tbuckley/cabot-search huggingface dataset:
Decreased Iron Overload and Oxidative Stress in Transfusion Dependent Patients with Myelodysplastic Syndromes (MDS) with the Oral Iron Chelator Deferiprone
Authors: Drorit Merkel, Shelly Soffer, Kalman Filanovsky, Andrei Braester, Eitan Fibach, Mutaz Mohammad Dana, Yishay Ofran, Uri Greenbaum, Arnon Nagler, Moshe Mittelman
Journal: Blood (2018)
P107 Polymorphisms in SLC2A9 and SLC22A12 genes are related to hyperuricemia, gout and also to hypouricemia
Authors: K Pavelcova, J Bohata, K Pavelka, B Stiburkova
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Student for a master or a PhD. <h3>Introduction</h3> Serum uric acid concentration is significantly influenced by urate transporters, such as ABCG2 (encoded by <i>ABCG2</i> gene), GLUT9 (<i>SLC2A9</i> gene) and URAT1 (<i>SLC22A12</i> gene). The main function of ABCG2 is uric acid secretion, whereas GLU9 and URAT1 also ensure reabsorption. Pathogenic allelic variants in <i>SLC2A9</i> and <i>SLC22A12</i> are not only associated with hyperuricemia and gout, but they also lead to rare hereditary renal hypouricemia (type 1 – OMIM #220150 or type 2 – OMIM # 612076). <h3>Objectives</h3> Previously, we analyzed <i>ABCG2</i> gene and detected non-synonymous variants that lead to hyperuricemia and early onset of the gout.<sup>1</sup> The aim of this study was to find a possible correlation between variants in <i>SLC2A9</i> and <i>SLC22A12</i> and hypouricemia, hyperuricemia and gout.<sup>2</sup> <h3>Methods</h3> We recruited a cohort of 232 individuals with primary gout and hyperuricemia. We examined coding regions of <i>SLC2A9</i> (13 exons) and <i>SLC22A12</i> (10 exons) by Sanger sequencing. We also analyzed <i>SLC2A9</i> and <i>SLC22A12</i> in five patients with suspect hypouricemia. <h3>Results</h3> In the cohort of 232 individuals, we detected five synonymous variants, 18 intron variants and seven missense variants in <i>SLC2A9</i>: A17T, G25R, T275M, D281H, V282I, R294H, and P350L. In <i>SLC22A12</i> gene, we found six synonymous variants and seven intron variants. We detected several pathogenic variants in patients with suspect hypouricemia. Intronic variant c.1419+1G&gt;A in <i>SLC2A9</i> most likely affects the splicing. In <i>SLC22A12</i>, we found rare pathogenic variants T467M and L415_G417del. These variants have according to our previous study high frequency in the Czech and Slovak Roma population.<sup>3</sup> <h3>Conclusions</h3> The uric acid level is determined by a complex mechanism that is not yet fully understood. Disorders of urate transporters can not only lead to hyperuricemia, but in rare cases also to hypouricemia. <h3>References</h3> Stiburkova B, <i>et al. Rheumatology (Oxford)</i> 2017 November 1;56(11):1982–1992. doi:10.1093/rheumatology/kex295 Hurba O, <i>et al. PLoS One</i> 2014 September 30;9(9):e107902. doi:10.1371/journal.pone.0107902 Gabrikova D, <i>et al. Urolithiasis</i> 2015 October;43(5):441–5. doi:10.1007/s00240-015-0790-4 <h3>Acknowledgements</h3> This study was supported by the grant from the Czech Republic Ministry of Health AZV 15-26693A. <h3>Disclosure of Interest</h3> None declared.
Provide doctors with rest spaces and on-call rooms, says mental health review
Authors: Abi Rimmer
Journal: BMJ (2019)

All NHS staff, including doctors, should have access to good occupational health, psychological support, and rest facilities, a report by Health Education England has said.

HEE’s NHS Staff and Learner Mental Wellbeing Commission report, published on Wednesday, sets out a number of recommendations to improve the mental health of NHS staff,1 including that they all have “suitable, accessible, psychologically safe, and confidential spaces in which to socialise, share and discuss experiences, and to rest.”

Earlier this year, The BMJ launched a campaign calling for doctors to be able to take the breaks that they need for their wellbeing and for patient safety.2

In its report the …
Abstract 15955: Race is Associated With Differences in Left Heart Dimensions on Echocardiography
Authors: Troy M LaBounty, David S Bach, Eduardo Bossone, Theodore J Kolias
Journal: Circulation (2017)

Introduction: The relationship between race and left heart size is incompletely understood in non-athletes. Hypothesis: There are race-specific differences in left heart measurements on echocardiography. Methods: We compared the relationship between left heart measurements and race among 19,958 individuals age 18-79 with an echocardiogram, and without prior hypertension, diabetes, left-sided valve disease, or myocardial infarction; patients with decreased left ventricular (LV) function were excluded. We compared left heart dimensions and mass between Caucasian, African American (AA), Hispanic, Asian, and Native American (NA) races. Multivariate analysis compared measurements between groups after adjusting for age, gender, and body surface area (BSA). Results: There were significant differences between groups in age, gender, BSA, and left heart measurements (Table 1). After multivariable adjustment and using Caucasians as a baseline, there were significant differences in LV end-diastolic diameters for AA (...
Characteristics of Digital Health Studies Registered in ClinicalTrials.gov
Authors: Connie E. Chen, Robert A. Harrington, Sumbul A. Desai, Kenneth W. Mahaffey, Mintu P. Turakhia
Journal: JAMA Internal Medicine (2019)

All authors are employed by and own stock in Google.In addition, as part of a broad-based equity portfolio intending to mirror the US and International equities markets (eg, MSCI All Country World, Russell 3000), Jeff Dean holds individual stock positions in many public companies in the health care and pharmacological sectors, and also has investments in managed funds that also invest in such companies, as well as limited partner and direct venture investments in private companies operating in these sectors.All other health care-related investments are managed by independent third parties (institutional managers) with whom Jeff Dean has no direct contact and over whom Jeff Dean has no control.
Advisory Committee on Immunization Practices Recommended Immunization Schedule for Children and Adolescents Aged 18 Years or Younger — United States, 2021
Authors: A. Patricia Wodi, Kevin Ault, Paul Hunter, Veronica McNally, Peter G. Szilagyi, Henry Bernstein
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

In October 2017, the Advisory Committee on Immunization Practices (ACIP) approved the Recommended Immunization Schedule for Children and Adolescents Aged 18 Years or Younger - United States, 2018. The 2018 child and adolescent immunization schedule summarizes ACIP recommendations, including several changes from the 2017 immunization schedules, in three figures and footnotes to the figures. These documents can be found on the CDC immunization schedule website (https://www.cdc.gov/vaccines/schedules/index.html). These immunization schedules are approved by ACIP (https://www.cdc.gov/vaccines/acip/index.html), the American Academy of Pediatrics (https://www.aap.org), the American Academy of Family Physicians (https://www.aafp.org), and the American College of Obstetricians and Gynecologists (https://www.acog.org). Health care providers are advised to use the figures and the footnotes together. The full ACIP recommendations for each vaccine, including contraindications and precautions, can be found at https://www.cdc.gov/vaccines/hcp/acip-recs/index.html. Providers should be aware that changes in recommendations for specific vaccines can occur between annual updates to the childhood/adolescent immunization schedules. If errors or omissions are discovered within the child and adolescent schedule, CDC posts revised versions on the CDC immunization schedule website.
Legionnaires’ disease in Europe 2007–2008
Authors: C A Joseph, K D Ricketts, Collective on behalf of the European Working G
Journal: Eurosurveillance (2010)

Each spring, countries that participate in the European Surveillance Scheme for Travel Associated Legionnaires Disease (EWGLINET) are requested to submit their annual dataset of all cases of Legionnaires disease in residents of their country with onset of illness in the preceding year. These data have been collected annually since 1994 and are used to analyse epidemiological and microbiological trends within and between countries over time. This paper presents an overview of the data collected for 2007 and 2008. A total of 5,907 cases were reported by 33 countries in 2007 and 5,960 cases by 34 countries in 2008, a similar two-year total to that recorded in 2005 and 2006 [1]. The only countries with a major difference in case numbers between 2007 and 2008 were Russia, due to a large outbreak in 2007, and Italy where cases increased by 256 in 2008 mainly due to an increase in community-acquired infections. The 779 reported deaths give a two-year case fatality rate of 6.6%. Some 243 outbreaks or clusters were detected, 150 of which were linked to travel-associated infections. As in previous years, the overall main method of diagnosis was by urinary antigen detection and the proportion of cases diagnosed by culture remained low at 8.8%, although isolation rates by country ranged from under 1% to over 40%.
A Fast and Accurate Cartridge-Based RT-qPCR Assay to Quantify PML-Rara mRNA Fusion Transcripts Near the Point of Care
Authors: Natalie Chi-hwa Wu, Monisha Malek, Ken Ho, Julia Chen, Anvita Komarla, Victor Chu, Huilin Wei, Gwo-Jen Day, Jean-Michel Cayuela, Christophe Ferrand, Bruno Cassinat
Journal: Blood (2018)
18F-fluorodeoxyglucose positron emission tomography (18FDG-PET) for patients with biliary tract cancer: Systematic review and meta-analysis
Authors: Angela Lamarca, Jorge Barriuso, Amarjot Chander, Mairéad G McNamara, Richard A Hubner, Derek ÓReilly, Prakash Manoharan, Juan W Valle
Journal: Journal of Hepatology (2019)
Abstract 2645: Role of embryonic signaling pathways in lung cancer.
Authors: Samer Singh, David Robbins, Anthony J. Capobianco, Dao M. Nguyen
Journal: Cancer Research (2013)

Abstract Background: Embryonic signaling pathways that play an important role during embryo development, later on support the maintenance of adult stem cells and are also found activated in various cancers. The activated embryonic signaling mainly Hedgehog (HH), WNT and NOTCH have been shown to be activated in a number of cancers and demonstrated to promote growth, provide survival advantage and resistance to various drugs. The role of these embryonic signaling pathways in the development of lung cancer is not well defined. Identification of particular pathways active in cancer and elucidation of their mechanism of action in cancer development could provide the basis of devising a successful therapeutic intervention. Objective: Define the role of embryonic signaling pathways in cancer cells. Methodology: The presence and functional interaction of various embryonic signaling pathways in lung cancer was evaluated using human non-small cell lung carcinoma cell lines (e.g. HOP62, A549, H23, H522) as model system. The signaling pathways were inhibited using specific small molecule inhibitors and shRNAs mediated knockdown of the pathway components. The lentiviruses expressing shRNA were made and used to deliver the shRNA in NSCLC cells. The effect on the target gene expression (quantitative real time RT-PCR and western blotting), cell proliferation (ATP quantitation), cell migration (scratch/wound assay) and anchorage independent growth (soft agar assay), was evaluated. Currently, the activation of pathways in cancer cells of primary lung cancer samples is being evaluated by immunohistochemistry (IHC) and RNA in situ hybridization (ISH). Preliminary Results and Conclusions: Attenuation of individual embryonic signaling pathways using specific small molecule inhibitors and shRNAs, indicated crosstalk and hierarchy of these pathways in controlling various processes in tested cancer cells. Our results suggest the predominance of HH signaling in non-small cell lung carcinoma. We are in the process of expanding our observation to more cell lines and human cancer samples. Our work will establish the role of embryonic signaling pathways in lung cancer and would further help in establishing a framework for future therapeutic intervention. Citation Format: Samer Singh, David Robbins, Anthony J. Capobianco, Dao M. Nguyen. Role of embryonic signaling pathways in lung cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2645. doi:10.1158/1538-7445.AM2013-2645 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
The role of cement augmentation with percutaneous vertebroplasty and balloon kyphoplasty for the treatment of vertebral compression fractures in multiple myeloma: a consensus statement from the International Myeloma Working Group (IMWG)
Authors: Charalampia Kyriakou, Sean Molloy, Frank Vrionis, Ronald Alberico, Leonard Bastian, Jeffrey A. Zonder, Sergio Giralt, Noopur Raje, Robert A. Kyle, David G. D. Roodman, Meletios A. Dimopoulos, S. Vincent Rajkumar, Brian B. G. Durie, Evangelos Terpos
Journal: Blood Cancer Journal (2019)

Abstract Multiple myeloma (MM) represents approximately 15% of haematological malignancies and most of the patients present with bone involvement. Focal or diffuse spinal osteolysis may result in significant morbidity by causing painful progressive vertebral compression fractures (VCFs) and deformities. Advances in the systemic treatment of myeloma have achieved high response rates and prolonged the survival significantly. Early diagnosis and management of skeletal events contribute to improving the prognosis and quality of life of MM patients. The management of patients with significant pain due to VCFs in the acute phase is not standardised. While some patients are successfully treated conservatively, and pain relief is achieved within a few weeks, a large percentage has disabling pain and morbidity and hence they are considered for surgical intervention. Balloon kyphoplasty and percutaneous vertebroplasty are minimally invasive procedures which have been shown to relieve pain and restore function. Despite increasing positive evidence for the use of these procedures, the indications, timing, efficacy, safety and their role in the treatment algorithm of myeloma spinal disease are yet to be elucidated. This paper reports an update of the consensus statement from the International Myeloma Working Group on the role of cement augmentation in myeloma patients with VCFs.
CADD-27. G-QUADRUPLEX DNA DRIVES GENOMIC INSTABILITY AND REPRESENTS A TARGETABLE MOLECULAR ABNORMALITY IN ATRX-DEFICIENT MALIGNANT GLIOMA
Authors: Yuxiang Wang, Jie Yang, Wei Wu, Rachna Shah, Carla Danussi, Gregory Riggins, Kasthuri Kannan, Erik Sulman, Timothy Chan, Jason Huse
Journal: Neuro-Oncology (2018)

Mutational inactivation of ATRX (a-thalassemia mental retardation X-linked) represents a defining molecular alteration in large subsets of malignant glioma. ATRX encodes a chromatin binding protein widely implicated in epigenetic regulation and remodeling. However, multiple studies have also associated its loss in cancer with replication stress, DNA damage, and copy number alterations (CNAs). The mechanisms by which ATRX deficiency drives this global genomic instability remain unclear. Here we report that ATRX inactivation in isogenic glioma model systems induces replication stress and DNA damage by promoting the formation of deleterious G-quadruplex (G4) secondary structure in DNA. Moreover, these effects are associated with the acquisition of disease-relevant CNAs over time. Prior work has linked G4s with genomic instability as well as CNAs in cancer. We then demonstrate, both in vitro and in vivo, that chemical G4 stabilization with CX-3543 (Quarfloxin) selectively enhances cell death in ATRX deficient isogenic cell lines as well as ATRX-mutant primary glioma stem cells derived from patients. Finally, we show that G4 stabilization synergizes with other DNA-damaging therapies, including ionizing radiation, in the ATRX-deficient context. Our findings clarify distinct mechanisms by which DNA secondary structure influences ATRX-deficient glioma pathogenesis and indicate that G4-stabilization may represent and attractive therapeutic strategy for the selective targeting of ATRX-mutant cancers. Opportunities for the development of radiosensitization approaches based on G4-stabilization are particularly intriguing, as ionizing radiation remains among the most effective non-surgical treatments for malignant glioma.
Debunking Myths About the Purpose and Intentions of Fundamentals of Laparoscopic Surgery Testing
Authors: Melina C. Vassiliou, John D. Mellinger, Steven D. Schwaitzberg
Journal: JAMA Surgery (2019)

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Treatment-refractory hypothyroidism
Authors: Laura J McNally, Catherine I Ofiaeli, Samson O Oyibo
Journal: BMJ (2019)

### What you need to know

A 40 year old woman complains of tiredness over the past few weeks. She had a total thyroidectomy three years ago for Graves’ thyrotoxicosis and has been taking levothyroxine since then. She weighs 80 kg and is taking 150 μg daily. A blood test done in the previous week showed thyroid stimulating hormone (TSH) levels above 30 mU/L (reference range 0.4-4.5 mU/L). 

Some hypothyroid patients continue to have symptoms or biochemical evidence of hypothyroidism (serum TSH above the upper laboratory reference range) despite standard thyroid replacement therapy. The prevalence of treatment-refractory hypothyroidism is not established. Studies in different populations report about a third of patients taking thyroid medications have TSH levels above the reference range, suggesting inadequate thyroid hormone replacement.12

Further dose increase may not always be appropriate. Patients may not be taking the treatment regularly as advised. Conditions that decrease absorption or increase demand …
Safety profile and therapeutic efficacy of one cycle of [177Lu]prostate-specific membrane antigen (PSMA) in end stage metastatic castration-resistant prostate cancer patients with low performance status
Authors: M. Gupta, P.S. Choudhury, S. Rawal, H.C. Goel, V. Talwar, K.D. Dutta, A. Singh
Journal: Annals of Oncology (2019)

Background: Prostate cancer patients with distant metastasis have poor prognosis and develop resistance to all standard drugs at various time intervals. Therapeutic options which can alleviate symptoms and prolong survival are required for these patients. [177Lu]prostate-specific membrane antigen ([177Lu]PSMA) is a novel drug based on a theranostic concept. Here, we have presented the safety and efficacy profile of one cycle of [177Lu]PSMA in metastatic castration-resistant prostate cancer (mCRPC) patients who have exhausted all standard therapeutic options. Methods: Twenty two patients treated with at least first line anti-androgens and docetaxel were treated with one cycle of [177Lu]PSMA therapy on a compassionate basis. Haemoglobin, total leukocyte counts, platelets and serum creatinine for toxicity profile while prostate specific antigen (PSA), Eastern Cooperative Oncology Group (ECOG) performance status, visual analogue scale (VAS) and analgesic quantification scale (AQS) for therapeutic efficacy were recorded pre and 8 weeks post therapy. Wilcoxon signed-rank and ANOVA tests were used for statistical analysis. Results: Partial response (PR), stable disease (SD) and progressive disease (PD) for PSA were seen in 5 (22.7%), 13 (59.1%) and 4 (18.2%) patients, respectively, treated with mean 6.88GBq dose of [177Lu]PSMA. 8/22 (36.4%) patients showed ≥ 30% drop in PSA. Grade 3 haemoglobin toxicity was seen in 5/22 (22.7%) patients. No patient developed grade 4 haemoglobin toxicity. No patients had grade 3 or 4 leukocytopenia or thrombocytopenia. Wilcoxon signed-rank test showed statistically significant (p < 0.05) difference in pre- and post-treatment ECOG, VAS, AQS scores while it was not significant for PSA (P > 0.05). ANOVA test showed a statistically significant difference in mean doses of [177Lu]PSMA used in the three PSA response groups while the difference was non-significant for other variables. Conclusions: We conclude that [177Lu]PSMA therapy delivers adequate pain palliation in all end-stage mCRPC patients and it has a potential to become an effective therapeutic option in properly selected patients. Legal entity responsible for the study: Manoj Gupta. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Increasing PET Use in Small Cell Lung Cancer: Survival Improvement and Stage Migration in the VA Central Cancer Registry
Authors: Julian C. Hong, Matthew J. Boyer, Daphna Y. Spiegel, Christina D. Williams, Betty C. Tong, Scott L. Shofer, Michael J. Moravan, Michael J. Kelley, Joseph K. Salama
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: Accurate staging for small cell lung cancer (SCLC) is critical for determining appropriate therapy. The clinical impact of increasing PET adoption and stage migration is well described in non-small cell lung cancer but not in SCLC. The objective of this study was to evaluate temporal trends in PET staging and survival in the Veterans Affairs Central Cancer Registry and the impact of PET on outcomes. Patients and Methods: Patients diagnosed with SCLC from 2001 to 2010 were identified. PET staging, overall survival (OS), and lung cancer-specific survival (LCSS) were assessed over time. The impact of PET staging on OS and LCSS was assessed for limited-stage (LS) and extensive-stage (ES) SCLC. Results: From 2001 to 2010, PET use in a total of 10,135 patients with SCLC increased from 1.1% to 39.2%. Median OS improved for all patients (from 6.2 to 7.9 months), those with LS-SCLC (from 10.9 to 13.2 months), and those with ES-SCLC (from 5.0 to 7.0 months). Among staged patients, the proportion of ES-SCLC increased from 63.9% to 65.7%. Among 1,536 patients with LS-SCLC treated with concurrent chemoradiotherapy, 397 were staged by PET. In these patients, PET was associated with longer OS (median, 19.8 vs 14.3 months; hazard ratio [HR], 0.78; 95% CI, 0.68-0.90; P<.0001) and LCSS (median, 22.9 vs 16.7 months; HR, 0.74; 95% CI, 0.63-0.87; P<.0001) with multivariate adjustment and propensity-matching. In the 6,143 patients with ES-SCLC, PET was also associated with improved OS and LCSS. Conclusions: From 2001 to 2010, PET staging increased in this large cohort, with a corresponding relative increase in ES-SCLC. PET was associated with greater OS and LCSS for LS-SCLC and ES-SCLC, likely reflecting stage migration and stage-appropriate therapy. These findings emphasize the importance of PET in SCLC and support its routine use.