tbuckley/cabot-search huggingface dataset:
Same sex twins should give consent for zygosity testing except when medically necessary
Authors: Sarah E A Smith, Lucy K A Carr, Elizabeth M Smith, Russell E A Smith
Journal: BMJ (2016)

Vadgama and colleagues recommend genetic testing for zygosity of all same sex twins at birth irrespective of medical need.1 As parents of same sex, dichorionic twins of unknown zygosity, we think that patient and parent choice and consent should be part of the decision, and this is supported …
Single Antiplatelet Therapy Following Left Atrial Appendage Closure in Patients With Contraindication to Anticoagulation
Authors: Tania Rodriguez-Gabella, Luis Nombela-Franco, Ander Regueiro, Pilar Jiménez-Quevedo, Jean Champagne, Gilles O’Hara, Mathieu Bernier, Carlos Macaya, Josep Rodés-Cabau
Journal: Journal of the American College of Cardiology (2016)
Self-assembled mirror DNA nanostructures for tumor-specific delivery of anticancer drugs
Authors: Kyoung-Ran Kim, Hyo Young Kim, Yong-Deok Lee, Jong Seong Ha, Ji Hee Kang, Hansaem Jeong, Duhee Bang, Young Tag Ko, Sehoon Kim, Hyukjin Lee, Dae-Ro Ahn
Journal: Journal of Controlled Release (2016)
Fast 3D Imaging of Spine, Dendritic, and Neuronal Assemblies in Behaving Animals
Authors: Gergely Szalay, Linda Judák, Gergely Katona, Katalin Ócsai, Gábor Juhász, Máté Veress, Zoltán Szadai, András Fehér, Tamás Tompa, Balázs Chiovini, Pál Maák, Balázs Rózsa
Journal: Neuron (2016)

Highlights•3D DRIFT AO scanning can extend each point to 3D lines, surfaces, or volume elements•Retained spatial information is used for post hoc movement correction of signals•Chessboard; snake; multi-cube; multi-3D line; and multi-layer, multi-frame scanning•Improved excitation efficiency for large 3D scanning volume with GECIsSummaryUnderstanding neural computation requires methods such as 3D acousto-optical (AO) scanning that can simultaneously read out neural activity on both the somatic and dendritic scales. AO point scanning can increase measurement speed and signal-to-noise ratio (SNR) by several orders of magnitude, but high optical resolution requires long point-to-point switching time, which limits imaging capability. Here we present a novel technology, 3D DRIFT AO scanning, which can extend each scanning point to small 3D lines, surfaces, or volume elements for flexible and fast imaging of complex structures simultaneously in multiple locations. Our method was demonstrated by fast 3D recording of over 150 dendritic spines with 3D lines, over 100 somata with squares and cubes, or multiple spiny dendritic segments with surface and volume elements, including in behaving animals. Finally, a 4-fold improvement in total excitation efficiency resulted in about 500 × 500 × 650 μm scanning volume with genetically encoded calcium indicators (GECIs).
What Is the Impact on Quality of Life of Various Treatments in Acute Myeloid Leukemia and High-Risk Myelodysplastic Syndrome? Rethinking the Goals
Authors: Sara M. Tinsley, Brent J Small, Jeffrey E Lancet, Susan C McMillan, Rami S. Komrokji, Eric Padron, Kenneth S. Zuckerman, Alan F. List
Journal: Blood (2015)
Giant-Cell Arteritis and Polymyalgia Rheumatica
Authors: Cornelia M. Weyand, Jörg J. Goronzy
Journal: New England Journal of Medicine (2014)

Both giant-cell arteritis and polymyalgia rheumatica are immune-mediated diseases that are treated with glucocorticoids, with higher doses used for giant-cell arteritis. Prompt initiation of high doses and a biopsy are recommended when ischemic optic neuropathy is suspected.
Treatment of malignant pleural effusion with the trifunctional antibody catumaxomab (anti-EpCAM x anti-CD3): Results of a phase I/II study
Authors: M. Sebastian, W. Schuette, F. Schneller, G. Nilius, S. Lodziewski, B. Passlick, G. Hoffken, H. Friccius-Quecke, M. Jaeger, A. Schmittel
Journal: Journal of Clinical Oncology (2006)

2548 Background: The trifunctional antibody catumaxomab specifically binds EpCAM + tumor cells, CD3+ T lymphocytes and accessory cells via the Fcγ RI/III. Thus the antibody induces tumor specific cell mediated cytotoxicity in vitro and in vivo. Its intraperitoneal administration has demonstrated safety and led to efficient tumor cell killing and reduction of malignant ascites in ovarian cancer patients (pts.). The present study was conducted to evaluate safety, tolerability and preliminary efficacy of catumaxomab administered intrapleurally (i.pl.) into pts. with EpCAM + malignant pleural effusion. Methods: This phase I/II trial was a multi-center uncontrolled, dose-escalating study. Pts. (ECOG ≤3) with recurrent malignant pleural effusion containing EpCAM + tumor cells were included. Three escalating doses from 5–200 μg catumaxomab were administered i.pl. Primary objectives were toxicity and definition of the maximum tolerated dose (MTD). In addition, preliminary data on efficacy (reduction of pleural fluid and tumor cell killing) were generated. Results: 13/24 pts. received 3 infusions as planned. Reasons for early termination of infusions were 3 deteriorations of performance status, 2 exanthemas, 2 dyspnoea, 2 others. The dose regimen of 20–50–100 μg catumaxomab was defined as MTD. Most frequent drug related AEs were symptoms of cytokine release syndrome. 32 SAEs were reported in 18 pts., 4 SAEs were possibly drug related (1 death due to pleural empyema, 1 pneumonia, 1 erythema, 1 increase of liver enzymes). 8/9 deaths were not drug related but due to underlying disease. Induction of human-anti-mouse (HAMA) or human-anti-rat (HARA) antibodies after treatment was found in 8/11 pts. 8/13 fully treated pts. were defined as responders (1 complete, 4 partial, 3 NA) showing reduction of effusion and of drainage necessity. 5/13 were non-responders. A reduction of tumor cells up to log 5 was seen in 10/13 pts. Conclusions: 20–50–100 μg of catumaxomab can safely be administered i. pl. This regimen will further be investigated in a randomized phase II trial comparing catumaxomab to talcum-based pleurodesis. [Table: see text]
Palliative Care–Led Meetings for Families of ICU Patients—Reply
Authors: Marion Danis, Shannon S. Carson, Laura C. Hanson
Journal: JAMA (2016)

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Part 5: Electrical Therapies
Authors: To treat VF SCA, rescuers must be able to rapidly integrate CPR with use of the AED. To give the victim the best chance of survival, 3 actions must occur within the first moments of a cardiac arrest: (1) activation of the emergency medical services (EMS) system or emergency medical response system, (2) provision of CPR, and (3) operation of an AED. When 2 or more rescuers are present, activation of EMS and initiation of CPR can occur simultaneously.
Journal: Circulation (2005)
ABT-263 activity and safety in patients with relapsed or refractory lymphoid malignancies in particular chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL)
Authors: W. Wilson, O. O. O'Connor, A. W. Roberts, M. Czuczman, J. Brown, H. Xiong, H. Xiong, Y. Chiu, A. Krivoshik, S. Enschede, R. Humerickhouse
Journal: Journal of Clinical Oncology (2009)

8574 Background: ABT-263, a novel, orally bioavailable, BH3 mimetic, binds with high affinity (K i ≤ 1nM) and inhibits multiple antiapoptotic Bcl-2 family proteins. ABT-263 displays activity (EC 50 ≤ 1μM) against human lymphoid and small cell lung cancer cell lines. Mechanism based preclinical toxicities include reductions in circulating lymphocytes, apoptosis of circulating platelets, and decreased spermatogenesis, mediated by inhibition of Bcl-2, Bcl-X L , and Bcl-w, respectively. Methods: Safety and activity of ABT-263 in 2 enrolling phase I studies in relapsed/refractory lymphoid malignancies (M06–814) and CLL (M06–873) was evaluated. Patients (pts) were dosed on days 1–14 of a 21 d cycle, 10–440mg (M06–814) or 10–250mg (M06–873). Continuous 21/21 d dosing (CD) post lead-in dose is being explored in both studies. Results: 55 pts, 14/21 d dosing, enrolled in the 2 studies. ABT-263 PK were linear from 10 - 440mg (N=55) and the terminal half-life was 14 - 20 h (n=35). Among 27 CLL/SLL pts, 3 have confirmed radiographic partial responses (PR) (99%, 92% and 72%) and 2 have unconfirmed regressions, 51% and 72%. 6 pts maintained a ≥50% decrease in circulating lymphocytes for ≥ 2 months and 11 pts have stable disease; of these 5 experienced minor radiographic responses (range of 36% to 49%). In addition, among 40 (M06–814) lymphoma pts, 3 with follicular lymphoma achieved PR and one had a minor response (49% regression). With CD dosing (16 pts), activity includes 1 unconfirmed PR in SLL &amp; and 3 CLL pts with ≥50% lymphocyte reduction for ≥2 months duration. Pharmacodynamic toxicities included dose-dependent thrombocytopenia (TCP) resulting from on-target activity against Bcl-X L . Dose limiting toxicities, 14/21 d dosing, in M06–814 occurred at 160mg (bronchitis), 315mg (elevated ALT and grade 4 TCP) and 440mg (worsening pleural effusion in a pt with underlying afib), and in M06–873 at 110mg (tumor lysis and grade 4 TCP) and 250mg (grade 4 TCP). Conclusions: ABT-263 showed favorable PK and safety profiles with anti-tumor activity in relapsed/refractory CLL/SLL and follicular lymphoma. Identification of optimal dose and schedule for phase II trials continues. [Table: see text]
Response to Open Peer Commentaries on “Withdrawing Versus Withholding Freedoms: Nudging and the Case of Tobacco Control”
Authors: Andreas T. Schmidt
Journal: The American Journal of Bioethics (2016)

I thank the commentators for their thoughtful pieces written in response to my “Withdrawing Versus Withholding Freedoms: Nudging and the Case of Tobacco Control” (Schmidt 2016b). In that article, I...
Hematopoietic Stem Cell Transplantation following Reduced Intensity Conditioning for High Risk Patients with Paroxysmal Nocturnal Hemoglobinuria
Authors: Agata Mikolajewska, Haifa Kathrin Al-Ali, Nadezda Basara, Elliot Epner, Ernst Holler, Laura Johnston, Dietger Niederwieser, Thoralf Lange
Journal: Blood (2008)
Pityriasis Rubra Pilaris Type V as an Autoinflammatory Disease by <i>CARD14</i> Mutations
Authors: Takuya Takeichi, Kazumitsu Sugiura, Toshifumi Nomura, Taiko Sakamoto, Yasushi Ogawa, Naoki Oiso, Yuko Futei, Aki Fujisaki, Akiko Koizumi, Yumi Aoyama, Kimiko Nakajima, Yutaka Hatano, Kei Hayashi, Akemi Ishida-Yamamoto, Sakuhei Fujiwara, Shigetoshi Sano, Keiji Iwatsuki, Akira Kawada, Yasushi Suga, Hiroshi Shimizu, John A. McGrath, Masashi Akiyama
Journal: JAMA Dermatology (2016)

We found CARD14 mutations (2 de novo novel mutations and another previously reported mutation) in 3 of 3 patients with pityriasis rubra pilaris (PRP) type V, but not in patients with PRP of other types. Our findings, combined with the published literature, suggest that type V PRP, both familial and sporadic, can be caused by CARD14 mutations. Detailed clinical observation revealed that all 3 patients displayed unique patchy macular brown hyperpigmentation.To further determine how often patients with PRP have pathogenic mutations in CARD14 and to elucidate which clinical subtype of PRP is caused by CARD14 mutations.We sequenced the entire coding regions of CARD14 in genomic DNA from patients with 5 clinical subtypes of PRP. The detailed clinical features were analyzed in all the patients. The pathogenicity of each mutation was evaluated by several computational predictions. PRP was classified into 6 subgroups, types I to VI, based on clinical criteria. We categorized all the patients with PRP into the clinical subtypes using the classic PRP classification; 22 cases of PRP with varying subtypes were studied.The prevalence of CARD14 mutations in each subtype of PRP was evaluated. Clinical features and characteristics of patients with PRP with CARD14 mutations were analyzed.Overall 22 patients with PRP were included in our study (12 men, 10 women; mean [SD] age, 26 [18] years). Among 3 patients with PRP type V, all were found to have CARD14 mutations: 2 de novo novel mutations (p.Cys127Ser and p.Gln136Leu), and another previously reported mutation (p.Gly117Ser). All were close to the reported pathogenic domains. In silico analysis of all 3 mutations suggested that they are functionally relevant to pathogenesis. All 3 patients displayed unique patchy macular brown hyperpigmentation additionally to other typical features of PRP. Patients with PRP type I and type IV, 1 patient each, had the rare variants in CARD14.Pityriasis rubra pilaris type V is a distinct variant of PRP that is caused by CARD14 mutations. In addition, a rare variant of CARD14 might also be implicated in the pathophysiology of other forms of PRP.
Oprozomib and Dexamethasone in Patients with Relapsed and/or Refractory Multiple Myeloma: Initial Results from the Dose Escalation Portion of a Phase 1b/2, Multicenter, Open-Label Study
Authors: Parameswaran N. Hari, Kenneth H. Shain, Peter M. Voorhees, Nashat Gabrail, Muneer H. Abidi, Jeffrey Zonder, Ralph V. Boccia, Paul G. Richardson, Linda L. Neuman, Sandra J. Dixon, Claudia Paba Prada
Journal: Blood (2014)
Free methylated DNA in association of clinical signs and circulating blood tumor cells in patients with breast cancer.
Authors: C. Matuschek, E. Boelke, W. Budach, H. Prisack, H. Taskin, M. Peiper, M. Rezai, H. Bojar
Journal: Journal of Clinical Oncology (2010)

1068 Background: Tumor-related methylated DNA and circulating tumor cells (CTC) in peripheral blood seem to be a prognostic factor for breast cancer. We investigated the correlations between free methylated DNA and CTC in the blood from patients with breast cancer as compared to healthy controls. Methods: We prospectively obtained matched peripheral blood and serum samples from 86 patients with breast cancer and 23 healthy volunteers. The AdnaTest BreastCancer Select & Detect was used to assay for circulating tumor cells in the peripheral blood. Sera were analyzed in parallel by methylation specific PCR (MethyLight PCR) for five genes: adenomatous polyposis coli (APC), ras association domain family protein 1A (RASSF1A), estrogen receptor 1 (ESR1), GSTP1 > glutathione s-transferase pi 1and CDKN2 > cyclin-dependent kinase inhibitor 2A. ACTB > beta actin served as control. Results: A significant difference was seen in methylated APC DNA between patients with cancer and healthy volunteers. Methylated APC and RASSF1 were significantly different in metastatic versus nonmetastatic disease. A strong correlation was observed between both molecular species (p=0.000). In addition, the presence of methylated APC and RASSF1A DNA significantly (p=0.001 and p=0.007, respectively) correlated with AJCC-staging. Methylated GSTP1 was predominantly found in the serum of patients with large primaries (p=0.023) and was highly significantly correlated with positive HER2/neu status (p=0.003). Elevated serum CA 15.3 was strongly correlated with methylated APC (p=0.000). The presence of CTC in peripheral blood was significantly associated with the methylated APC gene (p=0.013) as well as methylated GSTP1 (p= 0.022). Methylated ESR1 failed to exhibit significant correlations with any of the above parameters. Methylated CDKN2 was not detected in the serum of our patients with breast cancer. Conclusions: The detection of methylated serum APC and GSTP1 DNA correlated with the presence of CTC in the blood of patients with breast cancer. Both circulating DNA and CTC were a phenotypic feature of more aggressive tumor biology and advanced disease. No significant financial relationships to disclose.
Abstract C43: Role of microRNAs in determining the cancer associated fibroblast phenotype
Authors: Siti Amalina Zainal Abidin, Stuart Hunt, Dan Lambert
Journal: Cancer Research (2016)

Abstract Cancer-associated fibroblasts (CAF) are among the predominant cell types present within the tumour microenvironment. The presence of CAF expressing markers of myofibroblast transdifferentiation is associated with high-grade malignancies and poor prognoses in human diseases. The molecular mechanisms underlying myofibroblast transdifferentiation in CAF however, remain poorly understood. MicroRNAs regulate many biological processes, but their role in determining the fate of fibroblasts in the tumour microenvironment remains unclear. Objective: To elucidate the role of miRNA in the conversion of resident fibroblast to myofibroblastic CAF. Methods: Human primary oral fibroblasts were treated with different concentrations of TGF-β (0.05-5 ng/ml) for 24 and 48 hrs. Markers of CAF transdifferentiation such as alpha-smooth muscle actin (α-SMA) and fibronectin-EDA (FN-EDA) were analysed using qRT-PCR. Protein expression of α-SMA was analysed by western blot and formation of stress fiber was visualised using immunocytochemistry. Collagen gels were used to analyse fibroblast contractility and Taqman Low Density Array (TLDA) and qRT-PCR to determine miRNA expression profiles of experimentally-derived CAF. Results: qRT-PCR and western blotting demonstrated an increase in α-SMA expression in TGF-β-induced, experimentally-derived CAF. TGF-β induced stress fiber formation and enhanced contraction of fibroblasts. TGF-β induced differential expression of a number of miRNAs in experimentally-derived CAF, including; miR-424, miR-200c and miR-145. Conclusion: The role of miRNAs in the phenotypic changes observed in CAF has not been studied extensively. Here we show widespread alterations in miRNA expression profiles of experimentally-derived myofibroblastic CAF. Future studies will examine the role of these miRNA in reprogramming of normal fibroblasts to CAF-like phenotype and examine whether miRNA alterations contribute to the heterogeneity of the CAF phenotype observed in vivo. Citation Format: Siti Amalina Zainal Abidin, Stuart Hunt, Dan Lambert. Role of microRNAs in determining the cancer associated fibroblast phenotype. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr C43.
Naïve CD4+ T Cells Modified to Express a ROR1-Specific CAR Mediate Anti-Tumor Activity and Provide Superior Help to CD8+ ROR1-CAR T Cells
Authors: Michael Hudecek, Maria-Teresa Lupo-Stanghellini, Paula Kosasih, Jeannette Bet, Paulina Paszkiewicz, David G. Maloney, Michael C. Jensen, Christoph Rader, Stanley R. Riddell
Journal: Blood (2011)
Three Novel AML Cases Harboring the Semi-Cryptic t(7;21)(p22;q22) Translocation Expressing RUNX1-USP42 Fusion Transcripts Associated with Diploidy/Tetraploidy and/or 5q Alterations: a Probably Underestimated Combination
Authors: Eric Jeandidier, Carine Gervais, Isabelle Radford-Weiss, Catherine Gangneux, Valerie Rimelen, Georges Jung, Ines Harzallah, Bernard Drenou, Bruno Lioure, Laurent Mauvieux
Journal: Blood (2010)
Paclitaxel and pegylated liposomal doxorubicin in recurrent head/neck cancer: An unexpected administration interval-dependent pharmacokinetic interaction
Authors: M. Airoldi, L. Cattel, R. Passera, P. Milla, L. Delprino, C. Boselli, C. Buffa, F. Pedani
Journal: Journal of Clinical Oncology (2006)

2042 Background: Combination of paclitaxel (PTX) with pegylated liposomal doxorubicin (PLD) is an interesting opportunity for recurrent head/neck cancer treatment. Their pharmacokinetic (PK) behavior could be dependent not only on PTX excipient (polyethoxylated castor oil) interference, but also on different iv administration interval between the two drugs. The study endpoint was to evaluate any possible administration interval-dependent PK interaction, when PLD infusion start is delayed from 0 to 24 h after PTX infusion end. Methods: 24 patients affected by recurrent cisplatin pre-treated squamous cellhead/neck cancer were enrolled, receiving PTX 80 mg/m 2 q 1w and PLD 12.5 mg/m 2 q 2w for 6w/2w rest. Administration interval was 0 h at d1 (PTX-PLD 0) and 24 h at d15 (PTX-PLD 24). Blood sampling was performed at d1–15, PTX and PLD blood levels were analyzed by high performance liquid chromatography techniques, while PK parameters by non-compartmental analysis. Results: PTX PK parameters had large statistically significant differences (median/IQR, PTX-PLD 0 vs. PTX-PLD 24, Mann-Whitney test): Cmax 261/219–531 vs. 407/250–1473 ng/ml p=0.142, AUC 869/688–1331 vs. 3361/969–7853 ng*h/ml p=0.013, Kel 0.39/0.26–0.57 vs. 0.11/0.02–0.26 h⁁ −1 p=0.001, Cl 153/89–198 vs. 41/17–138 l/h p=0.013. Similarly, PLD Cmax and AUC were higher in PTX-PLD 24 (Cmax 5.1/3.3–8.1 vs. 6.8/5.3–7.8 mg/l p=0.043, AUC 341/104–1472 vs. 603/106–1006 mg*h/l p=1.000). The overall response rate was 37.5%, including 1 CR (4%); median response duration was 5.5 months (range, 2–16), median overall survival 10 months (range, 2–25+). Conclusions: This exploratory study, having a favourable palliative role in heavily pre-treated patients, showed that PTX PK profile is unexpectedly affected by a different administration interval. In PTX-PLD 0, PTX AUC is fourfold reduced, with a similar increase in Cl, totally due to Kel alteration: therefore, patients could be underexposed to PTX. PLD PK behavior confirmed previous studies results, in which PTX modified PLD disposition, prolonging the duration of its elimination phase and increasing total body exposure to PLD. No significant financial relationships to disclose.
Computed tomography findings in a confused patient
Authors: Joseph Dalby Sinnott, David C Howlett
Journal: BMJ (2016)

A 75 year old woman was referred to the emergency department from her nursing home because of increasing confusion. She had a history of falls and was taking warfarin for atrial fibrillation (international normalised ratio 2.6). On examination the patient appeared confused but had no focal neurological deficit. She underwent cranial computed tomography (CT) (fig 1⇓). What does this show?



Fig 1 

The CT scan shows two subdural haematomas: one on the right (fig 2 …
Frequency of Invasive Fungal Infections in Patients Undergoing Allogeneic Stem Cell Transplantation Conditioned with Reduced BUCY2 and Antifungal Prophylaxis with Low Dose Amphotericin B
Authors: Flor Maria Armillas Canseco, Monica M Rivera Franco, Eucario Leon Rodriguez, Ricardo Antonio Terrazas Marin
Journal: Blood (2015)
GW26-e0102 Loss of Angiotensin-Converting Enzyme 2 Exacerbates Renal Inflammation and Injury in the Apolipoprotein E-Deficient Mice
Authors: Jiuchang Zhong, Haiyan Jin, Zhenzhou Zhang, Laijiang Chen, Ran Xu, Yingle Xu, Pingjin Gao, Dingliang Zhu
Journal: Journal of the American College of Cardiology (2015)
Phase I/II, Open-Label, Dose-Escalating Study of MDX-060 Administered Weekly for 4 Weeks in Subjects with Refractory/Relapsed CD30 Positive Lymphoma.
Authors: Stephen M. Ansell, John C. Byrd, Steven M. Horwitz, Peter Borchmann, Andreas Engert, Roger Strair, Khuda D. Khan, Steven A. Fischkoff, Michael Yellin
Journal: Blood (2004)