tbuckley/cabot-search huggingface dataset:
Epidemiological characterisation of the first 785 SARS-CoV-2 Omicron variant cases in Denmark, December 2021
Authors: Laura Espenhain, Tjede Funk, Maria Overvad, Sofie Marie Edslev, Jannik Fonager, Anna Cäcilia Ingham, Morten Rasmussen, Sarah Leth Madsen, Caroline Hjorth Espersen, Raphael N. Sieber, Marc Stegger, Vithiagaran Gunalan, Bartlomiej Wilkowski, Nicolai Balle Larsen, Rebecca Legarth, Arieh Sierra Cohen, Finn Nielsen, Janni Uyen Hoa Lam, Kjetil Erdogan Lavik, Marianne Karakis, Katja Spiess, Ellinor Marving, Christian Nielsen, Christina Wiid Svarrer, Jonas Bybjerg-Grauholm, Stefan Schytte Olsen, Anders Jensen, Tyra Grove Krause, Luise Müller
Journal: Eurosurveillance (2021)

By 9 December 2021, 785 SARS-CoV-2 Omicron variant cases have been identified in Denmark. Most cases were fully (76%) or booster-vaccinated (7.1%); 34 (4.3%) had a previous SARS-CoV-2 infection. The majority of cases with available information reported symptoms (509/666; 76%) and most were infected in Denmark (588/644; 91%). One in five cases cannot be linked to previous cases, indicating widespread community transmission. Nine cases have been hospitalised, one required intensive care and no deaths have been registered.
CBIO-11. HISTONE H3.3 G34R/V MUTATIONS STIMULATE PEDIATRIC HIGH-GRADE GLIOMA FORMATION THROUGH THE INDUCTION OF CHROMOSOMAL INSTABILITY
Authors: Charles Day, Florina Grigore, Alyssa Langfald, Edward Hinchcliffe, James Robinson
Journal: Neuro-Oncology (2021)

Abstract H3.3 G34R/V mutations are drivers of high-grade pediatric glioma (pHGG). H3.3 G34R/V mutations are linked to altered H3.3 K36 trimethylation (H3K36me3); implicating epigenetic gene regulation as a possible contributor to pHGG formation. Here we show that H3.3 G34R/V also induces chromosomal instability (CIN); a hallmark of pHGG. If CIN promotes pHGG formation is unknown. We observed that H3.3 G34 mutant pHGG cells have reduced mitotic H3.3 S31 phosphorylation compare to WT H3.3 cell lines. And, H3.3 G34R reduced Chk1 phosphorylation at S31 by &amp;gt;90% in an in vitro kinase assay. Chk1 regulates chromosome segregation through phosphorylation of pericentromeric H3.3 S31 during early mitosis. Overexpression of H3.3 G34R or non-phosphorylatable S31A in H3.3 WT, diploid cells caused a significant increase in CIN. Likewise, H3.3 G34 mutant pHGG cells have significantly elevated rates of CIN as compare to H3.3 WT pHGG cells. During normal cell division, phospho-S31 is lost in anaphase. However, following chromosome missegregation, phospho-S31 spreads and stimulates p53-induced cell cycle arrest. Here we show that WT p53 cells expressing mutant G34 fail to arrest following chromosome mis-segregation. These studies demonstrate that H3.3 G34R/V mutations are sufficient to transform normal, diploid cells into proliferating CIN cells. To determine if this process contributes to tumorigenesis, we used RCAS Nestin-TVA mice to overexpress H3.3 WT, G34R, or S31A – P2A-linked to PDGFB expression in glial precursor cells of newborn mice. Over 100 days, S31A and G34R mice had drastically reduced survival (averaging 77, 81, and 100 days for S31A, G34R, and WT). Furthermore, most G34R and S31A mice developed HGG, while H3.3 WT mice remained tumor-free. Our work implicates CIN as a driver of H3.3 G34 mutant pHGG formation. Our ongoing studies utilize K36M and double mutants to further define the contributions of S31 phosphorylation (CIN) and H3K36me3 (epigenetic gene regulation) to tumorigenesis.
Abstract 11034: Extracorporeal Life-Support for Out-of-Hospital Cardiac Arrest: A Nationwide Multicenter Study
Authors: DAUN JEONG, Hansol Chang, SUNGYEON HWANG, Wonchul Cha, Tae Gun Shin, Sang Do Shin, Jin-Ho Choi
Journal: Circulation (2021)

Introduction: Despite promising survival and favorable neurological results in IHCA, the outcomes of ECLS for OHCA are more heterogeneous. The clinical setting for the survival and favorable neurological outcomes of ECLS in OHCA may differ from that in IHCA. Hypothesis: This study aimed to determine whether ECLS is associated with improved survival to hospital discharge with favorable neurological outcome compared to conventional cardiopulmonary resuscitation and identify in which OHCA patients the implementation of ECLS would be beneficial. Methods: The clinical outcome of OHCA treated by ECLS or CCPR between 2015 and 2020 was retrospectively investigated using KoCARC, a nationwide multicenter OHCA registry of Korea. Differences in baseline clinical characteristics were adjusted by matching propensity for ECLS. Primary outcome was 30-day survival with neurologically favorable status of cerebral performance category of 1 or 2. Restricted mean survival time (RMST) was used to compare outcome between groups. Result: Of 12,006 patients (mean age=71, male gender=65%) included, ECLS was performed in 272 patients (2.2%). In unadjusted analysis, the frequency of survival with favorable neurological status was higher in ECLS compared to CCPR (15% versus 7%, RMST 9.4 versus 3.8 days, p&lt;0.001). Subgroup analysis revealed that the benefit of ECLS was evident in high-risk groups including initial non-shockable rhythm or CPR duration≥20 min (p&lt;0.05, all). In analysis of propensity score-matched 271 pairs, there was no difference in the clinical outcome between ECLS and CCPR (15% versus 16%, RMST 9.4 versus 9.0 days, p=0.33), but ECLS was still better than CCPR in initial non-shockable rhythm or CPR duration≥20 min (p&lt;0.05, all). Conclusions: In this real-world data analysis, ECLS compared to CCPR did not result in better clinical outcome of OHCA in overall. However, ECLS might be beneficial for high-risk patients such as initial non-shockable rhythm or CPR duration≥20 min.
Legalization of Psychedelic Substances
Authors: Mason Marks
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
SurgiNet: Pyramid Attention Aggregation and Class-wise Self-Distillation for Surgical Instrument Segmentation
Authors: Zhen-Liang Ni, Xiao-Hu Zhou, Guan-An Wang, Wen-Qian Yue, Zhen Li, Gui-Bin Bian, Zeng-Guang Hou
Journal: Medical Image Analysis (2021)
Real-World Observations and Practical Considerations of Subcutaneous Daratumumab Administration in Multiple Myeloma
Authors: E. Bridget Kim, Elizabeth O'Donnell, Andrew R. Branagan, Jill N. Burke, Cynthia C. Harrington, Emerentia Agyemang, Noopur S. Raje, Andrew J. Yee
Journal: Blood (2021)
In a Dark Wood
Authors: Michael Wynn
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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
β-glucan-coupled superparamagnetic iron oxide nanoparticles induce trained immunity to protect mice against sepsis
Authors: Yuchen Pan, Jingman Li, Xiaoyu Xia, Jiali Wang, Qi Jiang, Jingjing Yang, Huan Dou, Huaping Liang, Kuanyu Li, Yayi Hou
Journal: Theranostics (2021)

Background: Innate immune memory, also termed "trained immunity", is thought to protect against experimental models of infection, including sepsis.Trained immunity via reprogramming monocytes/ macrophages has been reported to result in enhanced inflammatory status and antimicrobial activity against infection in sepsis.However, a safe and efficient way to induce trained immunity remains unclear.Methods: β-glucan is a prototypical agonist for inducing trained immunity.Ferumoxytol, superparamagnetic iron oxide (SPIO) with low cytotoxicity, has been approved by FDA for clinical use.We synthesized novel nanoparticles BSNPs by coupling β-glucan with SPIO.BSNPs were further conjugated with fluorescein for quantitative analysis and trace detection of β-glucan on BSNPs.Inflammatory cytokine levels were measured by ELISA and qRT-PCR, and the phagocytosis of macrophages was detected by flow cytometry and confocal microscopy.The therapeutic effect of BSNPs was evaluated on the well-established sepsis mouse model induced by both clinical Escherichia coli (E.coli) and cecal ligation and puncture (CLP).Results: BSNPs were synthesized successfully with a 3:20 mass ratio of β-glucan and SPIO on BSNPs, which were mainly internalized by macrophages and accumulated in the lungs and livers of mice.BSNPs effectively reprogrammed macrophages to enhance the production of trained immunity markers and phagocytosis toward bacteria.BSNP-induced trained immunity protected mice against sepsis caused by E. coli and CLP and also against secondary infection.We found that BSNP treatment elevated Akt, S6, and 4EBP phosphorylation, while mTOR inhibitors decreased the trained immunity markers and phagocytosis enhanced by BSNPs.Furthermore, the PCR Array analysis revealed Igf1, Sesn1, Vegfa, and Rps6ka5 as possible key regulators of mTOR signaling during trained immunity.BSNP-induced trained immunity mainly regulated cellular signal transduction, protein modification, and cell cycle by modulating ATP binding and the kinase activity.Our results indicated that BSNPs induced trained immunity in an mTOR-dependent manner.Conclusion: Our data highlight that the trained immunity of macrophages is an effective strategy against sepsis and suggest that BSNPs are a powerful tool for inducing trained immunity to prevent and treat sepsis and secondary infections.
American Cancer Society's report on the status of cancer disparities in the United States, 2021
Authors: Farhad Islami, Carmen E. Guerra, Adair Minihan, K. Robin Yabroff, Stacey A. Fedewa, Kirsten Sloan, Tracy L. Wiedt, Blake Thomson, Rebecca L. Siegel, Nigar Nargis, Robert A. Winn, Lisa Lacasse, Laura Makaroff, Elvan C. Daniels, Alpa V. Patel, William G. Cance, Ahmedin Jemal
Journal: CA A Cancer Journal for Clinicians (2021)

In this report, the authors provide comprehensive and up-to-date US data on disparities in cancer occurrence, major risk factors, and access to and utilization of preventive measures and screening by sociodemographic characteristics. They also review programs and resources that have reduced cancer disparities and provide policy recommendations to further mitigate these inequalities. The overall cancer death rate is 19% higher among Black males than among White males. Black females also have a 12% higher overall cancer death rate than their White counterparts despite having an 8% lower incidence rate. There are also substantial variations in death rates for specific cancer types and in stage at diagnosis, survival, exposure to risk factors, and receipt of preventive measures and screening by race/ethnicity, socioeconomic status, and geographic location. For example, kidney cancer death rates by sex among American Indian/Alaska Native people are ≥64% higher than the corresponding rates in each of the other racial/ethnic groups, and the 5-year relative survival for all cancers combined is 14% lower among residents of poorer counties than among residents of more affluent counties. Broad and equitable implementation of evidence-based interventions, such as increasing health insurance coverage through Medicaid expansion or other initiatives, could substantially reduce cancer disparities. However, progress will require not only equitable local, state, and federal policies but also broad interdisciplinary engagement to elevate and address fundamental social inequities and longstanding systemic racism.
Abstract 12975: Socioeconomic Status Impact on Out-of-Hospital Cardiac Arrest Post-Arrest Care and Outcomes
Authors: Ryan Huebinger, Summer Chavez, Benjamin Abella, Rabab Al-Araji, Jeffrey L Jarvis, Richard Witkov, John Waller-Delarosa, Normandy W Villa, Arjun Aggarwal, Micah Panczyk, Bentley Bobrow, Justin Northeim
Journal: Circulation (2021)

Introduction: Post-arrest care after out-of-hospital cardiac arrest (OHCA) is critical to optimizing outcomes. Large socioeconomic disparities in prehospital resuscitation interventions have been shown. Less is understood about disparities in post-arrest care and their impact on patient outcomes. We evaluated the association of socioeconomic status (SES) with post-arrest care and outcomes. Methods: We included adult OHCA patients who survived to hospital admission using the 2014-2020 data in Texas from the Cardiac Arrest Registry to Enhance Survival (CARES) . We linked CARES data to census tracts and stratified census tracts above and below the median for SES characteristics: household income, employment rate, and high school graduation. We defined outcomes as targeted temperature management (TTM), Percutaneous Coronary Intervention (PCI), survival to discharge, and survival with a Cerebral Performance Category (CPC) 1-2. We fit a mixed effects model, logistic regression evaluating the association between SES characteristics and outcomes, modeling receiving hospital as the random intercept. We adjusted for age, neighborhood race, sex, bystander witnessed arrest, bystander CPR, and initial shockable rhythm. Results: There were 37,055 adult cases of OHCA taken to 164 hospitals, 9,346 survived to admission; median age was 62, 60.7% were male, 32.5% received TTM, 5.7% received PCI, 34.9% survived to hospital discharge, and 22.0% had a good CPC score. Low employment was associated with low PCI (1.5% v 2.8%, aOR 0.5, 95% CI 0.3-0.9). Low education was linked to worse survival (32.3% v 37.5%, aOR 0.9, 95% CI 0.8-0.99). Low employment was linked to worse CPC (17.5% v 26.4%, aOR 0.8, 95% CI 0.7-0.9). Low income was not associated with TTM (aOR 1.05, 95% CI 0.9-1.2), PCI (aOR 0.9, 95% CI 0.9-1.3), survival (aOR 0.9, 95% CI 0.8-1.0), or good CPC (aOR 1.0, 95% CI 0.9-1.2). Low employment was not associated with TTM (aOR 1.0, 95% CI 0.8-1.1), or survival (aOR 1.0, 95% CI 0.9-1.1). Low education was not associated with low PCI (4.0% v 7.4%, aOR 0.8, 95% CI 0.6-0.1.01), low TTM (aOR 1.0, 95% CI 0.9-1.1), or survival (aOR 0.9, 95% CI 0.8-1.03). Conclusion: SES characteristics were linked to lower PCI rates and worse outcomes, but SES was not associated with TTM.
Letter to the editor: Serum thrombospondin‐2 as biomarker in liver diseases, a look beyond NASH
Authors: Tania Colasanti, Alessandra Di Giamberardino, Alessio Grimaldi, Vincenzo Cardinale, Guido Carpino, Carmine Mancone
Journal: Hepatology (2021)

Serum thrombospondin-2 as biomarker in liver diseases, a look beyond NASHTo the editor, With great interest, we read the study by Kozumi et al. [1] demonstrating that thrombospondin-2 (THBS2) is a valuable biomarker for NASH and advanced liver fibrosis.In particular, the authors showed that serum THBS2 levels promise to stratify patients with NAFLD according to the risk of hepatic complications, such as liver cancer and decompensated cirrhotic events.Concomitantly to this report, we published data showing that THBS2, along with thrombospondin-1 (THBS1) and pigment epitheliumderived factor (PEDF), was able to inhibit vascular growth in intrahepatic cholangiocarcinoma (iCCA), while promoting cancer-associated lymphangiogenesis. [2]We concluded that targeting these proteins could be a potential strategy to counteract the invasiveness of iCCA.Notably, among the presented data, we showed that serum THBS2 levels were significantly higher in patients with iCCA (92.3 ng/ml) compared with healthy donors (HDs) (24.6 ng/ml) (Figure 1A); no difference in serum THBS1 and PEDF expressions were found.In particular, THBS2 exhibited an area under the curve of 0.82 (95% CI, 0.681-0.957;p = 0.0005) when comparing iCCA versus HDs, resulting in a positive predictive value of 95% (Figure 1B).Our results predicted THBS2 as a potential noninvasive biomarker for the detection of iCCA.Recently, to extend our analysis in populations of patients with biopsy-proven NASH with advanced fibrosis (≥ F3) and patients with HCC cirrhosis, the latter not specifically considered in the study by Kozumi et al., [1] we found increased serum THBS2 levels with respect to HDs (Figure 1A,B).Hence, in addition to confirming the diagnostic value of circulating THBS2 levels in the frame of NASH, these data shed light on the pathogenic features of the most recurring liver diseases.In fact, considering iCCA, HCC, and NASH as a unique population, the serum levels of THBS2 showed a diagnostic ability in discriminating advanced liver disease from HDs (Figure 1C,D).Moreover, these data should be integrated with recent observations indicating the ability of THBS2 serum levels in detecting pancreatic cancer and distal cholangiocarcinoma. [3] the light of these considerations, we suggest the need to enroll a large cohort of patients in a multicenter research trial to strengthen these promising observations and to better define THBS2 efficacy in detecting liver and gastric diseases, particularly in early stages of cancer.
BIOM-28. SERIAL PLASMA AND CSF CELL-FREE TUMOR DNA (cf-tDNA) TRACKING IN DIFFUSE MIDLINE GLIOMA PATIENTS UNDERGOING TREATMENT WITH ONC201
Authors: Evan Cantor, Kyle Wierzbicki, Rohinton Tarapore, Karthik Ravi, Jack Wadden, Clarissa Babilla, Chase Thomas, Rodrigo Cartaxo, Vivek Anand Yadav, Ramya Ravindran, Amy K Bruzek, Jessica Cummings, Abed Rahman Kawakibi, Sunjong Ji, Alyssa Paul, Ian Wolfe, Marcia Leonard, Patricia Robertson, Andrea Franson, Rajen Mody, Hugh Garton, Yazmin Odia, Cassie Kline, Nicholas Vitanza, Soumen Khatua, Joshua Allen, Sabine Mueller, Sharon Gardner, Carl Koschmann
Journal: Neuro-Oncology (2021)

Abstract Diffuse midline glioma (DMG) with H3K27M mutation is a lethal childhood brain cancer, with limited means of monitoring beyond serial MRI scans. We conducted a multi-site Phase 1 trial of the imipridone ONC201 for children with H3K27M-mutant glioma (NCT03416530). Patients on Arm D of the trial (n=24) underwent serial lumbar puncture (baseline, 2 and 6-months) for cell-free tumor DNA (cf-tDNA) analysis at time of MRI. Additionally, patients on all arms of the trial at the University of Michigan underwent serial plasma collection. We collected a total of 96 plasma-samples and 53 CSF-samples from 29 patients. We performed ddPCR analysis of cf-tDNA samples and compared variant allele fraction (VAF) to radiographic change (maximal tumor area on MRI). For our H3F3A-mutated (K27M) patients, cf-tDNA was positive in 53/62 plasma samples (sensitivity 85.4%) and 28/29 CSF samples (sensitivity 96.5%) and overall specificity of 100%. There was no direct correlation between percent-change in tumor-area and plasma (p=0.47) or CSF VAF (p=0.89), implying that VAF provided information supplemental to radiographic assessments. “Spikes” in plasma cf-tDNA VAF (increase of ≥25%) co-occurred with progression in 2/9 (22%) cases and preceded progression in 5/9 cases (55%) by an average of 1.22 months. In CSF, spikes preceded progression in 4/6 cases (66%) by an average of 1.8 months. Two patients had increases in tumor-area with no increase in plasma VAF; both were later confirmed as pseudo-progressors, suggesting additional potential utility of cf-tDNA VAF monitoring. A 14yo male with spinal cord glioma received concurrent bevacizumab with ONC201, which resulted in a decrease in tumor area but continued increase in plasma VAF, predicting radiologic progression at the next time. In summary, we present data which suggests monitoring serial CSF/plasma H3K27M tDNA is a promising clinical tool. Changes in cf-tDNAVAF over time appear to correlate with response, predict progression, and differentiate pseudo-progression.