tbuckley/cabot-search huggingface dataset:
Development and evaluation of deep learning–based segmentation of histologic structures in the kidney cortex with multiple histologic stains
Authors: Catherine P. Jayapandian, Yijiang Chen, Andrew R. Janowczyk, Matthew B. Palmer, Clarissa A. Cassol, Miroslav Sekulic, Jeffrey B. Hodgin, Jarcy Zee, Stephen M. Hewitt, John O’Toole, Paula Toro, John R. Sedor, Laura Barisoni, Anant Madabhushi, J. Sedor, K. Dell, M. Schachere, J. Negrey, K. Lemley, E. Lim, T. Srivastava, A. Garrett, C. Sethna, K. Laurent, G. Appel, M. Toledo, L. Barisoni, L. Greenbaum, C. Wang, C. Kang, S. Adler, C. Nast, J. LaPage, John H. Stroger, A. Athavale, M. Itteera, A. Neu, S. Boynton, F. Fervenza, M. Hogan, J. Lieske, V. Chernitskiy, F. Kaskel, N. Kumar, P. Flynn, J. Kopp, J. Blake, H. Trachtman, O. Zhdanova, F. Modersitzki, S. Vento, R. Lafayette, K. Mehta, C. Gadegbeku, D. Johnstone, S. Quinn-Boyle, D. Cattran, M. Hladunewich, H. Reich, P. Ling, M. Romano, A. Fornoni, C. Bidot, M. Kretzler, D. Gipson, A. Williams, J. LaVigne, V. Derebail, K. Gibson, A. Froment, S. Grubbs, L. Holzman, K. Meyers, K. Kallem, J. Lalli, K. Sambandam, Z. Wang, M. Rogers, A. Jefferson, S. Hingorani, K. Tuttle, M. Bray, M. Kelton, A. Cooper, B. Freedman, J.J. Lin
Journal: Kidney International (2020)

The application of deep learning for automated segmentation (delineation of boundaries) of histologic primitives (structures) from whole slide images can facilitate the establishment of novel protocols for kidney biopsy assessment. Here, we developed and validated deep learning networks for the segmentation of histologic structures on kidney biopsies and nephrectomies. For development, we examined 125 biopsies for Minimal Change Disease collected across 29 NEPTUNE enrolling centers along with 459 whole slide images stained with Hematoxylin & Eosin (125), Periodic Acid Schiff (125), Silver (102), and Trichrome (107) divided into training, validation and testing sets (ratio 6:1:3). Histologic structures were manually segmented (30048 total annotations) by five nephropathologists. Twenty deep learning models were trained with optimal digital magnification across the structures and stains. Periodic Acid Schiff-stained whole slide images yielded the best concordance between pathologists and deep learning segmentation across all structures (F-scores: 0.93 for glomerular tufts, 0.94 for glomerular tuft plus Bowman's capsule, 0.91 for proximal tubules, 0.93 for distal tubular segments, 0.81 for peritubular capillaries, and 0.85 for arteries and afferent arterioles). Optimal digital magnifications were 5X for glomerular tuft/tuft plus Bowman's capsule, 10X for proximal/distal tubule, arteries and afferent arterioles, and 40X for peritubular capillaries. Silver stained whole slide images yielded the worst deep learning performance. Thus, this largest study to date adapted deep learning for the segmentation of kidney histologic structures across multiple stains and pathology laboratories. All data used for training and testing and a detailed online tutorial will be publicly available.
Predictors of aggressive end-of-life care among Hispanic and white advanced cancer patients
Authors: E. D. Trice, M. E. Nilsson, E. Paulk, S. DeSanto-Madeya, A. A. Wright, T. A. Balboni, H. Steiglitz, P. K. Maciejewski, S. D. Block, H. G. Prigerson
Journal: Journal of Clinical Oncology (2009)

9538 Background: Some ethnic/racial minority cancer patients (e.g. African Americans) have been shown to receive more life-prolonging care at the end-of-life (EOL) than white patients. Nevertheless, few studies have investigated whether Hispanic cancer patients receive more aggressive care than white patients and limited information exists on the predictors of aggressive care among Hispanic patients. The present study examined rates and predictors of aggressive EOL care among Hispanic and white cancer patients. Methods: Subjects participated in a US multi-site, prospective study between September 2002 - August 2008. Data were derived from interviews, conducted in English or Spanish, of 292 self-reported Hispanic (N=58) or white (N=234) stage IV cancer patients and their caregivers. Patients were followed until death, a median of 118.5 days later. Caregiver post-mortem interviews documented patient care in the last week of life. “Aggressive EOL care” was operationalized as cardiopulmonary resuscitation and/or ventilation and death in an intensive care unit. Aggressive EOL care was regressed on the following baseline, patient-reported, independent variables: a preference for life-prolonging care, EOL treatment discussion, do-not-resuscitate (DNR) order, terminal illness acknowledgement, and religious coping. Logistic regression models were stratified by ethnic status and controlled for significant confounds (e.g. socioeconomic status). Results: Hispanic and white advanced cancer patients were equally likely to receive aggressive EOL care (5.2% and 3.4%, respectively; p=0.878). Although religious coping and treatment preferences predicted aggressive EOL care for white patients (adjusted odds ratio 7.76 [p=0.025] and 13.20 [p=0.008]), they were not predictive among Hispanic patients. Hispanic patients were less likely than white patients to have DNR orders (22.4% vs 50.4%; p=0.007). For both white and Hispanic cancer patients, no patient who reported an EOL discussion or DNR order at baseline received aggressive EOL care. Conclusions: Given that EOL discussions and DNR orders may prevent aggressive EOL care among Hispanic cancer patients, further efforts to engage Hispanic patients and their caregivers in these activities may reduce aggressive EOL care. No significant financial relationships to disclose.
Effect of zoledronic acid on bone loss in postmenopausal women with early breast cancer treated with sequential tamoxifen and letrozole
Authors: T. Safra, R. Bernstein Molho, I. Stephansky, N. Yaal-Hahoshen, M. Inbar, A. Ackerstein, D. Geffen
Journal: Journal of Clinical Oncology (2009)

599 Background: Adjuvant treatment with aromatase inhibitors (AIs) in postmenopausal women (PMW) with early breast cancer (EBC) can be associated with decreased bone mineral density (BMD) and increased risk of osteoporosis and fractures. Tamoxifen (TAM) has bone protective effect. BIG 1–98 recent, 71 months update suggests that sequential therapy of TAM and letrozole (LET) in either order, have similar efficacy to 5 years of LET. This study is designed to evaluate the efficacy and safety of zoledronic acid (ZA) in preventing AIs bone loss after 2.5 years of TAM. Methods: This is an open-label, randomized phase II study of PMW with hormone receptor positive EBC previously treated with TAM for the last 2.5 years (with BMD T score ≥ -2.5). Patients are randomly assigned to receive LET (2.5mg/ daily) ± ZA. Patients on treatment arm receive 4 mg IV ZA every 6 months for 2 years. All patients are being evaluated every 6 (0–36) months with blood chemistry and BMD test. All patients receive vitamin D and calcium supplement. A comparison between groups and between time points is performed by one-way ANOVA with repeated measures using the Mixed model. Results: Seventy four patients were screened. Median age was 58.9 years (46.5–83.6). All patients are alive, one had an ipsilateral recurrence. Seventy two patients were evaluable (2 were screening failure), 33 randomized to receive ZA and 39 to the control group. Median follow-up (FU) was 18.2 months (1–47). At this point in time a significant interaction between groups and time trend was found, in favor of ZA treated group in lumbar T score (p = 0.0055). While in the control group a significant decline in lumbar BMD was noticed (p = 0.008), in the treatment group BMD did not change over time (p = 0.2971). Adverse events with ZA were mild with some flue like syndrome. No serious renal adverse event or ONJ (osteonecrosis of jaw) cases were reported. ZA was safe and well tolerated. Conclusions: Sequential adjuvant treatment with TAM and AIs in PMW with EBC can be associated with decreased BMD and increased risk of osteoporosis. In our study, LET-induced bone loss increases with time. A significant benefit in BMD was seen when ZA was added to LET. A longer follow up is needed to evaluate the real magnitude of ZA protective effects. [Table: see text]
Abstract 12904: Assessing Low-Density Lipoprotein Cholesterol Risk in Secondary Prevention Patients Within The PINNACLE National Outpatient Registry
Authors: Joseph M Allen, Suzanne V Arnold, Nicole L Lohr, Lonny Reisman, Ameen F Ghannam, Santosh K Sanganalmath, Irfan Khan, Serban Iorga, Dharam Kumbhani
Journal: Circulation (2019)

Introduction: Contemporary patterns of low density lipoprotein cholesterol (LDL-C) goal achievement and lipid-lowering strategies in cardiology or primary care practices are not well understood. Gi...
Anti-tumor effects of NK cells and anti-PD-L1 antibody with antibody-dependent cellular cytotoxicity in PD-L1-positive cancer cell lines
Authors: Ji-Eun Park, Seong-Eun Kim, Bhumsuk Keam, Ha-Ram Park, Soyeon Kim, Miso Kim, Tae Min Kim, Junsang Doh, Dong-Wan Kim, Dae Seog Heo
Journal: Journal for ImmunoTherapy of Cancer (2020)

Although programmed cell death-1/programmed death-ligand 1 (PD-L1) inhibitors show remarkable antitumor activity, a large portion of patients with cancer, even those with high PD-L1-expressing tumors, do not respond to their effects. Most PD-L1 inhibitors contain modified fragment crystallizable region (Fc) receptor binding sites to prevent antibody-dependent cellular cytotoxicity (ADCC) against PD-L1-expressing non-tumor cells. However, natural killer (NK) cells have specific antitumor activity in the presence of tumor-targeting antibody through ADCC, which could enhance NK cell-induced cytotoxicity. We evaluated the antitumor efficacy of ADCC via anti-PD-L1 monoclonal antibodies (mAbs) and NK cells against several PD-L1-positive cancer cell lines.Various cancer cell lines were used as target cell lines. Surface PD-L1 expression was analyzed by flow cytometry. IMC-001 and anti-hPD-L1-hIgG1 were tested as anti-PD-L1 mAbs with ADCC and atezolizumab as an anti-PD-L1 mAb without ADCC. NK cell cytotoxicity was measured by 51Cr-release assay and CD107a degranulation assay. Also, live cell imaging was performed to evaluate cytotoxicity in a single-cell level. NK-92-CD16 (CD16-transduced NK-92 cell line) and peripheral blood mononuclear cells from healthy donors, respectively, were used as an effector cell. FcγRIIIa (CD16a)-V158F genotyping was performed for healthy donors.We demonstrated that the cytotoxicity of NK-92-CD16 cells toward PD-L1-positive cancer cell lines was significantly enhanced in the presence of anti-PD-L1 mAb with ADCC. We also noted a significant increase in primary human NK cell cytotoxicity against PD-L1-positive human cancer cells when cocultured with anti-PD-L1 mAb with ADCC. Moreover, NK cells expressing a FCGR3A high-affinity genotype displayed higher anti-PD-L1 mAb-mediated ADCC lysis of tumor cells than donors with a low-affinity genotype.These results suggest that NK cells induce an ADCC response in combination with anti-PD-L1 mAbs, which helps promote ADCC antitumor activity against PD-L1-positive tumors. This study provides support for NK cell immunotherapy against high PD-L1-expressing tumors in combination with ADCC through anti-PD-L1 mAbs.
Pre-therapy fasting slows epithelial turnover and modulates the microbiota but fails to mitigate methotrexate-induced gastrointestinal mucositis
Authors: H. R. Wardill, A. R. da Silva Ferreira, S. Lichtenberg Cloo, R. Havinga, H. J. M. Harmsen, W. P. Vermeij, W. J. E. Tissing
Journal: Gut Microbes (2020)

Background Recent findings by Tang et al. (2020) show dietary restriction (30%, 2 weeks) prevents methotrexate-induced mortality by modulation of the microbiota, specifically the expansion of Lactobacillus. While fundamentally insightful, upscaling this schedule is a major obstacle to clinical uptake. Here, we evaluate a safe and clinically achievable schedule of pre-therapy fasting for 48 h on microbiota composition, body composition and intestinal proliferation, and assess its impact on the severity of methotrexate-induced gastrointestinal mucositis using a validated preclinical rat model.Methods Age- and weight-matched male Wistar rats were treated with a sublethal dose of 45 mg/kg methotrexate with or without pre-therapy fasting. The impact of acute fasting on epithelial proliferation, body composition and the microbiota was assessed using plasma citrulline, Ki67 immunohistochemistry, miniSpec and 16S rRNA sequencing. The severity of gastrointestinal mucositis was evaluated using plasma citrulline and body weight.Results Whilst pre-therapy fasting slowed epithelial proliferation and increased microbial diversity and richness, it also induced significant weight loss and was unable to attenuate the severity of mucositis in both age- and weight-matched groups. In contrast to Tang et al., we saw no expansion of Lactobacillus following acute fasting.Conclusions Our findings suggest that the beneficial effects of acute fasting are masked by the detrimental effects on body weight and composition and lacking influence on Lactobacillus. Future studies should consider alternative fasting schedules or aim to induce comparable microbial and mucosal manipulation without compromising body composition using clinically feasible methods of dietary or microbial intervention.
Clinical outcomes of patients with breast cancer in a phase I clinic: The M. D. Anderson Cancer Center experience
Authors: J. J. Wheler, A. Tsimberidou, S. Moulder, M. Cristofanill, D. Hong, A. Naing, R. Pathak, S. Liu, L. Feng, R. Kurzrock
Journal: Journal of Clinical Oncology (2009)

1054 Background: Patients with metastatic breast cancer refractory to standard therapy are eligible for phase I trials. We assessed prognostic factors and clinical outcomes for patients with breast cancer in a phase I clinic focused on targeted agents. Methods: We reviewed the medical records of sequential patients with metastatic breast cancer who presented to our phase I clinic from September 2004 to May 2008. We assessed the relationship between overall survival and patients’ demographic and clinical characteristics using both univariate and multivariate (Cox proportional hazard model) analyses. Results: Ninety-two patients were identified with median age of 53 years (range 28 to 83 years). The median number of prior therapies was 5 (range 1 to 16). The median follow-up of surviving patients is 7.4 months. The median overall survival is 6.7 (95% CI: 5.2, 9.7) months. In univariate analysis, factors predicting shorter survival were elevated Ca-125 (p = 0.001) (Ca27.29 was not significant), albumin &lt; 3.5 g/dL (p = 0.002), worsening ECOG performance status (p = 0.004), absolute neutrophil count &lt; 7.3 x 10 9 /L (p = 0.004), ≥ 10 prior treatment regimens (p = 0.008), ≥ 5 prior chemotherapy-only regimens (p = 0.008), body mass index (BMI) &lt; 25 (p = 0.018), and elevated platelet counts (p = 0.007). In multivariate analysis, independent factors predicting shorter survival were ≥10 prior treatments (vs. &lt;10 prior treatments) (HR = 3.27; 95% CI 1.37, 7.81; p = 0.0077), ECOG performance status 2–3 (vs. 0–1) (HR = 2.92; 95% CI 1.28, 6.66; p = 0.01), and albumin &lt; 3.5 g/dL (vs. &gt; 3.5g/dL) (hazard ratio [HR] = 2.88; 95% CI; 1.41, 5.89; p = 0.004). Of 78 patients treated on a first phase I trial, 14 (18%) demonstrated stable disease (SD), with a median duration of 18 weeks (range 10–25). Of those 19 patients treated on a second phase I trial, 6 (32%) had SD with a median duration of 12 weeks (range 8–17). Two of 4 (50%) patients treated on a third phase I trial had SD with a median duration of 20 weeks (range 16–24). Conclusions: Patients with metastatic breast cancer referred for our phase I studies had a median survival of 6.6 months. In this preliminary analysis, independent factors predicting shorter survival were ≥ 10 prior treatments, worsening ECOG performance status and low albumin levels. No significant financial relationships to disclose.
A phase Ib trial of IPI-504 (retaspimycin hydrochloride), a novel Hsp90 inhibitor, in combination with docetaxel
Authors: G. J. Riely, R. Stoller, M. Egorin, D. Solit, J. Dunbar, A. Savage, J. Walker, D. Grayzel, R. Ross, G. J. Weiss
Journal: Journal of Clinical Oncology (2009)

3547 Background: IPI-504 is a water-soluble heat shock protein 90 (Hsp90) inhibitor. IPI-504 causes the degradation of a variety of mutated or amplified oncoproteins, including epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2). The combination of IPI-504 and docetaxel demonstrates additive efficacy in murine xenograft models. This Phase 1b trial was undertaken to identify the maximum tolerated dose (MTD) of IPI-504 in combination with docetaxel. Methods: Eligible patients (pts) had advanced solid tumors that were either refractory to available therapies or for which docetaxel alone was an appropriate therapy. Intravenous (IV) 75 mg/m 2 docetaxel was given once every three weeks (q 3- weekly). IPI-504 was administered IV q 3-weekly, with 3 pts per cohort and inter-cohort dose escalation. All pts were evaluated for safety, pharmacokinetics (PK), and tumor response. Results: 16 pts have been enrolled at 3 dose levels of IPI-504 (7 at 300 mg/m 2 , 6 at 450 mg/m 2 , and 3 at 550 mg/m 2 ). 6 pts had non-small cell lung cancer (NSCLC). Median age was 59 yrs (range 33–77). Median number of cycles received was 3 (1–11), with 5 pts currently on study. There have been 4 dose-limiting toxicities (DLTs): 1 at 300 mg/m 2 (Grade 3 febrile neutropenia); 1 at 450 mg/m 2 (Grade 3 fatigue); and 2 at 550 mg/m 2 (Grade 1 asymptomatic sinus bradycardia requiring hospitalization for observation, and Grade 3 elevated AST with Grade 3 acute respiratory distress syndrome). All DLTs resolved on trial. No PK interactions between docetaxel and IPI-504 have been observed. The regimen of IPI-504 450 mg/m 2 with docetaxel 75 mg/m 2 has been identified as the recommended phase 2 dose on a q 3-weekly schedule. Conclusions: In this Phase 1b trial, the MTD of IPI-504 plus docetaxel q 3-weekly was identified. Toxicities were reversible and similar to those seen with docetaxel or IPI-504 alone in this patient population. Given the activity of single-agent IPI-504 against NSCLC and the standard use of docetaxel in that disease, an expanded evaluation of this regimen in pts with previously treated NSCLC is on-going. The combination of IPI-504 and docetaxel on a weekly schedule is also being explored. [Table: see text]
Medical Aid in Living
Authors: Benzi M. Kluger
Journal: JAMA Neurology (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Effects of weekly bevacizumab and pegylated liposomal doxorubicin in heavily pretreated patients with recurrent or progressed ovarian cancer
Authors: Y. Kikuchi, H. Kouta, R. Kikuchi, M. Takano, T. Kita, K. Kudoh, D. Aoki, T. Sugiyama, S. Isonishi
Journal: Journal of Clinical Oncology (2009)

5547 Background: Vascular endothelial growth factor (VEGF) plays a central role in tumor angiogenesis and is regarded a promising therapeutic target. Bevacizumab (A) has significant antitumor activity in combination with cytotoxic agents. Currently, pegylated liposomal doxorubicin (D) is provided as one of the standard treatment options in recurrent ovarian cancer. Thus, we attempted to determine effects in combination of A and D for heavily pretreated patients with recurrent or progressed ovarian cancer. Methods: Twenty-two patients with heavily pretreated (more than one regimen or more than 6 cycles by paclitaxerl and carboplatin) received at least more than 3 cycles of weekly A-D consisting of A: 2 mg/kg and D: 10 mg/m2 (3 weeks, one week rest). The primary endpoint was response according to CA 125 and response evaluation criteria in solid tumor (RECIST) criteria. Results: Of 22 patients evaluable for CA 125 response, 7 (32%) had a response (decrease of &gt;50%), and 8 (36%) patients had not progressed (doubling of CA 125) following 6 months on treatment. In RECIST evaluation, 2 (9%) patients had complete remission (CR) and 6 (27%) had partial remission (PR), resulting in 55% clinical benefit rate (CBR). Progression free interval (PFI) showed more than 6 months. Any hematological adverse effect was not observed in the present study. Gastrointestinal perforation was observed in only one case and was conservatively treated. Although nasal bleeding was frequently observed, no treatment was required. A induced hypertension was also observed and manageable. Hand-foot syndrome seemed due to D was seen in 3 of 22 patients and treatment was required in only one case. Conclusions: B seemed to enhance effect of D. This is the first study of weekly A-D in heavily pretreated ovarian cancer patients. Weekly A-D warrants further clinical study in such clinical settings. No significant financial relationships to disclose.
Letter to the editor: importance of a careful investigation to avoid attributing Legionnaires’ disease cases to an incorrect source of infection
Authors: Maria Cristina Rota, Maria Scaturro, Maria Luisa Ricci
Journal: Eurosurveillance (2020)

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