tbuckley/cabot-search huggingface dataset:
Molecular regulation of neuroinflammation in glaucoma: Current knowledge and the ongoing search for new treatment targets
Authors: Gülgün Tezel
Journal: Progress in Retinal and Eye Research (2021)

Neuroinflammation relying on the inflammatory responses of glial cells has emerged as an impactful component of the multifactorial etiology of neurodegeneration in glaucoma. It has become increasingly evident that despite early adaptive and reparative features of glial responses, prolonged reactivity of the resident glia, along with the peripheral immune cells, create widespread toxicity to retinal ganglion cell (RGC) axons, somas, and synapses. As much as the synchronized responses of astrocytes and microglia to glaucoma-related stress or neuron injury, their bi-directional interactions are critical to build and amplify neuroinflammation and to dictate the neurodegenerative outcome. Although distinct molecular programs regulate somatic and axonal degeneration in glaucoma, inhibition of neurodegenerative inflammation can provide a broadly beneficial treatment strategy to rescue RGC integrity and function. Since inflammatory toxicity and mitochondrial dysfunction are converging etiological paths that can boost each other and feed into a vicious cycle, anti-inflammatory treatments may also offer a multi-target potential. This review presents an overview of the current knowledge on neuroinflammation in glaucoma with particular emphasis on the cell-intrinsic and cell-extrinsic factors involved in the reciprocal regulation of glial responses, the interdependence between inflammatory and mitochondrial routes of neurodegeneration, and the research aspects inspiring for prospective immunomodulatory treatments. With the advent of powerful technologies, ongoing research on molecular and functional characteristics of glial responses is expected to accumulate more comprehensive and complementary information and to rapidly move the field forward to safe and effective modulation of the glial pro-inflammatory activities, while restoring or augmenting the glial immune-regulatory and neurosupport functions.
The neutralizing antibody response post COVID-19 vaccination in patients with myeloma is highly dependent on the type of anti-myeloma treatment
Authors: Evangelos Terpos, Maria Gavriatopoulou, Ioannis Ntanasis-Stathopoulos, Alexandros Briasoulis, Sentiljana Gumeni, Panagiotis Malandrakis, Despina Fotiou, Eleni-Dimitra Papanagnou, Magdalini Migkou, Foteini Theodorakakou, Maria Roussou, Evangelos Eleutherakis-Papaiakovou, Nikolaos Kanellias, Ioannis P. Trougakos, Efstathios Kastritis, Meletios A. Dimopoulos
Journal: Blood Cancer Journal (2021)

Abstract Recent data suggest a suboptimal antibody response to COVID-19 vaccination in patients with hematological malignancies. Neutralizing antibodies (NAbs) against SARS-CoV-2 were evaluated in 276 patients with plasma cell neoplasms after vaccination with either the BNT162b2 or the AZD1222 vaccine, on days 1 (before the first vaccine shot), 22, and 50. Patients with MM ( n = 213), SMM ( n = 38), and MGUS ( n = 25) and 226 healthy controls were enrolled in the study (NCT04743388). Vaccination with either two doses of the BNT162b2 or one dose of the AZD1222 vaccine leads to lower production of NAbs in patients with MM compared with controls both on day 22 and on day 50 ( p &lt; 0.001 for all comparisons). Furthermore, MM patients showed an inferior NAb response compared with MGUS on day 22 ( p = 0.009) and on day 50 ( p = 0.003). Importantly, active treatment with either anti-CD38 monoclonal antibodies (Mabs) or belantamab mafodotin and lymphopenia at the time of vaccination were independent prognostic factors for suboptimal antibody response following vaccination. In conclusion, MM patients have low humoral response following SARS-CoV-2 vaccination, especially under treatment with anti-CD38 or belamaf. This underlines the need for timely vaccination, possibly during a treatment-free period, and for continuous vigilance on infection control measures in non-responders.
SO-18 Safety and efficacy of trifluridine/tipiracil in previously treated metastatic colorectal cancer: Final results according to duration of treatment from the phase IIIb, international, open-label, early-access PRECONNECT study
Authors: J. Taieb, T. Price, L. Wyrwicz, L. Vidot, A. Raimond-Thibaut, H. Chrostek, J. Bachet, A. Falcone
Journal: Annals of Oncology (2021)
Clinical Features of Vaccine-Induced Immune Thrombocytopenia and Thrombosis
Authors: Sue Pavord, Marie Scully, Beverley J. Hunt, William Lester, Catherine Bagot, Brian Craven, Alex Rampotas, Gareth Ambler, Mike Makris
Journal: New England Journal of Medicine (2021)

Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a new syndrome associated with the ChAdOx1 nCoV-19 adenoviral vector vaccine against severe acute respiratory syndrome coronavirus 2. Data are lacking on the clinical features of and the prognostic criteria for this disorder.
Comparative Assessment of Diagnostic Homologous Recombination Deficiency–Associated Mutational Signatures in Ovarian Cancer
Authors: Zsofia Sztupinszki, Miklos Diossy, Judit Borcsok, Aurel Prosz, Nanna Cornelius, Maj K. Kjeldsen, Mansoor R. Mirza, Zoltan Szallasi
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Homologous recombination (HR) deficiency (HRD) is one of the key determinants of PARP inhibitor response in ovarian cancer, and its accurate detection in tumor biopsies is expected to improve the efficacy of this therapy. Because HRD induces a wide array of genomic aberrations, mutational signatures may serve as a companion diagnostic to identify PARP inhibitor–responsive cases. Experimental Design: From the The Cancer Genome Atlas (TCGA) whole-exome sequencing (WES) data, we extracted different types of mutational signature–based HRD measures, such as the HRD score, genome-wide LOH, and HRDetect trained on ovarian and breast cancer–specific sequencing data. We compared their performance to identify BRCA1/2-deficient cases in the TCGA ovarian cancer cohort and predict survival benefit in platinum-treated, BRCA1/2 wild-type ovarian cancer. Results: We found that the HRD score, which is based on large chromosomal alterations alone, performed similarly well to an ovarian cancer–specific HRDetect, which incorporates mutations on a finer scale as well (AUC = 0.823 vs. AUC = 0.837). In an independent cohort these two methods were equally accurate predicting long-term survival after platinum treatment (AUC = 0.787 vs. AUC = 0.823). We also found that HRDetect trained on ovarian cancer was more accurate than HRDetect trained on breast cancer data (AUC = 0.837 vs. AUC = 0.795; P = 0.0072). Conclusions: When WES data are available, methods that quantify only large chromosomal alterations such as the HRD score and HRDetect that captures a wider array of HRD-induced genomic aberrations are equally efficient identifying HRD ovarian cancer cases.
細胞培養次元はカドヘリン-2とカドヘリン-11を介して間葉系幹細胞運命に影響する【JST・京大機械翻訳】
Authors: R Passanha Fiona, Geuens Thomas, Konig Simon, A van Blitterswijk Clemens, L S LaPointe Vanessa
Journal: Biomaterials (2020)
Data mining in clinical big data: the frequently used databases, steps, and methodological models
Authors: Wen-Tao Wu, Yuan-Jie Li, Ao-Zi Feng, Li Li, Tao Huang, An-Ding Xu, Jun Lyu
Journal: Military Medical Research (2021)

Many high quality studies have emerged from public databases, such as Surveillance, Epidemiology, and End Results (SEER), National Health and Nutrition Examination Survey (NHANES), The Cancer Genome Atlas (TCGA), and Medical Information Mart for Intensive Care (MIMIC); however, these data are often characterized by a high degree of dimensional heterogeneity, timeliness, scarcity, irregularity, and other characteristics, resulting in the value of these data not being fully utilized. Data-mining technology has been a frontier field in medical research, as it demonstrates excellent performance in evaluating patient risks and assisting clinical decision-making in building disease-prediction models. Therefore, data mining has unique advantages in clinical big-data research, especially in large-scale medical public databases. This article introduced the main medical public database and described the steps, tasks, and models of data mining in simple language. Additionally, we described data-mining methods along with their practical applications. The goal of this work was to aid clinical researchers in gaining a clear and intuitive understanding of the application of data-mining technology on clinical big-data in order to promote the production of research results that are beneficial to doctors and patients.
P-202 Primary tumour location and efficacy of first-line anti-EGFR agents in the treatment of RAS wild-type metastatic colorectal cancer
Authors: J. Marinho, I. Leão, E. Neto, H. Guedes, T. Costa, A. Capela, A. Moreira Pinto, S. Custódio
Journal: Annals of Oncology (2021)
K<sub>2</sub>Mn<sub>3</sub>[Fe<sup>II</sup>(CN)<sub>6</sub>]<sub>2</sub> NPs with High <i>T</i><sub>1</sub>‐Relaxivity Attributable to Water Coordination on the Mn(II) Center for Gastrointestinal Tract MR Imaging
Authors: Murthi S. Kandanapitiye, Thiloka M. Dassanayake, Arosha C. Dassanayake, John Shelestak, Robert J. Clements, Can Fernando, Songping D. Huang
Journal: Advanced Healthcare Materials (2021)

Abstract The lack of acid stability in the stomach and of temporal stability when moving through the gastrointestinal (GI) tract has made the development of oral magnetic resonance imaging (MRI) contrast agents based on the platform of Gd 3+ –complexes problematic.On the other hand, the negative contrast enhancement produced by the T 2 ‐weighted magnetic metal oxide nanoparticles (NPs) often renders the image readout difficult. Biocompatible NPs of the manganese Prussian blue analog K 2 Mn 3 [Fe II (CN) 6 ] 2 exhibit extremely high stability under the acidic conditions of the gastric juice. Additionally, the high r 1 relaxivity, low toxicity, and high temporal stability of such NPs offer great potential for the development of a true T 1 ‐weighted oral contrast agent for MRI of the entire GI tract.
Use of Involuntary Emergency Treatment by Physicians and Law Enforcement for Persons With High-Risk Drug Use or Alcohol Dependence
Authors: Kathleen E. Coffey, Audrey Aitelli, Michael Milligan, Andrzej Niemierko, Thomas Broom, Helen A. Shih
Journal: JAMA Network Open (2021)

This cohort study evaluates the number of petitions for temporary involuntary commitment of individuals who pose a risk to themselves or others after implementation of a pilot program to streamline the process in Boston, Massachusetts.
Sex-Specific Outcomes of Transcatheter Mitral-Valve Repair and Medical Therapy for Mitral Regurgitation in Heart Failure
Authors: Ioanna Kosmidou, JoAnn Lindenfeld, William T Abraham, Michael J Rinaldi, Samir R Kapadia, Vivek Rajagopal, Ian J Sarembock, Andreas Brieke, Prakriti Gaba, Jason H Rogers, Bahira Shahim, Björn Redfors, Zixuan Zhang, Michael J Mack, Gregg W Stone
Journal: JACC Heart Failure (2021)
25532 Effects of upadacitinib on patient-reported symptoms of atopic dermatitis: Atopic Dermatitis Symptom Scale (ADerm-SS) results from two pivotal phase 3 studies (MEASURE UP 1 and MEASURE UP 2)
Authors: Jonathan I. Silverberg, Jacob P. Thyssen, David Rosmarin, Andrew E. Pink, Brian M. Calimlim, Henrique D. Teixeira, Xiaofei Hu, Yang Yang, Diamant Thaçi
Journal: Journal of the American Academy of Dermatology (2021)
Decision to suspend surgeon who put his initials on patients’ livers was flawed, says judge
Authors: Clare Dyer
Journal: BMJ (2021)

A decision by a medical practitioners tribunal to suspend a consultant surgeon for five months after he was convicted of assault for carving his initials into two transplant patients’ livers has been quashed by the High Court, which found “serious irregularity” in the tribunal’s conduct of its functions.1

Simon Bramhall admitted assault and was fined £10 000 (€11 700; $13 900) at Birmingham Crown Court in 2018, in a case described by prosecutors as “without precedent in criminal law.” A tribunal suspended him from the medical register for five months last December and a review tribunal in June decided that he was fit to practise again after remedying his misconduct and demonstrating significant insight.2

However, the General …
Longitudinal data on covid-19 immunity could be collected from medical records
Authors: Azeem Majeed
Journal: BMJ (2021)

Baraniuk reviews what we know about natural and vaccine induced immunity to SARS-CoV-2.1 Vaccines for covid-19 were eagerly awaited, and their rapid development, testing, approval, and implementation are a tremendous achievement by scientists, drug companies, drugs regulators, politicians, and healthcare professionals and by the patients who have received them.2 Early real world data from vaccine recipients in England, Scotland, and Israel show that vaccination provides …
A double-blind, 377-subject randomized study identifies <i>Ruminococcus, Coprococcus, Christensenella</i>, and <i>Collinsella</i> as long-term potential key players in the modulation of the gut microbiome of lactose intolerant individuals by galacto-oligosaccharides
Authors: M. A. Azcarate-Peril, J. Roach, A. Marsh, William D. Chey, William J. Sandborn, Andrew J. Ritter, Dennis A. Savaiano, T. R. Klaenhammer
Journal: Gut Microbes (2021)

Background. Our recent publication (Chey et al., Nutrients 2020) showed that a 30-day administration of pure galacto-oligosaccharides (GOS) significantly reduced symptoms and altered the fecal microbiome in patients with lactose intolerance (LI). Results. In this addendum, we performed an in-depth analysis of the fecal microbiome of the 377 LI patients randomized to one of two GOS doses (Low, 10–15 grams/day or High, 15–20 grams/day), or placebo in a multi-center, double-blinded, placebo-controlled trial. Sequencing of 16S rRNA amplicons was done on GOS or placebo groups at weeks zero (baseline), four (end of treatment), nine, 16 and 22. Taxa impacted by treatment and subsequent dairy consumption included lactose-fermenting species of Bifidobacterium, Lactobacillus, Lactococcus, and Streptococcus. Increased secondary fermentation microorganisms included Coprococcus and Ruminococcus species, Blautia producta, and Methanobrevibacterium. Finally, tertiary fermenters that use acetate to generate butyrate were also increased, including Faecalibacterium prausnitzii, Roseburia faecis, and C. eutactus. Conclusions. Results confirmed and expanded data on GOS microbiome modulation in LI individuals. Microbiome analysis at 16 and 22 weeks after treatment further suggested relatively long-term benefits when individuals continued consumption of dairy products.
Selective loss of resident macrophage-derived insulin-like growth factor-1 abolishes adaptive cardiac growth to stress
Authors: Rysa Zaman, Homaira Hamidzada, Crystal Kantores, Anthony Wong, Sarah A Dick, Yiming Wang, Abdul Momen, Laura Aronoff, Julia Lin, Babak Razani, Seema Mital, Filio Billia, Kory J Lavine, Sara Nejat, Slava Epelman
Journal: Immunity (2021)
Tuberculosis lymph node granulomas: using transcriptomics to discover immunopathology paradigms and guide host-directed therapy
Authors: James J. Phelan, Seónadh O’Leary, Joseph Keane
Journal: Journal of Clinical Investigation (2021)

Immunometabolism is a burgeoning field of investigation in tuberculosis host defense, susceptibility, and pathophysiology. Unbiased approaches to studying tuberculosis have, as expected, confirmed that pathways of immunometabolism are crucial in these disease processes. In this issue of the JCI, Reichmann et al. studied carefully controlled human lymph node tuberculosis and uncovered Sphingosine kinase 1 as a druggable target of interest that could support the infected host. Future host-directed therapy research might seek to establish the different cellular consequences of sphingolipid pathway manipulation. Animal models will be especially useful to establish the role of this pathway, which might target diseased organs to improve mycobactericidal effect and limit pathology.
Integrating metabolic reprogramming and metabolic imaging to predict breast cancer therapeutic responses
Authors: Yi Liu, Qian Zhou, Shaoli Song, Shuang Tang
Journal: Trends in Endocrinology and Metabolism (2021)

Metabolic reprogramming is not only an emerging hallmark of cancer, but also an essential regulator of cancer cell adaptation to the microenvironment. Metabolic imaging targeting metabolic signatures has been widely used for breast cancer diagnosis. However, limited implications have been explored for monitoring breast cancer therapy response, although metabolic plasticity is notably associated with therapy resistance. In this review, we focus on the metabolic alterations upon breast cancer therapy and their potential for evaluating breast cancer therapeutic responses. We summarize the metabolic network and regulatory changes upon breast cancer therapy in terms of cancer pathological and genetic differences and discuss the implications of metabolic imaging with various probes in selecting target beneficiaries for precision treatment.
Letter to the Editor: Is the <scp>HBsAg</scp> response to RO7062931 an antisense effect?
Authors: Andrew Vaillant
Journal: Hepatology (2021)

Gane et al(1) suggest that HBsAg responses in chronic HBV infection to RO7062931, a GalNAc-conjugated antisense oligonucleotide (GalNAc-ASO) indicate target engagement (cleavage of HBV mRNA). The highly conserved target engagement with GalNAc-ASOs is well known from studies with numerous liver targets in humans. Exemplary studies (2, 3) illustrate a rapid and uniform ~1 log10 protein reduction within 15 days in all subjects, occuring with only a single dose and saturating with weekly to monthly dosing from 60mg (0.9 mg/kg) to 90mg (1.4 mg/kg). Given the rapid turnover of HBsAg (4, 5), target engagement with RO7062931 should be accompanied by similar HBsAg responses.
Mutations in CRBN and other cereblon pathway genes are infrequently associated with acquired resistance to immunomodulatory drugs
Authors: J. R. Jones, A. Barber, Y-V Le Bihan, N. Weinhold, C. Ashby, B. A. Walker, C. P. Wardell, H. Wang, M. F. Kaiser, G. H. Jackson, F. E. Davies, R. Chopra, G. J. Morgan, C. Pawlyn
Journal: Leukemia (2021)
MYC: a multipurpose oncogene with prognostic and therapeutic implications in blood malignancies
Authors: Seyed Esmaeil Ahmadi, Samira Rahimi, Bahman Zarandi, Rouzbeh Chegeni, Majid Safa
Journal: Journal of Hematology & Oncology (2021)

Abstract MYC oncogene is a transcription factor with a wide array of functions affecting cellular activities such as cell cycle, apoptosis, DNA damage response, and hematopoiesis. Due to the multi-functionality of MYC, its expression is regulated at multiple levels. Deregulation of this oncogene can give rise to a variety of cancers. In this review, MYC regulation and the mechanisms by which MYC adjusts cellular functions and its implication in hematologic malignancies are summarized. Further, we also discuss potential inhibitors of MYC that could be beneficial for treating hematologic malignancies.
Digital Mammography Device for Mobile Mammography Complex
Authors: A. G. Larin, A. R. Dabagov
Journal: Radiology - Practice (2021)

The results of the development of a mammographic unit with a digital flat-panel detector designed for for installation in a mobile medical X-ray room are presented.The mammographic unit with a digital flat-panel detector is designed for screening and other specialized mammographic examinations, provides the ability to perform full-format raster (using a screening raster) mammography, X-ray of the armpits.
Chronic ethanol feeding decreases the sensitivity of hormone-mediated phospholipase C activation to the protein phosphatase inhibitor okadaic acid in isolated rat hepatocytes.
Authors: Hoek Jb, Ito M, Akita S, Mizuno Y, Sobue S, Takahashi Y, Nakao H, Nomura T, Saso K, Higashi K
Journal: Hepatology (1997)
Impact of Sofosbuvir-Based Direct-Acting Antivirals on Renal Function in Chronic Hepatitis C Patients With Impaired Renal Function: A Large Cohort Study From the Nationwide HCV Registry Program (TACR)
Authors: Chung-Feng Huang, Kuo-Chih Tseng, Pin-Nan Cheng, Chao-Hung Hung, Ching-Chu Lo, Cheng-Yuan Peng, Ming-Jong Bair, Ming-Lun Yeh, Chien-Hung Chen, Pei-Lun Lee, Chun-Yen Lin, Hsing-Tao Kuo, Chun-Ting Chen, Chi-Chieh Yang, Jee-Fu Huang, Chi-Ming Tai, Jui-Ting Hu, Chih-Lang Lin, Wei-Wen Su, Wei-Lun Tsai, Yi-Hsiang Huang, Chien-Yu Cheng, Chih-Lin Lin, Chia-Chi Wang, Sheng-Shun Yang, Lein-Ray Mo, Guei-Ying Chen, Chun-Chao Chang, Szu-Jen Wang, Chia-Sheng Huang, Tsai-Yuan Hsieh, Chih-Wen Lin, Tzong-Hsi Lee, Lee-Won Chong, Chien-Wei Huang, Shiuh-Nan Chang, Ming-Chang Tsai, Shih-Jer Hsu, Jia-Horng Kao, Chun-Jen Liu, Chen-Hua Liu, Han-Chieh Lin, Mei-Hsuan Lee, Pei-Chien Tsai, Chia-Yen Dai, Wan-Long Chuang, Chi-Yi Chen, Ming-Lung Yu
Journal: Clinical Gastroenterology and Hepatology (2021)
Early lung function testing in infants with aortic arch anomalies identifies infants at risk for airway obstruction
Authors: Charles Roehr, Hans Proquittè, Bernd Opgen-Rhein, Christoph Buehrer, Gerd Schmalisch
Journal: European Respiratory Journal (2011)

Aortic arch anomalies (AAA) (vascular rings) are rare anomalies (approx. 3% of all cardiac anomalies) that can obstruct the upper airway. The preferred strategies for diagnosis and treatment varies among institutions. The aim of this study was to investigate the degree of airway obstruction in infants with AAA by lung function testing (LFT).   Patients and methods:  Sixteen patients born between 2005-2010 with echo-cardiographic AAA (10 right sided (69%) and 6 double aortic arch (31%)) preoperative LFT was performed in the 39th (36th – 41th) postconceptional week (median (range)) body weight 3300 (2320 - 4360) g). Raw was measured by baby bodyplethysmography (Jaeger, Wurzburg, Germany). With the same equipment the maximal expiratory flow at functional residual capacity (V9maxFRC) was measured using the rapid thoraco-abdominal compression (RTC) technique, according to international guidelines. V9maxFRC was also expressed in standard deviation scores (Z-scores) based on sex-, age and hight-specific reference values of healthy infants published by Hoo et al. AJRCCM 2002.   Results:  Between Raw and the Z-score of V9maxFRC was a strong correlation (r=0.768, p 4.1 cmH2O/L/s, indicating upper airway obstruction.   Conclusion:  Most infants with AAA had no impairment of the upper airway conductivity. However, early LFT may help to indentify and to monitor patients who may be at risk for significant airway obstruction.
Abstract 11432: Combined Elevations of Asymmetric Dimethylarginine and Homocysteine Have Big Impact on Carotid Atherosclerosis [[Unable to Display Character: —]] The Tanushimaru Study [[Unable to Display Character: —]]
Authors: Yume Nohara, Hisashi Adachi, Mika Enomoto, Ako Fukami, Eita Kumagai, Kyoko Ohbu, Sachiko Nakamura, Aya Obuchi, Ayako Yoshimura
Journal: Circulation (2013)

Background: It is shown that elevated serum level of ADMA (asymmetric dimethylarginine) or homocystein (Hcy) is associated with atherosclerosis in humans. However, the impact of both elevations is ...
Single-cell analysis pinpoints distinct populations of cytotoxic CD4 <sup>+</sup> T cells and an IL-10 <sup>+</sup> CD109 <sup>+</sup> T <sub>H</sub> 2 cell population in nasal polyps
Authors: Junjie Ma, Christopher A. Tibbitt, Susanna Kumlien Georén, Murray Christian, Ben Murrell, Lars-Olaf Cardell, Claus Bachert, Jonathan M. Coquet
Journal: Science Immunology (2021)

Transcriptional profiling pinpoints the heterogeneity of T helper cells in human nasal polyps at the clonal level.
転写因子YY1は,p53非依存的方法で低酸素因子HIF-1αを安定させることで腫瘍増殖に寄与する
Authors: WU Shourong, Kasim Vivi, R Kano Mitsunobu, Tanaka Sayaka, Ohba Shinsuke, Miura Yutaka, Miyata Kanjiro, Liu Xueying, Matsuhashi Ako, Chung Ung-Il, Yang Li, Kataoka Kazunori, Nishiyama Nobuhiro, Miyagishi Makoto
Journal: Cancer Research (2013)