tbuckley/cabot-search huggingface dataset:
Prognostic Value of EndoPredict in Women with Hormone Receptor–Positive, HER2-Negative Invasive Lobular Breast Cancer
Authors: Ivana Sestak, Martin Filipits, Richard Buus, Margaretha Rudas, Marija Balic, Michael Knauer, Ralf Kronenwett, Florian Fitzal, Jack Cuzick, Michael Gnant, Richard Greil, Mitch Dowsett, Peter Dubsky
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Invasive lobular carcinoma (ILC) accounts for approximately 5%–15% of all invasive breast cancer cases. Most of the correlations between multigene assays and patient outcome were derived from studies based on patients with invasive ductal carcinoma (IDC) or without distinction between the subtypes. Here, we investigate the prognostic value of EndoPredict (EPclin) in a large cohort of ILCs pooled from three phase III randomized trials (ABCSG-6, ABCSG-8, TransATAC). Experimental Design: The primary objective of this analysis was to determine the prognostic value of EPclin for distant recurrence (DR) in years 0–10 in postmenopausal women with ILC. The primary outcome was DR. Results: 470 women (17.9%) presented with ILC, 1,944 (73.9%) with IDC, and 216 (8.2%) with other histologic types. EPclin was highly prognostic in women with ILC [HR = 3.32 (2.54–4.34)] and provided more prognostic value than the Clinical Treatment Score [CTS; HR = 2.17 (1.73–2.72)]. 63.4% of women were categorized into the low EPclin risk group and they had a 10-year DR of 4.8% (2.7–8.4) compared with 36.6% of women in the high-risk group with a 10-year DR risk of 26.6% (20.0–35.0). EPclin also provided highly prognostic information in women with node-negative disease [HR = 2.56 (1.63–4.02)] and node-positive disease [HR = 3.70 (2.49–5.50)]. Conclusions: EPclin provided highly significant prognostic value and significant risk stratification for women with ILC. Ten-year DR risk in the EPclin low-risk groups were similar between ILC and IDC. Our results show that EPclin is informative in women with ILC and suggest that it is equally valid in both histologic subtypes.
Patient-Level Factors Associated With Lack of Health Care Provider Recommendation for the Human Papillomavirus Vaccine Among Young Cancer Survivors
Authors: Jocelyn M. York, James L. Klosky, Yanjun Chen, James A. Connelly, Karen Wasilewski-Masker, Anna R. Giuliano, Leslie L. Robison, F. Lennie Wong, Melissa M. Hudson, Smita Bhatia, Wendy Landier
Journal: Journal of Clinical Oncology (2020)

Young cancer survivors are at increased risk for morbidities related to infection with the human papillomavirus (HPV), yet their HPV vaccine initiation rates remain low. Patient-/parent-reported lack of health care provider recommendation for HPV vaccination is strongly associated with vaccine noninitiation. We aimed to identify patient-level factors associated with survivor-/parent-reported lack of provider recommendation for HPV vaccination among young cancer survivors.Cancer survivors ages 9-26 years and 1-5 years off therapy completed a cross-sectional survey (parent-completed for survivors 9-17 years of age). Lack of health care provider HPV vaccine recommendation was the outcome of interest in a multivariable logistic regression model that included relevant patient-level sociodemographic, clinical, and vaccine-related variables.Of 955 survivors, 54% were male, 66% were non-Hispanic White, and 36% had leukemia. At survey participation, survivors were an average age (± standard deviation) of 16.3 ± 4.7 years and 32.8 ± 14.7 months off therapy. Lack of provider HPV vaccine recommendation was reported by 73% (95% CI, 70% to 75%) of survivors. For the entire cohort, patient-level factors associated with lack of reported provider recommendation included perceived lack of insurance coverage for the HPV vaccine (odds ratio [OR], 4.0; 95% CI, 2.7 to 5.9; P < .001), male sex (OR, 2.8; 95% CI, 1.9 to 4.0; P < .001), and decreased parent-survivor communication regarding HPV vaccination (OR, 1.7 per unit decrease in score; 95% CI, 1.3 to 2.2; P < .001). In the sex- and age-stratified models, perceived lack of insurance coverage (all models) and male sex (age-stratified models) were also significantly associated with lack of reported provider recommendation.We identified factors characterizing survivors at risk for not reporting receipt of a health care provider HPV vaccine recommendation. Future research is needed to develop interventions that facilitate effective provider recommendations for HPV vaccination among all young cancer survivors.
Unrepaired Tetralogy of Fallot in Adulthood
Authors: John Dickey, Christopher Phelan
Journal: New England Journal of Medicine (2020)

A 29-year-old man presented with worsening exertional dyspnea, blurred vision, and headaches. Symptoms had been present since childhood but had not been treated. Echocardiography was performed, and a diagnosis of tetralogy of Fallot was made.
Ectopic Parathyroid Adenoma of the Piriform Sinus on Parathyroid 4D-CT and 99mTc-MIBI SPECT/CT
Authors: Meng-Chieh P. Hsieh, John S. Nemer, Volkan Beylergil, Randy Yeh
Journal: Clinical Nuclear Medicine (2020)

Abstract Ectopic parathyroid adenomas are a common cause of postsurgical persistent primary hyperparathyroidism. Our case highlights a patient with a negative bilateral 4-gland exploration with follow-up parathyroid 4-dimensional CT and 99m Tc-MIBI SPECT/CT, yielding focal uptake in the right piriform sinus. Subsequent direct laryngoscopy revealed a mass in the piriform sinus, which was resected with surgical pathology yielding parathyroid adenoma.
Bleeding phenotype and diagnostic characterization of patients with congenital platelet defects
Authors: Maaike W. Blaauwgeers, Marieke J.H.A. Kruip, Erik A.M. Beckers, Michiel Coppens, Jeroen Eikenboom, Karin P.M. van Galen, Rienk Y.J. Tamminga, Rolf T. Urbanus, Roger E.G. Schutgens
Journal: American Journal of Hematology (2020)

Phenotypic characterization of congenital platelet defects (CPDs) could help physicians recognize CPD subtypes and can inform on prognostic implications. We report the analyses of the bleeding phenotype and diagnostic characteristics of a large cohort of adult patients with a confirmed CPD. A total of 96 patients were analyzed and they were classified as Glanzmann thrombasthenia, Bernard-Soulier syndrome, dense granule deficiency, defects in the ADP or thromboxane A2 (TxA2) pathway, isolated thrombocytopenia or complex abnormalities. The median ISTH-BAT bleeding score was nine (IQR 5-13). Heavy menstrual bleeding (HMB) (80%), post-partum hemorrhage (74%), post-operative bleeds (64%) and post-dental extraction bleeds (57%) occurred most frequently. Rare bleeding symptoms were bleeds from the urinary tract (4%) and central nervous system (CNS) bleeds (2%). Domains with a large proportion of severe bleeds were CNS bleeding, HMB and post-dental extraction bleeding. Glanzmann thrombasthenia and female sex were associated with a more severe bleeding phenotype.
Discovery of CD80 and CD86 as recent activation markers on regulatory T cells by protein-RNA single-cell analysis
Authors: Dominik Trzupek, Melanie Dunstan, Antony J. Cutler, Mercede Lee, Leila Godfrey, Lorna Jarvis, Daniel B. Rainbow, Dominik Aschenbrenner, Joanne L. Jones, Holm H. Uhlig, Linda S. Wicker, John A. Todd, Ricardo C. Ferreira
Journal: Genome Medicine (2020)

Abstract Background Traditionally, the transcriptomic and proteomic characterisation of CD4 + T cells at the single-cell level has been performed by two largely exclusive types of technologies: single-cell RNA sequencing (scRNA-seq) and antibody-based cytometry. Here, we present a multi-omics approach allowing the simultaneous targeted quantification of mRNA and protein expression in single cells and investigate its performance to dissect the heterogeneity of human immune cell populations. Methods We have quantified the single-cell expression of 397 genes at the mRNA level and up to 68 proteins using oligo-conjugated antibodies (AbSeq) in 43,656 primary CD4 + T cells isolated from the blood and 31,907 CD45 + cells isolated from the blood and matched duodenal biopsies. We explored the sensitivity of this targeted scRNA-seq approach to dissect the heterogeneity of human immune cell populations and identify trajectories of functional T cell differentiation. Results We provide a high-resolution map of human primary CD4 + T cells and identify precise trajectories of Th1, Th17 and regulatory T cell (Treg) differentiation in the blood and tissue. The sensitivity provided by this multi-omics approach identified the expression of the B7 molecules CD80 and CD86 on the surface of CD4 + Tregs, and we further demonstrated that B7 expression has the potential to identify recently activated T cells in circulation. Moreover, we identified a rare subset of CCR9 + T cells in the blood with tissue-homing properties and expression of several immune checkpoint molecules, suggestive of a regulatory function. Conclusions The transcriptomic and proteomic hybrid technology described in this study provides a cost-effective solution to dissect the heterogeneity of immune cell populations at extremely high resolution. Unexpectedly, CD80 and CD86, normally expressed on antigen-presenting cells, were detected on a subset of activated Tregs, indicating a role for these co-stimulatory molecules in regulating the dynamics of CD4 + T cell responses.
A multi-center, randomized, double-blinded, placebo-controlled trial of additive effect of duloxetine for neuropathic cancer pain refractory to opioids and gabapentinoids: JORTC- PAL08 (DIRECT study).
Authors: Eriko Satomi, Hiromichi Matsuoka, Satoru Iwase, Tempei Miyaji, Takashi Kawaguchi, Keisuke Ariyoshi, Shunsuke Oyamada, Hideaki Hasuo, Akihiro Tokoro, Toshiaki Shinomiya, Hiroaki Tsukuura, Yoichi Otake, Masatomo Otsuka, Yoshikazu Hasegawa, Yoshihisa Matsumoto, Yuki Kataoka, Hiroyuki Otani, Yasuhiro Kidera, Mayuri Aoyama, Takuhiro Yamaguchi
Journal: Journal of Clinical Oncology (2018)

10102 Background: Management of cancer patients experiencing neuropathic pain (NP) refractory to opioids remains an important challenge. Gabapentinoids are one of the most widely used therapies for NP. However, duloxetine is also used for NP. We have evaluated the efficacy of addition of duloxetine for neuropathic cancer pain refractory to opioids and gabapentinoids. Methods: Multicenter, randomized, double-blind, placebo-controlled trial. Patients with any cancer NP, currently being administered opioids, non-responsive or intolerant to gabapentinoids were eligible. Patients with chemotherapy-induced peripheral neuropathies were excluded. Patients were administrated 20 mg to 40 mg of duloxetine or placebo for 10 days. The primary endpoint was the average pain intensity (Brief Pain Inventory (BPI) item 5) at Day 10, the main analysis was t test (significance level one side 5%), Complete Case (CC) analysis was performed to handle missing primary data and Baseline Observation Carried Forward (BOCF) analysis was performed for sensitivity analysis. Results: 70 patients were registered at 12 sites in Japan. BPI item 5 at Day 10 was i) average of Group D (Duloxetine) 4.03 [90% CI 3.33, 4.74], Group P (Placebo) 4.88 [4.37, 5.38] (p = .053) (CC analysis); ii) Group D 4.06 [3.37, 4.74], Group P 4.91 [4.41, 5.41] (p = .048) (BOCF analysis). Point estimate of the difference of average values between the two groups was -0.84 [-1.71, 0.02] (CC analysis) and -0.85 [-1.69, -0.01] (BOCF analysis). Compared to Day 0, the improvement rate of 50% or more at Day 10 was 32.4% in Group D and 3.0% in Group P (p = .002). Conclusions: The minimum important difference (MID) with clinical significance in cancer pain is said to be 1 point in 11 stages of the Numerical Rating Scales (NRS), and our results were close to the MID (-0.84; CC analysis). Moreover, sensitivity analysis and secondary analysis show significant improvement in Group D. Overall, duloxetine is clinically effective for NP. Clinical trial information: UMIN000017647.
Covid-19: virtual occupational skin health clinics for healthcare workers
Authors: Mahbub M Chowdhury, Nicola Bevan, Karen Ryan
Journal: BMJ (2020)

Collaborative working is a key feature of remote team working during the covid-19 pandemic.Occupational health nurses and the dermatology team have worked together closely for many years in Cardiff.With corporate executive level support, we quickly set up a covid-19 occupational virtual skin clinic "seeing" up to 10 patients a week.
PET/CT-Guided Tissue Sampling in Patients With a Failed or Inconclusive CT-Guided Procedure
Authors: Rakesh Kumar, Anshul Sharma, Sanjay Thulkar, Venkateswaran K. Iyer, Atul Sharma
Journal: Clinical Nuclear Medicine (2020)

Background CT-guided tissue sampling is a very effective tool. However, false-negative results are obtained when regions such as necrotic core or surrounding reactive fibrosis and inflammation are sampled. PET/CT-guided sampling can circumvent these limitations. Purpose The aim of this study was to analyze the effectiveness of PET/CT-guided sampling in patients with at least 1 instance of failed or inconclusive CT-guided procedure and factors determining the accurate sampling and complications. Methods One hundred eleven patients were prospectively included. After feasibility analysis in a diagnostic 18 F-FDG PET/CT, sampling was performed in 106 patients (45 women, 61 men; mean age, 48.09 ± 15.42 years; biopsy in 80 and fine-needle aspiration cytology [FNAC] in 26 patients), using robotic arm and a lower IV injection dose of 74 to 111 MBq (2–3 mCi) 18 F-FDG. In all patients, final check scans revealed needle at the target site. Using planned needle path as reference, deviations in first check scan were measured. Patient (n = 30) and respiratory motion (n = 57) were also recorded. Results Accurate lesion targeting was achieved in 81 cases (63 positive lesions, 12 confounding lesions, and 7 inadequate samples). Lesion was missed in 5 instances, and blood/necrotic tissue sampled in 19. Overall 18 F-FDG–avid lesions were accurately targeted in 77.36% of patients (86.25% [biopsy] + 50% [FNAC]). Significant variables affecting targeting were needle gauge, deviation from intended entry point, procedure duration, procedure type, and patient movement. Using binomial regression, the significant parameters were procedure type (biopsy vs FNAC; odds ratio [OR], 5.916; P = 0.002), patient movement (OR, 0.275; P = 0.023), and procedure duration (OR, 1.195; P = 0.011). Overall complication rate was 21.70%, with 4.71% major complications. It was dependent on target depth (mean depth, 69.74 ± 20.29 mm [complications] vs 47.18 ± 22.60 mm; P &lt; 0.001). Positive correlation was seen between the target depth and distance of needle from the intended target (Spearman ρ = 0.307; P = 0.001). In 28 procedures, the physician was asked to wear a pocket dosimeter, who received a mean dose of 2.52 (SD, 3.10) μSv. Conclusions PET/CT-guided sampling should be considered where CT-guided biopsy has failed or is inconclusive. The outcome is impacted by needle gauge and patient movement, and complication rate is dependent on target depth.
Renin-Angiotensin-Aldosterone Inhibitors and Susceptibility to and Severity of COVID-19
Authors: Gregory Curfman
Journal: JAMA (2020)

Emil L. Fosbøl, MD, PhD; Jawad H. Butt, MD; Lauge Østergaard, MD; Charlotte Andersson, MD, PhD; Christian Selmer, MD, PhD; Kristian Kragholm, MD, PhD; Morten Schou, MD, PhD; Matthew Phelps, MSc; Gunnar H. Gislason, MD, PhD; Thomas A. Gerds, Dr rer nat; Christian Torp-Pedersen, MD, DMSc; Lars Køber, MD, DMSc
Targeted Remodeling of the Tumor Microenvironment Via Mechanical Stimulation Defines a Novel Therapeutic Strategy in Myeloma Bone Disease
Authors: Fani Ziouti, Maximilian Rummler, Anne Seliger, Andreas Brandl, Andreas Beilhack, Bjarne Bogen, Maureen Lynch, Franz Jakob, Regina Ebert, Bettina Willie, Franziska Jundt
Journal: Blood (2017)
Treatment adherence behaviours in rheumatic diseases during COVID-19 pandemic: a Latin American experience
Authors: Rita Angélica Pineda-Sic, Dionicio Angel Galarza-Delgado, Griselda Serna-Peña, Sergio A Castillo-Torres, Diana Elsa Flores-Alvarado, Jorge A Esquivel-Valerio, Iván De Jesús Hernández-Galarza
Journal: Annals of the Rheumatic Diseases (2020)

With great interest, we read the recommendations from the German Society of Rheumatology regarding the management of patients with rheumatic diseases during the COVID-19 pandemic,1 in line with The American College of Rheumatology recommendations2 of continuing immunosuppressive therapy (IT) despite concerns of increased susceptibility to infections, since interruption might trigger an increase in disease activity associated with higher infection risk. Thus, one of the greatest challenges of the COVID-19 pandemic for rheumatologists concerns the patient’s adherence to treatment. Despite rheumatologists agreeing that IT should not be interrupted,1 2 patient’s own beliefs, perceptions and information about their disease influence the behaviour towards treatment adherence. Late in April, Michaud et al reported that patients with rheumatic diseases believed that IT increased their risk of contracting COVID-19 and the severity of the disease and that stopping IT might reduce that risk,3 …
Scale-free architectures support representational diversity
Authors: Chris Fields, James F. Glazebrook
Journal: Behavioral and Brain Sciences (2020)

Gilead et al. propose an ontology of abstract representations based on folk-psychological conceptions of cognitive architecture. There is, however, no evidence that the experience of cognition reveals the architecture of cognition. Scale-free architectural models propose that cognition has the same computational architecture from sub-cellular to whole-organism scales. This scale-free architecture supports representations with diverse functions and levels of abstraction.
HDAC9 deficiency promotes tumor progression by decreasing the CD8<sup>+</sup>dendritic cell infiltration of the tumor microenvironment
Authors: Yongling Ning, Jun Ding, Xiao Sun, Yewen Xie, Mingming Su, Chenglong Ma, Jie Pan, Jie Chen, Hua Jiang, Chunjian Qi
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background The tumor microenvironment (TME) contains a variety of immune cells, which play critical roles during the multistep development of tumors. Histone deacetylase 9 (HDAC9) has been reported to have either proinflammatory or anti-inflammatory effects, depending on the immune environment. In this study, we investigated whether HDAC9 in the tumor stroma regulated inflammation and antitumor immunity. Methods Hdac9 knockout mice were generated to analyze the HDAC9-associated inflammation and tumor progression. Immune cells and cytokines in TME or draining lymph nodes were quantified by flow cytometry and quantitative reverse transcription-PCR. The antigen presentation and CD8 + T cell priming by tumor-infiltrating dendritic cells (DCs) were evaluated in vitro and in vivo. HDAC9-associated inflammation was investigated in a mouse model with dextran sulfate sodium–induced colitis. Correlation of HDAC9 with CD8 + expression was assessed in tissue sections from patients with non-small cell lung cancer. Results HDAC9 deficiency promoted tumor progression by decreasing the CD8 + DC infiltration of the TME. Compared with wild-type mice, the tumor-infiltrating DCs of Hdac9 -/- mice displayed impaired cross-presentation of tumor antigens and cross-priming of CD8 + T cells. Moreover, HDAC9 expression was significantly positively correlated with CD8 + cell counts in human lung cancer stroma samples. Conclusions HDAC9 deficiency decreased inflammation and promoted tumor progression by decreasing CD8 + DC infiltration of the TME. HDAC9 expression in the tumor stroma may represent a promising biomarker to predict the therapeutic responses of patients receiving CD8 + T cell-dependent immune treatment regimens.
Pronounced Therapeutic Benefit of a Single Bidirectional AAV Vector Administered Systemically in Sandhoff Mice
Authors: Hannah G. Lahey, Chelsea J. Webber, Diane Golebiowski, Cassandra M. Izzo, Erin Horn, Toloo Taghian, Paola Rodriguez, Ana Rita Batista, Lauren E. Ellis, Misako Hwang, Douglas R. Martin, Heather Gray-Edwards, Miguel Sena-Esteves
Journal: Molecular Therapy (2020)

The GM2 gangliosidoses, Tay-Sachs disease (TSD) and Sandhoff disease (SD), are fatal lysosomal storage disorders caused by mutations in the HEXA and HEXB genes, respectively. These mutations cause dysfunction of the lysosomal enzyme β-N-acetylhexosaminidase A (HexA) and accumulation of GM2 ganglioside (GM2) with ensuing neurodegeneration, and death by 5 years of age. Until recently, the most successful therapy was achieved by intracranial co-delivery of monocistronic adeno-associated viral (AAV) vectors encoding Hex alpha and beta-subunits in animal models of SD. The blood-brain barrier crossing properties of AAV9 enables systemic gene therapy; however, the requirement of co-delivery of two monocistronic AAV vectors to overexpress the heterodimeric HexA protein has prevented the use of this approach. To address this need, we developed multiple AAV constructs encoding simultaneously HEXA and HEXB using AAV9 and AAV-PHP.B and tested their therapeutic efficacy in 4- to 6-week-old SD mice after systemic administration. Survival and biochemical outcomes revealed superiority of the AAV vector design using a bidirectional CBA promoter with equivalent dose-dependent outcomes for both capsids. AAV-treated mice performed normally in tests of motor function, CNS GM2 ganglioside levels were significantly reduced, and survival increased by >4-fold with some animals surviving past 2 years of age. The GM2 gangliosidoses, Tay-Sachs disease (TSD) and Sandhoff disease (SD), are fatal lysosomal storage disorders caused by mutations in the HEXA and HEXB genes, respectively. These mutations cause dysfunction of the lysosomal enzyme β-N-acetylhexosaminidase A (HexA) and accumulation of GM2 ganglioside (GM2) with ensuing neurodegeneration, and death by 5 years of age. Until recently, the most successful therapy was achieved by intracranial co-delivery of monocistronic adeno-associated viral (AAV) vectors encoding Hex alpha and beta-subunits in animal models of SD. The blood-brain barrier crossing properties of AAV9 enables systemic gene therapy; however, the requirement of co-delivery of two monocistronic AAV vectors to overexpress the heterodimeric HexA protein has prevented the use of this approach. To address this need, we developed multiple AAV constructs encoding simultaneously HEXA and HEXB using AAV9 and AAV-PHP.B and tested their therapeutic efficacy in 4- to 6-week-old SD mice after systemic administration. Survival and biochemical outcomes revealed superiority of the AAV vector design using a bidirectional CBA promoter with equivalent dose-dependent outcomes for both capsids. AAV-treated mice performed normally in tests of motor function, CNS GM2 ganglioside levels were significantly reduced, and survival increased by >4-fold with some animals surviving past 2 years of age.