tbuckley/cabot-search huggingface dataset:
Characterization and anti-tumor activity of a chimeric tetravalent anti-CD22 monoclonal antibody
Authors: Xiao-yun Liu, Laurentiu Pop, Joan Smallshaw, Derry Roopenian, Victor Ghetie, Ellen Vitetta
Journal: Cancer Research (2007)

903  A tetravalent chimeric anti-human CD22 antibody (cRFB4-TetraMAb) with improved anti-tumor activity has been developed. The DNA encoding the single chain Fv (scFv) was spliced to the Fc of human IgG1 and expressed in Chinese hamster ovary cells. The construct was purified on Sepharose- Protein G followed by HPLC. The characteristics of the cTetraMAb were analyzed and compared to its parental divalent MAb, RFB4. The TetraMAb bound to CD22+ Daudi cells as well as the divalent RFB4, but had a slower dissociation rate. Both the TetraMAb and the divalent RFB4 bound equally well to FcγR-positive human cells, to human C1q, and to recombinant human FcRn in vitro. It also had comparable ADCC activity when human effector cells were used. Despite its slightly larger size, the TetraMAb penetrated normal tissues in Swiss Webster mice as well as the divalent MAb. The TetraMAb had a longer half-life in both Swiss Webster mice and mFcRn-/hFcRn+ transgenic mice, and it showed improved anti-tumor activity in SCID mice xenografted with various CD22 positive human tumor cell lines. Moreover, the enhanced activity of the TetraMAb was dose-related. In conclusion, these data suggest that this tetravalent RFB4 antibody should be further developed for human use.
A randomized phase 3 trial of zanubrutinib vs ibrutinib in symptomatic Waldenström macroglobulinemia: the ASPEN study
Authors: Constantine S. Tam, Stephen Opat, Shirley D'Sa, Wojciech Jurczak, Hui-Peng Lee, Gavin Cull, Roger G. Owen, Paula Marlton, Björn E. Wahlin, Ramón Garcia Sanz, Helen McCarthy, Stephen Mulligan, Alessandra Tedeschi, Jorge J. Castillo, Jaroslaw Czyz, Carlos Fernández de Larrea, David Belada, Edward Libby, Jeffrey V. Matous, Marina Motta, Tanya Siddiqi, Monica Tani, Marek Trneny, Monique C. Minnema, Christian Buske, Veronique Leblond, Judith Trotman, Wai Y. Chan, Jingjing Schneider, Sunhee Ro, Aileen Cohen, Jane Huang, Meletios Dimopoulos
Journal: Blood (2020)
Response to: ‘More evidences on which biologic and which pathway is key in severe-critical COVID-19 pneumonia’ by Ferraccioli
Authors: Emanuel Della-Torre, Corrado Campochiaro, Giulio Cavalli, Giacomo De Luca, Fabio Ciceri, Alberto Zangrillo, Lorenzo Dagna
Journal: Annals of the Rheumatic Diseases (2020)

H<i>elicobacter pylori</i>infection is a major cause of peptic ulcer disease, and its detection and eradication are now an important part of gastroenterology. Effective regimes are available which will eliminate the organism in about 90% of cases in developed countries.
Correction: Factors associated with complete clearance of difficult common bile duct stones after temporary biliary stenting followed by a second ERCP: a multicenter, retrospective, cohort study
Authors: Dong Kee Jang, Sang Hyub Lee, Dong Won Ahn, Woo Hyun Paik, Jae Min Lee, Jun Kyu Lee, Ji Kon Ryu, Yong-Tae Kim
Journal: Endoscopy (2020)

Correction to: Factors associated with complete clearance of difficult common bile duct stones after temporary biliary stenting followed by a second ERCP: a multicenter, retrospective, cohort studyEndoscopy 2020; 52(06): 462-468DOI: 10.1055/a-1117-3393
Remdesivir for severe covid-19: a clinical practice guideline
Authors: Bram Rochwerg, Arnav Agarwal, Linan Zeng, Yee-Sin Leo, John Adabie Appiah, Thomas Agoritsas, Jessica Bartoszko, Romina Brignardello-Petersen, Begum Ergan, Long Ge, Heike Geduld, Hayley B Gershengorn, Hela Manai, Minhua Huang, François Lamontagne, Seema Kanda, Leticia Kawano-Dourado, Linda Kurian, Arthur Kwizera, Srinivas Murthy, Nida Qadir, Reed Siemieniuk, Maria Asuncion Silvestre, Per Olav Vandvik, Zhikang Ye, Dena Zeraatkar, Gordon Guyatt
Journal: BMJ (2020)

Abstract Clinical question What is the role of remdesivir in the treatment of severe covid-19? This guideline was triggered by the ACTT-1 trial published in the New England Journal of Medicine on 22 May 2020. Current practice Remdesivir has received worldwide attention as a potentially effective treatment for severe covid-19. After rapid market approval in the US, remdesivir is already being used in clinical practice. Recommendations The guideline panel makes a weak recommendation for the use of remdesivir in severe covid-19 while recommending continuation of active enrolment of patients into ongoing randomised controlled trials examining remdesivir. How this guideline was created An international panel of patients, clinicians, and methodologists produced these recommendations in adherence with standards for trustworthy guidelines using the GRADE approach. The recommendations are based on a linked systematic review and network meta-analysis. The panel considered an individual patient perspective and allowed contextual factors (such as resources) to be taken into account for countries and healthcare systems. The evidence The linked systematic review (published 31 Jul 2020) identified two randomised trials with 1300 participants, showing low certainty evidence that remdesivir may be effective in reducing time to clinical improvement and may decrease mortality in patients with severe covid-19. Remdesivir probably has no important effect on need for invasive mechanical ventilation. Remdesivir may have little or no effect on hospital length of stay. Understanding the recommendation Most patients with severe covid-19 would likely choose treatment with remdesivir given the potential reduction in time to clinical improvement. However, given the low certainty evidence for critical outcomes and the fact that different perspectives, values, and preferences may alter decisions regarding remdesivir, the panel issued a weak recommendation with strong support for continued recruitment in randomised trials.
Abstract P139: Healthy Lifestyle Status, Antihypertensive Treatment and the Risk of Heart Failure among Finnish Men and Women
Authors: Yujie Wang, Jaakko Tuomilehto, Pekka Jousilahti, Riitta Antikainen, Markku Mähönen, Peter T. Katzmarzyk, Gang Hu
Journal: Circulation (2012)

Background: It is unclear which is more effective in preventing heart failure (HF) in hypertensive people: lifestyle intervention or antihypertensive drug treatment. Aim: To investigate whether there are differences in HF risk among hypertensive patients using antihypertensive drug treatment versus those engaging in a healthy lifestyle at baseline. Methods: Study cohorts included 38075 Finnish participants who were 25 to 74 years of age and free of HF at baseline. The study population was classified into five groups according to their blood pressure status at baseline. A healthy lifestyle was defined as having two or more healthy lifestyle factors including moderate or high level of physical activity, never smoking, body mass index &lt;25 kg/m 2 , and vegetable consumption ≥3 times/week. Results: During a median follow-up of 14.1 years, 638 men and 445 women developed HF. Compared with normotensive people, hypertensive patients with and without antihypertensive treatment had a higher risk of HF. Engaging in a healthy lifestyle was associated with a decreased risk of HF. The multivariable-adjusted hazard ratios (HRs) of HF in the ten subgroups (normotensive group with a healthy lifestyle; hypertensive, unaware, untreated group with a healthy lifestyle; hypertensive, aware, untreated group with a healthy lifestyle; hypertensive, treated, controlled group with a healthy lifestyle; hypertensive, treated, uncontrolled group with a healthy lifestyle; normotensive group without a healthy lifestyle; hypertensive, unaware, untreated group without a healthy lifestyle; hypertensive, aware, untreated group without a healthy lifestyle; hypertensive, treated, controlled group without a healthy lifestyle; and hypertensive, treated, uncontrolled group without a healthy lifestyle) were 1.00, 1.50, 1.54, 2.24, 1.91, 2.12, 2.68, 3.05, 2.27, and 3.21 (Ptrend &lt;0.001), respectively. Hypertensive subjects who used antihypertensive drugs but did not engage in a healthy lifestyle had a significantly higher risk of HF (HR 2.10; 95% CI 1.68–2.63) than hypertensive subjects who did not use antihypertensive drug but engaged in a healthy lifestyle. Hypertensive subjects who did not use antihypertensive drugs and did not engage in a healthy lifestyle had a significant higher risk of HF (HR 1.44; 95% CI 1.16–1.80) compared with hypertensive subjects who used antihypertensive drug and engaged in a healthy lifestyle. Conclusions: The present study demonstrates that the risk of HF was lower in hypertensive patients who engaged in a healthy lifestyle but higher in hypertensive people despite of antihypertensive drug treatment and adequate control of hypertension. Lifestyle intervention may be more effective in preventing HF than antihypertensive treatment in hypertensive subjects.
Successful Response to Treatment with Sirolimus in Pulmonary Sarcoidosis
Authors: Nishant Gupta, Jack H. Bleesing, Francis X. McCormack
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

"Successful Response to Treatment with Sirolimus in Pulmonary Sarcoidosis." American Journal of Respiratory and Critical Care Medicine, 202(9), pp. e119–e120
Response to: ‘Rational use of tocilizumab in COVID-19’ by Jain and Sharma
Authors: Nicola Potere, Marcello Di Nisio, Donatella Cibelli, Rosa Scurti, Antonella Frattari, Ettore Porreca, Antonio Abbate, Giustino Parruti
Journal: Annals of the Rheumatic Diseases (2020)

We thank Jain and Sharma1 for their interest in our recent report on interleukin-6 (IL-6) receptor blockade with subcutaneous tocilizumab (324 mg, given in two concomitant 162 mg doses) in patients with severe COVID-19 pneumonia and hyperinflammation.2 Jain and Sharma bring up an important point regarding the safety profile of subcutaneous tocilizumab in patients with COVID-19 at risk of concomitant bacterial infections.1 As already concisely described, in our case–control series, only relatively young patients with severe COVID-19 pneumonia, requiring oxygen support through nasal cannulas or masks, hyperinflammation (C-reactive protein >20 mg/dL) and no contraindications to tocilizumab, including suspected concomitant bacterial infection, were included.2 Well aware of the potential adverse effects of tocilizumab, our screening protocol to rule out concomitant bacterial infection was based on medical history, collected at the time of and during hospitalisation in advance of tocilizumab administration, absolute white blood cell, neutrophil and lymphocyte counts, serial procalcitonin (PCT) values, which were persistently <0.1 ng/mL in most patients, as well as imaging testing assessing for concomitant infection sites outside the lungs. Indeed, several patients were cautiously excluded due …
Genetic Validation of the Palmitoylation/Depalmitoylation Cycle As a Drug Target in NRAS Mutant Hematologic Malignancies In Vivo
Authors: Noemi A. Zambetti, Ari J. Firestone, Jasmine C. Wong, Amanda Long, Anagha Inguva, Radu M. Suciu, Benjamin F. Cravatt, Kevin M. Haigis, Kevin M. Shannon
Journal: Blood (2017)
To Be or Not to Be Improved: Patients’ Perception of Symptom Improvement – Linking the SCL-90-R to Patient-Rated Global Improvement in a Large Real-World Treatment Sample
Authors: Falk Leichsenring, Ulrich Jaeger, Oliver Masuhr, Andreas Dally, Michael Dümpelmann, Christian Fricke-Neef, Carsten Spitzer, Christiane Steinert
Journal: Psychotherapy and Psychosomatics (2020)

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; From both a clinical and research perspective, it is important to determine what constitutes a perceivable change in commonly used outcome measures. &lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; We aimed to do so for the Symptom Checklist-90-Revised (SCL-90-R). &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Patients from a large real-world sample treated with inpatient psychotherapy (&lt;i&gt;n&lt;/i&gt; = 4,791) rated improvements in symptoms on a global 5-point Likert scale at discharge. These ratings were related to pre-post changes in the Global Severity Index (GSI) of the SCL-90-R by use of equipercentile linking. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; A patient rating of 5 (“clearly improved”) was found to be equivalent to an absolute pre-post difference in the GSI of 0.67 or to a percentage improvement of 54%, with the latter corresponding to the common definition of response as a 50% reduction in symptoms. A rating of 1 (“clearly worse”) was equivalent to an increase in the GSI &amp;#x3e;0.50 and to a percentage worsening &amp;#x3e;55%. “Slightly improved” or “slightly worse” (ratings of 4 or 2) corresponded to pre-post changes in the GSI of 0.07 and 0.50. For severely disordered patients, larger changes were required for ratings of improvement, and for less severely disordered patients, larger changes were required for ratings of worsening. Results for depressive, anxiety, and personality disorders were widely consistent with those of the total sample. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; This study is the first to link patient ratings of improvement or worsening to changes in the SCL-90-R. Results are relevant to both the interpretation of changes in individual patients and of effect sizes in outcome research. Results require replication.
Reimagining Vaccines for Prostate Cancer: Back to the Future
Authors: Eugene Shenderov, Emmanuel S. Antonarakis
Journal: Clinical Cancer Research (2020)

Given the modest clinical benefits observed with immune checkpoint blockade in advanced prostate cancer, there is a renewed interest in exploring other forms of immunotherapy. Here, the authors report the use of a novel plasmid DNA vaccine encoding the androgen receptor, called pTVG-AR, in men with metastatic hormone-sensitive prostate cancer.
Is There a Right to Delay Determination of Death by Neurologic Criteria?
Authors: Ariane Lewis, Richard J. Bonnie, Thaddeus Pope
Journal: JAMA Neurology (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
<i>SLFN11</i> promotes stalled fork degradation that underlies the phenotype in Fanconi anemia cells
Authors: Yusuke Okamoto, Masako Abe, Anfeng Mu, Yasuko Tempaku, Colette B. Rogers, Ayako L. Mochizuki, Yoko Katsuki, Masato T. Kanemaki, Akifumi Takaori-Kondo, Alexandra Sobeck, Anja-Katrin Bielinsky, Minoru Takata
Journal: Blood (2020)
Abstract 18134: Phenome-wide Study of Electronic Medical Record Data Reveals Novel Association of Natriuretic Peptide A Genetic Variant With Rheumatoid Arthritis
Authors: Naveen Pereira, Gregory Jenkins, Ifthikar Kullo, Suzette Bielinski, John Burnett, Jyotishman Pathak
Journal: Circulation (2015)

Introduction: Phenome-wide association studies (PheWAS) using electronic medical record (EMR)-linked biobanks have been used not only to identify and replicate known associations of genetic variants with disease phenotypes but have also resulted in the discovery of potentially novel genotype-phenotype relationships. The natriuretic peptide (NP) system plays an important role in a broad range of disease processes including cardiovascular and inflammatory diseases. We hypothesized that performing a PheWAS using previously known functional genetic variants of the NP system may result in novel disease associations that could provide mechanistic insights in an unbiased manner. Methods: We scanned for associations between 9 single-nucleotide polymorphisms (SNPs) in the NP system and 27 EMR-derived chronic disease phenotypes in 3,025 individuals participating in a case-control study of peripheral arterial disease. The EMR phenotypes were identified using two or more ICD-9-CM diagnosis codes based on the AHRQ Clinical Classifications Software (CCS). The relationship of SNPs and phenotypes were modeled using logistic regression adjusting for gender. Results: We identified rs5065, a SNP located in the stop codon of exon 3 of the NPPA gene, to be the strongest associated SNP with rheumatoid arthritis (RA) (OR=0.78, p=0.0008, q-value=0.11). The SNP leads to the extension of atrial natriuretic peptide (ANP) by 2 additional arginines at the C terminus. Cardiovascular disease is known to be the leading cause of death in patients with RA and ANP plays an important immunomodulatory role by inhibiting inducible nitric oxide synthase, reducing TNF-α production and attenuating prostaglandin E2 production in macrophages. Circulating NPs have been used to screen for occult cardiac disease and are associated with mortality in RA. This study demonstrates for the first time the importance of the relationship between genetic variation in the NP system and RA. Conclusions: PheWAS was successfully used as a tool to identify a novel association of functional genetic variation in the NPPA gene with RA. The observation is hypothesis generating and further replication studies are required to determine the role of rs5065 in cardiovascular outcomes of RA.
SeroTracker: a global SARS-CoV-2 seroprevalence dashboard
Authors: Rahul K Arora, Abel Joseph, Jordan Van Wyk, Simona Rocco, Austin Atmaja, Ewan May, Tingting Yan, Niklas Bobrovitz, Jonathan Chevrier, Matthew P Cheng, Tyler Williamson, David L Buckeridge
Journal: The Lancet Infectious Diseases (2020)
Comprehensive Characterization of the Vascular Effects of Cisplatin-Based Chemotherapy in Patients With Testicular Cancer
Authors: Alan C. Cameron, Kelly McMahon, Mark Hall, Karla B. Neves, Francisco J. Rios, Augusto C. Montezano, Paul Welsh, Ashita Waterston, Jeff White, Patrick B. Mark, Rhian M. Touyz, Ninian N. Lang
Journal: JACC CardioOncology (2020)

Cisplatin-based chemotherapy increases the risk of cardiovascular and renal disease.We aimed to define the time course, pathophysiology, and approaches to prevent cardiovascular disease associated with cisplatin-based chemotherapy.Two cohorts of patients with a history of testicular cancer (n = 53) were recruited. Cohort 1 consisted of 27 men undergoing treatment with: 1) surveillance; 2) 1 to 2 cycles of bleomycin, etoposide, and cisplatin (BEP) chemotherapy (low-intensity cisplatin); or 3) 3 to 4 cycles of BEP (high-intensity cisplatin). Endothelial function (percentage flow-mediated dilatation) and cardiovascular biomarkers were assessed at 6 visits over 9 months. Cohort 2 consisted of 26 men previously treated 1 to 7 years ago with surveillance or 3 to 4 cycles BEP. Vasomotor and fibrinolytic responses to bradykinin, acetylcholine, and sodium nitroprusside were evaluated using forearm venous occlusion plethysmography.In cohort 1, the percentage flow-mediated dilatation decreased 24 h after the first cisplatin dose in patients managed with 3 to 4 cycles BEP (10.9 ± 0.9 vs. 16.7 ± 1.6; p < 0.01) but was unchanged from baseline thereafter. Six weeks after starting 3 to 4 cycles BEP, there were increased serum cholesterol levels (7.2 ± 0.5 mmol/l vs. 5.5 ± 0.2 mmol/l; p = 0.01), hemoglobin A1c (41.8 ± 2.0 mmol/l vs. 35.5 ± 1.2 mmol/l; p < 0.001), von Willebrand factor antigen (62.4 ± 5.4 mmol/l vs. 45.2 ± 2.8 mmol/l; p = 0.048) and cystatin C (0.91 ± 0.07 mmol/l vs. 0.65 ± 0.09 mmol/l; p < 0.01). In cohort 2, intra-arterial bradykinin, acetylcholine, and sodium nitroprusside caused dose-dependent vasodilation (p < 0.0001). Vasomotor responses, endogenous fibrinolytic factor release, and cardiovascular biomarkers were not different in patients managed with 3 to 4 cycles of BEP versus surveillance.Cisplatin-based chemotherapy induces acute and transient endothelial dysfunction, dyslipidemia, hyperglycemia, and nephrotoxicity in the early phases of treatment. Cardiovascular and renal protective strategies should target the early perichemotherapy period. (Clinical Characterisation of the Vascular Effects of Cis-platinum Based Chemotherapy in Patients With Testicular Cancer [VECTOR], NCT03557177; Intermediate and Long Term Vascular Effects of Cisplatin in Patients With Testicular Cancer [INTELLECT], NCT03557164).
Adult zebrafish ventricular electrical gradients as tissue mechanisms of ECG patterns under baseline vs. oxidative stress
Authors: Yali Zhao, Nicholas A James, Ashraf R Beshay, Eileen E Chang, Andrew Lin, Faiza Bashar, Abram Wassily, Binh Nguyen, Thao P Nguyen
Journal: Cardiovascular Research (2020)

In mammalian ventricles, electrical gradients establish electrical heterogeneities as essential tissue mechanisms to optimize mechanical efficiency and safeguard electrical stability. Electrical gradients shape mammalian electrocardiographic patterns; disturbance of electrical gradients is proarrhythmic. The zebrafish heart is a popular surrogate model for human cardiac electrophysiology thanks to its remarkable recapitulation of human electrocardiogram and ventricular action potential features. Yet, zebrafish ventricular electrical gradients are largely unexplored. The goal of this study is to define the zebrafish ventricular electrical gradients that shape the QRS complex and T wave patterns at baseline and under oxidative stress.We performed in vivo electrocardiography and ex vivo voltage-sensitive fluorescent epicardial and transmural optical mapping of adult zebrafish hearts at baseline and during acute H2O2 exposure. At baseline, apicobasal activation and basoapical repolarization gradients accounted for the polarity concordance between the QRS complex and T wave. During H2O2 exposure, differential regional impairment of activation and repolarization at the apex and base disrupted prior to baseline electrical gradients, resulting in either reversal or loss of polarity concordance between the QRS complex and T wave. KN-93, a specific calcium/calmodulin-dependent protein kinase II inhibitor (CaMKII), protected zebrafish hearts from H2O2 disruption of electrical gradients. The protection was complete if administered prior to oxidative stress exposure.Despite remarkable apparent similarities, zebrafish and human ventricular electrocardiographic patterns are mirror images supported by opposite electrical gradients. Like mammalian ventricles, zebrafish ventricles are also susceptible to H2O2 proarrhythmic perturbation via CaMKII activation. Our findings suggest that the adult zebrafish heart may constitute a clinically relevant model to investigate ventricular arrhythmias induced by oxidative stress. However, the fundamental ventricular activation and repolarization differences between the two species that we demonstrated in this study highlight the potential limitations when extrapolating results from zebrafish experiments to human cardiac electrophysiology, arrhythmias, and drug toxicities.