tbuckley/cabot-search huggingface dataset:
Reconceptualizing Risk-Benefit Assessment of Novel Cancer Therapies to Expand Global Access and Reduce Worldwide Mortality
Authors: Rebecca J. DeBoer, Hope S. Rugo, Lawrence N. Shulman
Journal: JAMA Oncology (2021)

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 Oncology 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 Oncology journal
Abstract 11560: Systematic Deployment of AEDs in BC Schools: A Utility and Cost-Effectiveness Study of In-School and Nearby OHCAs
Authors: Li (Danny) Liang, Benjamin Leung, Timothy Chan, Jennie Helmer, Garth Meckler, Jim Christenson, Brian Grunau
Journal: Circulation (2021)

Background: While pediatric out-of-hospital cardiac arrests (OHCAs) are relatively uncommon, they have a much higher number of potential years of life lost per event. School-located public access automated external defibrillators (AED) may be beneficial to school-aged OHCAs, but also other OHCAs within the school and in the surrounding community. We sought to identify the incidence of OHCAs within and nearby schools in British Columbia (BC), to estimate the number that may benefit from school-located AEDs. Methods: We used prospectively-collected data from the BC OHCA Registry from 2013 to 2018. We examined the addresses of all OHCAs to determine those occurring in public primary and secondary schools. We geo-plotted all OHCAs to identify the number of OHCAs within walking distance of a school. Assuming an average pedestrian speed for AED retrieval of 1.8 m/second, we calculated the number of school-vicinity OHCAs for which a bystander could retrieve an AED prior to a 6.5 minute emergency medical system response interval, assuming that AEDs would be located on the exterior of a school building. Results: There were a total of 401,423 children enrolled at 824 schools annually in the study footprint. Of a total of 12,480 EMS-treated OHCAs (220 aged &lt; 18 years), 20 were in in schools, of which 4 were &lt;18 years of age. Of school located OHCAs, 14 (70%) had initial shockable rhythms, 4 (20%) had an AED applied (of whom 3 survived), and 10 (50%) survived. Of the four school-located pediatric OHCAs, three were witnessed (75%), two had initial shockable rhythms (50%), and two (50%) survived until hospital discharge. A total of 1128/12,480 (9%) OHCAs were within retrieval distance of a school, corresponding to 0.228 per school per year (95% CI 0.201-0.255 year-to-year) , which is above current thresholds for cost-effectiveness. Conclusion: Outcomes of school-located OHCAs are encouraging, especially those with AED application. While the incidence of school-located OHCAs is low, a substantial proportion of OHCAs occur within a retrievable distance to a school, and thus accessible external school-located AEDs may improve overall OHCA outcomes of a community.
CTNI-22. A PHASE 0/1 ‘TRIGGER’ TRIAL OF RIBOCICLIB PLUS EVEROLIMUS IN RECURRENT HIGH-GRADE GLIOMA
Authors: Nader Sanai, An-Chi Tien, Jun Jiang, Yu-Wei Chang, Chelsea Pennington-Krygier, Anita DeSantis, Yoko Fujita, Seongho Kim, Jing Li, Shwetal Mehta
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND mTOR activation is a mechanism of resistance in CDK4/6 targeting. We evaluated tumor pharmacokinetics (PK) and tumor pharmacodynamics (PD) of combined CDK4/6 and mTOR inhibition in recurrent high-grade glioma (HGG) patients. METHODS Recurrent HGG patients with (1) intact RB, (2) CDKN2A/B deletion or CDK4/6 amplification, and (3) PTEN loss or PIK3CA mutations receive five days of presurgical ribociclib plus everolimus prior to resection at 2, 8 or 24 hours after the final dose. Beginning at 400mg QD ribociclib plus 2.5mg QD everolimus, six dose-escalations summit at 600mg QD plus 60mg QW. Gadolinium [Gd]-enhancing and nonenhancing tumor regions, CSF, and plasma are collected. Total and unbound drug concentrations are determined using validated LC-MS/MS methods. RB and S6 phosphorylation are compared to matched archival tissue. To select patients for a therapeutic expansion phase of combined drug therapy, the protocol includes a PK ‘trigger’ (i.e., for each drug, unbound concentration in Gd-nonenhancing tumor &amp;gt; 5-fold biochemical IC50) and a PD ‘trigger’ (i.e., for each tumor, &amp;gt; 30% decrease in pRB and pS6). RESULTS 21 patients with WHO Grade III (n=2) and IV (n=19) gliomas were enrolled into the Phase 0 component of the study. No dose-limiting toxicities were observed. In Gd-nonenhancing tumor regions, the median unbound concentration of ribociclib was 719 nM, whereas unbound everolimus tumor concentrations were undetectable. Across all dose-levels, 62% (13/21) and 22% (5/21) of tumors demonstrated decreased tumor RB and S6 phosphorylation, respectively. Tumor proliferation (MIB-1) was decreased in 67% (14/21) of all patients. No patients qualified for the therapeutic expansion phase. CONCLUSION In adult HGG, ribociclib achieves pharmacologically-relevant concentrations in Gd-nonenhancing tumor whereas everolimus exhibits no meaningful tumor penetration. These findings support further clinical development of ribociclib, but not everolimus, for the treatment of high-grade glioma patients.
Association of bilateral salpingo-oophorectomy with all cause and cause specific mortality: population based cohort study
Authors: Maria C Cusimano, Maria Chiu, Sarah E Ferguson, Rahim Moineddin, Suriya Aktar, Ning Liu, Nancy N Baxter
Journal: BMJ (2021)

Abstract Objectives To determine if bilateral salpingo-oophorectomy, compared with ovarian conservation, is associated with all cause or cause specific death in women undergoing hysterectomy for non-malignant disease, and to determine how this association varies with age at surgery. Design Population based cohort study. Setting Ontario, Canada from 1 January 1996 to 31 December 2015, and follow-up to 31 December 2017. Participants 200 549 women (aged 30-70 years) undergoing non-malignant hysterectomy, stratified into premenopausal (&lt;45 years), menopausal transition (45-49 years), early menopausal (50-54 years), and late menopausal (≥55 years) groups according to age at surgery; median follow-up was 12 years (interquartile range 7-17). Exposures Bilateral salpingo-oophorectomy versus ovarian conservation. Main outcomes measures The primary outcome was all cause death. Secondary outcomes were non-cancer and cancer death. Within each age group, overlap propensity score weighted survival models were used to examine the association between bilateral salpingo-oophorectomy and mortality outcomes, while adjusting for demographic characteristics, gynaecological conditions, and comorbidities. To account for comparisons in four age groups, P&lt;0.0125 was considered statistically significant. Results Bilateral salpingo-oophorectomy was performed in 19%, 41%, 69%, and 81% of women aged &lt;45, 45-49, 50-54, and ≥55 years, respectively. The procedure was associated with increased rates of all cause death in women aged &lt;45 years (hazard ratio 1.31, 95% confidence interval 1.18 to 1.45, P&lt;0.001; number needed to harm 71 at 20 years) and 45-49 years (1.16, 1.04 to 1.30, P=0.007; 152 at 20 years), but not in women aged 50-54 years (0.83, 0.72 to 0.97, P=0.018) or ≥55 years (0.92, 0.82 to 1.03, P=0.16). Findings in women aged &lt;50 years were driven largely by increased non-cancer death. In secondary analyses identifying a possible change in the association between bilateral salpingo-oophorectomy and all cause death with advancing age at surgery, the hazard ratio gradually decreased during the menopausal transition and remained around 1 at all ages thereafter. Conclusion In this observational study, bilateral salpingo-oophorectomy at non-malignant hysterectomy appeared to be associated with increased all cause mortality in women aged &lt;50 years, but not in those aged ≥50 years. While caution is warranted when considering bilateral salpingo-oophorectomy in premenopausal women without indication, this strategy for ovarian cancer risk reduction does not appear to be detrimental to survival in postmenopausal women.
An update on drugs with therapeutic potential for SARS-CoV-2 (COVID-19) treatment
Authors: Sylwester Drożdżal, Jakub Rosik, Kacper Lechowicz, Filip Machaj, Bartosz Szostak, Jarosław Przybyciński, Shahrokh Lorzadeh, Katarzyna Kotfis, Saeid Ghavami, Marek J. Łos
Journal: Drug Resistance Updates (2021)
170TiP A phase I study to characterize the safety and tolerability of MP0317, a tumor targeting FAP dependent CD40 agonist DARPin®, in patients with relapsed/refractory solid tumors
Authors: S. Jeger, O. Schönborn-Kellenberger, H. De Winter, N. Steeghs, E. Gort, C. Gomez-Roca, V. Stavropoulou, R. Kenefeck, E. Fernandez, H. Ji, C. Marchand, P. Legenne, P. Cassier
Journal: Annals of Oncology (2021)
Differentiating Diabetic Ketoacidosis and Hyperglycemic Ketosis Due to Cannabis Hyperemesis Syndrome in Adults With Type 1 Diabetes
Authors: Halis Kaan Akturk, Janet Snell-Bergeon, Gregory L. Kinney, Anagha Champakanath, Andrew Monte, Viral N. Shah
Journal: Diabetes Care (2021)

To differentiate diabetic ketoacidosis (DKA) from hyperglycemic ketosis due to cannabis hyperemesis syndrome (HK-CHS) in adults with type 1 diabetes.Of 295 adults with type 1 diabetes who were seen with DKA-related ICD-10 codes, 68 patients with 172 DKA events meeting the inclusion criteria were analyzed. Cannabis use was defined as a positive urine test result for cannabis. Linear mixed models were used to define HK-CHS (pH ≥7.4 with bicarbonate ≥15 mmol/L [mEq/L]), and sensitivity and specificity were calculated using the receiver operating characteristic (ROC) curve.Cannabis users had significantly higher pH (7.42 ± 0.01 vs. 7.09 ± 0.02) and bicarbonate (19.2 ± 0.61 vs. 9.1 ± 0.71 mmol/L) (P < 0.0001) compared with nonusers. The area under the ROC curve for a positive cannabis urine test result predicting HK-CHS was 0.9892.In patients who present with DKA and higher pH, especially pH ≥7.4, cannabis use should be considered in the differential diagnosis.
Dactylitis is an indicator of a more severe phenotype independently associated with greater SJC, CRP, ultrasound synovitis and erosive damage in DMARD-naive early psoriatic arthritis
Authors: Sayam Dubash, Oras A Alabas, Xabier Michelena, Leticia Garcia-Montoya, Richard J Wakefield, Philip S Helliwell, Paul Emery, Dennis G McGonagle, Ai Lyn Tan, Helena Marzo-Ortega
Journal: Annals of the Rheumatic Diseases (2021)

To characterise the impact of dactylitis in disease-modifying antirheumatic drug (DMARD)-naive early psoriatic arthritis (PsA).Patients with early PsA meeting the classification criteria for PsA (CASPAR) were recruited. Clinical outcomes were recorded, and ultrasonography was conducted to assess grey scale (GS) and power Doppler (PD) synovitis, periarticular cortical bone erosions and enthesitis. The cohort was dichotomised by the presence or absence of dactylitis.Of 177 patients with PsA, those with dactylitis (dactylitic PsA (81/177, 46%)) had higher tender joint count (p<0.01), swollen joint count (SJC) (p<0.001) and C reactive protein (CRP) (p<0.01) than non-dactylitic PsA. Dactylitis was more prevalent in toes (146/214 (68.2%)) than fingers (68/214 (31.8%)); 'hot' dactylitis was more prevalent than 'cold' (83.6% vs 16.4%). Ultrasound (US) synovitis and erosions were significantly more prevalent in dactylitic PsA (p<0.001 and p<0.001, respectively). Exclusion of dactylitis in dactylitic PsA confirmed significantly greater SJC (3 vs 1, p=0.002), US synovitis (GS ≥2: 20.6% vs 16.1%, p<0.001, or PD ≥1: 5.1% vs 3.3%, p<0.001) and erosions (1.1% vs 0.5% joints, p=0.008; 26.1% vs 12.8% patients, p=0.035%) than non-dactylitic PsA. Synovitis (GS ≥2 and/or PD ≥1) occurred in 53.7% of dactylitis. No substantial differences were observed for US enthesitis.Dactylitis signifies a more severe disease phenotype independently associated with an increased disease burden with greater SJC, CRP, US-detected synovitis and bone erosions in DMARD-naive early PsA and may be a useful discriminator for early risk stratification.
Dual enzyme-mimic nanozyme based on single-atom construction strategy for photothermal-augmented nanocatalytic therapy in the second near-infrared biowindow
Authors: Yutian Su, Fan Wu, Qiuxian Song, Mengjie Wu, Mohsen Mohammadniaei, Taiwei Zhang, Baolei Liu, Shishan Wu, Ming Zhang, Ao Li, Jian Shen
Journal: Biomaterials (2021)
Predicting changes in glycemic control among adults with prediabetes from activity patterns collected by wearable devices
Authors: Mitesh S. Patel, Daniel Polsky, Dylan S. Small, Sae-Hwan Park, Chalanda N. Evans, Tory Harrington, Rachel Djaraher, Sujatha Changolkar, Christopher K. Snider, Kevin G. Volpp
Journal: npj Digital Medicine (2021)

The use of wearables is increasing and data from these devices could improve the prediction of changes in glycemic control. We conducted a randomized trial with adults with prediabetes who were given either a waist-worn or wrist-worn wearable to track activity patterns. We collected baseline information on demographics, medical history, and laboratory testing. We tested three models that predicted changes in hemoglobin A1c that were continuous, improved glycemic control by 5% or worsened glycemic control by 5%. Consistently in all three models, prediction improved when (a) machine learning was used vs. traditional regression, with ensemble methods performing the best; (b) baseline information with wearable data was used vs. baseline information alone; and (c) wrist-worn wearables were used vs. waist-worn wearables. These findings indicate that models can accurately identify changes in glycemic control among prediabetic adults, and this could be used to better allocate resources and target interventions to prevent progression to diabetes.
Correction to: Role of total lung stress on the progression of early COVID‑19 pneumonia
Authors: Silvia Coppola, Davide Chiumello, Mattia Busana, Emanuele Giola, Paola Palermo, Tommaso Pozzi, Irene Steinberg, Stefano Roli, Federica Romitti, Stefano Lazzari, Simone Gattarello, Michela Palumbo, Peter Herrmann, Leif Saager, Michael Quintel, Konrad Meissner, Luigi Camporota, John J. Marini, Stefano Centanni, Luciano Gattinoni
Journal: Intensive Care Medicine (2021)
Spousal Concordance of Cardiovascular Risk Factors in Newly Married Couples in China
Authors: Ravi Retnakaran, Shi Wu Wen, Hongzhuan Tan, Shujin Zhou, Chang Ye, Minxue Shen, Graeme N. Smith, Mark C. Walker
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Several studies have shown that older married couples share a propensity for accruing the same cardiovascular risk factors such as hypertension and dyslipidemia. However, it remains unclear if these spousal associations reflect their shared home environment and lifestyle or the tendency to choose a partner with a similar perspective on lifestyle choices and behaviors (assortative mating). Evaluating these associations in young, newly married couples may help to differentiate between these 2 possibilities. <h3>Objective</h3> To evaluate the spousal concordance of cardiovascular risk factors in young, newly married couples. <h3>Design, Setting, and Participants</h3> This prospective cohort study recruited 831 couples around the time of marriage registration in Liuyang, China, from February 1, 2009, to November 4, 2015. Statistical analysis was performed from April to May 2021. <h3>Main Outcomes and Measures</h3> Spousal concordance of cardiovascular risk factors. Both partners underwent systematic assessment of cardiovascular risk factors, including evaluation of anthropometrics, blood pressure, and fasting lipids. <h3>Results</h3> Among the 831 participating couples, mean (SD) age was 24 (3) years in the women and 26 (4) years in the men. There were significant correlations between spouses in systolic blood pressure (<i>r</i> = 0.43;<i>P</i> &lt; .001), diastolic blood pressure (<i>r</i> = 0.36;<i>P</i> &lt; .001), total cholesterol (<i>r</i> = 0.13;<i>P</i> &lt; .001), low-density lipoprotein cholesterol (<i>r</i> = 0.11;<i>P</i> = .003), high-density lipoprotein (HDL) cholesterol (<i>r</i> = 0.22,<i>P</i> &lt; .001), and triglycerides (<i>r</i> = 0.13;<i>P</i> = .001). After adjustment for covariates (age, household income, education level, smoking, and either body mass index or waist circumference), significant correlations persisted between spouses in their systolic blood pressure (<i>r</i> = 0.42;<i>P</i> &lt; .001), diastolic blood pressure (<i>r</i> = 0.34;<i>P</i> &lt; .001), HDL cholesterol (<i>r</i> = 0.17;<i>P</i> &lt; .001), and triglycerides (<i>r</i> = 0.10;<i>P</i> = .04). <h3>Conclusions and Relevance</h3> This cohort study found spousal concordance of cardiovascular risk factors among young newly married couples. Assortative mating based on these concordant risk factors at the time of marriage may partially explain the shared vascular risk profile of older marital partners and raises the possibility of couple-based care.
Preconception Care to Optimize Pregnancy Outcomes—Reply
Authors: Methodius G. Tuuli
Journal: JAMA (2021)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Using placebo-controlled trials to define predictors of future exacerbations in severe asthma patients
Authors: Andriana I. Papaioannou, Andreas Photiades, Mina Gaga
Journal: European Respiratory Journal (2021)

Asthma exacerbations, particularly severe ones, are worrisome and dangerous events, they cause anxiety and fear to patients, and are associated with increased morbidity, mortality and higher healthcare costs, including more hospital admissions and emergency department visits [1–3]. Thus, along with symptom control, the reduction of exacerbation risk is a major treatment goal in asthma [1]. Exacerbation history and inflammatory profile are crucial predictors of exacerbation risk <https://bit.ly/3xmRSON>
The Cancer Surfaceome Atlas integrates genomic, functional and drug response data to identify actionable targets
Authors: Zhongyi Hu, Jiao Yuan, Meixiao Long, Junjie Jiang, Youyou Zhang, Tianli Zhang, Mu Xu, Yi Fan, Janos L. Tanyi, Kathleen T. Montone, Omid Tavana, Ho Man Chan, Xiaowen Hu, Robert H. Vonderheide, Lin Zhang
Journal: Nature Cancer (2021)
Stressing the personal benefits of the covid-19 vaccine might encourage more people to accept it
Authors: Helen Saul, Deniz Gursul
Journal: BMJ (2021)

The studyFreeman D, Loe BS, Yu LM, et al. Effects of different types of written vaccination information on COVID-19 vaccine hesitancy in the UK (OCEANS-III): a single-blind, parallel-group, randomised controlled trial. Lancet Public Health 2021;6:416-27.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/stressing-personal-benefits-of-covid-vaccine-could-reduce-hesitancy.
Quality of Life, Psychological Distress, and Prognostic Awareness in Patients with Multiple Myeloma
Authors: Elizabeth K. O'Donnell, Yael Shapiro, Omar Nadeem, Andrew J. Yee, Jacob P. Laubach, Andrew R. Branagan, Kenneth C. Anderson, Clifton C. Mo, Nikhil C. Munshi, Irene M. Ghobrial, Adam S. Sperling, Emerentia Agyemang, Cynthia C. Harrington, Jill N. Burke, Paul G. Richardson, Noopur S. Raje, Areej El-Jawahri
Journal: Blood (2021)
ALK1 signaling is required for the homeostasis of Kupffer cells and prevention of bacterial infection
Authors: Dianyuan Zhao, Fengjiao Yang, Yang Wang, Site Li, Yang Li, Fei Hou, Wenting Yang, Di Liu, Yuandong Tao, Qian Li, Jing Wang, Fuchu He, Li Tang
Journal: Journal of Clinical Investigation (2021)

Macrophages are highly heterogeneous immune cells that fulfill tissue-specific functions. Tissue-derived signals play a critical role in determining macrophage heterogeneity. However, these signals remain largely unknown. The BMP receptor activin receptor–like kinase 1 (ALK1) is well known for its role in blood vessel formation; however, its role within the immune system has never been revealed to our knowledge. Here, we found that BMP9/BMP10/ALK1 signaling controlled the identity and self-renewal of Kupffer cells (KCs) through a Smad4-dependent pathway. In contrast, ALK1 was dispensable for the maintenance of macrophages located in the lung, kidney, spleen, and brain. Following ALK1 deletion, KCs were lost over time and were replaced by monocyte-derived macrophages. These hepatic macrophages showed significantly reduced expression of the complement receptor VSIG4 and alterations in immune zonation and morphology, which is important for the tissue-specialized function of KCs. Furthermore, we found that this signaling pathway was important for KC-mediated Listeria monocytogenes capture, as the loss of ALK1 and Smad4 led to a failure of bacterial capture and overwhelming disseminated infections. Thus, ALK1 signaling instructs a tissue-specific phenotype that allows KCs to protect the host from systemic bacterial dissemination.