tbuckley/cabot-search huggingface dataset:
Direct-acting antivirals-based therapy decreases hepatic fibrosis serum biomarker microfibrillar-associated protein 4 in hepatitis C patients
Authors: Christian Mölleken, Maike Ahrens, Anders Schlosser, Julia Dietz, Martin Eisenacher, Helmut E. Meyer, Wolff Schmiegel, Uffe Holmskov, Christoph Sarrazin, Grith Lykke Sorensen, Barbara Sitek, Thilo Bracht
Journal: Clinical and Molecular Hepatology (2018)

See the commentary-article "Biomarker microfibril-associated glycoprotein 4 for non-invasive diagnosis and therapeutic evaluation of hepatic fibrosis in patients with hepatitis C" on page 37.
Busulfan/Fludarabine- or Treosulfan/Fludarabine-Based Conditioning Regimen in Patients with Wiskott-Aldrich Syndrome Given Allogeneic Hematopoietic Cell Transplantation — an EBMT Inborn Errors Working Party and Scetide Retrospective Analysis
Authors: Michael H. Albert, Mary Slatter, Andrew Gennery, Tayfun Guengoer, Henric-Jan Blok, Junfeng Wang, Virginie Courteille, Maria Ester Bernardo, Ivana Bodova, Benedicte Bruno, Tatjana A Bykova, Robert Chiesa, Alain Fischer, Renata Formankova, Krzysztof Kalwak, Christoph Klein, Svetlana Kozlovskaya, O. Alphan Kupesiz, Franco Locatelli, Nizar Mahlaoui, Despina Moshous, Benedicte Neven, Fulvio Porta, Ansgar Schulz, Karl-Walter Sykora, Ekrem Unal, Jacek H. Winiarski, Marco Zecca, Paul Veys, Arjan Lankester
Journal: Blood (2018)
Spec-seq unveils transcriptional subpopulations of antibody-secreting cells following influenza vaccination
Authors: Karlynn E. Neu, Jenna J. Guthmiller, Min Huang, Jennifer La, Marcos C. Vieira, Kangchon Kim, Nai-Ying Zheng, Mario Cortese, Micah E. Tepora, Natalie J. Hamel, Karla Thatcher Rojas, Carole Henry, Dustin Shaw, Charles L. Dulberger, Bali Pulendran, Sarah Cobey, Aly A. Khan, Patrick C. Wilson
Journal: Journal of Clinical Investigation (2018)

Vaccines are among the most effective public health tools for combating certain infectious diseases such as influenza. The role of the humoral immune system in vaccine-induced protection is widely appreciated; however, our understanding of how antibody specificities relate to B cell function remains limited due to the complexity of polyclonal antibody responses. To address this, we developed the Spec-seq framework, which allows for simultaneous monoclonal antibody (mAb) characterization and transcriptional profiling from the same single cell. Here, we present the first application of the Spec-seq framework, which we applied to human plasmablasts after influenza vaccination in order to characterize transcriptional differences governed by B cell receptor (BCR) isotype and vaccine reactivity. Our analysis did not find evidence of long-term transcriptional specialization between plasmablasts of different isotypes. However, we did find enhanced transcriptional similarity between clonally related B cells, as well as distinct transcriptional signatures ascribed by BCR vaccine recognition. These data suggest IgG and IgA vaccine-positive plasmablasts are largely similar, whereas IgA vaccine-negative cells appear to be transcriptionally distinct from conventional, terminally differentiated, antigen-induced peripheral blood plasmablasts.
Comparative study: Side effects of Folfox4 and folfiri for colorectal cancer chemotherapy regiment in Margono Soekarjo Hospital, Purwokerto
Authors: I.N.A. Wiratama, W. Djatmiko, I.R. Ardiansyah, M.B. Salipi, A.F.N. Ilmi, N. Maharani
Journal: Annals of Oncology (2018)
Abstract 16639: Low Yield of Additional Non-invasive Testing in Moderate Worst Stenosis by cCTA in Acute Chest Pain Patients - Results From a Clinical ED cCTA Registry
Authors: Sumbal A Janjua, Harshna V Vadvala, Pedro V Staziaki, Richard A Takx, Anand M Prabhakar, John T Nagurney, Tomas G Neilan, Udo Hoffmann, Brian B Ghoshhajra
Journal: Circulation (2015)

Introduction: Coronary computed tomography angiography (cCTA) allows efficient triage of low-intermediate risk patients with suspected acute coronary syndrome (ACS); appropriate management of patients with moderate stenosis by cCTA is unknown. We evaluated the yield of downstream testing in moderate stenosis patients in a clinical ED cCTA registry. Methods: All consecutive ED patients with acute chest pain undergoing cCTA as part of routine care between October 2012 and July 2014 were screened. Patients with moderate as their worst stenosis (50-69% stenosis) on cCTA were included. Plaque characteristics, resting left ventricular function (by cCTA), results of any functional downstream non-invasive testing, invasive coronary angiography (ICA) and interventions, and discharge diagnosis were reported. ACS was defined as acute myocardial infarction (MI) or unstable angina pectoris (UAP) and adjudicated by an independent committee. Ischemia was defined as clear, territorial abnormality by myocardial perfusion scintigraphy imaging (MPI) or rest or stress echocardiogram, significant dynamic ST-T shift by exercise treadmill test (ETT) and stenosis &gt;70% on ICA or fractional flow reserve (FFR) &lt;0.75. Results: 586 patients underwent cCTA, with 7.2% (n=42) deemed moderate stenosis. Rate of ACS was 14.2% (n=6) with all adjudicated as UAP. Of these, 83% had stenosis caused by lipid-rich plaque; 33% had wall motion abnormalities on cCTA. The majority (n=28; 66%) underwent downstream non-invasive testing. Overall, n=2 (6%) of the non-invasive tests were positive for ischemia while n=3 (42%) of the invasive tests were diagnosed as positive for ischemia (all revascularized) (Figure 1). Conclusions: Unstable angina but not myocardial infarction is frequent among acute chest pain patients with moderate stenosis by cCTA. cCTA findings of lipid-rich plaque and resting functional abnormalities had a relatively higher yield vs. other non-invasive tests to detect ischemia.
Patient-Specific and Gene-Corrected Induced Pluripotent Stem Cell-Derived Cardiomyocytes Elucidate Single-Cell Phenotype of Short QT Syndrome
Authors: Fengfeng Guo, Yaxun Sun, Xiaochen Wang, Hao Wang, Jue Wang, Tingyu Gong, Xianzhen Chen, Ping Zhang, Lan Su, Guosheng Fu, Jun Su, Shilong Yang, Ren Lai, Chenyang Jiang, Ping Liang
Journal: Circulation Research (2019)

Short QT syndrome (SQT) is a rare but arrhythmogenic disorder featured by shortened ventricular repolarization and a propensity toward life-threatening ventricular arrhythmias and sudden cardiac death.This study aimed to investigate the single-cell mechanism of SQT using patient-specific and gene-corrected induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs).One SQT patient carrying missense mutation T618I in potassium voltage-gated channel subfamily H member 2 ( KCNH2) was recruited as well as 2 healthy control subjects in this study. Control and SQT patient-specific iPSCs were generated from skin fibroblasts using nonintegrated Sendai virus. The KCNH2 T618I mutation was corrected by genome editing in SQT iPSC lines to generate isogenic controls. All iPSCs were differentiated into iPSC-CMs using monolayer-based differentiation protocol. SQT iPSC-CMs exhibited abnormal action potential phenotype featured by shortened action potential duration and increased beat-beat interval variability, when compared with control and gene-corrected iPSC-CMs. Furthermore, SQT iPSC-CMs showed KCNH2 gain-of-function with increased rapid delayed rectifying potassium current (IKr) density and enhanced membrane expression. Gene expression profiling of iPSC-CMs exhibited a differential cardiac ion-channel gene expression profile of SQT. Moreover, QTc of SQT patient and action potential durations of SQT iPSC-CMs were both normalized by quinidine, indicating that quinidine is beneficial to KCNH2 T618I of SQT. Importantly, shortened action potential duration phenotype observed in SQT iPSC-CMs was effectively rescued by a short-peptide scorpion toxin BmKKx2 with a mechanism of targeting KCNH2.We demonstrate that patient-specific and gene-corrected iPSC-CMs are able to recapitulate single-cell phenotype of SQT, which is caused by the gain-of-function mutation KCNH2 T618I. These findings will help elucidate the mechanisms underlying SQT and discover therapeutic drugs for treating the disease by using peptide toxins as lead compounds.
Phase I/IIb trial: In-situ vaccine for metastatic colorectal cancer.
Authors: Madappa N. Kundranda, Tomislav Dragovich, Andrew Price, Philippe Lanauze, Miriam Bloch, Michael Bishop, John Chang, Michael Har-Noy
Journal: Journal of Clinical Oncology (2018)

TPS871 Background: Except for MSI-H tumors, CRC does not respond to immunotherapy. CRC does respond to the graft vs. tumor (GVT) immune effect that occurs after allogeneic stem cell transplantation. GVT is associated with GVHD toxicity which limits the clinical application. A bioengineered allograft (BAG) has been developed which can elicit host-mediated GVT-like effects without GVHD toxicity, chemotherapy conditioning or a HLA-matched donor. BAG are Th1 memory cells derived from blood of healthy donors with CD3/CD28 microbeads attached. These cells have immunomodulatory properties which enable modulation of Th1/Th2 balance and dysregulation of immunosuppressive circuits. We are evaluating the safety and efficacy of BAG in third-line mCRC. Methods: The study uses a standard 3+3 design followed by an expansion phase with the optimal dosing pattern. The protocol has four components: (A) priming; (B) in-situ vaccination; (C) extravasation and trafficking; and (D) counter immune suppression/avoidance. Priming involves intradermal injections of BAG cells which activates NK cells and develops allo-specific Th1/Tc1 immunity. In-Situ vaccination involves tumor cryoablation to release endogenous HSP which chaperone tumor neoantigens, followed immediately by the intralesional injection of BAG cells as adjuvant. Released HSP are engulfed and processed by immature dendritic cells (DC) attracted to the tissue damage. The inflammatory microenvironment created by the BAG and the subsequent allo-rejection response amplified by the priming induces DC maturation. These DC display processed tumor antigens on upregulated MHCI/II and express co-stimulatory CD80/86 enabling priming of a tumor-specific Th1/Tc1 response. CD40L and interferon-gamma expressed by BAG activates allo-specific and tumor-specific memory cells upon intravenous infusion, permitting trafficking to tumor. The host rejection of BAG releases endogenous danger signals creating a sustained systemic inflammatory cytokine release which serves to counter-regulate immunosuppressive mechanisms. Longitudinal CT scans biopsies, PBMC and serum samples are collected for analysis to verify immune events within each phase of the protocol. Clinical trial information: NCT02380443.
Too many rib ticklers? Injuries in Australian women’s cricket (PhD Academy Award)
Authors: Nirmala Kanthi Panagodage Perera
Journal: British Journal of Sports Medicine (2018)

I provided the first detailed epidemiological profile of incidence, nature and mechanism of injuries sustained by Australian female cricketers, through compilation and analysis of multiple data sources.

I grew up playing ‘mixed’ cricket and now it is a popular sport among women around the world. While sports participation carries many health benefits, one negative consequence is an increased risk of injury in participants. Evidence-based injury prevention programmes can reduce this risk when the causes of injury are known.1 However, before my PhD, little was known about the injuries in women’s cricket.

First, I conducted a systematic review of the literature describing injuries across competitive team bat-or-stick sports played by women.2 

I then generated a population-based epidemiological profile of cricket injuries sustained by women from multiple existing data sets. This included: (1) Existing data sources …
Prognostic value of MRD in CLL patients with comorbidities receiving chlorambucil plus obinutuzumab or rituximab
Authors: Anton W. Langerak, Matthias Ritgen, Valentin Goede, Sandra Robrecht, Jasmin Bahlo, Kirsten Fischer, Michael Steurer, Marek Trněný, Stephen P. Mulligan, Ulrich J. M. Mey, Kerstin Trunzer, Günter Fingerle-Rowson, Kathryn Humphrey, Stephan Stilgenbauer, Sebastian Böttcher, Monika Brüggemann, Michael Hallek, Michael Kneba, Jacques J. M. van Dongen
Journal: Blood (2018)
Publisher Correction: An immunoregulatory and tissue-residency program modulated by c-MAF in human TH17 cells
Authors: Dominik Aschenbrenner, Mathilde Foglierini, David Jarrossay, Dan Hu, Howard L. Weiner, Vijay K. Kuchroo, Antonio Lanzavecchia, Samuele Notarbartolo, Federica Sallusto
Journal: Nature Immunology (2018)
Transplantation of photoreceptors into the degenerative retina: Current state and future perspectives
Authors: Sylvia J. Gasparini, Sílvia Llonch, Oliver Borsch, Marius Ader
Journal: Progress in Retinal and Eye Research (2018)

The mammalian retina displays no intrinsic regenerative capacities, therefore retinal degenerative diseases such as age-related macular degeneration (AMD) or retinitis pigmentosa (RP) result in a permanent loss of the light-sensing photoreceptor cells. The degeneration of photoreceptors leads to vision impairment and, in later stages, complete blindness. Several therapeutic strategies have been developed to slow down or prevent further retinal degeneration, however a definitive cure i.e. replacement of the lost photoreceptors, has not yet been established. Cell-based treatment approaches, by means of photoreceptor transplantation, have been studied in pre-clinical animal models over the last three decades. The introduction of pluripotent stem cell-derived retinal organoids represents, in principle, an unlimited source for the generation of transplantable human photoreceptors. However, safety, immunological and reproducibility-related issues regarding the use of such cells still need to be solved. Moreover, the recent finding of cytoplasmic material transfer between donor and host photoreceptors demands reinterpretation of several former transplantation studies. At the same time, material transfer between healthy donor and dysfunctional patient photoreceptors also offers a potential alternative strategy for therapeutic intervention. In this review we discuss the history and current state of photoreceptor transplantation, the techniques used to assess rescue of visual function, the prerequisites for effective transplantation as well as the main roadblocks, including safety and immune response to the graft, that need to be overcome for successful clinical translation of photoreceptor transplantation approaches.
Advances in HER2-Targeted Therapy: Novel Agents and Opportunities Beyond Breast and Gastric Cancer
Authors: Funda Meric-Bernstam, Amber M. Johnson, Ecaterina E. Ileana Dumbrava, Kanwal Raghav, Kavitha Balaji, Michelle Bhatt, Rashmi K. Murthy, Jordi Rodon, Sarina A. Piha-Paul
Journal: Clinical Cancer Research (2018)

Abstract The introduction of HER2-targeted therapy for breast and gastric patients with ERBB2 (HER2) amplification/overexpression has led to dramatic improvements in oncologic outcomes. In the past 20 years, five HER2-targeted therapies have been FDA approved, with four approved in the past 8 years. HER2-targeted therapy similarly was found to improve outcomes in HER2-positive gastric cancer. Over the past decade, with the introduction of next-generation sequencing into clinical practice, our understanding of HER2 biology has dramatically improved. We have recognized that HER2 amplification is not limited to breast and gastric cancer but is also found in a variety of tumor types such as colon cancer, bladder cancer, and biliary cancer. Furthermore, HER2-targeted therapy has signal of activity in several tumor types. In addition to HER2 amplification and overexpression, there is also increased recognition of activating HER2 mutations and their potential therapeutic relevance. Furthermore, there is a rapidly growing number of new therapeutics targeting HER2 including small-molecule inhibitors, antibody–drug conjugates, and bispecific antibodies. Taken together, an increasing number of patients are likely to benefit from approved and emerging HER2-targeted therapies.
Dynamics of clinical biomarkers as predictors of immunotherapy (IT) benefit in metastatic melanoma (MM) patients (pts) treated in reference institution
Authors: A. Hernando, R. Dienstmann, C. Ortiz Velez, G. Villacampa, F.J. Ros Montañá, J.F. Grau Béjar, A. Garcia-Alvarez, P.G. Nuciforo, A. Gros, V. Garcia-Patos, D. Bodet, B. Ferrer Fabrega, J. Recio, E. Muñoz-Couselo
Journal: Annals of Oncology (2018)
Abstract 14770: Extent of Dissection and Status of the False Lumen Determine D-Dimer Levels in Patients With Acute Type A Aortic Dissection
Authors: Ryo Itagaki, Naoyuki Kimura, Makiko Mieno, Daijiro Hori, Kei Akiyoshi, Koichi Yuri, Harunobu Matsumoto, Keisuke Tanno, Koji Kawahito, Atsushi Yamaguchi
Journal: Circulation (2017)

Introduction: Although D-dimer (DD) testing is used for diagnosing aortic dissection, the influence of dissection morphology on DD levels has not been clarified. Hypothesis: In cases of aortic diss...
Red Blood Cell Allo-Antibodies after Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Astrid Beerlage, Joerg Halter, Sabine Gerull, Michael Medinger, Tanja Ruefli, Georg Stussi, Dominik Heim, Beatrice Drexler, Laura Infanti, Andreas Holbro, Jakob R. Passweg, Andreas S. Buser
Journal: Blood (2018)
Sensitization of breast cancer cells to chemotherapy and ionizing radiation by Smac/DIABLO
Authors: Sharmila Shankar, Mohd Asim, Rakesh Srivastava
Journal: Cancer Research (2004)

4870  Development of resistance by cancer cells to chemotherapy and irradiation is main hurdle for successful treatment of human cancer. TRAIL induces apoptosis by binding to specific cell surface death receptors (TRAIL-R1/DR4 and TRAIL-R2/DR5). We have recently noticed that several breast, prostate and lung cancer cell lines are resistant to TRAIL (Oncogene 20: 6073-6083, 2002; Cancer Res. 62: 4929-4937, 2002; Cancer Res. 64: 6675-6686, 2003). Therefore, sensitization of drug- and irradiation-resistant cancer cells to undergo apoptosis will be a major advancement in cancer therapy. The objective of this research is to investigate the intracellular mechanisms by which drug and irradiation resistant breast, prostate and lung cancer cells can be sensitized by Smac/DIABLO. Overexpression of Smac/DIABLO gene or pretreatment with Smac/DIABLO peptide sensitized various tumor cells to undergo apoptosis induced by activation of extrinsic and intrinsic pathways. There were no defects in active DISC formation or caspase-8 activation in TRAIL-resistant tumor cells. Expression of cytosolic active form of Smac/DIABLO gene or cell-permeable Smac/DIABLO peptide bypassed the Bcl-2 / Bcl-XL block, which prevented the release of Smac/DIABLO from mitochondria. These data suggest that apoptotic events down-stream of mitochondria were intact in irradiation- and drug-resistant cells since ectopic expression of mature Smac/DIABLO or pretreatment of Smac N7 peptide completely restored sensitivity. The ability of Smac/DIABLO agonists to sensitize cells to chemotherapy and irradiation suggests that Smac/DIABLO may induce fundamental alterations in cell signaling pathways. Thus, Smac/DIABLO agonists can be used as promising new candidates for cancer therapy.
Genomic and Clinical Characterization of Adult Ph-Negative B-Cell Acute Lymphoblastic Leukemia
Authors: Takahiko Yasuda, Dai Nishijima, Shinya Kojima, Masahito Kawazu, Toshihide Ueno, Shinobu Tsuzuki, Hitoshi Kiyoi, Itaru Matsumura, Yasushi Miyazaki, Keizo Horibe, Hiroyuki Mano, Tomoki Naoe, Masashi Sanada, Fumihiko Hayakawa
Journal: Blood (2018)
Orexin supplementation in narcolepsy treatment: A review
Authors: Eugenie Nepovimova, Jana Janockova, Jan Misik, Stepan Kubik, Ales Stuchlik, Karel Vales, Jan Korabecny, Eva Mezeiova, Rafael Dolezal, Ondrej Soukup, Tereza Kobrlova, Ngoc Lam Pham, Thuy Duong Nguyen, Jan Konecny, Kamil Kuca
Journal: Medicinal Research Reviews (2018)

Abstract Narcolepsy is a rare, chronic neurological disease characterized by excessive daytime sleepiness, cataplexy, vivid hallucinations, and sleep paralysis. Narcolepsy occurs in approximately 1 of 3000 people, affecting mainly adolescents aged 15 to 30 years. Recently, people with narcolepsy were shown to exhibit extensive orexin/hypocretin neuronal loss. The orexin system regulates sleep/wake control via complex interactions with monoaminergic, cholinergic and GABA‐ergic neuronal systems. Currently, no cure for narcolepsy exists, but some symptoms can be controlled with medication (eg, stimulants, antidepressants, etc). Orexin supplementation represents a more sophisticated way to treat narcolepsy because it addresses the underlying cause of the disease and not just the symptoms. Research on orexin supplementation in the treatment of sleep disorders has strongly increased over the past two decades. This review focuses on a brief description of narcolepsy, the mechanisms by which the orexin system regulates sleep/wake cycles, and finally, possible therapeutic options based on orexin supplementation in animal models and patients with narcolepsy.
DNA Damage Response Gene Alterations in Urothelial Cancer: Ready for Practice?
Authors: Petros Grivas
Journal: Clinical Cancer Research (2018)

Cisplatin-based neoadjuvant chemotherapy prior to radical cystectomy is standard in fit patients. Inactivating mutations of the nucleotide excision repair gene ERCC2 can predict response to cisplatin-based chemotherapy. Evaluation of the functional impact of ERCC2 mutations can provide mechanistic frameworks supporting the potential predictive role of ERCC2 loss of function.See related article by Li et al., p. 977.