tbuckley/cabot-search huggingface dataset:
Abstract 3391: Dissecting intratumoral cell-cell interactions in myeloid reprogramming by single cell RNA-seq
Authors: Qianqian Song, Gregory A. Hawkins, Leonard Wudel, Ping-Chieh Chou, Elizabeth Forbes, Ashok K. Pullikuth, Liang Liu, Guangxu Jin, Lou Craddock, Umit Topaloglu, Gregory Kucera, Stacey O’Neill, Edward A. Levine, Peiqing Sun, Kounosuke Watabe, Yong Lu, Martha A. Alexander-Miller, Boris Pasche, Lance D. Miller, Wei Zhang
Journal: Cancer Research (2019)

Abstract Tumor-infiltrating myeloid cells are the most abundant leukocyte population within tumors. Molecular cues from the tumor microenvironment promote the differentiation of immature myeloid cells toward an immunosuppressive phenotype. However, the in situ dynamics of the transcriptional reprogramming underlying this process are poorly understood. Therefore, we applied single cell RNA-seq (scRNAseq) to computationally investigate the cellular composition and transcriptional dynamics of tumor and adjacent normal tissues from 4 early-stage non-small cell lung cancer (NSCLC) patients. Our scRNA-seq analyses identified 11,485 cells that varied in identity and gene expression traits between normal and tumor tissues. Among these, myeloid cell populations exhibited the most diverse changes between tumor and normal tissues, consistent with tumor-mediated reprogramming. Through trajectory analysis, we identified a differentiation path from CD14+ monocytes to M2 macrophages (monocyte-to-M2). This differentiation path was reproducible across patients, accompanied by increased expression of genes (e.g. MRC1/CD206, MSR1/CD204, PPARG, TREM2) with significantly enriched functions (Oxidative phosphorylation and P53 pathway) and decreased expression of genes (e.g. CXCL2, IL1B) with significantly enriched functions (TNFa signaling via NF-kB and inflammatory response). Our analysis further identified a co-regulatory network implicating upstream transcription factors (JUN, NFKBIA) in monocyte-to-M2 differentiation, and activated ligand-receptor interactions (e.g. SFTPA1-TLR2, ICAM1-ITGAM) suggesting intratumoral mechanisms whereby epithelial cells stimulate monocyte-to-M2 differentiation. Overall, our analysis identified the prevalent monocyte-to-M2 differentiation in NSCLC, accompanied by an intricate transcriptional reprogramming mediated by specific transcriptional activators and intercellular crosstalk involving ligand-receptor interactions. Citation Format: Qianqian Song, Gregory A. Hawkins, Leonard Wudel, Ping-Chieh Chou, Elizabeth Forbes, Ashok K. Pullikuth, Liang Liu, Guangxu Jin, Lou Craddock, Umit Topaloglu, Gregory Kucera, Stacey O’Neill, Edward A. Levine, Peiqing Sun, Kounosuke Watabe, Yong Lu, Martha A. Alexander-Miller, Boris Pasche, Lance D. Miller, Wei Zhang. Dissecting intratumoral cell-cell interactions in myeloid reprogramming by single cell RNA-seq [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3391.
Clinical characteristics and prognosis of primary breast lymphoma: Cleveland Clinic experience.
Authors: Tariq Zuheir Kewan, Fahrettin Covut, Bicky Thapa, Timothy Peter Spiro, Abdo S. Haddad, Hamed Daw
Journal: Journal of Clinical Oncology (2019)

e19035 Background: Primary Breast lymphoma (PBL) is a rare form of extranodal non-Hodgkin lymphoma (NHL). The majority of PBL are diffuse large B-cell lymphoma (DLBL). Current treatments can achieve an overall survival of 5 years in 80% of the patients. We evaluated prognostic factors and survival rates in PBL patients at Cleveland clinic foundation (CCF). Methods: We retrospectively identified patients diagnosed with PBL at CCF between January 2004 and January 2018. Baseline characteristics were compared between the indolent and aggressive lymphoma groups using two sample T-test for continuous variables, chi-square test and fisher’s exact test for categorical variables. Overall survival (OS) was estimated by the Kaplan-Meier method and compared by the log-rank test. Results: A total of 36 patients with PBL were identified, of whom 35 patients (97.2%) were females with a median age of 66 years (34-95). Of all patients, 23 (63.9%) were indolent lymphoma and 13 (36.1%) were aggressive lymphoma. The most common subtypes were marginal zone lymphoma (33.3%), DLBL (25%) and follicular lymphoma (19.4%). Only 2 patients (5.6%) had implant-associated anaplastic large T-cell lymphoma. There was significant difference in presentation between indolent and aggressive lymphoma patients; 78.3% of indolent lymphoma patients presented with incidental mammogram lesions compared to 30.8% of aggressive lymphoma patients (P-value = .019).Seventy five percent of the patients presented with stage IE, 16.7 % presented with stage IIE and 8.3% presented with stage IV. Treatment received included chemotherapy (55.6%), radiotherapy (47.2%), surgeries (16.7%), and rituximab (80% of patients received chemotherapy). Six patients (16.7%) didn’t receive treatment. Only one patient received central nervous system prophylaxis. Median follow-up of patients was 37.1 months. Three-year OS for patients with indolent and aggressive PBL was 94.4% (95% CI 84.4% - 100%) and 90.9% (95% CI 75.4% - 100%), respectively (p = 0.69). Conclusions: Marginal zone lymphoma was the most common subtype in our cohort. Indolent lymphoma commonly present as incidental mammogram finding. Prognosis of PBL is not affected by histologic subtype, tumor stage and bilateral breast involvement. Current treatments achieve good control of the disease.
Poly Combs the Immune System: PRC2 Loss in Malignant Peripheral Nerve Sheath Tumors Can Dampen Immune Responses
Authors: Siva Kumar Natarajan, Sriram Venneti
Journal: Cancer Research (2019)

Abstract Epigenetic modifications including altered DNA methylation and histone posttranslational modifications (PTM) are central to the biology of several cancers. These modifications can regulate DNA accessibility and consequently, gene expression. In this issue, Wojcik and colleagues explore epigenetic drivers of malignant peripheral nerve sheath tumors (MPNST) harboring loss-of-function polycomb-repressive complex 2 mutations. They demonstrate alterations in specific histone PTMs and a global increase in DNA methylation. Notably, epigenetic alterations related with aberrant upregulation of proteins involved in immune evasion, which informed identification of potential therapeutic vulnerabilities. This study helps understand the complex biology of MPNSTs and may enable future therapeutic development. See related article by Wojcik et al., p. 3205
Evidence-Based Medicine and the American Thoracic Society Guidelines
Authors: Laura C. Myers, David W. Bates
Journal: JAMA Internal Medicine (2019)

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Abstract 16955: Effects of Evolocumab (AMG 145) as a Monotherapy or in Combination with Statins on Lipoprotein Particles and Subclasses
Authors: Ren Xu, Matt Peach, Michael Tracy, Lisa Hamilton, Stephen Djedjos, Ricardo Dent, Dan Fitzpatrick, Rob Scott, Scott M Wasserman
Journal: Circulation (2014)

Background: Evolocumab (AMG 145) reduces LDL-C alone or in combination with statins. We evaluated the effect of evolocumab on lipoprotein particles from subjects receiving evolocumab as monotherapy or combined with statins using biomarker samples collected from 2 clinical studies. Methods: Exploratory biomarker samples, taken before and after evolocumab treatment from a phase 1b study evaluating evolocumab combined with statins in hypercholesterolemic (HCL) subjects and from a phase 2 study evaluating evolocumab as a monotherapy in HCL subjects, were analyzed by NMR at LipoScience, Inc. Lipoprotein particle concentrations and size were determined using the LP-3 module. Results: Evolocumab alone or in combination with statins significantly reduced total, small, and large LDL-P in a dose-dependent manner. As shown in the table, evolocumab monotherapy reduced total LDL-P by 45% and 54%, small LDL-P by 36% and 35%, and large LDL-P by 68% and 84%, after 140 mg and 420 mg doses, respectively. LDL-P values were reduced slightly less than LDL-C (52% at 140 mg and 62% at 420 mg), but LDL-P reductions were similar to those seen for ApoB. IDL-P, total VLDL-P, and small VLDL-P were also reduced. Total HDL-P increased, primarily due to increases in large HDL-P. Similar results were obtained when evolocumab was given combined with statins, but with greater reductions in total, small, and large LDL-P. Notably, greater reductions in LDL-P or LDL-C were correlated with higher concentrations of total LDL-P, small LDL-P, triglycerides, smaller LDL size, and lower HDL-C at baseline. Conclusion: Evolocumab either alone or in combination with statins affected lipoprotein particles similarly. In both treatment regimens, LDL-C and total LDL-P were significantly reduced and large LDL-P were reduced, on average, to a greater extent than small LDL-P. Total LDL-P was reduced to a lesser extent than LDL-C. Additionally, reductions in VLDL-P and IDL-P were observed along with increases in HDL-P.
Abstract 338: Inhibition of phosphatidylinositol 3-kinase signaling antagonizes paclitaxel-mediated resistance in cervical cancer
Authors: Youn Jin Choi, Yoo Yeon Jung, Jing Jing Liu
Journal: Cancer Research (2019)

Abstract Paclitaxel is used as an effective treatment against advanced cervical cancer. However, acquired resistance limits its success and results in cancer progression. We investigated whether the inhibition of phosphatidylinositol 3-kinase (PI3K) signaling overcomes paclitaxel resistance in cervical cancer. Two human cervical cancer cell lines (Me180 and HeLa) were used. We established paclitaxel-resistant cell lines (PTX-R Me180/PTX-R HeLa) and confirmed inhibitory concentrations (IC)50 and cell death rates by tetrazolium dye (MTT) and apoptosis assays, respectively, after exposure to a combination of paclitaxel with PI3K inhibitors (LY294002 and BYL-719). Migration and invasive abilities were explored by wound healing and transwell assays, respectively. Western blots were performed to determine the mechanism underlying the antitumor effects of PI3K inhibitors.PTX-R Me180 and PTX-R HeLa cells were gradually established from parental cell lines by stepwise exposure to paclitaxel over 7 months and with stable resistance at under 20 nM. We found that the activation of the PI3K pathway in paclitaxel-resistant lines increased tumor growth and invasiveness, and impeded cell apoptosis. The combination of LY294002 or BYL-719 with paclitaxel significantly enhanced drug sensitivity and synergistic apoptosis through the activation of Bax, caspase-3, and cleaved poly ADP ribose polymerase compared with paclitaxel alone. In addition, PI3K inhibition also suppressed tumor migration and invasive ability by targeting vimentin, matrix metalloproteinase-9 and vascular endothelial cell growth factor.We suggest that a combination of a PI3K inhibitor with paclitaxel may enhance antitumor activity through a cascade of PI3K signaling events. Note: This abstract was not presented at the meeting. Citation Format: Youn Jin Choi, Yoo Yeon Jung, Jing Jing Liu. Inhibition of phosphatidylinositol 3-kinase signaling antagonizes paclitaxel-mediated resistance in cervical cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 338.
Abstract 4777: Anti-tumor effect of adenovirus encoding APE1/Ref-1 in breast cancer xenografts: anti-inflammation and apoptotic cell death
Authors: Sunga Choi, Yu Ran Lee, Yeon Hyang Kim, Ki Mo Kim, Myoung Soo Park, Byeong Hwa Jeon
Journal: Cancer Research (2019)

Abstract In persistent inflammatory state involving the chronic activation of the immune system, the interplay between breast cancer and stromal cells is closely associated. We have previously shown that APE1/Ref-1 which could inhibit inflammatory signaling by reductive conformational change of cytokines receptors. In response to hyperacetylation, stimulation by secreted Ac-APE1/Ref-1 binding to RAGE initiated apoptotic cell death in TNBC models, in vitro and in vivo. In the present study, we used Ad-APE1/Ref-1 adenovirus, which can be overexpressed and be secreted into the blood of xenografts. We investigated how the Ad-APE1/Ref-1 influences growth retardation and apoptotic cell death of inflammation associated TNBC in vivo. The Ad-APE1/Ref-1-injection in MDA-MB 231 orthotopic xenografts caused a decrease in the volume and weight of tumors as shown in IVIS images. The treatment of Ad-APE1/Ref-1 also induced an inhibition of tumor growth and development, leading to apoptotic cell death, accompanied by generation of reactive oxygen species. Tumor tissues derived from Ad-APE1/Ref-1 exhibited apoptotic bodies compared with tumors of control or Adβ-galactosidase-injected mice. Moreover, level of inflammatory cytokines was evaluated in plasma of the xenografts; ratio of anti- to pro inflammatory cytokines was comparable with one of normal mice. The PAK1-STAT-3-NFkB axis in inflammatory signaling of tumor tissues derived from AdAPE1/Ref-1 injected mice was significantly inhibited compared to those of control or Adβ-galactosidase-injected mice. These results suggest that regulation of inflammatory signaling with adenoviral mediated APE1/Ref-1 in tumors of MDA-MB-231 xenografts modulates cytokine secretion, thereby inhibiting cancer cell growth. Note: This abstract was not presented at the meeting. Citation Format: Sunga Choi, Yu Ran Lee, Yeon Hyang Kim, Ki Mo Kim, Myoung Soo Park, Byeong Hwa Jeon. Anti-tumor effect of adenovirus encoding APE1/Ref-1 in breast cancer xenografts: anti-inflammation and apoptotic cell death [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4777.
Abstract 19826: Utility of Stroke Volume Index for Stratification of Patients With Low Gradient Severe Aortic Stenosis and Normal Left Ventricular Ejection Fraction
Authors: Hong Shen, Brandon Stacey, Bob Applegate, David Zhao, Sujethra Vasu, Bharathi Upadhya, Sanjay Gandhi, Rong Liu, Meng Wei, Min Pu
Journal: Circulation (2015)

Background: Decision of intervention for low gradient severe aortic stenosis (AS) with normal left ventricular ejection fraction (LVEF) is clinically challenging. The study was to determine the impact of stroke volume index (SVi) on prognosis in patients (pts) with AS. Methods: We examined 410 pts with moderate or severe AS and normal EF (≥50%). Pts were divided into four groups based on aortic valve area (AVA), mean pressure gradient (MPG) and SVi: Group I: low flow low gradient severe AS (AVA≤1.0cm 2 , MPG&lt;40mmHg and SVi&lt;35mL/m 2 , n=75); Group II: normal flow low gradient severe AS (AVA≤1.0cm 2 , MPG&lt;40mmHg and SVi≥35mL/m 2 , n=97); Group III: severe AS with matched gradient-AVA (AVA≤1.0cm 2 and MPG≥40mmHg, n=88); Group IV: moderate AS (AVA&gt;1.0cm 2 and MPG&gt;20mmHg, &lt;40 mmHg, n=150). Aortic valve gradients, AVA and SVi were assessed by echocardiography. Clinical charts were reviewed. Mean follow-up duration was 3.2±1.6 years. Results: Group I had higher prevalence of atrial fibrillation, more pronounced LV hypertrophy, lower SVi, smaller AVA, higher valvuloarterial impedance (Zva) (Table) and lower 3-year cumulative survival compared to Group II and Group IV (61% vs. 75% and 80%, p=0.004). Group II had a 3-year cumulative survival similar to moderate AS (75% vs. 80%, p&gt;0.05). In pts with medical management, Group I and Group III had lower 3-year cumulative survival in comparison with Group II and Group IV (48% and 56% vs. 73% and 76%, p=0.001). Multivariate analysis showed SVi was a strong predictor of mortality in low gradient severe AS (HR 0.95, CI: 0.91-0.99, P=0.02). However, in gradient-AVA matched severe AS and moderate AS, SVi was not associated with mortality (p&gt;0.05). Conclusions: Without AS intervention, low flow low gradient severe AS with normal EF carries poor prognosis similar to high gradient AS, but normal flow low gradient AS does not, suggesting that SVi may be used to identify the pts benefiting most from AS intervention in pts with low gradient AS.
Bacterial and Fungal Infections in Persons Who Inject Drugs — Western New York, 2017
Authors: Kathleen P. Hartnett, Kelly A. Jackson, Christina Felsen, Robert McDonald, Ana Cecilia Bardossy, Runa H. Gokhale, Ian Kracalik, Todd Lucas, Olivia McGovern, Chris A. Van Beneden, Michael Mendoza, Michele Bohm, John T. Brooks, Alice K. Asher, Shelley S. Magill, Anthony Fiore, Debra Blog, Elizabeth M. Dufort, Isaac See, Ghinwa Dumyati
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

During 2014-2017, CDC Emerging Infections Program surveillance data reported that the occurrence of invasive methicillin-resistant Staphylococcus aureus (MRSA) infections associated with injection drug use doubled among persons aged 18-49 years residing in Monroe County in western New York.*Unpublished surveillance data also indicate that an increasing proportion of all Candida spp.bloodstream infections in Monroe County and invasive group A Streptococcus (GAS) infections in 15 New York counties are also occurring among persons who inject drugs.In addition, across six surveillance sites nationwide, the proportion of invasive MRSA infections that occurred in persons who inject drugs increased from 4.1% of invasive MRSA cases in 2011 to 9.2% in 2016 (1).To better understand the types and frequency of these infections and identify prevention opportunities, CDC and public health partners conducted a rapid assessment of bacterial and fungal infections among persons who inject drugs in western New York.The goals were to assess which bacterial and fungal pathogens most often cause infections in persons who inject drugs, what proportion of persons who inject use opioids, and of these, how many were offered medication-assisted treatment for opioid use disorder.Medication-assisted treatment, which includes use of medications such as buprenorphine, methadone, and naltrexone, reduces cravings and has been reported to lower the risk for overdose death and all-cause mortality in persons who use opioids (2,3).In this assessment, nearly all persons with infections who injected drugs used opioids (97%), but half of inpatients (22 of 44) and 12 of 13 patients seen only in the emergency department (ED) were not offered medication-assisted treatment.The most commonly identified pathogen was S. aureus (80%), which is frequently found on skin.Health care visits for bacterial and fungal infections associated with injection opioid use are an opportunity to treat the underlying opioid use disorder with medication-assisted treatment.Routine care for patients who continue to inject should include advice on hand hygiene and not injecting into skin that has not been cleaned or to use any equipment contaminated by reuse, saliva, soil, or water (4,5).
Surgeon Awareness of the Relative Costs of Common Surgical Instruments
Authors: Beiqun Zhao, Christopher P. Childers, Ron D. Hays, Susan L. Ettner, Rodrigo F. Alban, Melinda Maggard-Gibbons, Bryan M. Clary
Journal: JAMA Surgery (2019)

Surgeon Awareness of the Relative Costs of Common Surgical InstrumentsThe operating room is a cost-dense environment, and disposable surgical instruments account for a large proportion of its costs. 1 Because surgeons often have a choice of instruments to use, they play a critical role in managing supply costs.Previous research on surgeon cost knowledge has shown that surgeons are unskilled at estimating the price of surgical supplies. 2However, it is unclear whether surgeons can correctly differentiate the more expensive item of 2 surgical instruments, a task that more accurately reflects real-world decisions.Furthermore, cost report cards (CRCs) have been proposed as a passive mechanism for educating surgeons about surgical supplies to reduce spending. 3However, the association between CRCs and cost knowledge is unknown.
Abstract 15738: The Awareness, Treatment, and Control of LDL-Cholesterol is Lower Among US Adults with Undiagnosed versus Diagnosed Diabetes
Authors: Todd Brown, Rikki Tanner, Huifeng Yun, Robert Rosenson, Michael Farkouh, April Carson, J. Michael Woolley, Stephen Glasser, Monika Safford, Paul Muntner
Journal: Circulation (2012)

Diabetes is a coronary heart disease (CHD) risk equivalent in the ATP III guidelines. Many individuals with diabetes are undiagnosed, resulting in a missed opportunity for the primary prevention of...
Abstract 175: Average Current is a Better Predictor of Shock Success in a Low Tilt Biphasic Waveform
Authors: Yongqin Li, Bihua Chen, Giuseppe Ristagno, Weilun Quan
Journal: Circulation (2013)

Background: Defibrillation current has been shown to be a better defibrillation dosing unit than energy. However, defibrillation current continuously decays in a biphasic truncated exponential (BTE...
Review into spousal expenses at BMA is already under way
Authors: Abi Rimmer
Journal: BMJ (2019)

The BMA appointed a non-executive member of its risk and audit committee in April to lead a review of historical expense claims and policies, the association has disclosed.

The news that Jacques Cadranel has reported his findings to the BMA’s board was revealed at the BMA’s annual representative meeting in Belfast on Thursday 27 June.

At the ARM representatives voted in favour of a motion calling for the association to commission a “fully independent enquiry” into the practice of BMA chief officers claiming travel expenses for their spouses.

Speaking to the motion, the BMA’s treasurer, Trevor Pickersgill, said that the association had responded to the concerns by appointing Cadranel in April to review the issue. “He has looked in great detail at this, and he and the board have seen over 100 pages of historical documents detailing claims and receipts etc,” Pickersgill said. “They have taken independent tax advice.”

Pickersgill said that Cadranel’s report was with the BMA board and would be going to the BMA Council, the body responsible for the lawful conduct of the association. “It is not yet finalised but it will, I am sure, …