tbuckley/cabot-search huggingface dataset:
Development of progastrin (PG) specific monoclonal antibodies (MAbs) and PG specific vaccine for attenuating growth factor effects of autocrine and endocrine PG-like peptides on colon cancer cells and colon carcinogenesis, respectively
Authors: Pomila Singh, Gurpreet Singh
Journal: Cancer Research (2007)

3546  The gastrin gene and PG peptides are expressed by > 70% colorectal carcinomas (CRCs). Down-regulation of gastrin gene expression results in apoptotic death of gastrin dependent CRCs. However, delivery of effective concentrations of anti-sense DNA to the tumor cells, in vivo, has proven to be a challenge. A vaccine, Gastrimmune, against the fully processed gastrin (G17) peptide is currently in clinical triasl with mixed results. We recently reported that Annexin II mediates anti-apoptotic effects of PG and G17-like peptides (Oncogene, 2006). G17 also binds CCK2R with high affinity, and unlike Annexin II, CCK2R mediates several biological effects on different cell types including differentiation and growth inhibition. This may explain the mixed results obtained with Gastrimmune. In the current studies, we targeted the colon cancer relevant peptide, PG, since elevated levels of PG, but not G17, have been reported in patients with CRCs. In the first set of studies, we generated MAb, specific for PG, with
A comment on “a prospective, multicenter study of low dose decitabine in adult patients with refractory immune thrombocytopenia” by Zhou et al
Authors: Ufuk Demirci, Elif G. Umit, Ahmet Muzaffer Demir
Journal: American Journal of Hematology (2020)

We have read the article “A prospective, multicenter study of low dose decitabine in adult patients with refractory immune thrombocytopenia” by Zhou et al.1 In this prospective study, refractory immune thrombocytopenia (ITP) patients were treated with a hypomethylating agent, decitabine, which is being used as a standard of care for myelodysplastic syndrome and unfit acute myeloid leukemia patients. Though ITP has been previously treated with other immunosuppresive chemotherapeutic agents like vinctistine, cyclosporine and mycofenolate, novel agents with reasonably mild toxicity profiles were not unusual or unexpected. The study has reported promising results however we have certain doubts. First of all, as the latest three guidelines have stated, spontaneous remissions are quite unlikely in patients who have reached the 12 months’ milestone, but not impossible.2-4 In this regard, the response to decitabine might attributable to probable spontaneous remissions, not entirely, but is still debatable. Bone marrow aspiration and biopsy with chromosome analysis is recommended to all patients at this point, both to prove the diagnosis and check the cellularity and morphology. Before starting a treatment with an agent novel for this group of patients, bone marrow examination would increase the quality of the knowledge. Likewise, the detection of antiplatelet antibodies, especially against the epitopes on GP Ib and IIb/IIIa may be used, not as an initial workup but in chronic or refractory patients to support the diagnosis of ITP. But, in this study, the value of the seropositivity in terms of response to decitabine is less valuable to bone marrow examination, especially after the completion of treatment.2 Second is the status of Helicobacter pylori in refractory ITP patients. It is suggested that H. pylori should be sought and eradicated if detected in all refractory patients with noninvasive methods, like urea breathe test or stool antigen test.2, 3 Response after eradication is not uncommon and in this study, H. pylori status should have been stated to increase the homogeneity of the patients. Our last comment is the value, guides have placed on combinations. Combination of all alternatives (which have failed as monotherapies) may be used in refractory patients, including corticosteroids with thrombopoietin receptor agonists (TPO-RAs) as a dual therapy, or addition of low dose immunosuppresants.2-4 In conclusion, it is debatable that immunosuppresants towards cell cycle even with a low toxicity profile may be a reasonable approach for ITP, which has an individual pathogenesis and progress in every patient. Supporting data of the bone marrow before and after treatment as well as the failures of all suggested steps of treatments are essential.
The clinical benefit of instituting a prospective clinical community-acquired respiratory virus surveillance program in allogeneic hematopoietic stem cell transplantation
Authors: JoséLuis Piñana, Juan Montoro, Carla Aznar, Ignacio Lorenzo, María Dolores Gómez, Manuel Guerreiro, Carlos Carretero, Eva María González-Barberá, Aitana Balaguer-Roselló, Rosa Sanz, Miguel Salavert, David Navarro, Miguel A. Sanz, Guillermo Sanz, Jaime Sanz
Journal: Journal of Infection (2020)

BackgroundThere is a lack of studies comparing clinical outcomes among retrospective versus prospective cohorts of allogeneic stem cell transplant (allo-HCT) recipients with community acquired respiratory virus (CARV) infections.MethodsWe compare outcomes in two consecutive cohorts of allo-HCT recipients with CARV infections. The retrospective cohort included 63 allo-HCT recipients with 108 CARV infections from January 2013 to April 2016 who were screened and managed following standard clinical practice based on influenza and respiratory syncytial virus rapid antigen detection methods. The prospective cohort was comprised of 144 consecutive recipients with 297 CARV episodes included in a prospective interventional clinical surveillance program (ProClinCarvSur-P) based on syndromic multiplex PCR as first-line test from May 2016 to December 2018 at a single transplant center.ResultsCARV infections in the retrospective cohort showed more severe clinical features at the time of diagnosis compared to the prospective cohort (fever 83% vs. 57%, hospital admission 69% vs. 28% and lower respiratory tract 58% vs. 31%, respectively, p ≤ 0.002 for all comparisons). Antiviral therapy was more commonly prescribed in the prospective cohort (69 vs. 43 treated CARV episodes), particularly at the upper respiratory tract disease stage (34 vs. 12 treated CARV episodes). Three-month all-cause mortality was significantly higher in the retrospective cohort (n = 23, 37% vs. n = 10, 7%, p < 0.0001). Multivariate logistic regression analysis showed that recipients included in ProClinCarvSur-P had lower mortality rate [odds ratio 0.31, 95% confidence interval 0.12–0.7, p = 0.01].ConclusionThis study report on outcome differences when reporting retrospective vs. prospective CARV infections after allo-HCT. Recipients included in a ProClinCarvSur-P had lower mortality.
Disrupted Gene Networks in Subfertile Hybrid House Mice
Authors: Katy Morgan, Bettina Harr, Michael A White, Bret A Payseur, Leslie M Turner
Journal: Molecular Biology and Evolution (2020)

The Dobzhansky-Muller (DM) model provides a widely accepted mechanism for the evolution of reproductive isolation: incompatible substitutions disrupt interactions between genes. To date, few candidate incompatibility genes have been identified, leaving the genes driving speciation mostly uncharacterized. The importance of interactions in the DM model suggests that gene coexpression networks provide a powerful framework to understand disrupted pathways associated with postzygotic isolation. Here, we perform weighted gene coexpression network analysis to infer gene interactions in hybrids of two recently diverged European house mouse subspecies, Mus mus domesticus and M. m. musculus, which commonly show hybrid male sterility or subfertility. We use genome-wide testis expression data from 467 hybrid mice from two mapping populations: F2s from a laboratory cross between wild-derived pure subspecies strains and offspring of natural hybrids captured in the Central Europe hybrid zone. This large data set enabled us to build a robust consensus network using hybrid males with fertile phenotypes. We identify several expression modules, or groups of coexpressed genes, that are disrupted in subfertile hybrids, including modules functionally enriched for spermatogenesis, cilium and sperm flagellum organization, chromosome organization, and DNA repair, and including genes expressed in spermatogonia, spermatocytes, and spermatids. Our network-based approach enabled us to hone in on specific hub genes likely to be influencing module-wide gene expression and hence potentially driving large-effect DM incompatibilities. A disproportionate number of hub genes lie within sterility loci identified previously in the hybrid zone mapping population and represent promising candidate barrier genes and targets for future functional analysis.
On-chip recapitulation of clinical bone marrow toxicities and patient-specific pathophysiology
Authors: David B. Chou, Viktoras Frismantas, Yuka Milton, Rhiannon David, Petar Pop-Damkov, Douglas Ferguson, Alexander MacDonald, Özge Vargel Bölükbaşı, Cailin E. Joyce, Liliana S. Moreira Teixeira, Arianna Rech, Amanda Jiang, Elizabeth Calamari, Sasan Jalili-Firoozinezhad, Brooke A. Furlong, Lucy R. O’Sullivan, Carlos F. Ng, Youngjae Choe, Susan Marquez, Kasiani C. Myers, Olga K. Weinberg, Robert P. Hasserjian, Richard Novak, Oren Levy, Rachelle Prantil-Baun, Carl D. Novina, Akiko Shimamura, Lorna Ewart, Donald E. Ingber
Journal: Nature Biomedical Engineering (2020)
Corrigendum to “Laparoscopic repair of perforated peptic ulcer is not prognostic factor for 30-day mortality (a nationwide prospective cohort study)” [Int. J. Surg. 72 (2019) 47–54]
Authors: Sergej Zogovic, Anders Bo Bojesen, Shadi Andos, Frank Viborg Mortensen
Journal: International Journal of Surgery (2020)
Recirculating IL-1R2+ Tregs fine-tune intrathymic Treg development under inflammatory conditions
Authors: Eirini Nikolouli, Yassin Elfaki, Susanne Herppich, Carsten Schelmbauer, Michael Delacher, Christine Falk, Ilgiz A. Mufazalov, Ari Waisman, Markus Feuerer, Jochen Huehn
Journal: Cellular and Molecular Immunology (2020)
Biomarkers May Provide Unique Insights Into Neurological Effects Associated With Sport-Related Concussions
Authors: Jeffrey J. Bazarian, Frederick Korley, Rebekah Mannix
Journal: JAMA Network Open (2020)

Michael McCrea, PhD, ABPP; Steven P. Broglio, PhD; Thomas W. McAllister, MD; Jessica Gill, PhD; Christopher C. Giza, MD; Daniel L. Huber, MPH; Jaroslaw Harezlak, PhD; Kenneth L. Cameron, PhD; Megan N. Houston, PhD; Gerald McGinty, DPT; Jonathan C. Jackson, MD; Kevin Guskiewicz, PhD; Jason Mihalik, PhD; M. Alison Brooks, MD, MPH; Stephan Duma, PhD; Steven Rowson, PhD; Lindsay D. Nelson, PhD; Paul Pasquina, MD; Timothy B. Meier, PhD; and the CARE Consortium Investigators; Tatiana Foroud, PhD; Barry P. Katz, PhD; Andrew J. Saykin, PsyD; Darren E. Campbell, MD; Steven J. Svoboda, MD; Joshua Goldman, MD; Jon DiFiori, MD
Role of atrial arrhythmia and ventricular response in atrial fibrillation induced atrial remodelling
Authors: Jean-Baptiste Guichard, Feng Xiong, Xiao-Yan Qi, Nathalie L’Heureux, Roddy Hiram, Jiening Xiao, Patrice Naud, Jean-Claude Tardif, Antoine Da Costa, Stanley Nattel
Journal: Cardiovascular Research (2020)

No studies have assessed the specific contributions of atrial fibrillation (AF)-related atrial vs. associated ventricular arrhythmia to remodelling. This study assessed the roles of atrial arrhythmia vs. high ventricular rate in AF-associated remodelling.Four primary dog-groups (12/group) were subjected to 3-week pacing: 600-b.p.m. atrial tachypacing maintaining AF [AF w/o- atrioventricular block (AVB)]; atrial tachypacing with atrioventricular-node ablation (AF+AVB) and ventricular-demand pacing (80 b.p.m.); 160-b.p.m. ventricular-tachypacing (V160) reproducing the response rate during AF; and sinus rhythm with AVB/ventricular-pacing at 80-b.p.m. (control group). At terminal study, left-atrial (LA) effective refractory period (ERP) was reduced equally in both AF groups (w/o-AVB and AF+AVB). AF-inducibility was increased strongly in AF groups (w/o-AVB and AF+AVB) and modestly in V160. AF duration was significantly increased in AF w/o-AVB but not in AF+AVB or V160. Conduction velocity was decreased in AF w/o-AVB, to a greater extent than in AF+AVB and V160. Atrial fibrous-tissue content was increased in AF w/o-AVB, AF+AVB and V160, with collagen-gene up-regulation only in AF w/o-AVB. Connexin43 gene expression was reduced only in AF w/o-AVB. An additional group of 240-b.p.m. ventricular tachypacing dogs (VTP240; to induce heart failure) was studied: vs. other tachypaced groups, VTP240 caused greater fibrosis, but no change in LA-ERP or AF-inducibility. VTP240 also increased AF duration, strongly decreased left ventricular ejection fraction, and was the only group with LA natriuretic-peptide activation.The atrial tachyarrhythmia and rapid ventricular response during AF produce distinct atrial remodelling; both contribute to the arrhythmogenic substrate, providing new insights into AF-related remodelling and novel considerations for ventricular rate-control.
Hyperactivation of TORC1 Drives Resistance to the Pan-HER Tyrosine Kinase Inhibitor Neratinib in HER2-Mutant Cancers
Authors: Dhivya R. Sudhan, Angel Guerrero-Zotano, Helen Won, Paula González Ericsson, Alberto Servetto, Mariela Huerta-Rosario, Dan Ye, Kyung-min Lee, Luigi Formisano, Yan Guo, Qi Liu, Lisa N. Kinch, Monica Red Brewer, Teresa Dugger, James Koch, Michael J. Wick, Richard E. Cutler, Alshad S. Lalani, Richard Bryce, Alan Auerbach, Ariella B. Hanker, Carlos L. Arteaga
Journal: Cancer Cell (2020)

We developed neratinib-resistant HER2-mutant cancer cells by gradual dose escalation. RNA sequencing identified TORC1 signaling as an actionable mechanism of drug resistance. Primary and acquired neratinib resistance in HER2-mutant breast cancer patient-derived xenografts (PDXs) was also associated with TORC1 hyperactivity. Genetic suppression of RAPTOR or RHEB ablated P-S6 and restored sensitivity to the tyrosine kinase inhibitor. The combination of the TORC1 inhibitor everolimus and neratinib potently arrested the growth of neratinib-resistant xenografts and organoids established from neratinib-resistant PDXs. RNA and whole-exome sequencing revealed RAS-mediated TORC1 activation in a subset of neratinib-resistant models. DNA sequencing of HER2-mutant tumors clinically refractory to neratinib, as well as circulating tumor DNA profiling of patients who progressed on neratinib, showed enrichment of genomic alterations that converge to activate the mTOR pathway.
Optimizing eligibility criteria and clinical trial conduct to enhance clinical trial participation for primary brain tumor patients
Authors: Eudocia Q Lee, Michael Weller, Joohee Sul, Stephen J Bagley, Solmaz Sahebjam, Martin van den Bent, Manmeet Ahluwalia, Jian L Campian, Evanthia Galanis, Mark R Gilbert, Matthias Holdhoff, Glenn J Lesser, Frank S Lieberman, Minesh P Mehta, Marta Penas-Prado, Karisa C Schreck, Roy E Strowd, Michael A Vogelbaum, Tobias Walbert, Susan M Chang, L Burt Nabors, Stuart Grossman, David A Reardon, Patrick Y Wen
Journal: Neuro-Oncology (2020)

Building on an initiative to enhance clinical trial participation involving the Society for Neuro-Oncology, the Response Assessment in Neuro-Oncology Working Group, patient advocacy groups, clinical trial cooperative groups, and other partners, we evaluate the impact of eligibility criteria and trial conduct on neuro-oncology clinical trial participation. Clinical trials often carry forward eligibility criteria from prior studies that may be overly restrictive and unnecessary and needlessly limit patient accrual. Inclusion and exclusion criteria should be evaluated based on the goals and design of the study and whether they impact patient safety and/or treatment efficacy. In addition, we evaluate clinical trial conduct as a barrier to accrual and discuss strategies to minimize such barriers for neuro-oncology trials.
Expression of Wilmśtumour Gene (WT1) is Associated with Survival in Malignant Pleural Mesothelioma: Retrospective Analysis in a Single Center Series
Authors: S. Cedres, D. Torrejon Castro, N. Stjepanovic, P. Martinez, A. Martinez, M. Salcedo, M.A. Montero, E. Felip
Journal: Annals of Oncology (2012)
Predicting Therapeutic Antibody Delivery into Human Head and Neck Cancers
Authors: Guolan Lu, Shayan Fakurnejad, Brock A. Martin, Nynke S. van den Berg, Stan van Keulen, Naoki Nishio, Ashley J. Zhu, Stefania U. Chirita, Quan Zhou, Rebecca W. Gao, Christina S. Kong, Nancy Fischbein, Mrudula Penta, Alexander D. Colevas, Eben L. Rosenthal
Journal: Clinical Cancer Research (2020)

The efficacy of antibody-based therapeutics depends on successful drug delivery into solid tumors; therefore, there is a clinical need to measure intratumoral antibody distribution. This study aims to develop and validate an imaging and computation platform to directly quantify and predict antibody delivery into human head and neck cancers in a clinical study.Twenty-four patients received systemic infusion of a near-infrared fluorescence-labeled therapeutic antibody followed by surgical tumor resection. A computational platform was developed to quantify the extent of heterogeneity of intratumoral antibody distribution. Both univariate and multivariate regression analyses were used to select the most predictive tumor biological factors for antibody delivery. Quantitative image features from the pretreatment MRI were extracted and correlated with fluorescence imaging of antibody delivery.This study not only confirmed heterogeneous intratumoral antibody distribution in-line with many preclinical reports, but also quantified the extent of interpatient, intertumor, and intratumor heterogeneity of antibody delivery. This study demonstrated the strong predictive value of tumor size for intratumoral antibody accumulation and its significant impact on antibody distribution in both primary tumor and lymph node metastasis. Furthermore, this study established the feasibility of using contrast-enhanced MRI to predict antibody delivery.This study provides a clinically translatable platform to measure antibody delivery into solid tumors and yields valuable insight into clinically relevant antibody tumor penetration, with implications in the selection of patients amenable to antibody therapy and the design of more effective dosing strategies.
Bone Replacement: The Secretome of Hypoxia Conditioned hMSC Loaded in a Central Depot Induces Chemotaxis and Angiogenesis in a Biomimetic Mineralized Collagen Bone Replacement Material (Adv. Healthcare Mater. 2/2020)
Authors: Mandy Quade, Pina Münch, Anja Lode, Sarah Duin, Corina Vater, Anastasia Gabrielyan, Angela Rösen‐Wolff, Michael Gelinsky
Journal: Advanced Healthcare Materials (2020)

In article number 1901426 by Anja Lode and co-workers, sustained release of hypoxia-conditioned MSC secretome from a central depot induces directed hBMSC migration and angiogenesis in biomimetic mineralized collagen scaffolds. This in situ tissue engineering concept is suggested to be a cell-free and ready-to-use therapeutic solution for accelerated bone defect healing.
cis-regulatory variation modulates susceptibility to enteric infection in the Drosophila genetic reference panel
Authors: Michael V. Frochaux, Maroun Bou Sleiman, Vincent Gardeux, Riccardo Dainese, Brian Hollis, Maria Litovchenko, Virginie S. Braman, Tommaso Andreani, Dani Osman, Bart Deplancke
Journal: Genome biology (2020)

Abstract Background Resistance to enteric pathogens is a complex trait at the crossroads of multiple biological processes. We have previously shown in the Drosophila Genetic Reference Panel (DGRP) that resistance to infection is highly heritable, but our understanding of how the effects of genetic variants affect different molecular mechanisms to determine gut immunocompetence is still limited. Results To address this, we perform a systems genetics analysis of the gut transcriptomes from 38 DGRP lines that were orally infected with Pseudomonas entomophila . We identify a large number of condition-specific, expression quantitative trait loci ( local -eQTLs) with infection-specific ones located in regions enriched for FOX transcription factor motifs. By assessing the allelic imbalance in the transcriptomes of 19 F1 hybrid lines from a large round robin design, we independently attribute a robust cis -regulatory effect to only 10% of these detected local -eQTLs. However, additional analyses indicate that many local -eQTLs may act in trans instead. Comparison of the transcriptomes of DGRP lines that were either susceptible or resistant to Pseudomonas entomophila infection reveals nutcracker as the only differentially expressed gene. Interestingly, we find that nutcracker is linked to infection-specific eQTLs that correlate with its expression level and to enteric infection susceptibility. Further regulatory analysis reveals one particular eQTL that significantly decreases the binding affinity for the repressor Broad, driving differential allele-specific nutcracker expression. Conclusions Our collective findings point to a large number of infection-specific cis- and trans- acting eQTLs in the DGRP, including one common non-coding variant that lowers enteric infection susceptibility.
Habitual physical activity, renal function and chronic kidney disease: a cohort study of nearly 200 000 adults
Authors: Cui Guo, Tony Tam, Yacong Bo, Ly-yun Chang, Xiang Qian Lao, G Neil Thomas
Journal: British Journal of Sports Medicine (2020)

There is limited information on the association between habitual physical activity (PA) and renal function.To report the longitudinal association between self-reported habitual PA and measures of renal function in a large cohort in Taiwan.A total of 199 421 participants (aged ≥20 years) were selected from a Taiwan cohort between 1996 and 2014. All participants underwent at least two standardised medical examinations between 1996 and 2014. Self-administrated questionnaires were used to collect information on habitual PA. We used a generalised linear mixed model to investigate the associations between habitual PA and yearly change in estimated glomerular filtration rate (eGFR). The Cox proportional hazard regression model was used to investigate the associations between habitual PA and incident chronic kidney disease (CKD).Participants had a median follow-up duration of 4.2 years (0.2-18.9). The yearly mean (±SD) decrease in eGFR in participants with baseline very low-PA, low-PA, moderate-PA and high-PA was 0.46±1.01, 0.36±0.97, 0.30±0.94 and 0.27±0.91 mL/min/1.73 m2, respectively. Relative to the participants with very low-PA, the coefficients of yearly eGFR change were -43.93 (95% CI -79.18 to -8.68), 35.20 (95% CI -2.56 to 72.96) and 53.56 (95% CI 10.42 to 96.70) µL/min/1.73 m2, respectively, for the participants with low-PA, moderate-PA and high-PA, after controlling for a wide range of covariates. Relative to the very low-PA participants, those who had low-PA, moderate-PA and high-habitual PA had HRs of 0.93 (95% CI 0.88 to 0.98), 0.94 (95% CI 0.89 to 0.99) and 0.91 (95% CI 0.85 to 0.96) to develop CKD, respectively, after controlling for the covariates.A higher level of habitual PA is associated with a smaller decrease in the level of eGFR and a lower risk of developing CKD.
Red blood cell microvesicles activate the contact system, leading to factor IX activation via 2 independent pathways
Authors: Denis F. Noubouossie, Michael W. Henderson, Micah Mooberry, Anton Ilich, Patrick Ellsworth, Mark Piegore, Sarah C. Skinner, Rafal Pawlinski, Ian Welsby, Thomas Renné, Maureane Hoffman, Dougald M. Monroe, Nigel S. Key
Journal: Blood (2020)
A38 Gemcitabine Improves Suppressive Immune Microenvironment Induced by Long-Term Treatment with EGFR-TKIs: Implications for Combination Chemotherapy and Immunotherapy
Authors: X. Wu, J. Tang, X. Liu, Q. Ma, P. Shu, Q. Deng, K. Li, B. Zhang, Y. Wang
Journal: Journal of Thoracic Oncology (2020)
Impact of pretransplant measurable residual disease on the outcome of allogeneic hematopoietic cell transplantation in adult monosomal karyotype AML
Authors: Linde M. Morsink, Megan Othus, Evandro D. Bezerra, Brent L. Wood, Min Fang, Brenda M. Sandmaier, Marco Mielcarek, Gary Schoch, Rainer Storb, H. Joachim Deeg, Frederick R. Appelbaum, Roland B. Walter
Journal: Leukemia (2020)