tbuckley/cabot-search huggingface dataset:
Hematologic characteristics and c-reactive protein of patients with sars-cov 2 admitted to a university hospital in brazil
Authors: M. Dias, M. Morgado, R. Portugal
Journal: HemaSphere (2021)

Background: COVID-19 is a new infectious disease. The risk of death depends on previous comorbidities, but prothrombin time and low platelets count are also related to death. Aims: In this study, risk factors for death on hospital admission were evaluated. Methods: We included patients admitted to the Emergency Department of University Hospital Clementino Fraga Filho (HUCFF), Federal University of Rio de Janeiro (UFRJ), Brazil, from March to May/2020 with laboratory- confirmed Covid-19 infection. A confirmed case was defined by a positive result on a reverse-transcriptase-polymerase-chain-reaction assay of a specimen collected on a nasopharyngeal swab secretion. Admission results were collected through retrospective review of medical records. Death was the primary outcome. Data were expressed as median (range), or n/N (%);P values were calculated by Mann-Whitney or Fisher's exact test, as appropriate. A two-sided α of less than 0.05 was considered statistically significant. Results: We analysed 116 patients. The median age was 61 years (range 22-94), and most were male (55%). Ninety-nine (85%) had one or more chronic underlying diseases, mostly hypertension (69%). Ninety-six (83%) patients had pulmonary CT scan compatible with viral pneumonia on admission, 87% necessitated supplementary oxygen therapy, 38% needed mechanical ventilation, of which 71% died. Thirty-one (27%) patients died. Non-survivors were older (66 X 59 years;p=0.077), had a higher proportion of cardiopathy (45% X 13%;p=0.001), renal failure (36% X 9%;p=0.002) and diabetes (52% x 31%;p=0.050), and on hospital arrival, higher neutrophils counts (6.9 x 103/mm3 X 5.4x103/ mm3;p=0,037), higher neutrophils / lymphocytes ratio (7.4 X 5.1;p=0.012), higher CRP (174.4 X 102.7;p=0.004) and higher LDH (478 X 376;p=0.009). Level of hemoglobin, white blood cells, RDW, platelet count, PT and APTT were similar in survivors and non-survivors. Most patients (97%) received any low molecular weight heparin (LMWH). All patients who died received LMWH. Summary/Conclusion: That patients admitted with COVID-19 with respiratory symptoms who needed mechanical ventilation had a high mortality rate (71%). On admission, cardiopathy, renal failure and CRP level were independently predictive of death. Basic coagulation profile and blood counts (CBC) on admission were similar between alive and dead cases. Almost universal use of low molecular weight heparin precluded any further discussion on this subject.
P04.04 Optimizing dasatinib for glioblastoma treatment
Authors: O Alhalabi, M Göttmann, M Gold, M Fletcher, T Hielscher, M Iskar, T Kessler, E Wittmann, S Schlue, S Rahman, L Hai, L Hansen-Palmus, L Puccio, I Nakano, C Herold-Mende, U Baumgartner, B Day, W Wick, F Sahm, E Fraenkel, E Phillips, V Goidts
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Glioblastoma is the most common primary malignancy of the central nervous system with a dismal prognosis, even with surgical and chemoradiotherapy. Expression profiling studies classify IDH-wildtype Glioblastoma into three subtypes: Proneural (PN), mesenchymal (MES) and classical (CL). A promising target to inhibit in Glioblastoma is the non-receptor tyrosine kinase and proto-oncogene SRC. After robust pre-clinical results, SRC inhibitors like dasatinib did not improve survival of Glioblastoma patients after recurrence in clinical trials. MATERIAL AND METHODS Consolidating efforts to personalize cancer therapy, we use in silico analyses backed by in vitro and in vivo experiments on Glioblastoma stem-like cells (GSCs) derived from primary patient tumors to present a novel stratification strategy for dasatinib therapy in glioblastoma. To further tackle dasatinib resistance in GSCs, a pooled shRNA library against 5000 genes was combined with dasatinib to identify genes whose knockdown sensitizes GSCs to dasatinib. This was integrated with proteomics and phosphoproteomics data of dasatinib inhibited GSCs. RESULTS We found MES tumors with high expression of SERPINH1 to be sensitive to dasatinib inhibition, compared to the CL and PN subtypes. Interestingly, SRC phosphorylation status did not predict the efficacy of dasatinib inhibition. Computational analyses integrating data from the loss-of-function dropout viability screen and proteomics/phosphoproteomics using a novel modification of the SamNet algorithm identified Wee1, a tyrosine kinase involved in cell-cycle signaling, as a potential combination inhibition target with dasatinib. Further validation experiments showed a robust synergistic effect through combination of dasatinib and the wee1 inhibitor, MK-1775 in PN GSCs. CONCLUSION This study highlights strategies to optimize dasatinib treatment in different glioblastoma subtypes. While the stratification of patients harboring mesenchymal glioblastoma with SERPINH1 overexpression could provide an option in this particular subtype, combining dasatinib or other SRC inhibitors with Wee1 inhibitors could present an additional possibility for treating resistant proneural tumors
Ovarian Cancer, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology
Authors: Deborah K. Armstrong, Ronald D. Alvarez, Jamie N. Bakkum-Gamez, Lisa Barroilhet, Kian Behbakht, Andrew Berchuck, Lee-may Chen, Mihaela Cristea, Maria DeRosa, Eric L. Eisenhauer, David M. Gershenson, Heidi J. Gray, Rachel Grisham, Ardeshir Hakam, Angela Jain, Amer Karam, Gottfried E. Konecny, Charles A. Leath, Joyce Liu, Haider Mahdi, Lainie Martin, Daniela Matei, Michael McHale, Karen McLean, David S. Miller, David M. O’Malley, Sanja Percac-Lima, Elena Ratner, Steven W. Remmenga, Roberto Vargas, Theresa L. Werner, Emese Zsiros, Jennifer L. Burns, Anita M. Engh
Journal: Journal of the National Comprehensive Cancer Network (2021)

Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States and is the country’s fifth most common cause of cancer mortality in women. A major challenge in treating ovarian cancer is that most patients have advanced disease at initial diagnosis. These NCCN Guidelines discuss cancers originating in the ovary, fallopian tube, or peritoneum, as these are all managed in a similar manner. Most of the recommendations are based on data from patients with the most common subtypes─high-grade serous and grade 2/3 endometrioid. The NCCN Guidelines also include recommendations specifically for patients with less common ovarian cancers, which in the guidelines include the following: carcinosarcoma, clear cell carcinoma, mucinous carcinoma, low-grade serous, grade 1 endometrioid, borderline epithelial, malignant sex cord-stromal, and malignant germ cell tumors. This manuscript focuses on certain aspects of primary treatment, including primary surgery, adjuvant therapy, and maintenance therapy options (including PARP inhibitors) after completion of first-line chemotherapy.
Physician-pharmacy integration and oral cancer drug use and quality.
Authors: Pragya Kakani
Journal: Journal of Clinical Oncology (2021)

39 Background: Public reports suggest increasing integration of in-house specialty pharmacies by independent and system-based oncology practices. Understanding the impact of such integration has important implications for state-level regulations limiting physicians’ ability to launch pharmacies in certain states and policies governing pharmacy network design. In this analysis, I document the growth of in-house pharmacies and estimate the impact of this growth on oral cancer drug use and quality. Methods: I used 2006-2017 data from Medicare Fee-for-Service and Part D claims, pharmacy names and characteristics from health plan pharmacy network lists and the National Plan and Provider Enumeration System, and a unique Health System and Practice Dataset, developed by National Bureau of Economic Research and Harvard University researchers, that tracks practice ownership relationships. I first linked physician organizations and pharmacies that they operate using a novel claims-based algorithm combining information on pharmacy characteristics, similarities in names of practices and pharmacies, and the share of total pharmacy spending attributable to a single practice or system. I then used an event study approach to compare oral oncolytic use and quality at practices launching a pharmacy between 2009 to 2014 compared with matched controls. Outcomes included total spending on oral oncolytics, use of oral drugs when an intravenous equivalent exists (capecitabine and 5-fluoruracil), timeliness of new prescription fills (# days from first fill to last office visit), medication adherence, and early discontinuation of lenalidomide, tyrosine kinase inhibitors, aromatase inhibitors, tamoxifen, enzalutamide, and abiraterone. Results: The number of independent or system-based oncology practices with an in-house pharmacy filling any oncology prescriptions increased from 135 in 2006 to 442 in 2017. In that time, the share of Medicare Part D spending on oral oncolytics filled at in-house pharmacies increased from 4% in 2006 to 27% in 2017. The launch of an in-house pharmacy was not associated with an overall increase in spending on oral oncolytics, but was associated with a 4.5 percentage point (p =.01) increase in the use of capecitabine relative to 5-fluorouracil, within 2 years of launch. In-house pharmacies were associated with a modest decrease in the time to fill an initial prescription (2.4 days, p &lt;.001) within 2 years of launch, but no improvements in adherence or reductions in early discontinuation. Conclusions: There has been substantial growth in the use of in-house pharmacies in oncology in recent years. Having an in-house pharmacy only had modest effects on cost and quality. Policymakers should therefore approach claims that in-house pharmacies meaningfully impact cost and quality with caution.
Subcutaneous immunoglobulins use in immunodeficiency secondary to chronic lymphocytic leukaemia: Monocentric experience in covid-19 era
Authors: I. Innocenti, F. Autore, A. Tomasso, G. Benintende, A. Fresa, F. Vuono, E. Galli, F. Sora, L. Laurenti
Journal: HemaSphere (2021)

Background: Secondary antibody deficiency (SAD) is a typical manifestation of haematological malignancies such as chronic lymphocytic leukaemia (CLL), or a side effect of their treatment. Immunological defects are observed in 25-85% of CLL patients (pts) and increases the risk of infections, with overall higher morbidity and mortality. Antibiotics administration and vaccinations are recommended as risk-reduction strategies in those pts. No real guidelines are available to recommend eligibility for prophylaxis, but many indications warrant immunoglobulins replacement therapy (IgRT) in selected pts with low IgG ( 600 mg/dl from 6 months onward. About cellular immunity, T-cells including CD4 and CD8 and NK cells displayed a stable fashion until 6 months. On the other hand, the CD19 B cells values reflect both the disease status and the ongoing treatment effects. Results were in Table 1. Finally we observed advantages on both QoL and costs, since pts did not need to go to the hospital with the help of a care-giver, rather they could comfortably get their SCIg at home without any assistance. Summary/Conclusion: SCIg administration in CLL pts is safe and efficacious as infectious prophylaxis, with higher median IgG levels, thanks to its pharmacokinetic advantages and improved adherence to treatment. Especially in the Covid-19 era, the subcutaneous route is preferred to the intravenous one, because of the self-administration at home and the granted availability to the drug itself.
mRNA vaccination of naive and COVID-19-recovered individuals elicits potent memory B cells that recognize SARS-CoV-2 variants
Authors: Aurélien Sokal, Giovanna Barba-Spaeth, Ignacio Fernández, Matteo Broketa, Imane Azzaoui, Andréa de La Selle, Alexis Vandenberghe, Slim Fourati, Anais Roeser, Annalisa Meola, Magali Bouvier-Alias, Etienne Crickx, Laetitia Languille, Marc Michel, Bertrand Godeau, Sébastien Gallien, Giovanna Melica, Yann Nguyen, Virginie Zarrouk, Florence Canoui-Poitrine, France Pirenne, Jérôme Mégret, Jean-Michel Pawlotsky, Simon Fillatreau, Pierre Bruhns, Felix A. Rey, Jean-Claude Weill, Claude-Agnès Reynaud, Pascal Chappert, Matthieu Mahévas
Journal: Immunity (2021)
Increasing severity of early‐onset atopic dermatitis, but not late‐onset, associates with development of aeroallergen sensitization and allergic rhinitis in childhood
Authors: Ann‐Marie Malby Schoos, Bo Lund Chawes, Klaus Bønnelykke, Jakob Stokholm, Morten Arendt Rasmussen, Hans Bisgaard
Journal: Allergy (2021)

Abstract Background Early exposure to allergens through a defect skin barrier has been proposed as a mechanism for inducing sensitization and development of allergic diseases. We hypothesized that early‐onset, severe atopic dermatitis (AD) is associated with development of aeroallergen sensitization and allergic rhinitis. Methods We included 368 children from the Copenhagen Prospective Studies on Asthma in Childhood 2000 (COPSAC 2000 ) at‐risk mother‐child cohort. AD was diagnosed prospectively based on Hanifin&amp;Rajka's criteria and severity assessed using the Scoring Atopic Dermatitis (SCORAD) index. Early‐onset AD was defined as debut ≤1 year, late‐onset as debut from 1–6 years. Aeroallergen sensitization and allergic rhinitis were diagnosed at ages 6–7 and 12 years. Associations between early‐onset and late‐onset AD and allergy endpoints were calculated using general estimating equations (GEE) models to compute the overall odds ratios (OR) for both time points. Results Early‐onset AD (yes/no) and severity (SCORAD) were associated with development of aeroallergen sensitization during childhood; GEE OR = 1.68 [1.08; 2.62], p = .02 and 1.08 [1.03; 1.12], p &lt; .001, whereas late‐onset AD showed a borderline significant association and late‐onset severity showed no association; GEE OR = 1.65 [0.92; 2.94], p = .08 and 1.01 [0.97; 1.06], p = .55. The same trend was seen for allergic rhinitis with significant association between early‐onset AD and allergic rhinitis; GEE OR = 1.56 [1.01; 2.41], p = .04 and severity; GEE OR = 1.09 [1.05; 1.13], p &lt; .001, whereas late‐onset AD showed no association. The effects on sensitization and rhinitis of early‐onset versus late‐onset AD severity were significantly different: p ‐interaction sensitization = .03 and p ‐interaction rhinitis &lt; .01. Conclusion Increasing severity of early‐onset AD, but not late‐onset AD, associates with aeroallergen sensitization and allergic rhinitis later in childhood.
Gene-by-environment modulation of lifespan and weight gain in the murine BXD family
Authors: Suheeta Roy, Maroun Bou Sleiman, Pooja Jha, Jesse F. Ingels, Casey J. Chapman, Melinda S. McCarty, Jesse D. Ziebarth, Michael Hook, Anna Sun, Wenyuan Zhao, Jinsong Huang, Sarah M. Neuner, Lynda A. Wilmott, Thomas M. Shapaker, Arthur G. Centeno, David G. Ashbrook, Megan K. Mulligan, Catherine C. Kaczorowski, Liza Makowski, Yan Cui, Robert W. Read, Richard A. Miller, Khyobeni Mozhui, Evan G. Williams, Saunak Sen, Lu Lu, Johan Auwerx, Robert W. Williams
Journal: Nature Metabolism (2021)
Increasing Access to HIV Testing Through Direct-to-Consumer HIV Self-Test Distribution — United States, March 31, 2020–March 30, 2021
Authors: Jen Hecht, Travis Sanchez, Patrick S. Sullivan, Elizabeth A. DiNenno, Natalie Cramer, Kevin P. Delaney
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

During 2019, approximately 34,800 new HIV infections occurred in the United States (1), and it is estimated that approximately 80% of HIV transmission occurs from persons who either do not know they have HIV infection or are not receiving regular care (2).Since 2006, CDC has recommended that persons who are disproportionately affected by HIV (including men who have sex with men [MSM]) should test for HIV at least annually (3,4).However, data from multiple sources indicate that these recommendations are not being fully implemented (5,6).TakeMeHome, a novel public-private partnership to deliver HIV self-testing kits to persons seeking HIV testing in the United States, was launched during March 2020 as home care options for testing became increasingly important during the COVID-19 pandemic.The initiation of the program coincided with the national COVID-19 Public Health Emergency declaration, issuance of stay-at-home orders, and other restrictions that led to disruption of traditional HIV testing services.During March 31, 2020-March 30, 2021, 17 state and local health departments participating in the program allowed residents of their jurisdictions to order test kits.Marketing for TakeMeHome focused on reaching gay, bisexual, and MSM through messages and embedded links in gay dating applications.Most participants in the program reported that they had either never tested for HIV (36%) or that they had last tested >1 year before receiving their self-test kit (56%).After receiving the self-test kit, >10% of respondents reported accessing additional prevention services.Health departments can increase options for HIV testing by distributing publicly funded self-test kits to persons without proximate access to clinic-based testing or who prefer to test at home.Increased and regular HIV testing among MSM will help meet annual testing goals.Self-testing is an effective HIV screening method for MSM (7) that can facilitate access to antiretroviral treatment, preexposure prophylaxis (PrEP), and other prevention services (8).The COVID-19 pandemic disrupted HIV testing services, persons reported not being able to access HIV testing services (9), and hundreds of thousands of HIV screening tests were either delayed or skipped (10).CDC sent a "Dear Colleague" letter on April 28, 2020* recommending that grantees consider HIV self-testing as an option to fill the gap in prevention services.
Combined immunodeficiency with autoimmunity caused by a homozygous missense mutation in inhibitor of nuclear factor 𝛋B kinase alpha (IKKα)
Authors: Wayne Bainter, Vassilios Lougaris, Jacqueline G. Wallace, Yousef Badran, Rodrigo Hoyos-Bachiloglu, Zachary Peters, Hazel Wilkie, Mrinmoy Das, Erin Janssen, Abdallah Beano, Khaoula Ben Farhat, Christy Kam, Luisa Bercich, Paolo Incardona, Vincenzo Villanacci, Maria Pia Bondioni, Antonella Meini, Manuela Baronio, Phammela Abarzua, Silvia Parolini, Giovanna Tabellini, Stefano Maio, Birgitta Schmidt, Jeffrey D. Goldsmith, George Murphy, Georg Hollander, Alessandro Plebani, Janet Chou, Raif S. Geha
Journal: Science Immunology (2021)

A mutation in human IKKα compromises noncanonical NF-κB signaling resulting in primary immunodeficiency associated with autoimmunity.
SREBP1-induced fatty acid synthesis depletes macrophages antioxidant defences to promote their alternative activation
Authors: Guillaume Bidault, Samuel Virtue, Kasparas Petkevicius, Helen E. Jolin, Aurélien Dugourd, Anne-Claire Guénantin, Jennifer Leggat, Betania Mahler-Araujo, Brian Y. H. Lam, Marcella K. Ma, Martin Dale, Stefania Carobbio, Arthur Kaser, Padraic G. Fallon, Julio Saez-Rodriguez, Andrew N. J. McKenzie, Antonio Vidal-Puig
Journal: Nature Metabolism (2021)
Treatment delays in older women with nonmetastatic breast cancer treated at minority-serving hospitals.
Authors: Julia Song, Elizabeth A. Mittendorf, Tari A. King, Christina Ahn Minami
Journal: Journal of Clinical Oncology (2021)

122 Background: Almost 60% of breast cancer in the U.S. occur in women aged &gt;65, but these women are less likely to receive guideline-concordant care. Given existing treatment disparities by race/ethnicity, older minority women may be especially prone to potential gaps in breast cancer care. Hospitals serving higher proportions of minority patients are at risk to deliver suboptimal care, but how site of care impacts aging patients with breast cancer is not well defined. We sought to evaluate the association between race/ethnicity and breast cancer treatment delays in older women treated at minority-serving hospitals (MSH) vs non-MSHs. Methods: Women &gt;65 years old with non-metastatic breast cancer diagnosed from 2010-2017 were identified in the National Cancer Database using data from Commission on Cancer (CoC)-accredited hospitals. Treatment delay was defined as &gt;90 days from diagnosis to first treatment (surgery, chemotherapy, endocrine therapy). MSHs were defined as the top decile of hospitals serving predominantly Black or Hispanic patients. Multivariable logistic regression models adjusted for patient, disease, and hospital characteristics were used to determine the odds of treatment delay for women at MSHs vs non-MSHs across racial/ethnic groups. Results: 529,128 women (84.5% non-Hispanic White, 3.3% Hispanic White, 9.6% non-Hispanic Black, 0.1% Hispanic Black, 0.2% Native American, 2.5% Asian/Pacific Islander) were identified among 41 MSHs and 1,146 non-MSHs. Overall, time to treatment was &lt;90 days in &gt;95% of women (mean 33.4 days; standard deviation 26.4 days). Older women regardless of race at MSHs were more likely to suffer treatment delays than those at non-MSHs (odds ratio 1.31; 95% confidence interval 1.22-1.41). Compared to non-Hispanic White women, all minority groups had a higher likelihood of treatment delay regardless of MSH status (Table). Conclusions: Although most older women with non-metastatic breast cancer treated at CoC hospitals received care in a timely fashion, minorities and those treated at MSHs were more likely to experience treatment delays. Effective interventions addressing barriers to timely care at MSHs and among racial/ethnic minorities are needed. [Table: see text]