tbuckley/cabot-search huggingface dataset:
Using smartphone and deep learning technology to help diagnose skin cancer
Authors: Y.Q. Jiang, J.H. Xiong, H.Y. Li, X.H. Yang, W.T. Yu, M. Gao, X. Zhao, Y.P. Ma, W. Zhang, Y.F. Guan, H. Gu, J.F. Sun
Journal: British Journal of Dermatology (2020)

Using smartphone and deep learning technology to help diagnose skin cancer SummaryBasal cell carcinoma (BCC) is the most common skin cancer with a rapidly rising incidence.The diagnosis of BCC requires careful inspection of microscopic skin images, which is labour-intensive due to the large number of images to be analyzed.Computer-aided diagnosis of diseases has been developed to help the analysis of microscopic images in pathology (which is the study and diagnosis of disease by examining tissue that has been removed.)In particular, deep learning approaches, which are ways in which a machine can 'learn' to perform a task, are able to identify and capture patterns in images and have shown significantly improved performance on pathological image-related tasks.In this study, from China, the authors aimed to develop deep learning frameworks for automatic recognition of BCC based on smartphone-captured microscopic ocular images (MOI) instead of whole slide images (WSIs).MOIs are photographed from microscope eyepieces using smartphone cameras.A total of 8046 MOIs and 128 WSIs were collected and used to build models.Two deep learning frameworks for recognizing BCC pathologically were developed with high sensitivity and specificity (meaning accuracy).Compared with the model trained on WSI, recognizing BCC through smartphones could be considered as a future clinical choice.This is a summary of the study: Recognizing basal cell carcinoma on smartphone-captured digital histopathology images with a deep neural network
Resource utilization and cost efficacy analysis of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (DD-MVAC) versus gemcitabine-cisplatin (GC) as neoadjuvant chemotherapy (NAC) for muscle invasive bladder cancer (MIBC).
Authors: Kamaneh Montazeri, George Dranitsaris, Catherine Curran, Jonathan David Thomas, Matthew D. Ingham, Mark A. Preston, Graeme S. Steele, Kerry L. Kilbridge, Xiao X. Wei, Bradley Alexander McGregor, Matthew Mossanen, Guru Sonpavde
Journal: Journal of Clinical Oncology (2020)

e19390 Background: DD-MVAC and GC are commonly used NAC regimens for MIBC. While efficacy across studies appears similar, resource utilization (RU) burden and cost efficacy have not been compared. Methods: We assessed RU and cost effectiveness of NAC with GC vs DD-MVAC among MIBC patients (pts) treated at Dana-Farber. Data on chemotherapy administered, supportive medications, relevant procedures, hospitalizations, clinic, infusion, and emergency room (ER) visits were collected retrospectively. Unit costs for each RU component were sought from the Centers for Medicare and Medicaid Website as well as relevant published sources. Utilization was compared between MVAC and GC using multivariate quantile regression (QR) analysis. Results: 147 pts were included; 51 received DD-MVAC and 86 GC. Baseline characteristics were similar, except lower mean age (59 vs 67 years, p &lt; 0.001) and higher proportion of ECOG-PS = 0 (96.1% vs 60.5%, p &lt; 0.001) for DD-MVAC. The mean cumulative cisplatin dosage was similar (DD-MVAC = 284 mg/m 2 , GC = 257 mg/m 3 ). More DD-MVAC pts required G-CSF analogues (100% vs 32.6%, p &lt; 0.001), central line placement (28.6% vs 11.8%, p = 0.017), and ER visits (35% vs 18%, p = 0.048). Infusion visits (12 vs 8/pt) and cardiac imaging (0.98 vs 0.58/pt, p &lt; 0.001) were higher for DD-MVAC, whereas GC pts required more frequent clinic visits (mean of 9 vs 5/pt), chemotherapy cycle delays (30.2% vs 9.8%, p = 0.008) and hospitalization days (mean of 0.88 vs 0.49/pt). After adjusting for PS, the mean total cost/pt was higher for DD-MVAC ($17360 vs $12112, p &lt; 0.001). Age was not statistically significant in the QR model (p = 0.628). Conclusions: DD-MVAC and GC exhibit different RU characteristics as NAC for MIBC. Although excess RU did not clearly favor one regimen, adjustment for PS indicated significant decrease in healthcare costs by approximately 30% using GC compared to DD-MVAC. Given that similar overall delivery of cumulative cisplatin dosage was feasible with both regimens, the values and costs affixed to different resources may impact the selection of DD-MVAC vs GC. Limitations were retrospective design and costs being specific to the US.
Abstract 24: Hydrogen Sulfide Potentiates Bone Marrow-derived Angiogenic Progenitor Cell-mediated Ischemic Limb Angiogenesis in Diabetic Animals
Authors: Zhongjian Cheng, Venkata NS Garikipati, Emily Nickoloff, Chunlin Wang, David Polhemus, Jibin Zhou, Cynthia Benedict, Suresh K Verma, Mohsin Khan, Joseph E Rabinowitz, David Lefer, Raj Kishore
Journal: Circulation Research (2016)

Rationale: Critical hindlimb ischemia (CLI) represents an outcome of peripheral artery disease with a high incidence in diabetic patients. Recently, insufficient hydrogen sulfide (H 2 S) production has been implicated in cardiovascular disease. Objective: Explore the role of H 2 S in diabetes-induced bone marrow-derived angiogenic progenitor cells (BMAPC) dysfunction and its therapeutic effects on ischemic hindlimb injury of diabetes. Methods and Results: Diabetic BMAPCs from db/db mice showed decreased intracellular H 2 S production and blunted cystathionine γ-lyase (CSE) expression-an enzyme required for H 2 S generation. High glucose (HG) inhibited H 2 S production, migration and increased apoptosis of BMPAC that was rescued by H 2 S donor diallyl trisulfide (DATS) or overexpression of CSE. Administration DATS or local injection of diabetic BMAPCs overexpressing CSE significantly potentiated BMAPC-mediated blood flow recovery, capillary and arteriole formation, skeletal muscle architecture preservation, cell survival and decrease of perivascular infiltration of monocytes (CD68 + ) cells in ischemic skeletal muscle. Moreover, overexpression of CSE increased diabetic BMAPCs homing and engraftment in ischemic hindlimb. HG-impaired human cardiac microvascular endothelial cells (HCMVECs) tube formation and migration were rescued by DATS or overexpression of CSE. Mechanistically, HG increased threonine-495 phosphorylation of eNOS (eNOS-pT495) and inhibited nitric oxide (NO) production in HCMVECs which were rescued by DATS or overexpression of CSE. Silencing CSE by siRNA impaired tube formation and increased eNOS-pT495 expression in HCMVECs. Finally, HG-treated BMAPCs impaired mouse microvascular endothelial cell tube formation that was rescued by DATS. Conclusions: Our data suggests that CSE downregulation-induced H 2 S insufficient plays a critical role in diabetes-mediated BMAPC dysfunction. Administration of DATS or overexpression of CSE improves diabetic BMAPC-mediated angiogenesis/neovascularization via, at least partially, eNOS inactivation/NO reduction pathways. Our data indicate that H 2 S and overexpression of CSE in diabetic BMAPCs may open novel avenues for cell-based therapeutics of CLI in diabetic patients.
The failure of DAC to induce OCT2 expression and its remission by hemoglobin-based nanocarriers under hypoxia in renal cell carcinoma
Authors: Lu Chen, Zeyang Wang, Qingwen Xu, Yuxi Liu, Le Chen, Suhang Guo, Hua Wang, Kui Zeng, Junqing Liu, Su Zeng, Lushan Yu
Journal: Theranostics (2020)

Human organic cation transporter 2 (OCT2) is the most abundant and important uptake transporter involved in the renal excretion of cationic drugs. Abnormal hypermethylation- mediated silencing of OCT2 results in oxaliplatin resistance in renal cell carcinoma (RCC). The epigenetic activation of OCT2 by decitabine (DAC) reversed this resistance in normoxic conditions. Given the hypoxic characteristic of RCC, it is still unclear whether hypoxia promotes DAC resistance and is involved in the regulation of OCT2.
Predictive value of fibroblast growth factor receptor (FGFR) alterations on anti-PD-(L)1 treatment outcomes in patients (Pts) with advanced urothelial cancer (UC): Pooled analysis of real-world data.
Authors: William Y. Kim, Tracy L. Rose, Florian Roghmann, Markus Eckstein, Jonas Jarczyk, Friedemann Zengerling, Danijel Sikic, Johannes Breyer, Christian Bolenz, Arndt Hartmann, Gregory Mayhew, Yoichiro Shibata, Joshua M. Uronis, Aaron Galluzzi, Ramesh Sundaram, Qi Xia, Kathy Wu, Ademi E. Santiago-Walker, Philipp Erben, Ralph Wirtz
Journal: Journal of Clinical Oncology (2020)

493 Background: The tumor microenvironment in UC harboring FGFR gene alterations is characterized by decreased T-cell infiltration and low immune marker expression, potentially implicating suboptimal response to immune checkpoint inhibitors. The association between FGFR gene mutations/fusions and anti-PD-(L)1 treatment outcomes in advanced UC was assessed using real-world pt data. Methods: A pooled dataset of matched clinical and genomic data for advanced UC pts treated with anti-PD-(L)1 in any line from the Bladder Cancer Research Initiative for Drug Targets in Germany (BRIDGE) Consortium and UNC-CH was assessed. FGFR status was defined by a prespecified panel of FGFR2/3 mutations and fusions. Overall survival (OS) was analyzed using Kaplan-Meier estimates and Cox proportional hazards models. Multivariate analyses were performed using potential prognostic covariates (sex, age, baseline tumor stage, urothelial histology, smoking history, primary tumor location, and ECOG) in a Cox regression model for OS to assess their impact on the effect of FGFR alterations. Results: Median OS for FGFR+ pts (n=28) who received any line of anti-PD-(L)1 therapy was 9.5 mo vs 7.5 mo for FGFR− pts (n=139) (HR: 1.03, 95% CI: 0.60-1.76, p=0.93). Median OS for pts treated with first-line anti-PD-(L)1 was 5.42 mo in FGFR+ pts (n=10) and was not reached for FGFR− pts (n=31) (HR: 2.06, 95% CI: 0.68-6.24, p=0.19); median OS in second-line anti-PD-(L)1 was 6.5 mo (FGFR+; n=14) vs 5.7 mo (FGFR−; n=86) (HR: 0.89, 95% CI: 0.44-1.81, p=0.74). The multivariate analyses showed a significant trend of poorer OS in FGFR+ pts with first-line anti-PD-(L)1 (HR: 10.42, 95% CI: 1.45-74.97, p=0.02); wide CI may be attributed to small sample size for some categories in several covariates. Conclusions: Treatment with first-line anti-PD-(L)1 in FGFR+ pts may be associated with poorer OS outcomes in FGFR+ pts; however, this trend was not observed in FGFR+ pts treated with any line and second-line anti-PD-(L)1. Investigation of the predictive value of FGFR alterations to immunotherapy outcomes in larger real-world pt datasets is warranted.
Alteration of gut microbiota and microbial products in distinct allergic phenotypes: data from an Asian birth cohort study
Authors: Pannipa Kittipongpattana, Pantipa Chatchatee, Anchalee Senavonge, Wanwipa Vongsangnak, Preecha Patumcharoenpol, Wanlapa Weerapakorn, Sunee Nitisinprasert, Sittiruk Roytrakul, Massalin Nakphaichit, Narissara Suratannon
Journal: Journal of Allergy and Clinical Immunology (2020)
Where do we stand with immune checkpoint blockade for advanced cutaneous squamous cell carcinoma? A systematic review and critical appraisal of the existing evidence
Authors: T. Steeb, A. Wessely, F. Heppt, M. Harlaß, C. Berking, M.V. Heppt
Journal: British Journal of Dermatology (2020)

and 15Á5% reporting, respectively.However, our results show persistent under-representation of patients with skin of colour.Limitations of the study include incomplete race/ethnicity reporting, which may misrepresent certain groups.Race is also currently broadly categorized (white, black etc.).While individuals within the same racial groups share phenotypic and genetic characteristics, variations exist within racial subgroups (e.g.South Asian, East Asian).As globalization continues, evolving definitions of race and ethnicity are needed.Bhattacharya and Silverberg found potential differences in the efficacy of nonbiologic systemic AD treatments based on racial or ethnic subgroups. 8With over 25 pipeline AD medications under investigation, 3 AD treatments provide a unique window for identifying gaps to improve future RCTs.Low representation of patients with skin of colour in clinical trials limits the generalizability of trial outcomes.Including trial sites within diverse areas, promoting awareness to patients with skin of colour, standardizing race/ethnicity classifications, and including race/ethnicity subanalysis can all help to encompass global racial and ethnic heterogeneity better.While progress has been made to diversify AD trials, our results highlight continued under-representation of patients with skin of colour.By encouraging transparent reporting of race and ethnicity data, practitioners may provide more individualized patient care and improve patient outcomes.
Cognitive status of prostate cancer (PCa) patients aged 60 years and older initiating gonadotropin-releasing hormone agonist (GnRHa) therapy, by age group.
Authors: Francois Rozet, Christophe Hennequin, Morgan Roupret, Nathalie Pello Leprince Ringuet, Aude Houchard, Pierre Mongiat Artus
Journal: Journal of Clinical Oncology (2020)

74 Background: Age is a risk factor for both PCa and cognitive impairment. Moreover, androgen deprivation therapy (ADT) is suspected to alter cognition, but little is known about the cognitive status of men starting ADT. Our purpose was to analyze cognitive status in 3 groups of age ([60-70[, [70-75[ and ≥ 75 years). Methods: Initiated in March 2018, a prospective, multicenter, longitudinal, non-interventional study is conducted in France (PRISME, NCT03516110). Urologists, radiation oncologists and medical oncologists recruited patients aged 60 years and older, with histologically confirmed PCa, candidate for GnRHa therapy. Patients were included (1:2:1) in prespecified age groups ([60-70[, [70-75[, ≥ 75 years). Cognitive status was evaluated through Mini Mental State Evaluation (MMSE) questionnaire (scores 0-30), and through a visual analog scale (VAS) measuring satisfaction of patients with memory (score 0-10 cm). Significant differences (*) were concluded in case of non-overlapping of the means 95% CIs. Results: 528 patients were included in the pre-planned interim analysis of baseline results. Mean (±SD) age was 72.9±6.5years. There were 145, 207 and 176 patients, in the [60-70[, [70-75[ and ≥75y age groups, respectively. 93.8% of patients had a Karnofsky score ≥ 80%; 73.4% had at least one comorbidity at baseline and 67.9% were receiving at least one concomitant systemic treatment. Reason for GnRHa initiation was high risk localized or locally advanced tumor (57.6%), metastatic stage (19.8%), biochemical recurrence after local treatment (14.7%). Mean [95% CI] MMSE score was significantly* lower in the ≥75y age group (26.1 [25.5-26.8]) than in the [60-70[ (27.6 [27.0-28.1]) and [70-75[ (27.5 [27.1-28.0]) age groups. Cognitive impairment (MMSE &lt; 26) concerned 18.2%, 17.6% and 32.0% of patients, respectively. Similarly, memory VAS mean score was significantly* lower in the ≥75y age group (6.4 [6.0-6.8]) than in the [70-75[ age group (7.2 [6.9-7.5]). Conclusions: Analysis of the cognitive status of 3 age groups at initiation of GnRHa therapy showed a higher rate of cognitive impairment in the eldest group. Clinical trial information: NCT03516110.
Cardiolipin Synthase 1 Ameliorates NASH Through Activating Transcription Factor 3 Transcriptional Inactivation
Authors: Chuyue Tu, Hui Xiong, Yufeng Hu, Wen Wang, Gui Mei, Hua Wang, Ya Li, Zelin Zhou, Fengping Meng, Peng Zhang, Zhinan Mei
Journal: Hepatology (2020)

Background and Aims NASH is an increasingly prevalent disease that is the major cause of liver dysfunction. Previous research has indicated that adipose cardiolipin synthase 1 (CRLS1) levels are associated with insulin sensitivity; however, the precise roles of CRLS1 and underlying mechanisms involving CRLS1 in the pathological process of NASH have not been elucidated. Approach and Results Here, we discovered that CRLS1 was significantly down‐regulated in genetically obese and diet‐induced mice models. In vitro studies demonstrated that overexpression of CRLS1 markedly attenuated hepatic steatosis and inflammation in hepatocytes, whereas short hairpin RNA‐mediated CRLS1 knockdown aggravated these abnormalities. Moreover, high‐fat diet–induced insulin resistance and hepatic steatosis were significantly exacerbated in hepatocyte‐specific Crls1 ‐knockout ( Crls1 ‐HKO) mice. It is worth noting that Crls1 depletion significantly aggravated high‐fat and high‐cholesterol diet‐induced inflammatory response and fibrosis during NASH development. RNA‐sequencing analysis systematically demonstrated a prominently aggravated lipid metabolism disorder in which inflammation and fibrosis resulted from Crls1 deficiency. Mechanically, activating transcription factor 3 (ATF3) was identified as the key differentially expressed gene in Crls1 ‐HKO mice through transcriptomic analysis, and our investigation further showed that CRLS1 suppresses ATF3 expression and inhibits its activity in palmitic acid‐stimulated hepatocytes, whereas ATF3 partially reverses lipid accumulation and inflammation inhibited by CRLS1 overexpression under metabolic stress. Conclusions In conclusion, CRLS1 ameliorates insulin resistance, hepatic steatosis, inflammation, and fibrosis during the pathological process of NASH by inhibiting the expression and activity of ATF3.
Abstract 19355: Sequential Shock-No Shock Algorithm to Reduce Interruption During Cardiopulmonary Resuscitation
Authors: Chenguang Liu, Stacy Gehman, Dawn Jorgenson, Thomas Lyster, Jason Coult, Mickey S Eisenberg, Peter J Kudenchuk, Thomas D Rea, Lawrence D Sherman
Journal: Circulation (2016)

Introduction: Pauses in CPR especially those around shocks have been associated with lower likelihood of survival in cardiac arrest. Chest compressions (CC) can induce artifacts that obscure ECG si...
Standing by the Bystander
Authors: Eric S. Silberman
Journal: JAMA Neurology (2020)

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Associations between active maternal atopy in pregnancy and offspring asthma risk: Effect modification by prenatal dietary long-chain polyunsaturated fatty acid intake
Authors: Julie Flom, Whitney Cowell, Maria Jose Rosa, Harish Ganguri, Yueh-Hsiu Mathilda Chiu, Srimathi Kannan, Rosalind Wright
Journal: Journal of Allergy and Clinical Immunology (2020)
Significance of increased tissue transglutaminase expression in androgen-refractory prostate carcinoma
Authors: Jansina Fok, Kapil Mehta
Journal: Cancer Research (2008)

4106  Prostate cancer is the second most common cancer in males in the United States. Although androgen ablation remains the standard treatment for prostate cancer, the progression to hormone refractory disease becomes inevitable - occurring within 2-5 years. Androgen refractory prostate cancer (AIPC) cells acquire resistance to drugs and can no longer be cured by conventional therapy of any type. Therefore, understanding molecular mechanisms which contribute to the progression of androgen-sensitive prostate cancer to AIPC is likely to reveal new targets for effective treatment of prostate cancer.  In this context, our initial observations that AIPC cell lines (DU145 and PC3) express high basal levels of the multifunctional protein, transglutaminase type-2 (TGm2), may be of interest. Indeed, increased expression of TGm2 has been reported in many aggressive forms of cancers and is implicated in development of drug-resistant and metastatic phenotype.  In order to determine the significance of increased TGm2 expression in AIPC cells, we induced ectopic expression of TGm2 in TGm2-deficient LnCap cells by adenoviral-TG2 construct infection. Overexpression of TGm2 resulted in androgen-independent growth of LnCaP cells as established by their culture in charcoal-stripped serum and MTS assay. Moreover, TGm expression induced the activation of cell survival signaling pAkt pathway in LnCaP cells. Furthermore, TGm2 expression in LnCap cells was associated with increased invasiveness through the Matrigel transmembrane inserts. Conversely, we studied the effect of TGm2 downregulation in PC3 AIPC cells. Interestingly, downregulation of endogenous TGm2 by siRNA in AIPC PC3 cells reversed their sensitivity to therapeutic drugs. Prolonged downregulation of TGm2 induced cell death in PC3 cells. These results clearly suggest that aberrant expression of TG2 plays a critical role in promoting in cell survival and invasive functions in prostate cancer cells and therefore may represent an important factor in development of AIPC phenotype.
Safety and efficacy of immune checkpoint inhibitors (ICI) in metastatic non-clear cell renal cell carcinoma (nccRCC): An institutional experience.
Authors: William Schwartzman, Roy Elias, Viral M. Patel, Alex Isaac Bowman, Suneetha Chintalapati, Payal Kapur, Hans J. Hammers, James Brugarolas
Journal: Journal of Clinical Oncology (2020)

640 Background: ICIs have improved outcomes in clear cell RCC patients (pts), and emerging data suggest that they may be effective against nccRCC. nccRCC comprises ~25% of renal tumors and consist of a diverse group of diseases. Despite recent evidence, data regarding the efficacy of ICIs in nccRCC remain limited, especially among rarer nccRCC subtypes. Methods: We identified all cases of metastatic nccRCC that received at least one dose of ICI therapy at UT Southwestern Medical Center from 2014 – 2018. Baseline characteristics and IMDC criteria were evaluated at the time of ICI initiation. Outcomes included objective response rate (ORR) per RECIST v1.1 criteria, time to next treatment (TNT), and overall survival (OS). Immune-related adverse events (irAE) were graded per CTCAE 4.0 criteria. Survival estimates were evaluated using Kaplan Meier methods. Results: We identified 28 pts with metastatic nccRCC; 12 (42.9%) unclassified RCC (uRCC), 8 (28.6%) papillary RCC (pRCC), 3 (10.7%) chromophobe RCC (chRCC), 3 (10.7%) hereditary leiomyomatosis and renal cell cancer (HLRCC), 1 (3.6%) translocation RCC (tRCC) and 1 (3.6%) acquired cystic disease-associated RCC (ACD-RCC). 23 (82.1%) pts were intermediate or poor risk by IMDC criteria. In total, 13 (46.4%) pts received nivolumab monotherapy, and 15 (53.6%) in combination with ipilimumab. 12 (42.9%) pts received ICI in the first line. The median TNT and OS amongst all nccRCC subtypes was 4.9 (95% CI: 1.7-8.1) and 15.9 (95% CI: 5.9 – 25.9) months respectively. The ORR was 3/28 (10.7%), with 2 complete responses. All responses were restricted to the pRCC and uRCC subtypes. 11 (39.3%) pts experienced any irAE and 5 (17.9%) had a grade 3/4 irAE, including one case of grade 4 myocarditis. The median time to onset of an irAE was 1.9 months (Range: 0.1 to 12.0). At a median follow up of 10.8 months (95% CI: 10.2 – 17.9), 4 pts remain on therapy and 13 pts have died. Conclusions: ICI therapy demonstrated modest efficacy in this cohort with comparable irAE profiles to ccRCC. Objective responses were not seen in pts with HLRCC, ACD-RCC, tRCC, or chRCC in this study.