tbuckley/cabot-search huggingface dataset:
The Effect of Various β Values on Image Quality and Semiquantitative Measurements in 68Ga-RM2 and 68Ga-PSMA-11 PET/MRI Images Reconstructed With a Block Sequential Regularized Expectation Maximization Algorithm
Authors: Lucia Baratto, Heying Duan, Valentina Ferri, Mehdi Khalighi, Andrei Iagaru
Journal: Clinical Nuclear Medicine (2020)

Purpose To compare the block sequential regularized expectation maximization (BSREM) algorithm with the ordered subsets expectation maximization (OSEM) algorithm and to evaluate how different penalty factors ( b values) influence image quality and SUV measurements. Methods We analyzed data from 78 prostate cancer patients who underwent 68 Ga-RM2 (n = 42) or 68 Ga-prostate-specific membrane antigen (PSMA)-11 (n = 36) PET/MRI. The raw PET data were retrospectively reconstructed using both time-of-flight (TOF)–BSREM with b values of 250, 350, 500, 750, and 1000 and TOF-OSEM. Each reconstruction was reviewed independently by 3 nuclear medicine physicians and scored qualitatively using a Likert scale (1 = poor, 5 = excellent quality). SUV measurements were analyzed as well. Results Fifty-seven lesions were detected (21 on 68 Ga-RM2 and 36 on 68 Ga-PSMA-11 PET/MRI); SUVmax decreased with the increase of β values for both tracers. Background noise (SUV sd ) decreased with increasing of β values for both tracers. The mean ± SD scores for 68 Ga-RM2 PET images were 2.4 ± 0.5 for b = 250 reconstructions, 3.2 ± 0.6 for b = 350, 4 ± 0.6 for b = 500, 4.5 ± 0.5 for b = 750, 4.4 ± 0.7 for b = 1000, and 3.4 ± 0.6 for TOF-OSEM. The mean ± SD scores for 68 Ga-PSMA-11 PET images were 3.2 ± 0.8 for b = 250 reconstructions, 4.1 ± 0.8 for b = 350, 4.7 ± 0.6 for b = 500, 4.8 ± 0.4 for b = 750, 4.7 ± 0.6 for b = 1000, and 3.8 ± 0.5 for TOF-OSEM. Conclusions Time-of-flight–BSREM algorithm improves image quality. Different b values should be used for different 68 Ga-labeled radiopharmaceuticals such as those targeting GRPR and PSMA receptors. Once selected, the same b value should be consistently used because SUVmax measurements differ with different b values.
41P A window-of-opportunity study with atezolizumab and the oncolityc virus pelareorep in early breast cancer (REO-027, AWARE-1)
Authors: L. Manso, P. Villagrasa, N. Chic, J.M. Cejalvo, Y. Izarzugaza, B. Cantos, S. Blanch, M. Juan, B. González-Farré, R. Laeufle, G. Nuovo, G. Wilkinson, M. Coffey, A. González, D. Martínez, L. Paré, F. Salvador, X. González-Farré, A. Prat, J. Gavila Gregori
Journal: Annals of Oncology (2020)
The Lettsomian Lectures on Diseases of the Nose and Throat in Relation to General Medicine: Delivered before the Medical Society of London
Authors: F. D. H. Hall
Journal: BMJ (1897)

MTRBt8e 319 cases is, they carry conviction to my own mind.It gives me the most profound satisfaction to be able to state, on the authority of the India Office, that the Bombay Government intend to employ M. Yersin, now on his way to the stricken region, and to give a full trial to his method.I have also learned through another channel that within a fortnight of this time (February Ist) the serum treatment will probably have begun in Bombay.]
Targeting of Formyl Peptide Receptor 2 for i<i>n vivo</i> imaging of acute vascular inflammation
Authors: Tamara Boltersdorf, Junaid Ansari, Elena Y. Senchenkova, Jieny Groeper, Denise Pajonczyk, Shantel A. Vital, Gaganpreet Kaur, J. Steve Alexander, Thomas Vogl, Ursula Rescher, Nicholas J. Long, Felicity N. E. Gavins
Journal: Theranostics (2020)

Inflammatory conditions are associated with a variety of diseases and can significantly contribute to their pathophysiology.Neutrophils are recognised as key players in driving vascular inflammation and promoting inflammation resolution.As a result, neutrophils, and specifically their surface formyl peptide receptors (FPRs), are attractive targets for non-invasive visualization of inflammatory disease states and studying mechanistic details of the process.Methods: A small-molecule Formyl Peptide Receptor 2 (FPR2/ALX)-targeted compound was combined with two rhodamine-derived fluorescent tags to form firstly, a targeted probe (Rho-pip-C1) and secondly a targeted, pH-responsive probe (Rho-NH-C1) for in vivo applications.We tested internalization, toxicity and functional interactions with neutrophils in vitro for both compounds, as well as the fluorescence switching response of Rho-NH-C1 to neutrophil activation.Finally, in vivo imaging (fluorescent intravital microscopy [IVM]) and therapeutic efficacy studies were performed in an inflammatory mouse model. Results:In vitro studies showed that the compounds bound to human neutrophils via FPR2/ALX without causing internalisation at relevant concentrations.Additionally, the compounds did not cause toxicity or affect neutrophil functional responses (e.g.chemotaxis or transmigration).In vivo studies using IVM showed Rho-pip-C1 bound to activated neutrophils in a model of vascular inflammation.The pH-sensitive ("switchable") version termed Rho-NH-C1 validated these findings, showing fluorescent activity only in inflammatory conditions.Conclusions: These results indicate a viable design of fluorescent probes that have the ability to detect inflammatory events by targeting activated neutrophils.
Molecular mechanisms of action of epigallocatechin gallate in cancer: Recent trends and advancement
Authors: Vaishali Aggarwal, Hardeep Singh Tuli, Mousumi Tania, Saumya Srivastava, Erin E Ritzer, Anjana Pandey, Diwakar Aggarwal, Tushar Singh Barwal, Aklank Jain, Ginpreet Kaur, Katrin Sak, Mehmet Varol, Anupam Bishayee
Journal: Seminars in Cancer Biology (2020)
Immunotherapy with Grass Pollen Major Allergens
Authors: O. ØSterballe, H. Løwenstiiin, S. Norn, P. Prahl, P. Skov, P. S. Skov, B. Wekke
Journal: Allergy (1982)

Preseasonal hyposensitization stimulated an intercorrelated increase in both serum‐specific IgE and allergen‐specific IgG. Subsequent perennial treatment depressed the stimulated IgE response and the basophil cell sensitivity, whereas the allergen‐specific IgE response showed further increase and persisted at a high level. Nasal IgE response was stimulated from the second pollen season and subsequently became depressed. One year after the end of hyposensitization the allergen‐specific IgE response had fallen by 25–50%.
CDK12 and PAK2 as novel therapeutic targets for human gastric cancer
Authors: Hui Liu, Seung Ho Shin, Hanyong Chen, Tingting Liu, Zhi Li, Yamei Hu, Fangfang Liu, Chengjuan Zhang, Doon Jun Kim, Kangdong Liu, Zigang Dong
Journal: Theranostics (2020)

Background: Gastric cancer remains the second leading cause of cancer-related death, and the third in mortality due to lack of effective therapeutic targets for late stage cancer patients. This study aims to identify potential druggable target biomarkers as potential therapeutic options for patients with gastric cancer. Methods: Immunohistochemistry of human gastric tumor tissues was conducted to determine the expression level of cyclin-dependent kinase 12 (CDK12). Multiple in vitro and in vivo assays such as RNAi, mass spectrometry, computer docking models, kinase assays, cell xenograft NU/NU mouse models (CDXs) and patient-derived xenograft NOD/SCID mouse models (PDXs) were conducted to study the function and molecular interaction of CDK12 with p21 activated kinase 2 (PAK2), as well as to find CDK12 inhibitors as potential treatment options for human gastric cancer. Results: Here we identified that CDK12 is a driver gene in human gastric cancer growth. Mechanistically, CDK12 directly binds to and phosphorylates PAK2 at T134/T169 to activate MAPK signaling pathway. We further identified FDA approved clinical drug procaterol can serve as an effective CDK12 inhibitor, leading to dramatic restriction of cancer cell proliferation and tumor growth in human gastric cancer cells and PDXs. Conclusions: Our data highlight the potential of CDK12/PAK2 as therapeutic targets for patients with gastric cancer, and we propose procaterol treatment as a novel therapeutic strategy for human gastric cancer.
Genome sequence analysis of the first human West Nile virus isolated in Italy in 2009
Authors: L Barzon, E Franchin, L Squarzon, E Lavezzo, S Toppo, T Martello, S Bressan, S Pagni, M Cattai, A Piazza, M Pacenti, R Cusinato, G Palù
Journal: Eurosurveillance (2009)

In 2009, six new human cases of West Nile neuroinvasive disease (WNND) were identified in Veneto region, following the six cases already reported in 2008. A human West Nile virus (WNV) isolate was obtained for the first time from an asymptomatic blood donor. Whole genome sequence of the human WNV isolate showed close phylogenetic relatedness to the Italy-1998-WNV strain and to other WNV strains recently isolated in Europe, with the new acquisition of the NS3-Thr249Pro mutation, a trait associated with avian virulence, increased virus transmission, and the occurrence of outbreaks in humans.
Deregulated Regulators: Disease-Causing cis Variants in Transcription Factor Genes
Authors: Robin van der Lee, Solenne Correard, Wyeth W. Wasserman
Journal: Trends in Genetics (2020)

Whole-genome sequencing is accelerating identification of noncoding variants that disrupt gene expression, although reports of such regulatory variants implicated in disease remain rare. A notable subset of described variants affect transcription factor (TF) genes and other master regulators in cis through dosage effects. From the literature, we compiled 46 regulatory variants linked to 40 TF genes implicated in rare diseases. We discuss the genomic geography of these variants and the evidence presented for their potential pathogenicity. To help advance research on candidate disease variants into the literature, we introduce an evidence framework specific to regulatory variants, which are under-represented in current variant classification guidelines. The clinical research interpretation of patient genomes may be advanced by considering regulatory variants, particularly those that deregulate TF genes.
Letter: Hypnosis and acupuncture
Authors: R. T. London
Journal: JAMA (1974)

<h3>To the Editor.—</h3> Just as hypnosis and biofeedback show excellent results when part of an overall medical plan, so, too, can acupuncture. Dr. Herbert Spiegel of the College of Physicians and Surgeons, Columbia University, has developed a hypnotic induction profile that uses an eye-roll test to determine hypnotizability.<sup>1,2</sup>In this test, the capacity to roll the eyes upward is clinically measured on a scale of 0 to 4. Based on his extensive use of this eye-roll test, Dr. Spiegel estimates that approximately 74% of the population possesses some degree of hypnotizability. That is, they are in the 1 to 4 range. The 3s and 4s make up almost 40% of the population and many of these people are potential candidates for surgical anesthesia by hypnosis. Also, the ability of the "highs" to use suggestion is so great that many chronic organic diseases are better managed in conjunction with hypnosis
17P Dysregulation of immune checkpoint proteins in newly diagnosed early breast cancer patients
Authors: B. Rapoport, A. Theron, H. Steel, S. Nayler, C. Benn, N. Hlatswayo, L. Kwofie, L. Heyman, T. Smit, L. Jooste, F. Moosa, R. Anderson
Journal: Annals of Oncology (2020)
Pseudopatients and Pseudoresearch
Authors: Samuel Vaisrub
Journal: JAMA (1975)

It is difficult to be sure which "pseudo" invaded medicine first. It might have been pseudocyeisis—an erstwhile not infrequent source of embarrassment to the physician—or pseudoleukemia described by Wilkes in 1856. Whatever and whenever its beginnings, this prefix now commands several pages in any standard medical dictionary, where pseudodiseases range from pseudoacanthosis to pseudoxanthoma elasticum. But nowhere in<i>Stedman's</i>or<i>Dorland's</i>, search hard as you may, will you find a reference to "pseudopatient." This term is an innovation and one we could often do without. Pseudopatients come in two types: "artists" and "scientists." The former are professional actors trained to simulate various diseases for teaching purposes.<sup>1</sup>They have proved useful in demonstrating various clinical conditions to medical students. Some actors have even been coached to enact specific psychiatric problems for teaching principles of psychiatry to general practitioners.<sup>2,3</sup>And, not to be outdone by professionals, doctors themselves (pseudopseudopatients?) have
Institutionalized Mental Patients
Authors: Vernon H. Mark
Journal: JAMA (1975)

<h3>To the Editor.—</h3> Charles D. Aring's commentary (230:849, 1974) on the plight of institutionalized mental patients raises some interesting questions. His humanitarian aims in writing such an article are to be applauded. However, some of his statements require careful documentation. He quite correctly states that villages and towns adjacent to state hospitals whose doors have been opened experience uneasiness (particularly when an act of extreme violence is committed by a released inmate). But his assertion that "these former inmates are glad for their new-found freedom" is unsupported by any study of recently released inmates. The unpleasant plight of chronic mental patients recently released from psychiatric institutions was described by Robert Riech in an editorial (<i>Am J Psychiatry</i>130:911, 1973); he called it a "national disgrace." This deplorable situation received attention in New York State when the State Board of Social Welfare refused to license new proprietary homes for released mental
Patient‐reported outcomes in sickle cell disease and association with clinical and psychosocial factors: Report from the sickle cell disease implementation consortium
Authors: Mitchell R. Knisely, Norma Pugh, Barbara Kroner, Rita Masese, Victor Gordeuk, Allison A. King, Sharon M. Smith, James G. Gurney, Robert Adams, Ted Wun, Angela Snyder, Jeffrey Glassberg, Nirmish Shah, Marsha Treadwell
Journal: American Journal of Hematology (2020)

Abstract Understanding patient experiences, quality of life, and treatment needs in individuals with sickle cell disease (SCD) is essential in promoting health and well‐being. We used measures from the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ‐Me), Patient Reported Outcomes Measurement Information System (PROMIS), and Quality of Life in Neurological Disorders (NeuroQol) to evaluate pain impact, sleep impact, social functioning, depressive symptoms, tiredness, and cognitive function (collectively, patient reported outcomes [PROs]) and to identify associated demographic and clinical characteristics. Participants (n = 2201) between 18 and 45 years were recruited through the eight Sickle Cell Disease Implementation Consortium (SCDIC) sites. In multivariate models, PROs were significantly associated with one another. Pain impact was associated with age, education, employment, time since last pain attack, hydroxyurea use, opioid use, sleep impact, social functioning, and cognitive function ( F = 88.74, P &lt; .0001). Sleep impact was associated with household income, opioid use, pain impact, social functioning, depressive symptoms, and tiredness ( F = 101.40, P &lt; .0001). Social functioning was associated with employment, pain attacks in the past year, autoimmune/inflammatory comorbidities, pain impact, sleep impact, depressive symptoms, tiredness, and cognitive function ( F = 121.73, P &lt; .0001). Depressive symptoms were associated with sex, sleep impact, social functioning, tiredness, and cognitive function ( F = 239.51, P &lt; .0001). Tiredness was associated with sex, education, sleep impact, social functioning, depressive symptoms, and cognitive function ( F = 129.13, P &lt; .0001). These findings reflect the baseline PRO assessments among SCDIC registry participants. Further research is needed to better understand these outcomes and new targets for interventions to improve quality of life and function in people with SCD.
Malignant Lymphomas of Follicular Center Cell Origin in Man. II. Immunologic Studies23
Authors: J. H. Leech, A. D. Glick, J. A. Waldron, J. M. Flexner, R. G. Horn, R. D. Collins
Journal: JNCI Journal of the National Cancer Institute (1975)

Tissues from malignant lymphomas with both nodular and diffuse growth patterns, thought by light microscopy to be composed of cells of follicular center cell (FCC) origin, Were examined by electron microscopy; the tumor cells were similar to lymphoid cells found in reactive follicular centers. Tumor cells from neoplasms thought to be composed of cleaved FCC often had more pronounced nuclear folding than did cleaved FCC of reactive follicles, whereas cells in tumors of noncleaved FCC type were indistinguishable from their presumed counterparts in reactive follicles. Large cell noeplasms, previously classified as "histiocytic" lymphomas were composed of cells with ultrastructural characteristics of transformed lymphocytes; they showed neither ultrastructural nor cytochemical features of mononuclear phagocytes. These findings support the concept that a major group of lymphomas arises from lymphocytes of follicular centers.
<i>BRCA1</i>Promoter Methylation and Clinical Outcomes in Ovarian Cancer: An Individual Patient Data Meta-Analysis
Authors: Roshni D Kalachand, Britta Stordal, Stephen Madden, Benjamin Chandler, Julie Cunningham, Ellen L Goode, Ilary Ruscito, Elena I Braicu, Jalid Sehouli, Atanas Ignatov, Herbert Yu, Dionyssios Katsaros, Gordon B Mills, Karen H Lu, Mark S Carey, Kirsten M Timms, Jolanta Kupryjanczyk, Iwona K Rzepecka, Agnieszka Podgorska, Jessica N McAlpine, Elizabeth M Swisher, Sarah S Bernards, Ciaran O’Riain, Sharon O’Toole, John J O’Leary, David D Bowtell, David M Thomas, Katharina Prieske, Simon A Joosse, Linn Woelber, Parvesh Chaudhry, Norman Häfner, Ingo B Runnebaum, Bryan T Hennessy
Journal: JNCI Journal of the National Cancer Institute (2020)

BRCA1 methylation has been associated with homologous recombination deficiency, a biomarker of platinum sensitivity. Studies evaluating BRCA1-methylated tubal and ovarian cancer (OC) do not consistently support improved survival following platinum chemotherapy. We examine the characteristics of BRCA1-methylated OC in a meta-analysis of individual participant data.Data of 2636 participants across 15 studies were analyzed. BRCA1-methylated tumors were defined according to their original study. Associations between BRCA1 methylation and clinicopathological characteristics were evaluated. The effects of methylation on overall survival (OS) and progression-free survival (PFS) were examined using mixed-effects models. All statistical tests were 2-sided.430 (16.3%) tumors were BRCA1-methylated. BRCA1 methylation was associated with younger age and advanced-stage, high-grade serous OC. There were no survival differences between BRCA1-methylated and non-BRCA1-methylated OC (median PFS = 20.0 vs 18.5 months, hazard ratio [HR] = 1.01, 95% CI = 0.87 to 1.16; P = .98; median OS = 46.6 vs 48.0 months, HR = 1.02, 95% CI = 0.87 to 1.18; P = .96). Where BRCA1/2 mutations were evaluated (n = 1248), BRCA1 methylation displayed no survival advantage over BRCA1/2-intact (BRCA1/2 wild-type non-BRCA1-methylated) OC. Studies used different methods to define BRCA1 methylation. Where BRCA1 methylation was determined using methylation-specific polymerase chain reaction and gel electrophoresis (n = 834), it was associated with improved survival (PFS: HR = 0.80, 95% CI = 0.66 to 0.97; P = .02; OS: HR = 0.80, 95% CI = 0.63 to 1.00; P = .05) on mixed-effects modeling.BRCA1-methylated OC displays similar clinicopathological features to BRCA1-mutated OC but is not associated with survival. Heterogeneity within BRCA1 methylation assays influences associations. Refining these assays may better identify cases with silenced BRCA1 function and improved patient outcomes.
Early Observation and Mitigation of Challenges in Diabetes Management of COVID-19 Patients in Critical Care Units
Authors: Osama Hamdy, Robert A. Gabbay
Journal: Diabetes Care (2020)

Clinical studies of patients with coronavirus disease 2019 (COVID-19) have found diabetes to be a major risk factor for disease severity and mortality (1,2).One new study showed that COVID-19 patients with diabetes and/or uncontrolled hyperglycemia had a longer length of stay and markedly higher mortality than patients without diabetes or uncontrolled hyperglycemia (3).Given rising numbers of cases of patients with COVID-19 and diabetes, understanding their interaction on insulin requirement and glycemic control is prudent.As seen in other infections, blood glucose starts to rise with the beginning of clinical symptoms.By the time the patient is admitted to the intensive care unit (ICU), insulin requirement is at its highest, and blood glucose remains high if not properly managed.Treating physicians face several challenges that need careful attention.Here are some of the potential issues that we encountered in our ICUs and their suggested mitigating plans.We thought that sharing them at this early stage is important.Continuous tube feeding in patients on artificial ventilation.Continuous tube feeding is the ideal nutrition method for intubated patients with COVID-19.Typically, this has been managed by a combination of continuous intravenous insulin infusion and frequent glucose
Therapy Approved for Hard-to-Treat Upper Tract Urothelial Cancer
Authors: Rebecca Voelker
Journal: JAMA (2020)

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The role of reflectance confocal microscopy in differentiating melanoma in situ from dysplastic nevi with severe atypia: A cross-sectional study
Authors: Naiara Fraga-Braghiroli, Jane M. Grant-Kels, Margaret Oliviero, Harold Rabinovitz, Katalin Ferenczi, Alon Scope
Journal: Journal of the American Academy of Dermatology (2020)
Association Between Delays in Mechanical Ventilation Initiation and Mortality in Patients With Refractory Cardiogenic Shock
Authors: Sean van Diepen, Judith S. Hochman, Amanda Stebbins, Carlos L. Alviar, John H. Alexander, Renato D. Lopes
Journal: JAMA Cardiology (2020)

Acute myocardial infarction (MI) is complicated by cardiogenic shock (CS) in 4% to 10% of patients, and contemporary mortality rates range from 31% to 51%. 1 A common sequela of CS is an elevated end-diastolic pressure leading to pulmonary congestion, and mechanical ventilatory (MV) support is required in up to 88% of patients. 2Positive end-expiratory pressure (PEEP) imparts favorable cardiovascular hemodynamic changes in patients with CS and reduced left ventricular (LV) function.Positive end expiratory pressure lowers pulmonary wedge pressure, LV afterload, myocardial oxygen demand, work of breathing, and improves cardiac index and oxygenation. 3Consequently, the timely initiation of MV in this population could theoretically attenuate physiologic deterioration or the ischemic cascade and improve outcomes; however, to our knowledge, the association between timing of MV initiation and mortality in patients with CS has not been described.