tbuckley/cabot-search huggingface dataset:
A global panel database of pandemic policies (Oxford COVID-19 Government Response Tracker)
Authors: Thomas Hale, Noam Angrist, Rafael Goldszmidt, Beatriz Kira, Anna Petherick, Toby Phillips, Samuel Webster, Emily Cameron-Blake, Laura Hallas, Saptarshi Majumdar, Helen Tatlow
Journal: Nature Human Behaviour (2021)

COVID-19 has prompted unprecedented government action around the world. We introduce the Oxford COVID-19 Government Response Tracker (OxCGRT), a dataset that addresses the need for continuously updated, readily usable and comparable information on policy measures. From 1 January 2020, the data capture government policies related to closure and containment, health and economic policy for more than 180 countries, plus several countries' subnational jurisdictions. Policy responses are recorded on ordinal or continuous scales for 19 policy areas, capturing variation in degree of response. We present two motivating applications of the data, highlighting patterns in the timing of policy adoption and subsequent policy easing and reimposition, and illustrating how the data can be combined with behavioural and epidemiological indicators. This database enables researchers and policymakers to explore the empirical effects of policy responses on the spread of COVID-19 cases and deaths, as well as on economic and social welfare.
Antibody response to first BNT162b2 dose in previously SARS-CoV-2-infected individuals
Authors: Charlotte Manisty, Ashley D Otter, Thomas A Treibel, Áine McKnight, Daniel M Altmann, Timothy Brooks, Mahdad Noursadeghi, Rosemary J Boyton, Amanda Semper, James C Moon
Journal: The Lancet (2021)
Abstract IA020: Mechanics, multinucleation, and EMT
Authors: Celeste M. Nelson
Journal: Cancer Research (2021)

Abstract Multinucleation is found in more than one third of tumors and is linked to increased tolerance for mutation, resistance to chemotherapy, and invasive potential. The integrity of the genome depends on proper execution of the cell cycle, which can be altered through mechanotransduction pathways as the tumor microenvironment stiffens during tumorigenesis. We recently found that inducers of epithelial-mesenchymal transition (EMT), including transforming growth factor-beta (TGFbeta), also promote multinucleation in stiff microenvironments through Snail-dependent expression of the filament-forming protein septin-6, resulting in midbody persistence, abscission failure, and multinucleation. Consistently, we observed elevated expression of Snail and septin-6 as well as multinucleation in a human patient sample of metaplastic carcinoma of the breast, a rare classification characterized by deposition of collagen fibers and active EMT. In contrast, a soft microenvironment protected mammary epithelial cells from becoming multinucleated by preventing Snail-induced upregulation of septin-6. I will describe data suggesting that tissue stiffening during tumorigenesis synergizes with oncogenic signaling to promote genomic abnormalities that drive cancer progression. Citation Format: Celeste M. Nelson. Mechanics, multinucleation, and EMT [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr IA020.
A targeted antisense therapeutic approach for Hutchinson–Gilford progeria syndrome
Authors: Michael R. Erdos, Wayne A. Cabral, Urraca L. Tavarez, Kan Cao, Jelena Gvozdenovic-Jeremic, Narisu Narisu, Patricia M. Zerfas, Stacy Crumley, Yoseph Boku, Gunnar Hanson, Dan V. Mourich, Ryszard Kole, Michael A. Eckhaus, Leslie B. Gordon, Francis S. Collins
Journal: Nature Medicine (2021)
Potentiation of electrochemotherapy effectiveness by immunostimulation with IL-12 gene electrotransfer in mice is dependent on tumor immune status
Authors: Katja Ursic, Spela Kos, Urska Kamensek, Maja Cemazar, Simona Miceska, Bostjan Markelc, Simon Bucek, Barbara Staresinic, Veronika Kloboves Prevodnik, Richard Heller, Gregor Sersa
Journal: Journal of Controlled Release (2021)

Electrochemotherapy (ECT) exhibits high therapeutic effectiveness in the clinic, achieving up to 80% local tumor control but without a systemic (abscopal) effect. Therefore, we designed a combination therapy consisting of ECT via intratumoral application of bleomycin, oxaliplatin or cisplatin with peritumoral gene electrotransfer of a plasmid encoding interleukin-12 (p. t. IL-12 GET). Our hypothesis was that p. t. IL-12 GET potentiates the effect of ECT on local and systemic levels and that the potentiation varies depending on tumor immune status. Therefore, the combination therapy was tested in three immunologically different murine tumor models. In poorly immunogenic B16F10 melanoma, IL-12 potentiated the antitumor effect of ECT with biologically equivalent low doses of cisplatin, oxaliplatin or bleomycin. The most pronounced potentiation was observed after ECT using cisplatin, resulting in a complete response rate of 38% and an abscopal effect. Compared to B16F10 melanoma, better responsiveness to ECT was observed in more immunogenic 4 T1 mammary carcinoma and CT26 colorectal carcinoma. In both models, p. t. IL-12 GET did not significantly improve the therapeutic outcome of ECT using any of the chemotherapeutic drugs. Collectively, the effectiveness of the combination therapy depends on tumor immune status. ECT was more effective in more immunogenic tumors, but GET exhibited greater contribution in less immunogenic tumors. Thus, the selection of the therapy, namely, either ECT alone or combination therapy with p. t. IL-12, should be predominantly based on tumor immune status.
20P IGN002 (antiCD20-IFNα2b) intravenously administered tumour targeted delivery of IFNα2b and its effects in non-Hodgkin lymphoma
Authors: S. Lakshmikanthan, P.S. Kolli, M. Tugnait, J. Dalsing-Hernandez, D. Diaz, P. Gonzales, F. Lebel, J.A. Barrett
Journal: Annals of Oncology (2021)
Effectiveness of first-line immune checkpoint inhibitors (ICI) in advanced non-clear cell renal cell carcinoma (ccRCC).
Authors: Jeffrey Graham, Connor Wells, Shaan Dudani, Chun Loo Gan, Frede Donskov, Jae-Lyun Lee, Christian K. Kollmannsberger, Sumanta K. Pal, Benoit Beuselinck, Aaron Richard Hansen, Scott A. North, Georg A. Bjarnason, Neeraj Agarwal, Ravindran Kanesvaran, Lori Wood, Sebastien J. Hotte, Rana R. McKay, Toni K. Choueiri, Daniel Yick Chin Heng
Journal: Journal of Clinical Oncology (2021)

316 Background: Immune checkpoint inhibitors (ICI) have demonstrated impressive activity in metastatic clear-cell renal cell carcinoma (ccRCC) and have become standard treatment options in this setting. Data supporting the effectiveness of ICI based therapy in non-clear cell RCC (nccRCC) is more limited. Methods: We performed a retrospective analysis using the International Metastatic RCC Database Consortium (IMDC). Patients with nccRCC were classified into 3 groups based on first-line therapy: ICI based therapy (in monotherapy or in combination), vascular endothelial growth factor targeted therapy (VEGF-TT) monotherapy, or mammalian target of rapamycin (mTOR) inhibitor monotherapy. Primary outcome was overall survival (OS). Secondary outcomes were time to treatment failure (TTF) and objective response rate (ORR). We used Kaplan-Meier method to compare OS and TTF between treatment groups and Cox proportional hazards models to adjust for prognostic covariates. Results: We identified 1181 patients with nccRCC. In first-line, 78.2% received VEGF-TT, 15.8% mTOR inhibitors, and 5.5% ICI based therapy, of which 41.5% in monotherapy, 30.8% doublet-ICIs and 27.7% an ICI combined with VEGF-TT. Median OS in the ICI group was 28.6 months, compared to 19.2 and 12.6 in the VEGF-TT and mTOR groups, respectively. Median TTF was 6.9 months vs. 5.1 and 3.9 and ORR was 25% vs. 17.8% and 5.8% in the ICI, VEGF-TT and mTOR groups, respectively. After adjusting for IMDC risk group, histological subtype, and age, the hazard ratio (HR) for OS was 0.58 (95% CI 0.35-0.94, p=0.03) for ICI vs. VEGF-TT and 0.48 (95% CI 0.29-0.80, p=0.005) for ICI vs. mTOR. Conclusions: In advanced nccRCC, first-line ICI based treatment appears to be associated with improved OS compared to VEGF and mTOR targeted therapy. These results need to be confirmed in prospective randomized trials. [Table: see text]
The effects of bright white light therapy on obese frailty in older men with prostate cancer on hormonal therapy: A pilot randomized control trial.
Authors: Cristiane Decat Bergerot, Marianne Razavi, Ashley Celis, Karen L. Clark, Tanya B. Dorff, Sumanta K. Pal, Matthew J. Loscalzo, William Dale
Journal: Journal of Clinical Oncology (2021)

75 Background: Exposure to bright white light (BWL) has been shown to improve outcomes including fatigue, depression, and sleep disturbances among the general older population but the benefit has not been demonstrated as yet in prostate cancer. Older men with prostate cancer on androgen deprivation therapy (ADT) are at risk for obese frailty (components: fatigue, weakness, poor mood, slowness and obesity). In this pilot study, we aimed to determine if BWL, compared to dim white wight (DWL), reduces obese frailty in older prostate cancer patients starting anti-androgens. Methods: Men age ≥ 65 with prostate cancer initiating ADT were randomly assigned to either the BWL (exposure to full spectrum light, 500-1500 lux) or DWL cohort (exposure to low dose white light (&lt;50 lux)) and were blinded to assignment. Men received daily 30-minute morning light session from special glasses (Luminette) for 3 months. Participants were assessed at the beginning of treatment and 3 months later with the Short Physical Performance Battery (SPPB) - including timed 4m walk, tandem balance, and timed chair stands (range: 0 to 12) - energy levels (self-reported 5-point Likert scale), waist circumference (measured via tape (mm)), and muscle strength (handgrip: assessed via dynamometer (kg)). Pre-post outcomes (means differences) were evaluated using paired t-tests with a p-value of 0.05 considered significant. Results: 18 patients (9 per cohort) were recruited. Patients in the BWL arm showed a statistically significant improvement in muscle strength (BWL p=0.012 versus in DWL p=0.22). Compared with DWL, BWL arm showed no decline in energy levels, (BWL p=0.28 vs. DWL p=0.035) nor gain in waist circumference (BWL p=0.51, DWL p=0.046). There were no statistically significant differences in either arm on the SPPB (BWL p=0.44, and in DWL p=0.09). Conclusions: BWL may offset negative effects of ADT for older men with prostate cancer, through improved muscle strength, maintained energy levels, and no waist circumference gain. While a small pilot study, the intervention warrants further research in a larger sample.
Targeted Single-Cell RNA-seq Identifies Minority Cell Types of Kidney Distal Nephron
Authors: Lihe Chen, Chun-Lin Chou, Mark A. Knepper
Journal: Journal of the American Society of Nephrology (2021)

Proximal tubule cells dominate the kidney parenchyma numerically, although less abundant cell types of the distal nephron have disproportionate roles in water and electrolyte balance.Coupling of a FACS-based enrichment protocol with single-cell RNA-seq profiled the transcriptomes of 9099 cells from the thick ascending limb (CTAL)/distal convoluted tubule (DCT) region of the mouse nephron.Unsupervised clustering revealed Slc12a3+/Pvalb+ and Slc12a3+/Pvalb- cells, identified as DCT1 and DCT2 cells, respectively. DCT1 cells appear to be heterogeneous, with orthogonally variable expression of Slc8a1, Calb1, and Ckb. An additional DCT1 subcluster showed marked enrichment of cell cycle-/cell proliferation-associated mRNAs (e.g., Mki67, Stmn1, and Top2a), which fit with the known plasticity of DCT cells. No DCT2-specific transcripts were found. DCT2 cells contrast with DCT1 cells by expression of epithelial sodium channel β- and γ-subunits and much stronger expression of transcripts associated with calcium transport (Trpv5, Calb1, S100g, and Slc8a1). Additionally, scRNA-seq identified three distinct CTAL (Slc12a1+) cell subtypes. One of these expressed Nos1 and Avpr1a, consistent with macula densa cells. The other two CTAL clusters were distinguished by Cldn10 and Ptger3 in one and Cldn16 and Foxq1 in the other. These two CTAL cell types were also distinguished by expression of alternative Iroquois homeobox transcription factors, with Irx1 and Irx2 in the Cldn10+ CTAL cells and Irx3 in the Cldn16+ CTAL cells.Single-cell transcriptomics revealed unexpected diversity among the cells of the distal nephron in mouse. Web-based data resources are provided for the single-cell data.
Usefulness of a papilla fixation method with an innovative clipping system for bile duct cannulation
Authors: Ikuhiro Kobori, Yasumi Katayama, Masaru Kuwada, Kei Funada, Yoshinori Gyotoku, Akihiro Kitahama, Masaya Tamano
Journal: Endoscopy (2021)

Selective bile duct cannulation (SBDC) is difficult when the papilla of Vater is unstable because of a long narrow distal segment. Pancreatic duct guidewire placement techniques, such as the double-guidewire technique (DGT), are used to fix the papilla and facilitate SBDC [1] [2], but it is difficult to approach the pancreatic duct when the papilla is unstable. A simple and easy method of fixing the papilla and stretching a narrow distal segment using SureClips (Micro-Tech Co., Nanjing, China) is presented.
Targeting Bruton tyrosine kinase using non-covalent inhibitors in B cell malignancies
Authors: Danling Gu, Hanning Tang, Jiazhu Wu, Jianyong Li, Yi Miao
Journal: Journal of Hematology & Oncology (2021)

Abstract B cell receptor (BCR) signaling is involved in the pathogenesis of B cell malignancies. Activation of BCR signaling promotes the survival and proliferation of malignant B cells. Bruton tyrosine kinase (BTK) is a key component of BCR signaling, establishing BTK as an important therapeutic target. Several covalent BTK inhibitors have shown remarkable efficacy in the treatment of B cell malignancies, especially chronic lymphocytic leukemia. However, acquired resistance to covalent BTK inhibitors is not rare in B cell malignancies. A major mechanism for the acquired resistance is the emergence of BTK cysteine 481 (C481) mutations, which disrupt the binding of covalent BTK inhibitors. Additionally, adverse events due to the off-target inhibition of kinases other than BTK by covalent inhibitors are common. Alternative therapeutic options are needed if acquired resistance or intolerable adverse events occur. Non-covalent BTK inhibitors do not bind to C481, therefore providing a potentially effective option to patients with B cell malignancies, including those who have developed resistance to covalent BTK inhibitors. Preliminary clinical studies have suggested that non-covalent BTK inhibitors are effective and well-tolerated. In this review, we discussed the rationale for the use of non-covalent BTK inhibitors and the preclinical and clinical studies of non-covalent BTK inhibitors in B cell malignancies.
Socioeconomic deprivation and cancer survival in a metropolitan area: An analysis of cancer registry data from Hamburg, Germany
Authors: Lina Jansen, Cynthia Erb, Alice Nennecke, Isabelle Finke, Ron Pritzkuleit, Bernd Holleczek, Hermann Brenner
Journal: The Lancet Regional Health - Europe (2021)

Few studies have investigated socioeconomic inequalities within cities. Yet, such analyses are particularly important given the increasing international trend to urbanization. Here we investigated area-based socioeconomic inequalities in cancer survival in Hamburg, a port city in the North of Germany (population: 1.84 million people).Patients with a diagnosis of colorectal, lung, female breast, and prostate cancer in 2004-2018 (follow-up until 31.12.2018) and registered in the Hamburg cancer registry were included. Area-based socioeconomic deprivation on urban district level was assigned to the patients and grouped in five quintiles. Relative survival in 2014-2018 was calculated using the period approach. Trend analyses between 2004 and 2018 were conducted. Relative excess risks adjusted for age and stage were computed with model-based period analyses.For the 73,106 included patients, age-standardized 5-year relative survival in 2014-2018 decreased with increasing deprivation with significant differences between the most and least deprived group of 14·7 (prostate), 10·8 (colorectal), 8·0 (breast), and 2·5 (lung) percent units. Standardization by cancer stage decreased the difference for prostate cancer to 8·5 percent units and for breast cancer to 3·6 percent units but had only a minor effect for colorectal and lung cancer. Similar socioeconomic inequalities were already present in 2004-08.Strong socioeconomic inequalities in cancer survival were observed in Hamburg, which could be partly explained by differences in the stage distribution. Further research including information on screening participation as well as information on cancer care are important to further understand and finally overcome these inequalities.German Cancer Aid.
Abstract 3332: Fractional Flow Reserve (FFR) And MIBI SPECT: A comparison In Patients With Multi-vessel Coronary Disease
Authors: Narbeh Melikian, Pieter De Bondt, Thomas Cuisset, Eric Wyffels, Jozef Bartunek, Guy Heyndrickx, William Wijns, Bernard De Bruyne
Journal: Circulation (2007)

INTRODUCTION In patients with angiographic 3 vessel disease only 29% have been reported to have perfusion defects. However the association between physiological evidence for ischemia per vessel derived from fractional flow reserve (FFR) and MIBI SPECT (SPECT) in multivessel disease (MVD) is unknown. We comapred this association in patients with MVD. METHOD In 84 vascular territories in 28 patients (mean age 63.9±9.8 years, LV ejection fraction 69±12%) with angiographic MVD (&gt;50% stenosis in at least 2 vessels) results of SPECT (rest / stress adenosine) were compared to FFR measurements in each coronary vessel. AHA semi-quantitative 5 point scorning system using a 17-segment model was used to report SPECT scans. A FFR &lt;0.80 was taken as evidence for ischemia. RESULTS MIBI was positive in at least 1 territory in 19 (67%) and FFR &lt;0.80 in at least 1 territory in 23 (82%) of patients. 7 (25%) patients with no perfusion defect on SPECT had FFR &lt;0.80 in at least 2 territories. The association between MIBI and FFR in each patient and per vascular territory are summarised below. Per patient there was no concordance between SPECT and FFR (Kappa −0.11) and per vascular territory there was poor concordance between SPECT and FFR (Kappa 0.23). In 8 (29%) patients both SPECT and FFR detected identical ischemic territories [mean number of ischemic territories: 1.5±0.9 for both; P=1.00]. In the remaining 20 patients in comparison to FFR, SPECT either underestimated [9 (32%) patients − mean number of ischemic territories, SPECT: 0.3±0.7, FFR: 1.9±0.6; P=0.001] or overestimated [11 (39%) patients -mean number of ischemic territories, MIBI: 2.0±1.0, FFR: 1.0±0.9; P=0.02] the number of ischemic territories. There was a weak correlation between severity of ischemia as assessed by SPECT in each vascular territory and the actual FFR value (r=0.34; P=0.001). CONCLUSION In patients with multivessel disease, the concordance between SPECT and FFR to localise hemodynamically significant stenosis is poor. Per Patient and per vascular territory comparison of MIBI SPECT and FFR
The Role of Alcohol and Social Stress in Russia's Mortality Rate—Reply
Authors: Francis C. Notzon, Yuri M. Komarov, Sergei P. Ermakov, Christopher T. Sempos, James S. Marks, Elena V. Sempos
Journal: JAMA (1999)

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
Case 22-1965
Authors: Donald B. Martin, Benjamin Castleman
Journal: New England Journal of Medicine (1965)

Presentation of Case First admission. A sixty-year-old tombstone salesman was admitted to the hospital because of hemoptysis.Ten years previously, after a statue that he was lifting toppled against his chest, he began to experience a sensation of tightness in the anterior portion of the chest, with radiation to both arms and aggravation by exertion. No abnormality was found on physical examination. At that time an electrocardiogram (Fig. 1) showed a normal rhythm at a rate of 90; the ST segments were elevated in Leads 2, 3 and aVF, the T waves were inverted in Leads V1 through V . . .