tbuckley/cabot-search huggingface dataset:
Pulse Oximeters: 3D Printing Silicone Elastomer for Patient‐Specific Wearable Pulse Oximeter (Adv. Healthcare Mater. 15/2020)
Authors: Sara Abdollahi, Eric J. Markvicka, Carmel Majidi, Adam W. Feinberg
Journal: Advanced Healthcare Materials (2020)

In article number 1901735 by Adam W. Feinberg and co-workers, a wearable pulse oximeter with pressure sensing is developed using freeform reversible embedding 3D printing of silicone elastomer. The 3D prints are based on anatomical scans of the finger or toe, resulting in patient-specific, soft cuffs that are integrated with flexible electronics to calculate heart rate, blood oxygen content, and activity state.
Heart Failure With Reduced Ejection Fraction
Authors: Sean P. Murphy, Nasrien E. Ibrahim, James L. Januzzi
Journal: JAMA (2020)

<h3>Importance</h3> Worldwide, the burden of heart failure has increased to an estimated 23 million people, and approximately 50% of cases are HF with reduced ejection fraction (HFrEF). <h3>Observations</h3> Heart failure is a clinical syndrome characterized by dyspnea or exertional limitation due to impairment of ventricular filling or ejection of blood or both. HFrEF occurs when the left ventricular ejection fraction (LVEF) is 40% or less and is accompanied by progressive left ventricular dilatation and adverse cardiac remodeling. Assessment for heart failure begins with obtaining a medical history and physical examination. Also central to diagnosis are elevated natriuretic peptides above age- and context-specific thresholds and identification of left ventricular systolic dysfunction with LVEF of 40% or less as measured by echocardiography. Treatment strategies include the use of diuretics to relieve symptoms and application of an expanding armamentarium of disease-modifying drug and device therapies. Unless there are specific contraindications, patients with HFrEF should be treated with a β-blocker and one of an angiotensin receptor–neprilysin inhibitor, angiotensin-converting enzyme inhibitor, or angiotensin receptor blocker as foundational therapy, with addition of a mineralocorticoid receptor antagonist in patients with persistent symptoms. Ivabradine and hydralazine/isosorbide dinitrate also have a role in the care of certain patients with HFrEF. More recently, sodium-glucose cotransporter 2 (SGLT2) inhibitors have further improved disease outcomes, significantly reducing cardiovascular and all-cause mortality irrespective of diabetes status, and vericiguat, a soluble guanylate cyclase stimulator, reduces heart failure hospitalization in high-risk patients with HFrEF. Device therapies may be beneficial in specific subpopulations, such as cardiac resynchronization therapy in patients with interventricular dyssynchrony, transcatheter mitral valve repair in patients with severe secondary mitral regurgitation, and implantable cardiac defibrillators in patients with more severe left ventricular dysfunction particularly of ischemic etiology. <h3>Conclusions and Relevance</h3> HFrEF is a major public health concern with substantial morbidity and mortality. The management of HFrEF has seen significant scientific breakthrough in recent decades, and the ability to alter the natural history of the disease has never been better. Recent developments include SGLT2 inhibitors, vericiguat, and transcatheter mitral valve repair, all of which incrementally improve prognosis beyond foundational neurohormonal therapies. Disease morbidity and mortality remain high, with a 5-year survival rate of 25% after hospitalization for HFrEF.
Association of Blood Pressure With Cause-Specific Mortality in Mexican Adults
Authors: Roberto Tapia-Conyer, Jesus Alegre-Díaz, Louisa Gnatiuc, Rachel Wade, Raúl Ramirez-Reyes, William G. Herrington, Sarah Lewington, Robert Clarke, Rory Collins, Richard Peto, Pablo Kuri-Morales, Jonathan Emberson
Journal: JAMA Network Open (2020)

Elevated blood pressure is a major cause of premature death, but there is little direct evidence demonstrating this association in studies of Hispanic populations.To assess the association between blood pressure and cause-specific mortality in a large cohort of Mexican adults with a high prevalence of uncontrolled diabetes.A total of 159 755 adults aged 35 years or older from 2 districts in Mexico City were recruited to this cohort study between April 1998 and September 2004 and followed up until January 2018. The present analyses focused on 133 613 participants who were aged 35 to 74 years and had no history of chronic disease besides diabetes.Blood pressure.Cox regression, adjusted for confounders, yielded mortality rate ratios (RRs) for deaths of participants occurring between ages 35 and 74 years.Of the 133 613 participants (43 263 [32.4%] men; mean [SD] age, 50 [11] years), 16 911 (12.7%) had self-reported previously diagnosed diabetes (including 8435 [6.3%] with uncontrolled diabetes, defined as hemoglobin A1c ≥9%) and 6548 (4.9%) had undiagnosed diabetes. Systolic blood pressure (SBP) was associated with vascular mortality between ages 35 to 74 years, with each 20 mm Hg lower usual SBP associated with 35% lower vascular mortality (RR, 0.65; 95% CI, 0.61-0.68), including 48% lower stroke mortality (RR, 0.52; 95% CI, 0.47-0.59) and 32% lower ischemic heart disease mortality (RR, 0.68; 95% CI, 0.63-0.74). These RRs were broadly similar in those with and without diabetes. Compared with those without diabetes and SBP less than 135 mm Hg at recruitment, the vascular mortality RR was 2.8 (95% CI, 2.4-3.3) for those without diabetes and SBP of 155 mm Hg or greater, 4.7 (95% CI, 4.1-5.4) for those with uncontrolled diabetes and SBP less than 135 mm Hg, and 8.9 (95% CI, 7.2-11.1) for those with uncontrolled diabetes and SBP of 155 mm Hg or greater. Lower SBP was also associated with decreased kidney-related mortality (RR per 20 mm Hg lower usual SBP, 0.69; 95% CI, 0.64-0.74), decreased mortality from infection (RR, 0.81; 95% CI, 0.71-0.91), and decreased mortality from hepatobiliary disease (RR, 0.87; 95% CI, 0.78-0.98), but not decreased neoplastic or respiratory mortality. SBP was more informative for vascular mortality than other blood pressure measures (eg, compared with SBP, diastolic blood pressure was only two-thirds as informative).Blood pressure was most strongly associated with vascular and kidney-related mortality in this Mexican population, with particularly high absolute excess mortality rates among individuals with diabetes. The findings reinforce the need for more widespread use of blood pressure-lowering medication in Mexico, particularly among those with diabetes.
Comparison of protocols for the isolation and amplification of biomarker RNA from small numbers of formalin-fixed human breast cancer cells following thin layer preparation and laser capture microdissection.
Authors: Teresa Phillips, Brian Petroff, Carol Fabian
Journal: Cancer Research (2007)

1668  Breast cancer prevention trials rely on the measurement of biomarkers of risk and response in small specimens of breast tissue collected by random periareolar fine needle aspiration or biopsy. The combination of laser capture microdissection, linear RNA amplification, and polymerase chain reaction (PCR) theoretically overcomes the limitations of small specimen size and allows the examination of a panel of breast biomarkers genes from specific cellular populations, even following fixation. In order to optimize RNA quality and yield from microdissected breast epithelial cells, three commercially available RNA isolation systems (low and mid volume spin column and low volume salt fractionation protocols) and three linear RNA amplification kits based upon the Eberwine protocol (low, mid and high RNA capacity systems) were compared in a factorial experimental design using fixed and microdissected MCF7, SK-BR-3 and T-47D breast cancer cells (n=3 aliquots of 1000-5000 cells per reagent combination). RNA/cDNA quality was assessed using the relative amplifiablility of the 3’ vs 5’ region of the β-actin mRNA . cDNA yield and the relative expression of three breast biomarker genes (estrogen receptor-α, ER; pS2 and survivin) were measured by real time PCR. The column-based RNA extraction kits isolated more RNA than the commercially available salt fractionation/precipitation protocol with comparable RNA quality. Because of the low RNA yields from the microprecipitation protocol, this method was excluded from further analysis. The intermediate volume RNA amplification protocol yielded 3-5 times more amplified RNA than the alternative linear amplification methods tested. Although total quantities varied with the amplification kit used, the relative expression of pS2 and survivin (normalized to TATA box binding protein housekeeping gene) were similar with all isolation and amplification combinations. ER mRNA expression (relative to β-actin) was approximately 4 times greater with the low capacity RNA amplification protocol than with the other amplification protocols. The combination of a column-based RNA isolation method with an intermediate volume RNA amplification protocol provided optimal RNA yield and quality with fixed breast cancer cells following thin layer preparation and laser capture microdissection in this study.
Abstract PR04: Locoregionally administered B7H3-targeting CAR T cells mediate potent antitumor effects in atypical teratoid/rhabdoid tumor
Authors: Johanna Theruvath, Elena Sotillo, Claus Moritz Graef, Sabine Heitzeneder, Louai Labanieh, Robbie Majzner, Crystal Mackall
Journal: Cancer Research (2020)

Abstract Atypical teratoid/rhabdoid tumors (ATRT) are highly malignant embryonal brain tumors, arising in very young children, and are associated with inactivation of SMARCB1. The prognosis is extremely poor. Hence new treatments are urgently needed. We show that 100% of ATRT express B7-H3 and residual SMARCA4 SWI/SNF activity drives B7-H3 expression. Further, we demonstrate that prenatal brain expresses high levels of B7-H3, but expression is absent on pediatric brain, suggesting that the cell of origin may conserve high B7-H3 expression. We recently created a 4-1BB second-generation CAR targeting B7-H3. To date, there are little data on the most efficacious route of administration of CAR T cells in malignant brain tumors. The goal of this study was to test the antitumor activity of the B7-H3 CAR in highly aggressive ATRT xenograft models and compare intracavitary (IT), intraventricular (ICV), and intravenous (IV) administration in terms of efficacy, toxicity, and persistence of CAR T cells. Locoregionally (IT and ICV) administered B7H3.BB.z-CAR T cells mediate potent antitumor effects against cerebral ATRT xenografts, with more rapid kinetics, greater potency, and diminished systemic levels of inflammatory cytokines compared to CAR T cells administered intravenously. ICV-administered CAR T cells also demonstrate robust trafficking from the CNS into the periphery, and following clearance of ATRT xenografts, ICV or IV administered B7H3.BB.z-CAR T cells mediate antigen specific protection from tumor rechallenge in the CNS or in the flank. In summary, B7H3 is a promising immune target for this largely incurable pediatric tumor. We demonstrate that CNS delivered CAR T cells cure ATRT xenografts and efficiently traffic from the CNS into the periphery and can mediate long-term immune protection from disease recurrence in the CNS or in peripheral tissues. This abstract is also being presented as Poster A12. Citation Format: Johanna Theruvath, Elena Sotillo, Claus Moritz Graef, Sabine Heitzeneder, Louai Labanieh, Robbie Majzner, Crystal Mackall. Locoregionally administered B7H3-targeting CAR T cells mediate potent antitumor effects in atypical teratoid/rhabdoid tumor [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr PR04.
Prevalence and management of oropharyngeal candidiasis in cancer patients: Results of a prospective French multicentric survey
Authors: D. Azria, J. Gligorov
Journal: Journal of Clinical Oncology (2009)

e20590 Background: Oropharyngeal candidiasis (OPC) is usually considered as a frequent and manageable complication of cancer treatments. International guidelines recommend the use of broad spectrum local antifungal agents as first line treatment using old published data. In 2008, we elaborated a prospective pharmaco- epidemiological survey (Candidoscope) to update the prevalence and the management of OPC in France. Methods: Candidoscope concerned patients suffering from solid tumors or non-Hodgkin's lymphoma (NHL) and still under treatments. Thirty-five French centres participated in this survey. Patients were screened during a consecutive period of 15 days and were included in a registry to estimate OPC prevalence. Exclusion criteria was the use of antifungal agents within the last 15 days before the beginning of the the present study. OPC was defined clinically. Patients diagnosed for OPC were selected to the second part of the study detailing OPC treatments. Results: Overall, 2,027 patients were registered. OPC prevalence was 9.6% (n=195). Breast cancer population was the most frequent disease presenting untreated OPC (n= 47, 24%). The prevalence of OPC in head and neck, digestive cancer, and NHL patients was 30%, 20%, and 20%, respectively. Patients with combined treatments presented the highest OPC prevalence (nearly 22%). The most common clinical presentation for OPC was the erythematous form (62%). Main OPC symptoms were dry mouth (63%), altered taste (60%), pain (43%), dysphagia (42%), and appetite disorders (31%) with an average weight loss of 4kg. Local antifungal agents (amphotericin B, nystatin, and miconazole muco-adhesive buccal tablet (MBT)) were given in 75% of patients (41%, 12%, and 22%, respectively). Compliance to treatment was respectively 19%, 40%, and 88% for nystatin, amphotericin B with mouthwashes, and MBT. Conclusions: The prevalence of OPC in treated cancer patients is frequent with important clinical consequences. Systemic treatment compliance delivered according to the international guidelines is often poor and are strongly improved by the use of daily MBT. No significant financial relationships to disclose.
Debio 1143 and high-dose cisplatin chemoradiotherapy in high-risk locoregionally advanced squamous cell carcinoma of the head and neck: a double-blind, multicentre, randomised, phase 2 study
Authors: Xu-Shan Sun, Yungan Tao, Christophe Le Tourneau, Yoann Pointreau, Christian Sire, Marie-Christine Kaminsky, Alexandre Coutte, Marc Alfonsi, Pierre Boisselier, Laurent Martin, Jessica Miroir, Jean-Francois Ramee, Jean-Pierre Delord, Florian Clatot, Frederic Rolland, Julie Villa, Nicolas Magne, Olgun Elicin, Elisabeta Gherga, France Nguyen, Cedrick Lafond, Guillaume Bera, Valentin Calugaru, Lionnel Geoffrois, Bruno Chauffert, Angela Zubel, Claudio Zanna, Silvano Brienza, Philippa Crompton, Elisabeth Rouits, Kathrin Gollmer, Sergio Szyldergemajn, Jean Bourhis
Journal: The Lancet Oncology (2020)
Abstract 16333: The Prognostic Significance of Highly Sensitive Cardiac Troponin I Elevation in Patients Presenting With Hypertensive Crisis
Authors: Muhammad Talha Ayub, Christian Torres, Juan Del Cid, Mohammad S Khan, Wajeeha Rasool, Talha Aijaz, Aakash Putta, Sunny Singh, Rami Doukky
Journal: Circulation (2019)

Background: The prognostic significance of troponin elevation in the setting of hypertensive crisis is unclear. We sought to investigate the long-term prognostic significance of detectable levels o...
Osteonecrosis after Allogeneic HSCT in Children with High-Risk or Relapsed ALL Treated in the ALL-SCT 2003 Trial
Authors: Michaela Kuhlen, Michael H. Albert, Peter Bader, Karoline Ehlert, Tayfun Guengoer, Thomas Klingebiel, Peter J. Lang, Martin Schrappe, Johanna Schrum, Ansgar S. Schulz, Arend von Stackelberg, Brigitte Strahm, Karl-Walter Sykora, Irene Teichert-von Luettichau, Arndt Borkhardt, Roland Meisel, Ulrike Poetschger, Evgenia Glogova, Christina Peters
Journal: Blood (2017)
Prevalence, Characteristics, and Costs of Urgent Care Center Membership Programs
Authors: Walter Hsiang, Grace Jin, Howard Forman, Daniel Wiznia
Journal: JAMA (2020)

Prevalence, Characteristics, and Costs of Urgent Care Center Membership ProgramsDemand for urgent care centers (UCCs) has increased significantly over the last decade as patients seek timely and affordable health care. 1 Some UCCs have begun membership programs that offer access to discounted visits for recurrent fees.We examined the prevalence, characteristics, and costs of UCCs offering membership programs in the United States.
Influence of MHC Class I Chain-Related Gene Α (MICA) Polymorphisms on Cytomegalovirus Infection after Allogeneic Hematopoietic Cell Transplantation
Authors: Sagar S. Patel, Lisa Rybicki, Melissa A. Yurch, Dawn Thomas, Robert M. Dean, Hien D. Liu, Deepa Jagadeesh, Aaron T. Gerds, Brian T. Hill, Rabi Hanna, Betty K. Hamilton, Brad Pohlman, Matt Kalaycio, Brian J. Bolwell, Aiwen Zhang, Navneet S. Majhail, Medhat Askar, Ronald Sobecks
Journal: Blood (2017)
Inequities in the Mortality Rates of Older Americans—Race, Sex, Place, and Time
Authors: Zinzi Bailey, Natalia Linos, Mary T. Bassett
Journal: JAMA Network Open (2020)

Nasim B. Ferdows, PhD; María P. Aranda, PhD; Julie A. Baldwin, PhD; Soroosh Baghban Ferdows, MA; Jasjit S. Ahluwalia, MD, MPH; Amit Kumar, MPH, PhD
Abstract A32: Selective inhibition of AuroraA by LY3295668 erbumine in neuroblastoma models induces apoptosis through a combination of S-phase DNA damage and mitotic arrest
Authors: Michele Dowless, Jill Kremer, Caitlin Lowery, Xueqian Gong, Joseph Klahn, Jennifer Stephens, Yu-Hua Hui, Wayne Blosser, Ricardo Martinez, Jian Du, Louis Stancato
Journal: Cancer Research (2020)

Abstract Aurora kinase A (AuroraA) is a serine/threonine protein kinase critical for centrosome maturation, mitotic spindle formation, and spindle checkpoint activation. Aberrant expression of AuroraA promotes tumor initiation and disease progression, making it a promising therapeutic target in several cancer types. However, recent clinical trials of purported selective AuroraA inhibitors failed due to lack of efficacy and/or hematologic toxicity, likely due to concurrent inhibition of Aurora kinase B (AuroraB). Selective AuroraA inhibition leads to mitotic arrest and apoptosis, while AuroraB inhibition causes persistent DNA endoreduplication and polyploidy leading to genomic instability. LY3295668 erbumine (LY3295668) is a selective AuroraA inhibitor with preclinical activity in multiple models of cancer including neuroblastoma (NBL). High-risk NBL, a devastating pediatric cancer with few effective treatment options, is mainly stratified by MYCN amplification status. In NBL, AuroraA stabilizes N-MYC post-transcriptionally; moreover, AuroraA also controls N-MYC-dependent transcription during S-phase. Here, we evaluated LY3295668 in multiple NBL cell lines and in vivo mouse models where treatment resulted in apoptosis and tumor regressions, respectively. We compared LY3295668 to alisertib (a dual AuroraA/B inhibitor) in multiple cell-based assays that differentiate AuroraA activity from that of AuroraB and showed that LY3295668 has a distinct pharmacologic profile from alisertib. In addition, we determined the mechanism of action for LY3295668 includes DNA damage prior to mitotic block. Our results further support that AuroraA controls MYC-dependent transcription in S-phase and selective inhibition of AuroraA with LY3295668 promotes transcription-replication conflicts leading to DNA damage. In addition to AuroraA-mediated mitotic arrest, this DNA damage may contribute to the hypersensitivity of MYC-driven tumors such as NBL. In summary, LY3295668 is a selective AuroraA inhibitor with a dual mechanism of action in NBL involving DNA damage in S-phase and a cell cycle block in mitosis. These combined activities contribute to sensitivity of preclinical NBL models. Citation Format: Michele Dowless, Jill Kremer, Caitlin Lowery, Xueqian Gong, Joseph Klahn, Jennifer Stephens, Yu-Hua Hui, Wayne Blosser, Ricardo Martinez, Jian Du, Louis Stancato. Selective inhibition of AuroraA by LY3295668 erbumine in neuroblastoma models induces apoptosis through a combination of S-phase DNA damage and mitotic arrest [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr A32.
To immunosuppress: whom, when and how? That is the question with COVID-19
Authors: Kevin L Winthrop, Xavier Mariette
Journal: Annals of the Rheumatic Diseases (2020)

In ARD , Ramiro et al report a number of sophisticated primary and sensitivity analyses from an observational cohort study conducted in the Netherlands during the height of the COVID-19 ‘first wave’ in Europe.1 After a difficult March 2019 of high hospitalisation and death rates with COVID-19, on 1 April their institution started a standard protocol of treating patients with COVID-19 with high-dose methylprednisolone for 5–7 days during which time individuals not showing clinical improvement were also given the interleukin 6 (IL-6) receptor-blocking agent tocilizumab. The authors of the present study observed outcomes with this strategy and retrospectively compared these outcomes with similarly ill patients with COVID-19 treated with standard of care within the month prior. This comparison group included no patients treated with either methylprednisolone or tocilizumab. Patients eligible for the study included those with hypoxia, evidence of COVID-19 pneumonia and an elevation of at least two of the following: high C-reactive protein (>100 mg/L), high serum ferritin (>900 µg/L at one occasion, or a twofold increase of the level at admission within 48 hours) and high D-dimer level (>1500 µg/L). It should be noted that only one patient enrolled into this interventional study was on mechanical ventilation at the time of enrolment. While the two cohorts appeared similar in levels of illness, slight differences in anticoagulation use between the two groups were observed and the authors could not control for other potential unmeasured confounders related to the two different time periods (eg, changing practices in ventilation). The authors explicitly and elegantly discuss the potential for such unmeasured confounding, acknowledge the limitations of observational studies and conducted a number of sensitivity analyses to mitigate these concerns. All of their analyses suggest the same direction and magnitude of effect, namely that patients in the steroid with/without tocilizumab group fared …
Functional Signatures Revealed By Deep Phenotyping of CMV-Specific CD8+ T Cells Predict Risk of Early CMV Reactivation after Allogeneic Hematopoietic Cell Transplantation
Authors: Jose F Camargo, Eric Wieder, Erik Kimble, Cara Benjamin, Despina Kolonias, Gabriela Bravo, Krishna Komanduri
Journal: Blood (2017)