tbuckley/cabot-search huggingface dataset:
Abstract 15522: Multiple Brachial ‘Tornado’ Loops Encountered During Transradial Access - A Case Report With Review of Literature
Authors: Aditi S Vaishnav, Avani Vaishnav, Shankar Iyer, Sudhir Vaishnav
Journal: Circulation (2020)

Introduction: Although transradial access (TRA) is widely accepted for cardiac catheterization, technical difficulties may occur due to variations in the radial-brachial-subclavian artery anatomy. Clinical Vignette: A 70-year old man presented with typical angina, positive stress test and normal LV function. Elective coronary angiography via TRA was planned since there were no contraindications. A guidewire was inserted and advanced via right radial puncture. Due to resistance above the elbow, the wire was withdrawn and check shoots were taken. These revealed a brachial loop, which was crossed and straightened with a Teflon coated angioplasty wire (0.014BMW wire). On advancing further, resistance was encountered again. Check-shoots at this point revealed multiple tortuous tornado-like brachial loops. Attempts to cross these using a BMW wire and 4F-RCA guiding catheter were unsuccessful as the artery went into spasm, preventing further manipulation. Ipsilateral TRA was abandoned due to risk of arterial perforation and severe pain; contralateral TRA was not attempted due to patient’s refusal. The procedure was completed via femoral access. Discussion: To the best of our knowledge, this is the first report of multiple brachial loops, which highlights certain unique challenges- 1. Complex anatomic variations can occur exclusive of signs used to assess TRA amenability 2. No guidelines on procedural techniques 3. No data to guide the alternative access site as it is unknown whether brachial loops tend to occur bilaterally, unlike radial loops 4. Unlike radial and subclavian arteries, there are no data on association of demographic factors with brachial artery variations. Conclusion: Anatomic variations of upper limb arteries, although rare, can cause technical difficulties and TRA failure. If resistance is encountered, an angiogram should be performed through the sheath to assess anatomy, to prevent severe spasm and perforation from forceful catheter advancement.
Auto-antibodies to type I IFNs can underlie adverse reactions to yellow fever live attenuated vaccine
Authors: Paul Bastard, Eleftherios Michailidis, Hans-Heinrich Hoffmann, Marwa Chbihi, Tom Le Voyer, Jérémie Rosain, Quentin Philippot, Yoann Seeleuthner, Adrian Gervais, Marie Materna, Patricia Mouta Nunes de Oliveira, Maria de Lourdes S. Maia, Ana Paula Dinis Ano Bom, Tamiris Azamor, Deborah Araújo da Conceição, Ekaterini Goudouris, Akira Homma, Günther Slesak, Johannes Schäfer, Bali Pulendran, Joseph D. Miller, Ralph Huits, Rui Yang, Lindsey B. Rosen, Lucy Bizien, Lazaro Lorenzo, Maya Chrabieh, Lucia V. Erazo, Flore Rozenberg, Mohamed Maxime Jeljeli, Vivien Béziat, Steven M. Holland, Aurélie Cobat, Luigi D. Notarangelo, Helen C. Su, Rafi Ahmed, Anne Puel, Shen-Ying Zhang, Laurent Abel, Stephen J. Seligman, Qian Zhang, Margaret R. MacDonald, Emmanuelle Jouanguy, Charles M. Rice, Jean-Laurent Casanova
Journal: The Journal of Experimental Medicine (2021)

Yellow fever virus (YFV) live attenuated vaccine can, in rare cases, cause life-threatening disease, typically in patients with no previous history of severe viral illness. Autosomal recessive (AR) complete IFNAR1 deficiency was reported in one 12-yr-old patient. Here, we studied seven other previously healthy patients aged 13 to 80 yr with unexplained life-threatening YFV vaccine–associated disease. One 13-yr-old patient had AR complete IFNAR2 deficiency. Three other patients vaccinated at the ages of 47, 57, and 64 yr had high titers of circulating auto-Abs against at least 14 of the 17 individual type I IFNs. These antibodies were recently shown to underlie at least 10% of cases of life-threatening COVID-19 pneumonia. The auto-Abs were neutralizing in vitro, blocking the protective effect of IFN-α2 against YFV vaccine strains. AR IFNAR1 or IFNAR2 deficiency and neutralizing auto-Abs against type I IFNs thus accounted for more than half the cases of life-threatening YFV vaccine-associated disease studied here. Previously healthy subjects could be tested for both predispositions before anti-YFV vaccination.
Helen Salisbury: Trust me, I’m the family doctor
Authors: Helen Salisbury
Journal: BMJ (2021)

“Family doctor” might be an old fashioned way of describing a general practitioner, but it has some useful connotations. It indicates a relationship that stretches from postnatal checks and childhood illnesses, through pregnancies and long term conditions, to palliative and end-of-life care. I might consult with several members of the same family in the space of a week and sometimes have to listen carefully to multiple versions of the same events. A core skill of being a GP is remembering who told you what and being careful not to betray a confidence by responding: “Yes, …
Too big to go out: gastric endoscopic submucosal dissection of giant lipoma complicated by intestinal obstruction
Authors: Giuseppe Grande, Flavia Pigò, Angelo Caruso, Salvatore Russo, Marinella Lupo, Micaela Piccoli, Rita Conigliaro
Journal: Endoscopy (2021)

Gastrointestinal sub-epithelial tumors are frequently diagnosed during endoscopy but they are usually small and do not require any treatment owing to benign behavior [1] [2]. Sometimes these lesions can cause symptoms and their resection is needed [3].
Neutralization of SARS-CoV-2 spike 69/70 deletion, E484K and N501Y variants by BNT162b2 vaccine-elicited sera
Authors: Xuping Xie, Yang Liu, Jianying Liu, Xianwen Zhang, Jing Zou, Camila R. Fontes-Garfias, Hongjie Xia, Kena A. Swanson, Mark Cutler, David Cooper, Vineet D. Menachery, Scott C. Weaver, Philip R. Dormitzer, Pei-Yong Shi
Journal: Nature Medicine (2021)

We engineered three severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses containing key spike mutations from the newly emerged United Kingdom (UK) and South African (SA) variants: N501Y from UK and SA; 69/70-deletion + N501Y + D614G from UK; and E484K + N501Y + D614G from SA. Neutralization geometric mean titers (GMTs) of 20 BTN162b2 vaccine-elicited human sera against the three mutant viruses were 0.81- to 1.46-fold of the GMTs against parental virus, indicating small effects of these mutations on neutralization by sera elicited by two BNT162b2 doses.
Cyclic-Di-GMP promotes STING-dependent ILC2 to ILC1 shift and abrogates eosinophilia in ILC2-driven lung inflammation
Authors: Kellen Cavagnero, Jana Badrani, Luay Naji, Michael Amadeo, Anthea Leng, Lee Lacasa, Alyssa Strohm, Taylor Doherty
Journal: Journal of Allergy and Clinical Immunology (2021)
Downregulated METTL14 accumulates BPTF that reinforces super-enhancers and distal lung metastasis via glycolytic reprogramming in renal cell carcinoma
Authors: Chuanjie Zhang, Li Chen, Yihan Liu, Jingyi Huang, Ao Liu, Yang Xu, Yan Shen, Hongchao He, Danfeng Xu
Journal: Theranostics (2021)

Background: Methyltransferase-like 14 (METTL14) participates in tumorigenesis in several malignancies, but how METTL14 mediates the metastasis of renal cell carcinoma (RCC) has never been reported. Methods: Western blotting, quantitative real-time PCR, and immunohistochemistry were used to determine the mRNA and protein levels of relevant genes. Methylated RNA immunoprecipitation sequencing and RNA sequencing were utilized to screen potential targets of METTL14. Chromatin immunoprecipitation sequencing and assay for transposase-accessible chromatin sequencing were performed to investigate epigenetic alterations. The biological roles and mechanisms of METTL14/BPTF in promoting lung metastasis were confirmed in vitro and in vivo using cell lines, patient samples, xenograft models, and organoids. Results: Utilizing the TCGA-KIRC and Ruijin-RCC datasets, we found low expression of METTL14 in mRCC samples, which predicted poor prognosis. METTL14 deficiency promoted RCC metastasis in vitro and in vivo. Mechanistically, METTL14-mediated m6A modification negatively regulated the mRNA stability of bromodomain PHD finger transcription factor (BPTF) and depended on BPTF to drive lung metastasis. Accumulated BPTF in METTL14-deficient cells remodeled the enhancer landscape to reinforce several oncogenic crosstalk. Particularly, BPTF constituted super-enhancers that activate downstream targets like enolase 2 and SRC proto-oncogene nonreceptor tyrosine kinase, leading to glycolytic reprogramming of METTL14-/- cells. Finally, we determined the efficacy of the BPTF inhibitor AU1 in suppressing mRCC of patient-derived cells, mRCC-derived organoids (MDOs), and orthotopic xenograft models. Conclusions: Our study is the first to investigate the essential role of m6A modification and the METTL14/BPTF axis in the epigenetic and metabolic remodeling of mRCC, highlighting AU1 as a vital therapeutic candidate.
Calcium phosphate engineered photosynthetic microalgae to combat hypoxic-tumor by <i>in-situ</i> modulating hypoxia and cascade radio-phototherapy
Authors: Danni Zhong, Wanlin Li, Shiyuan Hua, Yuchen Qi, Tingting Xie, Yue Qiao, Min Zhou
Journal: Theranostics (2021)

Rationale: Hypoxia is one of the crucial restrictions in cancer radiotherapy (RT), which leads to the hypoxia-associated radioresistance of tumor cells and may result in the sharp decline in therapeutic efficacy. Methods: Herein, living photosynthetic microalgae (Chlorella vulgaris, C. vulgaris), were used as oxygenators, for in situ oxygen generation to relieve tumor hypoxia. We engineered the surface of C. vulgaris (CV) cells with calcium phosphate (CaP) shell by biomineralization, to form a biomimetic system (CV@CaP) for efficient tumor delivery and in-situ active photosynthetic oxygenation reaction in tumor. Results: After intravenous injection into tumor-bearing mice, CV@CaP could remarkably alleviate tumor hypoxia by continuous oxygen generation, thereby achieving enhanced radiotherapeutic effect. Furthermore, a cascade phototherapy could be fulfilled by the chlorophyll released from photosynthetic microalgae combined thermal effects under 650 nm laser irradiation. The feasibility of CV@CaP-mediated combinational treatment was finally validated in an orthotropic breast cancer mouse model, revealing its prominent anti-tumor and anti-metastasis efficacy in hypoxic-tumor management. More importantly, the engineered photosynthetic microalgae exhibited excellent fluorescence and photoacoustic imaging properties, allowing the self-monitoring of tumor therapy and tumor microenvironment. Conclusions: Our studies of this photosynthetic microsystem open up a new dimension for solving the radioresistance issue of hypoxic tumors.
Intracranial Atherosclerotic Plaque as a Potential Cause of Embolic Stroke of Undetermined Source
Authors: Lin Tao, Xiao-Qiu Li, Xiao-Wen Hou, Ben-Qiang Yang, Cheng Xia, George Ntaios, Hui-Sheng Chen
Journal: Journal of the American College of Cardiology (2021)
Ovarian hormones-autophagy-immunity axis in menstruation and endometriosis
Authors: Hui-Hui Shen, Tao Zhang, Hui-Li Yang, Zhen-Zhen Lai, Wen-Jie Zhou, Jie Mei, Jia-Wei Shi, Rui Zhu, Feng-Yuan Xu, Da-Jin Li, Jiang-Feng Ye, Ming-Qing Li
Journal: Theranostics (2021)

Menstruation occurs in few species and involves a cyclic process of proliferation, breakdown and regeneration under the control of ovarian hormones. Knowledge of normal endometrial physiology, as it pertains to the regulation of menstruation, is essential to understand disorders of menstruation. Accumulating evidence indicates that autophagy in the endometrium, under the regulation of ovarian hormones, can result in the infiltration of immune cells, which plays an indispensable role in the endometrium shedding, tissue repair and prevention of infections during menstruation. In addition, abnormal autophagy levels, together with resulting dysregulated immune system function, are associated with the pathogenesis and progression of endometriosis. Considering its potential value of autophagy as a target for the treatment of menstrual-related and endometrium-related disorders, we review the activity and function of autophagy during menstrual cycles. The role of the estrogen/progesterone-autophagy-immunity axis in endometriosis are also discussed.
Abstract 14566: Mild Elevation in Cardiac Troponin T is Independently Associated With Long-Term Mortality After Intermediate or High-Risk Vascular Surgery
Authors: Grant W Reed, Samuel Horr, Stephen G Ellis, A. Michael Lincoff, Steven E Nissen, Venu Menon
Journal: Circulation (2015)

Introduction: Myocardial injury is a risk factor for adverse outcomes after non-cardiac surgery. However, the prevalence of cardiac troponin T (cTnT) sampling after vascular surgery in real-word practice has not been well studied. Further, whether mild perioperative cTnT elevation is associated with long-term mortality is not established. Methods: This was a retrospective study of 13,196 patients who underwent intermediate or high-risk vascular surgery at a single center from January 1, 2010 - May 1, 2015. Patients were assessed for cTnT sampling within 96 hours of surgery. Cumulative 3 year mortality was stratified by absence of cTnT sampling, a normal value of 0.10 ng/mL. Cox proportional hazards analysis was used to adjust mortality for Revised Cardiac Risk Index (RCRI) score and other patient characteristics. Results: Mean age was 66.2±14.4 years, and 5,357 (40.6%) were female. Troponin was sampled in 3,296 (25.0%) patients, and among those 747 (5.7%) were elevated (positive yield 22.7%). There were 1,858 (14.1%) deaths. On Kaplan-Meier analysis, all-cause mortality was greatest with elevated cTnT (p&lt;0.0001, Figure - A) and was higher across degrees of cTnT elevation (p&lt;0.0001, Figure - B). After adjusting for RCRI score, age, gender, and diabetes, degree of cTnT elevation remained independently associated with mortality (Table). Conclusions: The degree of cTnT elevation independently predicts long-term mortality after vascular surgery. Even mild elevations of cTnT above threshold are associated with heightened risk of mortality, which extends well beyond the acute post-operative period.
Role of 53BP1 in double strand break recognition mechanisms and cell survival after exposure to ionizing radiation : relative p53 and Chk2 dependency
Authors: Ping Zhang, Jean Bourhis, Nicolas Dorvault, Yungan Tao, Maria Castedo, Didier Metivier, Guido Kroemer, Eric Deutsch
Journal: Cancer Research (2007)

889  DNA double strand break (DSB) are largely recognized as the central cellular cause of cell death after exposure to IR. In a recent study we have shown that γ-irradiation induced mitotic catastrophe occurs through a caspase-independent way in the human colorectal cancers (Zhang et al. Oncogene 2006). DSB recognition by the ATM protein is a central event during cellular response to IR leading to phosphorylation of cell cycle regulating proteins, DNA repair and apoptosis. 53BP1 is a conserved nuclear protein that is implicated in the DNA damage response, accumulates at or near sites of DNA damage, and participates in the intra S and G2/M checkpoints. The 53BP1 and NBS1 proteins are shown to be a regulators of ATM. The aim of this study was to assess the relative dependence of p53 and Chk2, two mains ATM substrates in radiation response, in the context of 53BP1 inhibition.  Methods: γ-radiation was delivered by Cobalt source at a dose rate of 0.823 Gy/min. Radiosensitivity of A549 cell line and HCT116 cell lines (wild type or knocked out for Chk2 and Bax genes) with/withoutsiRNA-53BP1 or NBS1 were studied by clonogenic survival assay.The foci of53BP1, and γ-H2AX were analyzed by fluorescence immunocytochemistry. Apoptosis induction 24h after 6Gy IR with/without siRNA-53BP1 or NBS1 was determined by FACS analysis.  Results: The number of foci about 53BP1 and γ-H2AX were increased 29 and 22 folds respectively in A549 as well as HCT116 WT cell lines 10 min after 2Gy IR, there is a co-localisation of 53BP1 and γ-H2AX foci. This enhancement of 53BP1 foci in response to IR was decreased 53.7% and 40.9% respectively in HCT116 p53 and Chk2-/- cells by contrast to HCT116 WT, but this decrease is not significant in Bax-/- cells . Radiation sensitivity was increased after transfection by siRNA-53BP1 in both HCT116 WT and Chk2 KO cell lines but not in p53-/- neither Bax-/- cells.  SiRNA-53BP1 also enhanced the radiosensitivity in A549 cell line. This suggests that 53BP1 is involved in the recognition of DNA damage in a cell cycle check-point dependant manner. Moreover, cells exposed to 6 Gy IR manifest apoptosis signs (phosphatidyl serine exposure on the cell surface, sub-diploid DNA content) after si-53BP1 transfection by FACS analysis.  Our results indicate that 53BP1 plays an important role radiation sensitivity, it is an integral component of the DNA damage-response network. The 53BP1 role in radiation response seems to be different in terms of cell survival in the absence of p53 or Chk2 suggesting a different role for these ATM substrates after DNA damage recognition by 53BP1.
Longitudinal change in fine motor skills after brain radiotherapy and in vivo imaging biomarkers associated with decline
Authors: Mia Salans, Michelle D Tibbs, Roshan Karunamuni, Anthony Yip, Minh-Phuong Huynh-Le, Anna Christina Macari, Anny Reyes, Kathryn Tringale, Carrie R McDonald, Jona A Hattangadi-Gluth
Journal: Neuro-Oncology (2021)

Abstract Background We explored fine motor skills (FMS) before and after brain radiotherapy (RT), analyzing associations between longitudinal FMS and imaging biomarkers of cortical and white matter (WM) integrity in motor regions of interest (ROIs). Methods On a prospective trial, 52 primary brain tumor patients receiving fractionated brain RT underwent volumetric brain MRI, diffusion tensor imaging, and FMS assessments (Delis-Kaplan Executive Function System Trail Making Test Motor Speed [DKEFS-MS], Grooved Pegboard Dominant Hands [PDH], and Grooved Pegboard Nondominant Hands [PNDH]) at baseline and 3-, 6-, and 12-month post-RT. Motor ROIs autosegmented included: sensorimotor cortices and superficial WM, corticospinal tracts, cerebellar cortices and WM, and basal ganglia. Volume (cc) was measured in all ROIs at each timepoint. Diffusion biomarkers (FA [fractional anisotropy] and MD [mean diffusivity]) were additionally measured in WM ROIs. Linear mixed-effects models assessed biomarkers as predictors of FMS scores. P values were corrected for multiple comparisons. Results Higher RT dose was associated with right paracentral cortical thinning (β = −2.42 Gy/(month × mm), P = .03) and higher right precentral WM MD (β = 0.69 Gy/(month × µm2/ms), P = .04). Higher left (β = 38.7 points/(month × µm2/ms), P = .004) and right (β = 42.4 points/(month × µm2/ms), P = .01) cerebellar WM MD, left precentral cortical atrophy (β = −8.67 points/(month × mm), P = .02), and reduced right cerebral peduncle FA (β = −0.50 points/month, P = .01) were associated with worse DKEFS-MS performance. Left precentral cortex thinning was associated with worse PDH scores (β = −17.3 points/(month × mm), P = .02). Left (β = −0.87 points/(month × cm3), P = .001) and right (β = −0.64 points/(month × cm3), P = .02) cerebellar cortex, left pons (β = −19.8 points/(month × cm3), P = .02), and right pallidum (β = −10.8 points/(month × cm3), P = .02) atrophy and reduced right internal capsule FA (β = −1.02 points/month, P = .03) were associated with worse PNDH performance. Conclusions Biomarkers of microstructural injury in motor-associated brain regions were associated with worse FMS. Dose avoidance in these areas may preserve FMS.
Pregnancy, Postpartum Care, and COVID-19 Vaccination in 2021
Authors: Sonja A. Rasmussen, Denise J. Jamieson
Journal: JAMA (2021)

Oscar Martínez-Perez, MD, PhD; Manon Vouga, MD, PhD; Sara Cruz Melguizo, MD, PhD; Laura Forcen Acebal, MD; Alice Panchaud, PhD; Mar Muñoz-Chápuli, MD; David Baud, MD, PhD
The Impact of Breast Density Information or Notification on Women’s Cognitive, Psychological, and Behavioral Outcomes: A Systematic Review
Authors: Brooke Nickel, Tessa Copp, Meagan Brennan, Rachel Farber, Kirsten McCaffery, Nehmat Houssami
Journal: JNCI Journal of the National Cancer Institute (2021)

Abstract Background Breast density (BD) is an independent risk factor for breast cancer and reduces the sensitivity of mammography. This systematic review aims to synthesize evidence from existing studies to understand the impact of BD information and/or notification on women’s cognitive, psychological, and behavioral outcomes. Methods Studies were identified via relevant database searches up to March 2020. Two authors evaluated the eligibility of studies with verification from the study team, extracted and crosschecked data, and assessed the risk of bias. Results Of the 1134 titles identified, 29 studies were included. Twenty-three studies were quantitative, including only 1 randomized controlled trial of women receiving BD information, and 6 were qualitative. Twenty-seven studies were conducted in the United States, with 19 conducted post-BD legislation. The overall results in terms of BD awareness, knowledge, attitudes, perceptions, and intentions were heterogeneous across included studies, with the strongest consistency demonstrated regarding the importance of communication with and involvement of health-care professionals. Together, the studies did, however, highlight that there is still limited awareness of BD in the community, especially in more socioeconomic disadvantaged communities, and limited knowledge about what BD means and the implications for women. Importantly, BD information in the context of overall breast cancer risk has not yet been studied. Conclusions There are important gaps in the understanding of the impact of BD information or notification on women and how best to communicate BD information to women. More high-quality evidence to inform both current and future practice related to BD is still needed.
ネオアジュバント化学療法は,手術可能な乳癌との比較において,炎症性もしくは局所性の進行性乳癌患者における同様の反応を示す: GeparTrio試験データの二次的分析
Authors: Costa Serban Dan, Loibl Sibylle, Kaufmann Manfred, Zahm Dirk-Michael, Hilfrich Joern, Huober Jens, Eidtmann Holger, DU Bois Andreas, Blohmer Jens-Uwe, Ataseven Beyhan, Weiss Erich, Tesch Hans, Gerber Bernd, H Baumann Klaus, Thomssen Christoph, Breitbach Georg Peter, Ibishi Shaip, Jackisch Christian, Mehta Keyur, Von Minckwitz Gunter
Journal: Journal of Clinical Oncology (2010)
Abstract IA017: Molecular classification and stratification: Diving deeper
Authors: Jessica N. McAlpine
Journal: Clinical Cancer Research (2021)

Abstract As we move forward with integration of molecular classification into clinical care the assessment of additional clinicopathological and molecular features in the context of molecular subtype will enable us to further refine prognosis. In addition, molecular classification can enable stratification of clinical cohorts that have been often thought of as homogeneous but are clearly more diverse than recognized. These last few years have produced an abundance of literature supporting not only the value of consistent categorization and prognostic value but also predictive implications enabling action/change in practice. Molecular classification-driven care in endometrial cancer will reduce variation in practice with improved knowledge translation critical to implementation and uptake. Citation Format: Jessica N. McAlpine. Molecular classification and stratification: Diving deeper [abstract]. In: Proceedings of the AACR Virtual Special Conference: Endometrial Cancer: New Biology Driving Research and Treatment; 2020 Nov 9-10. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(3_Suppl):Abstract nr IA017.