, Georgina Pedrals, María Rozman, Montserrat Torrebadell, Xavier Setoain, Sonia Rodríguez, Jordi Esteve, Mariona Pascal, Álvaro Urbano‐Ispizua, Manel Juan, Julio Delgado, Susana Rives
Journal: American Journal of Hematology (2022)

We evaluated outcomes of 18 patients with isolated extramedullary disease (iEMD) relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) treated with the CD19-directed CAR T cells ARI-0001 in two centers (adult and pediatric), including patients treated in the CART19-BE-01 trial and the consecutive compassionate use program. iEMD was detected by PET-CT in 78% (14/18), and/or by cerebrospinal fluid analysis in 28% (5/18). Patients received cyclophosphamide and fludarabine followed by 1 × 106 ARI-0001 cells/kg, initially as a single dose (first patient) and later split into three fractions (10%, 30%, and 60%). Cytokine release syndrome (CRS) occurred in 50% (9/18) of patients, with no cases of grade ≥3 CRS, and 1 case (6%) of grade 1 neurotoxicity. Tocilizumab was used in 6% of patients (1/18). Procedure-related mortality was 0% at 2 years. Objective responses were seen in 94% (95% confidence interval [CI]: 73%-99%) of patients, with complete responses (CR) seen in 78% (95% CI: 52%-94%) of them. Progression-free and overall survival were 49% (95% CI: 30%-79%) and 61% (95% CI: 40%-92%) at 2 years. In conclusion, the use of ARI-0001 cells in patients with R/R ALL and iEMD was associated with a safety and efficacy profile that is comparable with what is observed in patients with marrow involvement and in line with other CART19 products.
ESTABLISHING A NOVEL MODEL TO STUDY CARDIAC ELECTROPORATION ABLATION UTILIZING HUMAN INDUCED PLURIPOTENT STEM CELLS
Authors: Leonid Maizels, Eyal Heller, Michal Landesberg, Irit Huber, Gil Arbel, Amira Gepstein, Roy Beinart, Amit Segev, Lior Gepstein, Elad Maor
Journal: Journal of the American College of Cardiology (2022)
REPRESENTATION OF WOMEN AND MINORITIES ACROSS US ACADEMIC PEDIATRIC CARDIOLOGY PROGRAMS
Authors: Sowmya Balasubramanian, Sara K. Pasquali, Melissa K. Cousino, Ray E. Lowery, Andrea S. Les, Amanda D. McCormick, Caroline L. West, Carlen G. Fifer, Caren S. Goldberg, Jennifer C. Romano, Sonal T. Owens
Journal: Journal of the American College of Cardiology (2022)
Comparative effectiveness of statins on non-high density lipoprotein cholesterol in people with diabetes and at risk of cardiovascular disease: systematic review and network meta-analysis
Authors: Alexander Hodkinson, Dialechti Tsimpida, Evangelos Kontopantelis, Martin K Rutter, Mamas A Mamas, Maria Panagioti
Journal: BMJ (2022)

To compare the efficacy of different statin treatments by intensity on levels of non-high density lipoprotein cholesterol (non-HDL-C) for the prevention of cardiovascular disease in people with diabetes.
The replacement of helper lipids with charged alternatives in lipid nanoparticles facilitates targeted mRNA delivery to the spleen and lungs
Authors: Samuel T. LoPresti, Mariah L. Arral, Namit Chaudhary, Kathryn A. Whitehead
Journal: Journal of Controlled Release (2022)

The broad clinical application of mRNA therapeutics has been hampered by a lack of delivery vehicles that induce protein expression in extrahepatic organs and tissues. Recently, it was shown that mRNA delivery to the spleen or lungs is possible upon the addition of a charged lipid to a standard four-component lipid nanoparticle formulation. This approach, while effective, further complicates an already complex drug formulation and has the potential to slow regulatory approval and adversely impact manufacturing processes. We were thus motivated to maintain a four-component nanoparticle system while achieving shifts in tropism. To that end, we replaced the standard helper lipid in lipidoid nanoparticles, DOPE, with one of eight alternatives. These lipids included the neutral lipids, DOPC, sphingomyelin, and ceramide; the anionic lipids, phosphatidylserine (PS), phosphatidylglycerol, and phosphatidic acid; and the cationic lipids, DOTAP and ethyl phosphatidylcholine. While neutral helper lipids maintained protein expression in the liver, anionic and cationic lipids shifted protein expression to the spleen and lungs, respectively. For example, replacing DOPE with DOTAP increased positive LNP surface charge at pH 7 by 5-fold and altered the ratio of liver to lung protein expression from 36:1 to 1:56. Similarly, replacing DOPE with PS reduced positive charge by half and altered the ratio of liver to spleen protein expression from 8:1 to 1:3. Effects were consistent across ionizable lipidoid chemistries. Regarding mechanism, nanoparticles formulated with neutral and anionic helper lipids best transfected epithelial and immune cells, respectively. Further, the lung-tropic effect of DOTAP was linked to reduced immune cell infiltration of the lungs compared to neutral or anionic lipids. Together, these data show that intravenous non-hepatocellular mRNA delivery is readily achievable while maintaining a four-component formulation with modified helper lipid chemistry.
USE OF DUAL PATHWAY INHIBITION FOR SECONDARY PREVENTION IN PATIENTS WITH ATHEROTHROMBOTIC DISEASE: THE PROSPECTIVE REAL-WORLD XATOA STUDY
Authors: Uwe Zeymer, Victor Aboyans, Martin R. Cowie, E. Sebastian Debus, Alain Gay, Kai Vogtländer, Sonia Anand, Keith A.A. Fox
Journal: Journal of the American College of Cardiology (2022)
METABOLIC CHANGES MEASURED BY IN-VIVO CARDIAC MAGNETIC RESONANCE SPECTROSCOPY IS ASSOCIATED WITH CARDIAC INJURY AND FIBROTIC DEVELOPMENT IN AN ANIMAL MODEL OF DOXORUBICIN CARDIOTOXICITY
Authors: Xiaoying Cai, Selcuk Kucukseymen, Kei Nakata, Maria-Alexandra Olaru, Patrick Pierce, Beth Goddu, Warren J. Manning, Reza Nezafat
Journal: Journal of the American College of Cardiology (2022)
A LABOUR OF LOVE: A SYSTEMATIC REVIEW AND META-ANALYSIS OF LONG-TERM (&gt;1 YEAR) CARDIAC OUTCOMES OF PERIPARTUM CARDIOMYOPATHY
Authors: Daniel Koerber, Shawn Khan, Abirami Kirubarajan, Alexandra Spivak, Rachel Wine, John Matelski, Mara Sobel
Journal: Journal of the American College of Cardiology (2022)
A nanovaccine for enhancing cellular immunity via cytosolic co-delivery of antigen and polyIC RNA
Authors: Carcia S. Carson, Kyle W. Becker, Kyle M. Garland, Hayden M. Pagendarm, Payton T. Stone, Karan Arora, Lihong Wang-Bishop, Jessalyn J. Baljon, Lorena D. Cruz, Sebastian Joyce, John T. Wilson
Journal: Journal of Controlled Release (2022)
LONGITUDINAL FUNCTIONAL, STRUCTURAL AND BIOMECHANICAL REMODELING OF THE POSTMYOCARDIAL INFARCTION LEFT VENTRICLE IN SWINE USING CARDIAC MAGNETIC RESONANCE IMAGING
Authors: Daniella Corporan, Michael Silverman, Chase King, Kirthana Sreerangathama Suresh, Dongyang Xu, Daisuke Onohara, Muralidhar Padala
Journal: Journal of the American College of Cardiology (2022)
Abstract P3-18-02: Breast conservation plus radiotherapy provides superior survival benefit than mastectomy in triple negative breast cancer: A propensity matched national cancer database analysis
Authors: Lifen Cao, Christopher W Towe, Megan E Miller, Alberto J Montero, Robert Shenk
Journal: Cancer Research (2022)

Abstract Background: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with a higher risk of locoregional and distance recurrence. Consequently, this population was considered poor candidate for breast conservation (BCT). Our study aim was to determine whether BCT plus radiotherapy (RT) was equivalent to mastectomy for TNBC after adjustment of selection bias of demographic and clinical characteristics. Methods: The National Cancer Database was queried for women diagnosed as primary unilateral invasive clinical T1-2N0-2 TNBC from 2004-2016. Patients who underwent mastectomy or breast conservation (partial mastectomy plus radiation) were included. A 1:1 propensity match with replacement was performed to compare breast conservation vs. mastectomy. Overall survival was analyzed using stratified multivariable Cox proportional hazard regression analysis.Results: Of 59,599 clinical T1-2N0-2 TNBC patients, 26,325 (44.2%) underwent mastectomy and 33,274 (55.8%) were treated with BCT. BCT patients were older (median age 59 vs. 54, p&amp;lt;0.001), had smaller tumors (cT1 61.7% vs. 42.9%, p&amp;lt;0.001) and node negative (cN0 85.8% vs. 73.7%, p&amp;lt;0.001). Propensity matching reduced the bias between mastectomy and breast conservation groups and generated 30,980 pairs for analysis. Median follow-up times were 41 months (range 6.97-95.8) and 39 months (range, 0.62 -94.06) for BCT and mastectomy groups, respectively. After matching, BCT+RT was associated with significantly higher OS compared to mastectomy ( 86.8% vs. 79.7%, p&amp;lt;0.001). The survival advantage was also present in multivariate cox regression after controlling age, race, insurance, facility type, clinical T and clinical N stage.Conclusions: Using both propensity matching and multivariate cox regression controlling for potential confounders, BCT+RT survival was superior to mastectomy in a retrospective analysis of a large cancer database. Citation Format: Lifen Cao, Christopher W Towe, Megan E Miller, Alberto J Montero, Robert Shenk. Breast conservation plus radiotherapy provides superior survival benefit than mastectomy in triple negative breast cancer: A propensity matched national cancer database analysis [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-18-02.
REAL WORLD EFFICACY AND SAFETY OF DIRECT ORAL ANTICOAGULANTS VERSUS VITAMIN K ANTAGONISTS IN PATIENTS WITH NONVALULAR ATRIAL FIBRILLATION AT THE UPPER EXTREMES OF BODY WEIGHT AND BMI. RESULTS FROM A LARGE INTEGRATED HEALTHCARE SYSTEM
Authors: Stephen John Voyce, Joseph Chronowski, Stacey Grassi, Erin Van Enkevort, Patrick Roman, C. Logan (Christopher) SanCraint, Anna Griffith
Journal: Journal of the American College of Cardiology (2022)
IMPACT OF RENIN-ANGIOTENSIN SYSTEM INHIBITORS ON CLINICAL OUTCOMES IN PATIENTS WITH SEVERE SYMPTOMATIC AORTIC STENOSIS UNDERGOING TRANSCATHETER AORTIC VALVE REPLACEMENT WITH A SELF-EXPANDING BIOPROSTHESIS
Authors: Sachin S. Goel, Neal S. Kleiman, Stanley J. Chetcuti, G. Michael Deeb, Steven J. Yakubov, Sarah Verdoliva Boatman, Nicolas M. Van Mieghem, Michael J. Reardon
Journal: Journal of the American College of Cardiology (2022)