tbuckley/cabot-search huggingface dataset:
Learning to detect lymphocytes in immunohistochemistry with deep learning
Authors: Zaneta Swiderska-Chadaj, Hans Pinckaers, Mart van Rijthoven, Maschenka Balkenhol, Margarita Melnikova, Oscar Geessink, Quirine Manson, Mark Sherman, Antonio Polonia, Jeremy Parry, Mustapha Abubakar, Geert Litjens, Jeroen van der Laak, Francesco Ciompi
Journal: Medical Image Analysis (2019)
Phase II trial of trastuzumab (T), paclitaxel (P) and cisplatin (C) in metastatic (M) or recurrent (R) head and neck squamous cell carcinoma (HNSCC): Response by tumor EGFR and HER2/neu status
Authors: M. L. Gillison, B. S. Glisson, E. O’Leary, B. A. Murphy, M. A. Levine, M. S. Kies, D. Chan, A. A. Forastiere
Journal: Journal of Clinical Oncology (2006)

5511 Background: EGFR expression is associated with poor prognosis and resistance of HNSCC to therapy. EGFR/Her2/neu heterodimers may potentiate receptor signaling and therapy resistance. T enhances cytotoxic effects of C and P in Her2/neu + cell lines. Methods: A phase II trial evaluated the response rate (RR) of HNSCC pts to TPC as a function of Her2/neu and EGFR expression by immunohistochemistry (IHC). Secondary outcomes included toxicity, one-year progression-free (PFS) and overall (OS) survival. Eligible pts had M or R HNSCC, ECOG PS 0–1, CrCl &gt;50 ml/min, and ANC &gt;1500. Chemotherapy regimen consisted of P (175 mg/m 2 ) and C (75 mg/m 2 ) IV on day 1 and T (4 mg/kg day 1, cycle 1, 2 mg/kg subsequent) IV on day 1, 8 and 15 of 21. Paraffin embedded tumor was analyzed for Her2/neu (HercepTest) and EGFR (Zymed Lab) expression by IHC and for Her2/neu amplification by FISH (−/+) at LabCorp. Two-stage Simon design had 80% power for a 15% improvement in RR over 35% and required response in ≥ 14/42 pts by ECOG response criteria. Results: 61 pts (55 R HNSCC) received a median of 4 cycles (range 1–14) of TPC. Membrane staining of ≥ 10% of cells was observed for Her2/neu in 4/58 (6.9%, 95% CI 2–17) and for EGFR in 41/57 (72%, 95% CI 58–83). Her2/neu amplification was absent in 55/55 (0%, one-sided 97.5% CI 0–6.7) tumors. A RR of 36% (95% CI 24–50) was observed in 58 evaluable pts. RR was lower in pts with ≥ 10% staining by EGFR (25% versus 62.5%, p = 0.01). Her2/neu expression had no effect on RR (p = 0.75). Toxicities included two grade 5 dehydration/hypokalemia, and grade 3–4 neutropenia, fatigue, infection, nausea, vomiting, and neuropathy were common. Median follow-up was 4.2 yrs. For all 61 pts: median TTP was 4.3 mos, PFS 19.8% (95% CI 10.6–30.9) and OS 44% (95% CI 31.6–56.2) at 1 yr. Pts with &lt;10% EGFR membrane staining had improved median PFS (6.7 vs 3.1 mos, p = 0.003) and OS (16.1 vs 7.4 mos, p = 0.005) when compared to patients with tumors with ≥ 10% EGFR. Conclusions: T did not improve RR to PC, likely because Her2/neu gene amplification and expression was rare. Tumor EGFR status significantly affected RR, PFS, and OS to the underlying regimen of PC. Sponsored by Bristol-Myers Squibb, Genentech, and Damon Runyon Cancer Research Foundation (MG). [Table: see text]
Correlations between Transcranial Doppler Velocities and Laboratory Markers of SCA Severity
Authors: Corynne Stephanie A. Adanho, Rayra Pereira Santiago, Camilo Vieira, Caroline Conceicao Guarda, Sanzio Santana, Camylla Vilas Boas Figueiredo, Luciana Magalhaes Fiuza, Karoline Brito Coelho Caetano, Thassila Nogueira Pitanga, Setondji Cocou Modeste Alexandre Yahouedehou, Milena Aleluia, Junia Raquel Dutra Ferreira, Vitor Valerio Maffili, Dalila Luciola Zanette, Isa Menezes Lyra, Marilda Goncalves
Journal: Blood (2017)
Abstract 16248: Impact of Continuous Reduction in B-Type Natriuretic Peptide Bioactivity During Hospitalization in Patients With Advanced Heart Failure
Authors: Hiroyuki Takahama, Seiji Takashio, Tomohiro Hayashi, Chiaki O Nagai, Toshio Nishikimi, Yasuaki Nakagawa, Makoto Amaki, Takahiro Ohara, Takuya Hasegawa, Yasuo Sugano, Hideaki Kanzaki, Satoshi Yasuda, Kenji Kangawa, Naoto Minamino, Toshihisa Anzai
Journal: Circulation (2017)

Introduction: Some studies have demonstrated that the proportion of bioactive mature B-type natriuretic peptide (BNP) among total secreted BNP forms is low and that circulating levels of biological...
Phase II trial of tamoxifen for progressive advanced urothelial carcinoma following prior chemotherapy.
Authors: Seth P. Lerner, Cora N. Sternberg, Mamoun Younes, Fabio Calabro, Linda Cerbone, A Chandrashekar, Carmen Mitchell, Steven S. Shen, Guru Sonpavde
Journal: Journal of Clinical Oncology (2012)

e15003 Background: Urothelial carcinoma (UC) expresses estrogen receptor (ER)-β, which increases with stage and grade. The selective estrogen receptor modulators, tamoxifen and raloxifene have displayed anti-tumor activity in preclinical UC. Effective therapy for progressive UC following chemotherapy is lacking. A rationale can be made to evaluate the activity of tamoxifen following prior chemotherapy for advanced UC. Methods: A non-randomized two-center 2-stage phase II trial was planned. Eligible patients were required to have bladder or upper tract urothelial cancer, measurable metastatic disease, 1-2 prior chemotherapy regimens, adequate organ function and ECOG performance status (PS) 0-2. The primary endpoint was freedom from progression (FFP) at 4 months (mo), with secondary endpoints of response, survival, toxicities and association of tumor ER studies with FFP. FFP of ≥30% was considered important and ≤10% was felt to reflect poor activity. Twenty-five evaluable subjects were required, 15 during stage 1 and 10 during stage 2 for α=0.05 and power =0.8. If ≥2 patients attained FFP during stage-1, the trial proceeded to stage-2. Tamoxifen was administered as 20 mg orally once daily until progression by RECIST or intolerable toxicities. Clinical assessments were performed every 4 weeks and imaging every 8 weeks or earlier if indicated. ER isoforms were measured in archival formalin fixed tumor. Results: The trial has completed accrual with 28 patients enrolled of whom 18 are currently evaluable (16 male and 2 female). Number of prior chemotherapy regimens was 2 in 15, ≥3 in 2 and unknown in 1 patient. ECOG-PS was 0 in 9, 1 in 7 and 2 in 2 patients. Liver metastasis was present in 4 and anemia (Hb &lt;10 gm/dL) in 7 patients. Four patients (22.2%) attained FFP at 4 mo. Minor tumor regression was seen in 1 patient. One grade 3 toxicity (deep vein thrombosis) possibly related to therapy was observed. Tumor ER isoform studies and correlation with FFP will be presented. Conclusions: Tamoxifen exhibited potential activity in a subset of patients with advanced UC following chemotherapy. Given the excellent tolerability, further study may be warranted to identify factors predictive of benefit in less heavily pretreated patients.
Acquired Resistance Mutations to ALK Inhibitors Identified by Single Circulating Tumor Cell Sequencing in<i>ALK</i>-Rearranged Non–Small-Cell Lung Cancer
Authors: Emma Pailler, Vincent Faugeroux, Marianne Oulhen, Laura Mezquita, Mélanie Laporte, Aurélie Honoré, Yann Lecluse, Pauline Queffelec, Maud NgoCamus, Claudio Nicotra, Jordi Remon, Ludovic Lacroix, David Planchard, Luc Friboulet, Benjamin Besse, Françoise Farace
Journal: Clinical Cancer Research (2019)

Patients with anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) inevitably develop resistance to ALK inhibitors. New diagnostic strategies are needed to assess resistance mechanisms and provide patients with the most effective therapy. We asked whether single circulating tumor cell (CTC) sequencing can inform on resistance mutations to ALK inhibitors and underlying tumor heterogeneity in ALK-rearranged NSCLC.Resistance mutations were investigated in CTCs isolated at the single-cell level from patients at disease progression on crizotinib (n = 14) or lorlatinib (n = 3). Three strategies including filter laser-capture microdissection, fluorescence activated cell sorting, and the DEPArray were used. One hundred twenty-six CTC pools and 56 single CTCs were isolated and sequenced. Hotspot regions over 48 cancer-related genes and 14 ALK mutations were examined to identify ALK-independent and ALK-dependent resistance mechanisms.Multiple mutations in various genes in ALK-independent pathways were predominantly identified in CTCs of crizotinib-resistant patients. The RTK-KRAS (EGFR, KRAS, BRAF genes) and TP53 pathways were recurrently mutated. In one lorlatinib-resistant patient, two single CTCs out of 12 harbored ALK compound mutations. CTC-1 harbored the ALKG1202R/F1174C compound mutation virtually similar to ALKG1202R/F1174L present in the corresponding tumor biopsy. CTC-10 harbored a second ALKG1202R/T1151M compound mutation not detected in the tumor biopsy. By copy-number analysis, CTC-1 and the tumor biopsy had similar profiles, whereas CTC-10 harbored multiple copy-number alterations and whole-genome duplication.Our results highlight the genetic heterogeneity and clinical utility of CTCs to identify therapeutic resistance mutations in ALK-rearranged patients. Single CTC sequencing may be a unique tool to assess heterogeneous resistance mechanisms and help clinicians for treatment personalization and resistance options to ALK-targeted therapies.
Time for Neurologists to Drop the Reflex Hammer on Hypertension
Authors: John Betjemann, J. Claude Hemphill, Urmimala Sarkar
Journal: JAMA Neurology (2019)

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
Re: Lee et al.: Temporal raphe sign for discrimination of glaucoma from optic neuropathy in eyes with macular ganglion cell inner plexiform layer thinning (Ophthalmology. 2019;126:1131-1139)
Authors: Mayuri Borgohain, Prafulla Sarma, Shahinur Tayab, Chengchira A. Sangma, Susmita Paul
Journal: Ophthalmology (2019)
Foodborne Botulism From Eating Home-Pickled Eggs--Illinois, 1997
Authors: G. Rifkin, K. Sibounheuang, L. Peterson, K. Kelly, C. Langkop, D. Kauerauf, E. Groeschel, B. Adam, C. Austin, S. Bornstein
Journal: JAMA (2000)

Since Legionnaires' Disease (LD) was first reported in 1976, outbreaks have been associated with airborne transmission of Legionella bacteria through cooling towers, showers, and other aerosolizing devices (1 ).However, most LD cases are sporadic, and the source and mode of infection in many cases are unknown.Infections with one species, Legionella longbeachae, have been associated with gardening and use of potting soil in Australia and Japan (2,3 ).This report summarizes the findings of LD investigations in California, Oregon, and Washington, that suggest that transmission from potting soil has occurred for the first time in the United States, and that active surveillance and case finding are warranted to explore this association.On June 13, 2000, CDC was alerted by a county health official in Washington of L. longbeachae infection in a 46-year-old woman who had been hospitalized with pneumonia.The patient reported that she had been potting plants during the 10 days before her symptoms began in May.An isolate from the patient's sputum was sent to CDC for species confirmation, and two samples of potting soil and one of compost from the original packages obtained from the patient's residence were sent for analysis.L. longbeachae was isolated from one potting soil sample.The compost contained other Legionella species but not longbeachae.In May, two L. longbeachae isolates had been received at CDC from bronchial wash samples taken from both a 77-year-old Oregon woman and a 45-year-old California man who were both diagnosed with legionellosis.The California patient died and his house was cleaned before an investigation could be undertaken.State and local health officials determined that the Oregon patient had been potting plants using commercial potting soil mixtures and had been working in a home garden during the 10 days before her symptoms began in April.Two potting soil samples taken from her residence were tested for Legionella at CDC; one was positive for L. longbeachae.Isolates of L. longbeachae from the patients and soils will be compared using amplified fragment length polymorphism typing.
FRI0134 Shrinking lung syndrome as a clinical manifestation of patients with sle: 5 cases report
Authors: J Gratacós, E Naval, M Larrosa, CH Domingo, M Bosque, C Tolosa, E Casado, A Marín
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To describe the clinical manifestations and pulmonary function tests (PFTs) of 5 patients with SLE and shrinking lung syndrome (SLS). <h3>Methods</h3> 5 patients (3F/2M) with an age range between 11–76 years. Rewiew of clinical manifestations; laboratory testing (hemogram, antinuclear antibodies, rheumatoid factor-RF- and muscular enzimes); PFTs; X-rays; thoracic CT scan; treatment and follow-up. <h3>Results</h3> SLR was detected 2 months to 20 years after the diagnosis of SLE. All cases were ANA and AntiDNA positives and quiescent disease. Only one patient had visceral manifestations (nephropathy). The SLEDAI score ranged between 6 and 13. Poliarthritis was present in two cases (erosive in one) with RF negative. Dispnea was the manifestation which led lo SLS diagnosis with no clinical or laboratory evidence of peripheral miopathy. PTFs showed: FVC 1954 ± 563 ml (65.4 ± 15.4%), FEV1 1562 ± 384 ml (69.8 ± 15%), FEV1/FVC 81.4 ± 7.2%, TLC 3400 ± 1032 ml (68 ± 10%), RV 1148 ± 626 ml (59 ± 17.6%), DLCO 13.2 ± 3.4 ml/min/mmHg (60.6 ± 17.9%), KCO 4.4 ± 2.2 (86.2+/_15.9%), MIP 59.5 ± 17.5 cmH<sub>2</sub>O (77 ± 21%), MEP 88.7 ± 25.4 cmH2O (97.7 ± 16%), PaO2 86.5 ± 4.3 mmHg, PaCO2 26.4 ± 14.7 mmHg, Aa gradient 17 ± 8. Radiological studies showed reduced lung size with no parenchimal disease. MIP was impaired in two patients at 3 and 24 months from SLS diagnosis. All patients were treated with corticosteroids (4–20 mg/day). Theophilin (10 mg/kg/day) was added to one patient. No effective responsiveness was detected on the follow-up (2 to 24 months). <h3>Conclusion</h3> All patients with SLS met 4 or more revised ARA criteria of SLE. Dispnea was the main clinical manifestation at SLS onset. Characteristically, SLS presented with restrictive PFTs without parenchimatous disturbances. Treatment response was ineffective and functional and clinical stabilitation was the rule on follow-up.
The Cdk2–c-Myc–miR-571 Axis Regulates DNA Replication and Genomic Stability by Targeting Geminin
Authors: Yi Zhang, Zhuqing Li, Qiang Hao, Wei Tan, Jing Sun, Jing Li, Chi-wei Chen, Zongzhu Li, Yunxiao Meng, Yuan Zhou, Zhiyong Han, Huadong Pei, Melvin L. DePamphilis, Wenge Zhu
Journal: Cancer Research (2019)

Abstract DNA rereplication leads to genomic instability and has been implicated in the pathology of a variety of human cancers. Eukaryotic DNA replication is tightly controlled to ensure it occurs only once during each cell cycle. Geminin is a critical component of this control, it prevents DNA rereplication from occurring during S, G2, and early M phases by preventing MCM helicases from forming prereplication complexes. Geminin is targeted for degradation by the anaphase-promoting complex (APC/C) from anaphase through G1-phase, however, accumulating evidence indicates that Geminin is downregulated in late S-phase due to an unknown mechanism. Here, we used a high-throughput screen to identify miRNAs that can induce excess DNA replication and found that miR-571 could reduce the protein level of Geminin in late S-phase independent of the APC/C. Furthermore, miR-571 regulated efficient DNA replication and S-phase cell-cycle progression. Strikingly, c-Myc suppressed miR-571 expression by binding directly to the miR-571 promoter. At the beginning of S-phase, Cdk2 phosphorylated c-Myc at Serine 62, promoting its association with the miR-571 promoter region. Collectively, we identify miR-571 as the first miRNA that prevents aberrant DNA replication and the Cdk2–c-Myc–miR-571 axis as a new pathway for regulating DNA replication, cell cycle, and genomic stability in cancer cells. Significance: These findings identify a novel regulatory mechanism that is critical for maintaining genome integrity by regulating DNA replication and cell-cycle progression.
Polypill cuts major cardiovascular events by a third, study finds
Authors: Stijntje Dijk, Pat Lok
Journal: BMJ (2019)

A once daily, low cost polypill combining four cardiovascular drugs reduced the risk of major cardiovascular events by a third over a five year period when compared with lifestyle advice, a large study has found.1

Poor adherence is particularly common among patients with cardiovascular disease, as previous studies suggest that around a third of patients stop taking their medicine as early as 90 days after a myocardial infarction.2

The concept of a polypill was first proposed over 15 years ago as a simple, cost saving approach to improve medicine adherence and reduce the burden of cardiovascular disease.3 But …
CORRIGENDUM FOR “Children Born Small for Gestational Age: Differential Diagnosis, Molecular Genetic Evaluation, and Implications”
Journal: Endocrine Reviews (2018)

In the above-named article by Finken MJJ, van der Steen M, Smeets CCJ, Walenkamp MJE, de Bruin C, Hokken-Koelega ACS, andWit JM (Endocrine Reviews (2018) 39(6):851-894 doi: 10.210/er.2018-00083), the following error occurred: On page 878, the footnote for Table 9 reads, aIn prepuberty twice yearly. It should read, aIn prepuberty biennially..
Differences among Asian/Asian American, and Caucasian breast and gynecologic cancer patient-reported survivorship needs, symptoms, and illness mindsets (N=220).
Authors: Lidia Schapira, Elisa Hofmeister, Allison W. Kurian, Sean Zion, Hanyang Shen, Tara Torres, Jonathan S. Berek, Oxana Palesh
Journal: Journal of Clinical Oncology (2019)

11620 Background: Cancer experiences are mediated by host and disease factors and affected by social and cultural determinants of health. We sought to characterize perceived supportive care needs and domains of psychosocial functioning among a diverse group of women attending routine appointments for treatment or follow-up of breast and gynecologic cancers. Methods: From July 2018 until January 2019, all patients seen at the Stanford Women’s Cancers Program (serving women treated for breast and gynecologic cancers) were approached to participate. 220 cancer patients (78% breast and 22% gynecologic), mean age 54 (SD = 12) completed an online survey on their supportive care needs assessment (The Short-form Supportive Care Needs Survey Questionnaire) which contains physical, social, information, sexual and psychological scales, anxiety and depression (Patient Health Questionnaire-4) and mindsets about illness and the body mindset (Brief Illness Mindset Inventory). Only 14% of patients refused to take part in the survey. Results: T-test showed that Asian/Asian-American cancer patients (n = 57, 26%) reported fewer needs related to coping with physical symptoms, side effects of treatment and performing usual tasks and activities compared to Caucasian patients (n = 137, 62%), p = .038. Moreover, Asian/Asian-American cancer patients reported fewer depression symptoms (p = .049). Chi-square analyses showed that Asian/Asian-American patients reported less use of psychotherapy over their lifetimes (24.6% vs. 54.0%, p &lt; .001), but significantly higher utilization of Chinese Medicine for cancer symptom management (24.6% vs. 5.8%; p &lt; . 001) compared to the Caucasian patients. T-tests showed that Asian/Asian American patients reported significantly greater agreement with the mindsets that ‘cancer is a catastrophe’ (p = .006) and that their ‘body is an adversary’ (p = .047). Conclusions: In this population of breast and gynecologic patients and survivors we found differences in cancer mindsets, coping and use of mental health and complementary therapies between Asian and Asian-American and Caucasian women. Further analysis to understand the cultural differences are ongoing.
Find Meat on Bones
Authors: Daniel Bosch
Journal: Annals of Internal Medicine (2019)

Ad Libitum20 August 2019Find Meat on BonesDaniel BoschDaniel BoschAtlanta, Georgia (D.B.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M19-0948 Audio Reading - “Find Meat on Bones” Audio. Virginia Hood, MD, reads “Find Meat on Bones” by Daniel Bosch Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail From the Index of Titles and First Lines to Dylan Thomas' Collected Poems.A grief ago,(Grief, thief of time),I dreamed my genesis,I fellowed sleepIn the mustard seed sun,In the White Giant's thigh.Her woven hands beckoned me,Feeding the worm:“Here lie the beastsHigh on a hill.Find meat on bones,Foot, head, or traces.They are the only dead who did not love.”Hourly I sigh.My hero bares his nerves,Never to reach the oblivious dark.How shall my animalConceive these images in air,Take the needles and the knivesThat the sum sanity might add to naught?Do not go ... Author, Article, and Disclosure InformationAffiliations: Atlanta, Georgia (D.B.)Corresponding Author: Daniel Bosch; e-mail, [email protected]com. PreviousarticleNextarticle Advertisement Audio Reading - “Find Meat on Bones” Audio. Virginia Hood, MD, reads “Find Meat on Bones” by Daniel Bosch Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 20 August 2019Volume 171, Issue 4Page: 298KeywordsBoneMeatNervesSleep ePublished: 20 August 2019 Issue Published: 20 August 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Prostaglandin signals from adult germline stem cells delay somatic ageing of Caenorhabditis elegans
Authors: Hyun Ju Lee, Alireza Noormohammadi, Seda Koyuncu, Giuseppe Calculli, Milos S. Simic, Marija Herholz, Aleksandra Trifunovic, David Vilchez
Journal: Nature Metabolism (2019)