tbuckley/cabot-search huggingface dataset:
Use of hormone replacement therapy and risk of breast cancer: nested case-control studies using the QResearch and CPRD databases
Authors: Yana Vinogradova, Carol Coupland, Julia Hippisley-Cox
Journal: BMJ (2020)

Abstract Objective To assess the risks of breast cancer associated with different types and durations of hormone replacement therapy (HRT). Design Two nested case-control studies. Setting UK general practices contributing to QResearch or Clinical Practice Research Datalink (CPRD), linked to hospital, mortality, social deprivation, and cancer registry (QResearch only) data. Participants 98 611 women aged 50-79 with a primary diagnosis of breast cancer between 1998 and 2018, matched by age, general practice, and index date to 457 498 female controls. Main outcome measures Breast cancer diagnosis from general practice, mortality, hospital, or cancer registry records. Odds ratios for HRT types, adjusted for personal characteristics, smoking status, alcohol consumption, comorbidities, family history, and other prescribed drugs. Separate results from QResearch or CPRD were combined. Results Overall, 33 703 (34%) women with a diagnosis of breast cancer and 134 391 (31%) controls had used HRT prior to one year before the index date. Compared with never use, in recent users (&lt;5 years) with long term use (≥5 years), oestrogen only therapy and combined oestrogen and progestogen therapy were both associated with increased risks of breast cancer (adjusted odds ratio 1.15 (95% confidence interval 1.09 to 1.21) and 1.79 (1.73 to 1.85), respectively). For combined progestogens, the increased risk was highest for norethisterone (1.88, 1.79 to 1.99) and lowest for dydrogesterone (1.24, 1.03 to 1.48). Past long term use of oestrogen only therapy and past short term (&lt;5 years) use of oestrogen-progestogen were not associated with increased risk. The risk associated with past long term oestrogen-progestogen use, however, remained increased (1.16, 1.11 to 1.21). In recent oestrogen only users, between three (in younger women) and eight (in older women) extra cases per 10 000 women years would be expected, and in oestrogen-progestogen users between nine and 36 extra cases per 10 000 women years. For past oestrogen-progestogen users, the results would suggest between two and eight extra cases per 10 000 women years. Conclusion This study has produced new generalisable estimates of the increased risks of breast cancer associated with use of different hormone replacement preparations in the UK. The levels of risks varied between types of HRT, with higher risks for combined treatments and for longer duration of use.
Diagnosis- and Cell Type-Specific Mitochondrial Functional Pathway Signatures in Schizophrenia and Bipolar Disorder
Authors: Jill R. Glausier, John F. Enwright, David A. Lewis
Journal: American Journal of Psychiatry (2020)

The shared risk factors and clinical features in schizophrenia and bipolar disorder may be linked via mitochondrial dysfunction. However, the severity of mitochondrial dysfunction, and/or the specific mitochondrial functional pathways affected, may differ between diagnoses, especially at the level of individual cell types.
Interim Positron Emission Tomography (iPET) Assessed Using Deauville Score for Patients with Follicular Lymphoma Receiving First-Line Chemoimmunotherapy
Authors: Reid W Merryman, Gabriela Spilberg, Patrizia Mondello, Robert A. Redd, Eleanor Taranto, Gulrayz Ahmed, Erin Jeter, Matthew Chase, Gilles Salles, Andrew D Zelenetz, Jennifer R Brown, Jennifer Crombie, Matthew S. Davids, David C. Fisher, Arnold S. Freedman, Eric D Jacobsen, Caron A. Jacobson, Austin I. Kim, Ann S. LaCasce, Benjamin L. Lampson, Samuel Y. Ng, Oreofe Odejide, Philippe Armand, Heather A. Jacene
Journal: Blood (2020)
SAT0243 The effect on toxicity of reducing the size of available paracetamol pack sizes in the united kingdom
Authors: CL Sheen, JF Dillon, DN Bateman, K Simpson, TM MacDonald
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Analgesia, using such drugs as paracetamol, is vital in the treatment of arthritis. Unfortunately, the incidence of paracetamol overdose, a common cause of hepatotoxicity and death, has been increasing. In the United Kingdom as a means of reducing adverse event risk, the Medicines Control Agency (MCA) limited the pack size of over-the-counter paracetamol in September 1998. This reduction in the amount that can be purchased may make obtaining paracetamol more difficult for people with arthritis. <h3>Objectives</h3> To determine paracetamol overdose rates for patients presenting to Ninewells Hospital, Dundee and to assess whether the action by the MCA has had any measurable effect. <h3>Methods</h3> Using serum paracetamol levels as a robust marker for overdose, the biochemistry database was searched for all paracetamol assay requests for each 12-month period from September 1995 to September 2000. We recorded all requests, all assays with measurable paracetamol and results that were potentially hepatotoxic 4 h after ingestion (&gt; 1.3 mmol/l). The numbers of presentations of paracetamol overdose were compared before and after September 1998. <h3>Results</h3> A total of 6336 tests were performed of which 4454 (70.1%) were negative for paracetamol. The Table 1 shows the number of tests by year and result. Using the Chi Squared test there were no significant differences before and after September 1998 (p = 0.7). <h3>Conclusion</h3> These results do not suggest that the incidence of paracetamol overdose has been affected by the over-the-counter pack size reduction at least in the Tayside region of Scotland. Further measures to reduce the burden of paracetamol overdose to the healthcare system must be considered along with effective ways of obtaining paracetamol for appropriate clinical use.
Ibrutinib and Obinutuzumab in CLL: MRD Responses Sustained for Several Years with Deepest MRD Depletion in Patients with &amp;gt;1 Year Prior Ibrutinib Exposure
Authors: Andy C. Rawstron, Peter Hillmen, Shanna Maycock, Nichola Webster, Kristian Brock, Rebecca H. Boucher, Francesca Yates, Rebecca Jarvis, Surita Dalal, Ruth M. de Tute, Paul Moss, Donald Macdonald, Piers Patten, Christopher Fegan, Andrew Pettitt, Christopher P. Fox, Adrian Bloor, Oonagh Sheehy, Peter Hillmen
Journal: Blood (2020)
Carfilzomib-associated renal toxicity is common and unpredictable: a comprehensive analysis of 114 multiple myeloma patients
Authors: Despina Fotiou, Maria Roussou, Charikleia Gakiopoulou, Erasmia Psimenou, Maria Gavriatopoulou, Magdalini Migkou, Nikolaos Kanellias, Ioanna Dialoupi, Evangelos Eleutherakis-Papaiakovou, Stavroula Giannouli, Christina Delavinia, Kostantinos Efstathiou, Sofoklis Kontogiannis, Evangelos Terpos, Meletios A. Dimopoulos, Efstathios Kastritis
Journal: Blood Cancer Journal (2020)

Abstract Carfilzomib (CFZ) is a non-reversible proteasome inhibitor approved for the treatment of patients with relapsed and refractory myeloma (RRMM). Its use has been associated with cardiovascular toxicity but although recently a signal of clinically significant renal complications has also been identified, it is less extensively investigated. We analyzed data of 114 consecutive patients with RRMM who received CFZ-based regimens. Renal complications not related to MM progression were observed in 19 (17%) patients; thrombotic microangiopathy (TMA) was seen in 6 (5%) patients, albuminuria &gt;1 gr/day in 7 patients (6%) and at least grade 3 acute kidney injury (AKI) which could not be otherwise explained in 6 patients (5%). A total of 15 patients discontinued CFZ and dosing was reinitiated at a lower level in one patient with AKI. Albuminuria was associated with focal segmental glomerulosclerosis in the renal biopsy (performed in a total of 6 patients). Renal complications during CFZ therapy are common, occur mostly early and are unpredictable. A potential effect of CFZ on the renal endothelium could be implicated in the pathogenesis of these complications and may also share common pathophysiology with cardiovascular effects of CFZ.
First Results from the Dose Escalation Segment of the Phase I Clinical Study Evaluating Cyad-02, an Optimized Non Gene-Edited Engineered NKG2D CAR T-Cell Product, in Relapsed or Refractory Acute Myeloid Leukemia and Myelodysplastic Syndrome Patients
Authors: Dries Deeren, Johan A. Maertens, Tara Lin, Yves Beguin, Benjamin Demoulin, Martina Fontaine, Panagiota A. Sotiropoulou, Erik Alcantar-Orozco, Eytan Breman, Marie-Sophie Dheur, Nathalie Braun, Caroline Lonez, David E Gilham, Anne Flament, Frédéric F. Lehmann
Journal: Blood (2020)
AB1312-HPR A COMPARISON OF THE EFFECTIVENESS OF TWO DIFFERENT KINESIO TAPE APPLICATIONS ON PAIN, FATIGUE AND HEALTH STATUS IN WOMEN WITH FIBROMYALGIA
Authors: S. Toprak Celenay, B. Anaforoglu Kulunkoglu, O. Mete
Journal: Annals of the Rheumatic Diseases (2020)

Background: Fibromyalgia (FM) is a syndrome characterized mainly by chronic widespread pain, fatigue and a decrease in health status. Kinesio tape (KT), one of complementary approaches, has favorable effects on clinic findings in FM, but studies investigating which types of the KT applications are more effective in FM are scarce. Objectives: This study aimed to compare the effectiveness of fascial correction and FanCut KT applications on pain, fatigue and health status in women with FM. Methods: A total of 27 women with FM were included, allocated into fascial correction (Group 1) (n:14, age: 41.50 (30.25) years, body mass index (BMI): 24.85 (5.28) kg/m 2 ) and FanCut techniques (Group 2) (n:13, age: 45.00 (21.00) years, BMI: 25.60 (4.55) kg/m 2 ) groups. The fascial correction technique performed with approximately 25% to 50% of tension and oscillated in longitudinal direction on overall back was used in the Group 1; while, the FanCut technique performed with 0% tension on the overall back was used in the Group 2. Exercise program was carried out 2 days a week for 6 weeks under the supervision of a physiotherapist in both groups. Pain intensity and severity of fatigue with the Visual Analog Scale and health status with the Fibromyalgia Impact Questionnaire were evaluated at the baseline and after the 6-weeks treatment. Results: Physical characteristics of the groups were similar (p age =0.190, p bmi =0.808). After the treatment, it was found that pain intensity (p=0.001; p=0.001) and the severity of fatigue (p=0,001; p=0.003) decreased and health status (p=0.001; p=0.002) improved in both the group 1 and 2, respectively. Moreover, fatigue decreased (p=0.008) and health status improved (p=0.021) in the group 1 in comparison to the group 2; but pain intensity (p=0.085) did not differ between the groups. Conclusion: In this study, it was observed that both the fascial correction and the FanCut KT applications were effective in decreasing pain and fatigue, and improving the health status of women with FM. In addition, the study suggested that the fascial correction KT application was superior in decreasing fatigue and improving health status in comparison to the FanCut KT application in women with FM. In clinics, the KT application may be considered as a non-pharmacologic and complementary therapy to improve the symptoms of FM. Moreover, the fascial correction KT application may be more effective in improving some parameters due to fascia dysfunction in FM. References: [1]G.V. Espí-López, M. Inglés, A.C. Ferrando, P. Serra-Añó, Effect of Kinesio taping on clinical symptoms in people with fibromyalgia: A randomized clinical trial, J. Back Musculoskelet. 32 (4) (2019) 561-567 [2]K. Kase, J. Wallis, T. Kase, Clinical therapeutic applications of the Kinesio taping method, Kení-kai information, Tokyo, Japan, 2003. Disclosure of Interests: None declared
Change of Hepatitis B Virus DNA Status in Anti-HBc Positive Liver Graft
Authors: 권준혁 ( Choon Hyuck Kwon ), 서경석 ( Kyung Suk Suh ), 조재영 ( Jai Young Cho ), 이남준 ( Nam Joon Yi ), 장자준 ( Ja June Jang ), 이건욱 ( Kuhn Uk Lee )
Journal: Clinical and Molecular Hepatology (2006)
Abstract 505: Diabetes Mellitus-Induced Metabolic Remodeling is Alleviated by Transgenic Overexpression of Mir-133a in the Heart
Authors: Tyler Kambis, Paras K Mishra
Journal: Circulation Research (2020)

Diabetic mellitus (DM) cardiomyopathy is a DM-induced metabolic disorder where energy dependence on fatty acid (FA) metabolism causes FA influx overload. While we reported that miR-133a overexpression prevented deleterious lipid accumulation in the diabetic Akita heart, it is unclear whether miR-133a regulates diabetes-induced metabolic remodeling in the DM heart. Thus, we performed deep sequencing on the heart from DM Akita (Ak), cardiac-specific miR-133aTg (Tg), Ak/Tg mice, and sibling wild-type (WT) mice. Ingenuity pathway analysis showed that FAO was the highest activated pathway in the DM heart (p-value=4.59E-11). Therefore, we hypothesized that miR-133a overexpression in the DM heart improves cardiac metabolism by increasing FA clearance via enhancing FA oxidation (FAO). Notably, mitochondrial FA transport protein carnitine palmitoyltransferase I (CPT1) was upregulated (WT: 0.02±0.01, Ak: 0.06±0.02, Ak/Tg: 0.17±0.02, Tg: 0.06±0.01) while changes in the intracellular FA transport protein CD36 were not significant. Interestingly, the rate-limiting enzyme of ketogenesis, the FAO spillover pathway, 3-Hydroxy-3-Methylglutaryl-CoA Synthase 2 (HMGCS2) was downregulated (WT: 0.13±0.02, Ak: 0.74±0.13, Ak/Tg: 0.39±0.07, Tg: 0.05±0.01) in Ak/Tg mice. These results support that increased miR-133a in the diabetic heart contributes to improved FAO and FA metabolism in addition to downregulating FA deposition and ketogenesis in the diabetic heart.
Intravenous Iron Induced Cytopenias(Leukopenia,Neutropenia,Lymphocytopenia) Among Arab Population with Iron Deficiency Anemia
Authors: Hussam A Almasri, Ashraf Tawfiq Soliman, Vincenzo Desanctis, Rita Wafik Ahmad, Mustafa A Al-Tikrity, Mahmoud S Eisa, Mohammad N Kloub, Majd M Aldwairi, Shaima Ahmed, Mona M Babikir, Ruoa Alhashimy, Arwa E Alsaud, Mohamed A Yassin
Journal: Blood (2020)
Real World (RW) Outcomes and Prognostication of Older Patients with Primary Central Nervous System Lymphoma (PCNSL) in the Contemporary Era
Authors: Kevin A. David, Suchitra Sundaram, Seo-Hyun Kim, Ryan Vaca, Yong Lin, Samuel Singer, Mary-Kate Malecek, Jordan Carter, Adam Zayac, Myung Sun Kim, Nishitha Reddy, Alma Habib, Christopher Strouse, Jerome Graber, Veronika Bachanova, Mazie Tsang, Ajay Major, David A. Bond, Prashasti Agrawal, Angel Mier-Hicks, Pallawi Torka, Priya Rajakumar, Parameswaran Venugopal, Michael Glantz, Samuel Goldlust, Rahul Matnani, Pallavi Kumar, Thomas A Ollila, Johnny Cai, Stephen E. Spurgeon, Alex G Sieg, Joseph Cleveland, Narendranath Epperla, Reem Karmali, Seema Naik, Peter Martin, Sonali M. Smith, James L. Rubenstein, Brad S. Kahl, Andrew M. Evens
Journal: Blood (2020)
Abstract PD5-07: Mapping the tumor and microenvironmental evolution underlying DCIS progression throughmultiplexed ion beam imaging
Authors: Michael Angelo
Journal: Cancer Research (2021)

Abstract Ductal Carcinoma in Situ (DCIS) is a pre-invasive lesion that accounts for nearly 20% of new breast cancer diagnoses. Of these cases, about half will progress to invasive breast cancer (IBC) within ten years. However, because diagnostic criteria for delineating low risk lesions from those likely to progress to IBC have not been identified, many patients are receiving unnecessary chemotherapy and surgery that can result in therapy-related morbidity and death. With this in mind, we used Multiplexed Ion Beam Imaging by time of flight (MIBI-TOF) and RNA-seq laser-capture microdissection (SMART-3SEQ) to construct a comprehensive spatial atlas describing the structure, function, and cellular composition of DCIS. MIBI-TOF and SMART-3SEQ were used to compare lesions from patients that later developed IBC with those from age- and history matched DCIS controls without recurrence. Using a 37-marker staining panel to interrogate 137 lesions, we identified 17 distinct cell populations of epithelial, stromal, and immune cells that were arranged in recurrent cellular microenvironments specific for DCIS or invasive disease. We observe a coordinated shift in the immune and stromal compartments as invasive disease arises, including a robust influx of lymphocytes and expansion reactive stromal phenotypes in synchronous DCIS + IBC, which was distinct from the macrophage-dominant, highly vascularized microenvironment of recurrent IBC. Further, single cell segmentation using a deep learning model was combined with pixel-level coexpression analysis to extensively evaluate how the thickness, continuity, and phenotype of ductal myoepithelium changes as tumors progress from a pre-invasive state. These data were incorporated into a comprehensive model which was subsequently used to identify a subset of features that correlate with disease-free survival following DCIS tumor resection. Taken together, these features represent important prognostic metrics that can be used to separate pre-invasive from indolent DCIS tumors, and allow for tailored therapy that improves patient outcomes and quality of life in this disease. Citation Format: Michael Angelo. Mapping the tumor and microenvironmental evolution underlying DCIS progression throughmultiplexed ion beam imaging [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD5-07.
Unbiased Metabolomic Screening Reveals Pre-Existing Plasma Signatures in Large B-Cell Lymphoma Patients Treated with Anti-CD19 Chimeric Antigen Receptor (CAR) T-Cells: Association with Cytokine Release Syndrome (CRS) and Neurotoxicity (ICANS)
Authors: Akansha Jalota, Courtney E. Hershberger, Manishkumar S. Patel, Agrima Mian, Daniel M. Rotroff, Brian T. Hill, Neetu Gupta
Journal: Blood (2020)
Effects of Delayed Treatment on Patients with Acute Myeloid Leukemia; Treatment Delay Matters in Younger Patients
Authors: Daehun Kwag, Byung Sik Cho, Gi June Min, Sung-Soo Park, Silvia Park, Jae-Ho Yoon, Sung-Eun Lee, Ki-Seong Eom, Yoo-Jin Kim, Seok Lee, Chang-Ki Min, Seok-Goo Cho, Dong-Wook Kim, Jong Wook Lee, Hee-Je Kim
Journal: Blood (2020)
Identification of a Metabolic, Transcriptomic, and Molecular Signature of Patatin‐Like Phospholipase Domain Containing 3–Mediated Acceleration of Steatohepatitis
Authors: Bubu A. Banini, Divya P. Kumar, Sophie Cazanave, Mulugeta Seneshaw, Faridoddin Mirshahi, Prasanna K. Santhekadur, Liangsu Wang, Hong Ping Guan, Abdul M. Oseini, Cristina Alonso, Pierre Bedossa, Srinivas V. Koduru, Hae‐Ki Min, Arun J. Sanyal
Journal: Hepatology (2020)

Background and Aims The mechanisms by which the I148M mutant variant of the patatin‐like phospholipase domain‐containing 3 (PNPLA3 I148M ) drives development of nonalcoholic steatohepatitis (NASH) are not known. The aim of this study was to obtain insights on mechanisms underlying PNPLA3 I148M ‐induced acceleration of NASH. Approach and Results Hepatocyte‐specific overexpression of empty vector (luciferase), human wild‐type PNPLA3, or PNPLA3 I148M was achieved using adeno‐associated virus 8 in a diet‐induced mouse model of nonalcoholic fatty liver disease followed by chow diet or high‐fat Western diet with ad libitum administration of sugar in drinking water (WDSW) for 8 weeks. Under WDSW, PNPLA3 I148M overexpression accelerated steatohepatitis with increased steatosis, inflammation ballooning, and fibrosis ( P &lt; 0.001 versus other groups for all). Silencing PNPLA3 I148M after its initial overexpression abrogated these findings. PNPLA3 I148M caused 22:6n3 docosahexanoic acid depletion and increased ceramides under WDSW in addition to increasing triglycerides and diglycerides, especially enriched with unsaturated fatty acids. It also increased oxidative stress and endoplasmic reticulum stress. Increased total ceramides was associated with signature of transducer and activator of transcription 3 (STAT3) activation with downstream activation of multiple immune‐inflammatory pathways at a transcriptomic level by network analyses. Silencing PNPLA3 I148M reversed STAT3 activation. Conditioned media from HepG2 cells overexpressing PNPLA3 I148M increased procollagen mRNA expression in LX2 cells; this was abrogated by hepatocyte STAT3 inhibition. Conclusions Under WDSW, PNPLA3 I148M overexpression promotes steatosis and NASH by metabolic reprogramming characterized by increased triglycerides and diglycerides, n3 polyunsaturated fatty acid depletion, and increased ceramides with resultant STAT3 phosphorylation and downstream inflammatory pathway activation driving increased stellate cell fibrogenic activity.
OP0235 ACHIEVING A LOW DAS IN THE FIRST 4-MONTHS AFTER DIAGNOSIS IS IMPORTANT FOR THE LONG-TERM CHANCE OF ACHIEVING DMARD-FREE REMISSION
Authors: M. Verstappen, E. Niemantsverdriet, A. Van der Helm - van Mil
Journal: Annals of the Rheumatic Diseases (2020)

Background: Sustained DMARD-free remission (SDFR) is increasingly achievable in RA. The pathogenesis underlying SDFR-development is unknown and patient-characteristics at diagnosis poorly explain whether SDFR will be achieved. This limits substantiated decisions to discontinue DMARD-treatment in clinical practice. Objectives: To increase the understanding of SDFR, we studied the course of disease activity scores (DAS) over time in relation to SDFR-development. Subsequently, we explored whether DAS-time course could be helpful to identify patients likely to achieve SDFR. Methods: 761 RA-patients consecutively included in the Leiden Early Arthritis Clinic, treated with initial methotrexate and treat-to-target treatment, were studied (median follow-up 7 years). The course of DAS was compared between patients achieving SDFR within 7 years and those who did not, using linear mixed models, stratified for ACPA. Subsequently, the relation between DAS at 4 months and the probability of achieving SDFR within 7 years was studied with logistic regression. Kaplan-Meier curves were constructed to illustrate cumulative incidence of SDFR for different DAS categories at 4 months, respectively &lt;1.6, 1.6-2.4, 2.4-3.6, &gt;3.6. Results: Patients achieving SDFR were characterized by a remarkedly different DAS response within 4 months after diagnosis. Compared to patients who did not achieve SDFR, the SDFR-group showed a prominently stronger decline in DAS between baseline and 4 months; 1.59 units decline (95%CI,1.24-1.95) versus 0.96 units (95%CI, 0.85-1.07) decline (p&lt;0.001) (figure 1). Stratification for ACPA yielded a similar and statistically significant effect in ACPA-negative RA. In ACPA-positive RA this effect was absent. Subsequently, the probability of achieving SDFR during 7 years was studied in ACPA-negative RA and it was observed to be lower for patients with higher DAS at 4 months. After 7 years of disease, the cumulative incidence for SDFR in ACPA-negative patients with DAS&lt;1.6 at 4 months was high (71.0%), whilst SDFR was rare among those with DAS&gt;3.6 at 4 months (7.1%) (figure 2). Conclusion: In RA-patients treated according to current guidelines, SDFR is predominantly achieved in patients with a strong decline in DAS during the first four months after diagnosis. Especially in ACPA-negative RA, the DAS at 4-months can be useful for later decisions to stop DMARDs. Disclosure of Interests: None declared