tbuckley/cabot-search huggingface dataset:
Phase I trial of α-particle therapy with actinium-225 (<sup>225</sup>Ac)-lintuzumab (anti-CD33) and low-dose cytarabine (LDAC) in older patients with untreated acute myeloid leukemia (AML.
Authors: Joseph G. Jurcic, Farhad Ravandi, John M. Pagel, Jae Hong Park, B. Douglas Smith, Dan Douer, Moshe Yair Levy, Elihu Estey, Hagop M. Kantarjian, Dennis Earle, Dragan Cicic, David A. Scheinberg
Journal: Journal of Clinical Oncology (2015)

7050 Background: 225Ac-lintuzumab consists of a radiometal that emits 4 α-particles linked to an anti-CD33 antibody. A phase I trial showed safety and efficacy of 225Ac-lintuzumab in relapsed AML. We are conducting a multicenter, phase I trial to determine the maximum tolerated dose (MTD), toxicity, and activity of fractionated-dose 225Ac-lintuzumab combined with LDAC. Methods: Patients ≥ 60 yrs with untreated AML not suitable for standard induction were eligible. Patients received LDAC 20 mg BID for 10 d every 4-6 wks for up to 12 cycles. During Cycle 1, 2 doses of 225Ac-lintuzumab were given one week apart, 4-7 d following LDAC. 225Ac doses were escalated using a 3+3 design. Results: Twelve patients (median age, 77 yrs; range, 68-87 yrs) were treated. Eight (67%) had prior myelodysplastic syndrome, for which 6 (75%) received hypomethylating agents (n = 5) or allogeneic stem cell transplant (n = 1). One (8%) had chronic myeloid leukemia in molecular remission prior to AML. Nine patients (75%) had intermediate-risk and 3 (25%) had poor-risk AML. Median CD33 expression was 74% (range, 45-100%). 225Ac-lintuzumab was given at 0.5 (n = 3), 1 (n = 6), or 1.5 (n = 3) μCi/kg/fraction. Up to 4 cycles were given, and 2 patients remain on therapy. DLT was seen in one patient at 1 µCi/kg/fraction who had grade 4 thrombocytopenia and marrow aplasia > 6 wks after therapy. Grade 3/4 toxicities included neutropenia (n = 2), thrombocytopenia (n = 3), febrile neutropenia (n = 6), pneumonia (n = 3), bacteremia (n = 1), cellulitis (n = 1), transient creatinine increase (n = 1), hypokalemia (n = 1), rectal hemorrhage (n = 1), and generalized weakness (n = 1). Six of 8 patients (75%) evaluated after Cycle 1 had bone marrow blast reductions (mean reduction, 68%; range, 34-100%). Five patients (63%) had blast reductions of ≥ 50%, but no remissions were observed to date. Median progression-free survival (PFS) was 2.4 mos (range, 1.3+-16.9 mos). Conclusions: Fractionated-dose 225Ac-linutuzmab can be combined safely with LDAC and has antileukemic activity. Accrual continues to define the MTD. Additional patients will be treated at the MTD to determine response rate, PFS, and OS. Clinical trial information: NCI-2014-01360, NCT01756677.
Identification of small-molecule inhibitors of Zika virus infection and induced neural cell death via a drug repurposing screen
Authors: Miao Xu, Emily M Lee, Zhexing Wen, Yichen Cheng, Wei-Kai Huang, Xuyu Qian, Julia TCW, Jennifer Kouznetsova, Sarah C Ogden, Christy Hammack, Fadi Jacob, Ha Nam Nguyen, Misha Itkin, Catherine Hanna, Paul Shinn, Chase Allen, Samuel G Michael, Anton Simeonov, Wenwei Huang, Kimberly M Christian, Alison Goate, Kristen J Brennand, Ruili Huang, Menghang Xia, Guo-li Ming, Wei Zheng, Hongjun Song, Hengli Tang
Journal: Nature Medicine (2016)
P0014 : The effect of different nutritional support in liver surgery
Authors: M.M. Braz, B. Kleuser, S. Fayyaz, M.B. Jiménez Castro, J.G. Sancho, F.S. Ramalho, M.E.P. Cornide, L. Torrens, J. Rodes, C. Peralta
Journal: Journal of Hepatology (2015)
Abstract P27: Microglial Activity and Therapeutic Hypothermia Post Cardiac Arrest Resuscitation in Rats
Authors: Xiaofeng Jia, Shinyi Tsai, Gehua Zhen, Adrian Velasquez, Matthew A Koenig, Carlos A Pardo, Nitish V Thakor, Romergryko G Geocadin
Journal: Circulation (2008)

Background Therapeutic hypothermia after cardiac arrest (CA) improves survival and functional outcomes, but its neuroprotective mechanism remains unclear. We previously showed that immediate initiation of hypothermia post-CA led to better neuro-electrical and behavioral recovery. In this study, we quantified the impact of immediate versus conventional hypothermia with stereological technique on microglia (using expression of ionized calcium binding adaptor molecule 1 - Iba1), astrocytes (using expression of glial fibrillary astrocyte protein - GFAP), and neurons (by Cresyl-violet staining with histopathological damage scoring - HDS). Methods Forty-eight rats were randomly divided into 3 groups (n=16 per group), based on normothermia (NT, T=37°C), 6 hours of immediate hypothermia (IH, T=33°C, initiated immediately after CA), or 12 hours of conventional hypothermia (CH, T=33°C, initiated one hour after CA) after CA. Each group was then evenly divided to 2 subgroups (n=8 based on 7 or 9 min asphyxial time). Hypothermia was maintained using surface cooling. Neurological recovery was evaluated using serial Neurological Deficit Score (NDS) calculation. Results Better recovery by NDS 72 hours post-CA was noted in rats treated with IH (median, interquartile range: 72, 63–74), compared to CH (66, 43–70), and NT (51, 0 – 65) (p=0.005). There was a significantly different proportion of ischemic neurons by HDS in cortex (IH: 18.9±2.5%, CH: 33.2±4.4%, NT: 36.2±4.7%, p=0.002) and CA1 (IH: 14.4±2.9%, CH: 24.6±5.4%, NT: 49.2±5.3%, p&lt;0.001). There was significant less Iba-1 expression in CH compared to IH (p=0.042) and NT (p=0.012) in cortex and CA1. There was no difference for GFAP expression in cortex or CA1. Conclusions Immediate hypothermia leads to better functional outcome and lower ischemic neuronal injury in rats after CA. Temperature manipulation seems to affect the immune response to CA, with increased microglial activity in the IH and NT groups compared to CH group in this injury model. The longer hypothermia duration may decrease the microglia activation in response of central nervous system to CA than short duration in this injury model. No difference was noted in the astrocytic activity in the different groups.
Sexual problems are common in under 55s after acute MI, study finds
Authors: Jacqui Wise
Journal: BMJ (2016)

Problems with sexual function are common in younger adults after a myocardial infarction (MI), particularly among women, a study published in JAMA Cardiology has shown.1 The researchers also found that very few participants reported talking to a doctor about resuming sex after an MI.

Nearly 20% of acute MIs occur in people aged 18 to 55, and one third of these are women. Most people in this age range who have …
Comparative Methylome Analyses Identify Epigenetic Regulatory Loci of Human Brain Evolution
Authors: Isabel Mendizabal, Lei Shi, Thomas E. Keller, Genevieve Konopka, Todd M. Preuss, Tzung-Fu Hsieh, Enzhi Hu, Zhe Zhang, Bing Su, Soojin V. Yi
Journal: Molecular Biology and Evolution (2016)

How do epigenetic modifications change across species and how do these modifications affect evolution? These are fundamental questions at the forefront of our evolutionary epigenomic understanding. Our previous work investigated human and chimpanzee brain methylomes, but it was limited by the lack of outgroup data which is critical for comparative (epi)genomic studies. Here, we compared whole genome DNA methylation maps from brains of humans, chimpanzees and also rhesus macaques (outgroup) to elucidate DNA methylation changes during human brain evolution. Moreover, we validated that our approach is highly robust by further examining 38 human-specific DMRs using targeted deep genomic and bisulfite sequencing in an independent panel of 37 individuals from five primate species. Our unbiased genome-scan identified human brain differentially methylated regions (DMRs), irrespective of their associations with annotated genes. Remarkably, over half of the newly identified DMRs locate in intergenic regions or gene bodies. Nevertheless, their regulatory potential is on par with those of promoter DMRs. An intriguing observation is that DMRs are enriched in active chromatin loops, suggesting human-specific evolutionary remodeling at a higher-order chromatin structure. These findings indicate that there is substantial reprogramming of epigenomic landscapes during human brain evolution involving noncoding regions.
Chemoablation of metastatic melanoma with rose bengal (PV-10).
Authors: S. S. Agarwala, J. F. Thompson, B. M. Smithers, M. I. Ross, B. J. Coventry, D. R. Minor, C. R. Scoggins, E. A. Wachter
Journal: Journal of Clinical Oncology (2010)

8534 Background: Intralesional rose bengal (PV-10, 10% RB in saline) can elicit selective chemoablation of solid tumors and an apparent bystander response in untreated lesions. In phase I (20 subjects with AJCC stage III-IV melanoma), a single injection into a total of 114 lesions was well tolerated, yielding durable objective response (OR) at 12-24 weeks in 40% of subjects (20% CR + 20% PR by modified RECIST) and locoregional disease control (CR + PR + SD) in 75% of subjects; 15% of subjects achieved an OR in their bystander lesions (43 lesions). Methods: Phase II testing (80 subjects with measurable Stage III-IV melanoma) commenced at 7 centers in Australia and the USA in October 2007 with enrollment completed in May 2009. After initial treatment of 1-20 cutaneous, subcutaneous or nodal lesions, new or incompletely responsive lesions could be retreated at weeks 8, 12 or 16, with follow-up to 52 weeks. Another 1-2 lesions, including visceral lesions, could remain untreated for assessment of bystander response. The primary end-point is OR of injected target lesions; secondary endpoints include OR of bystander lesions, PFS of target lesions, and plasma PK assessment. Results: The first 40 subjects (median age 75, range 37-92) have completed the study, receiving PV-10 into 486 lesions (mean 1.9 treatment sessions per subject). Adverse events were predominantly mild to moderate, locoregional and transient, the most common being pain at the treatment site (82% of subjects), vesicles or edema (50% each) followed by swelling, pruritus, skin discoloration or headache (18% each), with no grade 4 or 5 AEs attributed to PV-10. Among all 40 subjects, 33% achieved CR, 28% PR and 18% SD of their target lesions; 33% of 21 subjects with evaluable bystander lesions achieved CR in these lesions, along with 10% PR and 14% SD. Mean PFS was 8.5 months (all subjects), while the OR cohort had significantly longer PFS (11.1 months) than SD or PD subjects (2.8 and 2.7 months, respectively). Plasma clearance was bi-exponential (t½ ca. 15 and 120 hrs) consistent with rapid uptake of extravasate and prolonged intralesional retention. Conclusions: Overall, the safety and efficacy profile of PV-10 compares favorably with available and emerging options for this patient population. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Provectus Pharmaceuticals Provectus Pharmaceuticals Provectus Pharmaceuticals
Diffuse Elevated Abdominal Activity on 99mTc-Labeled Red Blood Cell Imaging in a Pediatric Patient With Klippel Trenaunay Syndrome
Authors: Summer L. Kaplan, Hongming Zhuang
Journal: Clinical Nuclear Medicine (2016)

Klippel Trenaunay syndrome commonly manifests as lower limb hypertrophy where vascular malformation occurs. However, up to 20% of patients with Klippel Trenaunay syndrome can have gastrointestinal involvement. An 18-year-old man with known Klippel Trenaunay syndrome in the left lower extremity underwent Tc-labeled red blood cell imaging to determine the site of gastrointestinal bleeding. The images did not reveal the site of active bleeding. However, diffuse non-moving activity in the left abdomen and pelvis was noted, which corresponded to hypertrophied colon and related blood vessels, consistent with intestinal involvement of Klippel Trenaunay syndrome.
Details emerge of plans to cut NHS services in England
Authors: Gareth Iacobucci
Journal: BMJ (2016)

Details have emerged of plans to cut NHS services as part of a major reorganisation of care across England.

Proposals to close hospital wards, shut or downgrade emergency departments, and reduce hospital bed numbers were included in draft “sustainability and transformation plans” (STPs) drawn up by leaders in the NHS, local government, and other local healthcare services.

The details of the plans, which are subject to consultation and sign off from NHS England, were disclosed by the campaign group 38 Degrees,1 which commissioned the healthcare consultancy firm Incisive Health to collate and analyse the proposals.2

The draft plans were drawn up after NHS England, in December 2015, instructed local leaders to work together to establish 44 STP “footprints” covering the whole of England. These footprints must meet the triple aims of improving health outcomes, improving …
Subsequent Breast Cancer Risk Following Diagnosis of Atypical Ductal Hyperplasia on Needle Biopsy
Authors: Tehillah S. Menes, Karla Kerlikowske, Jane Lange, Shabnam Jaffer, Robert Rosenberg, Diana L. Miglioretti
Journal: JAMA Oncology (2016)

Atypical ductal hyperplasia (ADH) is a known risk factor for breast cancer. Published risk estimates are based on cohorts that included women whose ADH was diagnosed before widespread use of screening mammograms and did not differentiate between the methods used to diagnose ADH, which may be related to the size of the ADH focus. These risks may overestimate the risk in women with presently diagnosed ADH.To examine the risk of invasive cancer associated with ADH diagnosed using core needle biopsy vs excisional biopsy.A cohort study was conducted comparing the 10-year cumulative risk of invasive breast cancer in 955 331 women undergoing mammography with and without a diagnosis of ADH. Data were obtained from 5 breast imaging registries that participate in the National Cancer Institute-funded Breast Cancer Surveillance Consortium.Diagnosis of ADH on core needle biopsy or excisional biopsy in women undergoing mammography.Ten-year cumulative risk of invasive breast cancer.The sample included 955 331 women with 1727 diagnoses of ADH, 1058 (61.3%) of which were diagnosed by core biopsy and 635 (36.8%) by excisional biopsy. The mean (interquartile range) age of the women at diagnosis was 52.6 (46.9-60.4) years. From 1996 to 2012, the proportion of ADH diagnosed by core needle biopsy increased from 21% to 77%. Ten years following a diagnosis of ADH, the cumulative risk of invasive breast cancer was 2.6 (95% CI, 2.0-3.4) times higher than the risk in women with no ADH. Atypical ductal hyperplasia diagnosed via excisional biopsy was associated with an adjusted hazard ratio (HR) of 3.0 (95% CI, 2-4.5) and, via core needle biopsy, with an adjusted HR of 2.2 (95% CI, 1.5-3.4). Ten years after an ADH diagnosis, an estimated 5.7% (95% CI, 4.3%-10.1%) of the women had a diagnosis of invasive cancer. Women with ADH diagnosed on excisional biopsy had a slightly higher risk (6.7%; 95% CI, 3.0%-12.8%) compared with those with ADH diagnosed via core needle biopsy (5%; 95% CI, 2.2%-8.9%).Current 10-year risks of invasive breast cancer after a diagnosis of ADH may be lower than those previously reported. The risk associated with ADH is slightly lower for women whose ADH was diagnosed by needle core biopsy compared with excisional biopsy.
Low natural killer (NK) cell counts in peripheral blood adversely affect clinical outcome of patients with follicular lymphoma
Authors: L He, H-Y Zhu, S-C Qin, Y Li, Y Miao, J-H Liang, Y Xia, Y Wang, Y-J Wu, L Wang, L Fan, J-Y Li, W Xu
Journal: Blood Cancer Journal (2016)

Low natural killer (NK) cell counts in peripheral blood adversely affect clinical outcome of patients with follicular lymphoma
Fish Oil vs Olive Oil for Postoperative Atrial Fibrillation
Authors: John G. F. Cleland, Anil Joseph, Pierpaolo Pellicori
Journal: JAMA (2013)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Identification of selective inhibitors of dedifferentiated liposarcoma cells by high-throughput screening (HTS).
Authors: C. V. Angeles, B. Laxa, D. Shum, P. DeCarolis, R. Gobble, E. Brill, S. Ugras, R. O'Connor, H. Djaballah, S. Singer
Journal: Journal of Clinical Oncology (2010)

10005 Background: Current chemotherapy for dedifferentiated liposarcoma (DDLS) is largely ineffective demanding a need for new therapeutics. An HTS was performed to discover compounds that selectively promote differentiation and cytotoxicity in DDLS cells but not in adipose-derived stem cells (ASC). Methods: A 3,119 molecule HTS was performed using two DDLS cell lines (DDLS8817 and LPS141) and ASC. Cells were incubated with 10uM of compounds and immunofluorescently stained with C/EBPα and Hoechst nuclear stain to quantify differentiation and cytotoxicity. Images were analyzed by laser confocal microscopy. Hits for C/EBPα were validated by immunoblotting. CyQuant proliferation and annexin V staining confirmed cytotoxicity. SCID mice were transplanted with DDLS tumor (BWH) and treated with adriamycin 0.9mg/kg daily or emetine 20mg/kg biweekly. Results: 48 of 3,119 compounds (2%) were positive for C/EBPα induction in both DDLS lines but not in ASC. 32 compounds (1%) were selectively cytotoxic to DDLS lines. 16 compounds, including deguelin and emetine, were selective C/EBPα inducers and cytotoxic. Immunoblotting confirmed increased C/EBPα expression in treated cells (100nM emetine, 4uM deguelin) compared to untreated controls. Emetine completely inhibited proliferation in DDLS lines. Deguelin decreased proliferation by 24% in DDLS8817 (p<0.05) and 48% in LPS141 (p<0.05). ASC treated with deguelin or emetine had no significant change in proliferation. Emetine increased apoptosis 2-fold and 3.4-fold (p<0.05), while deguelin increased apoptosis 1.1-fold and 4.8-fold (p<0.05) compared to controls in DDLS8817 and LPS141. BWH mice treated with emetine had a 49% reduction in tumor growth compared to untreated controls, yet adriamycin only had an 18% reduction. Conclusions: A chemical screen was used to discover compounds that induce differentiation and show selective cytotoxicity for DDLS cells. Emetine inhibits proliferation and induces apoptosis at nM concentrations and inhibits tumor growth in vivo more than adriamycin, a commonly used LS chemotherapeutic. These results show the promise of this approach for the discovery of novel differentiation-based agents for the treatment of DDLS. No significant financial relationships to disclose.
Pharmacologic Monitoring of Dasatinib As First Line Therapy in Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia (CP-CML) Identifies Patients At Higher Risk of Pleural Effusion: A Sub-Analysis of the OPTIM-Dasatinib Trial
Authors: Philippe Rousselot, Luigina Mollica, Gabriel Etienne, Stephane Bouchet, Agnès Guerci, Franck E Nicolini, Emmanuelle Chauzit, Pascale Cony-Makhoul, Valérie Coiteux, Martine Gardembas, Laurence Legros, Lydia Roy, Aude Charbonnier, Caroline Dartigeas, Jean-Michel Cayuela, Lambert Busque, Mathieu Molimard, Joelle Guilhot, Francois Guilhot, Francois-Xavier Mahon
Journal: Blood (2012)
Interim Results of a Phase I Study of Lenalidomide (CC-5013) Plus Intraventricular/Intravenous Rituximab for Recurrent/Refractory CNS and Intraocular Lymphoma
Authors: James L. Rubenstein, Paul Formaker, Xiaomin Wang, Nianhang Chen, Michael Seider, Pamela Munster, Bertil Damato
Journal: Blood (2014)
Benign male genital dermatoses
Authors: Tang Ngee Shim, Iaisha Ali, Asif Muneer, Christopher B Bunker
Journal: BMJ (2016)

Males with genital skin disease may present to clinicians in primary care, dermatology, genitourinary medicine, or urology clinics. Male genital dermatoses encompass a wide variety of skin lesions and rashes, some of which are limited to the genital area whereas others, such as psoriasis, can be part of a more generalised skin disorder. Genital skin disease can impact on the physical, psychological, and sexual wellbeing of men. Some dermatoses are precancerous, and cancer of the penis is associated with morbidity and mortality and litigation.1 This clinical update provides a guide to normal anatomical variations of the penis, how to recognise and manage common benign male genital dermatoses, and when to refer for specialist opinion.

#### Sources and selection criteria

We searched PubMed and Google Scholar for clinically relevant studies (Jan 2000 to Jul 2016), and the Cochrane Library, using the search terms “Balanitis”, “Balanoposthitis”, “Penile Dermatoses”, “Genital Dermatoses”, along with terms specific to each condition. We consulted the Cochrane Library, National Institute for Health and Care Excellence, British Association of Dermatologists, and British Association for Sexual Health and HIV for guidelines.

Patients may be asymptomatic or describe pruritus, soreness, pain, dyspareunia, splitting of the foreskin, non-retractile foreskin (phimosis) or foreskin fixed in retraction (paraphimosis), scaling, erosion, and ulceration.2 3 The foreskin is a delicate tissue that is in close contact with urine, sweat, moisture, sexual secretions, desquamative products, detergents, potential allergens, and microbes. These factors may expose the foreskin to general irritation, pain, and dysfunction (eg, paraphimosis or phimosis, dribbling of urine, dyspareunia).3 4 Further progression of infection and inflammation can cause scarring, disfigurement, and, rarely, precancerous or cancerous lesions. Most men presenting to a specialist male genital dermatology clinic are uncircumcised.5 Circumcision protects men from inflammatory genital dermatoses, including psoriasis, seborrhoeic dermatitis, lichen planus, and lichen sclerosus.5 Predisposition to …
Comparison of Outcomes after Double or Single-Unit Cord Blood Transplantation in Patients with Hematological Malignancies Using TBI-Containing Myeloablative Conditioning Regimen, a Retrospective Matched Control Study on Behalf of C-SHOT0507 and JSHCT Registry Data in Japan
Authors: Atsushi Wake, Shunro Kai, Masaya Okada, Koji Kato, Naoyuki Uchida, Naoki Kobayashi, Nobuyuki Aotsuka, Jun Ishikawa, Satoshi Takahashi, Tetsuya Eto, Shuichi Taniguchi, Yoshiko Atsuta, Shunichi Kato
Journal: Blood (2014)
Risk of thromboembolic events (TEE) in metastatic colorectal cancer (mCRC) patients with single nucleotide polymorphisms (SNPs) in Factor V Leiden (FVL), Prothrombin, Plasminogen Activator Inhibitor-1 (PAI-1) and Methylenetetrahydrofolate Reductase (MTHFR)
Authors: S. Falvella, C. Cremolini, R. Miceli, M. Niger, R. Berenato, S. Cheli, C. Antoniotti, F. Nichetti, G. Infante, M. Caporale, A. Martinetti, F. Marmorino, E. Sottotetti, A. Colombo, I. Bossi, M. Di Bartolomeo, F. de Braud, E. Clementi, F. Loupakis, F. Pietrantonio
Journal: Annals of Oncology (2015)