tbuckley/cabot-search huggingface dataset:
A phase II trial <sup>90</sup>y-ibritumomab tiuxetan in combination with reduced intensity regimen of fludarabine (flu) and melphalan (mel) followed by allo-HCT in patients with refractory B-cell lymphoma.
Authors: Auayporn Nademanee, Andrew Antony Raubitschek, Ni-Chun Tsai, Jennifer Simpson, Neil Martin Kogut, Leslie Popplewell, Firoozeh Sahebi, Maria L. Delioukina, Stephen J. Forman
Journal: Journal of Clinical Oncology (2012)

6545 Background: RIC allo-HCT has reduced transplant-related mortality (TRM) in patients with relapsed NHL. However, relapses do occur despite potential graft vs. lymphoma (GVL) effect. We hypothesized that adding Zevalin to Flu/Mel may improve disease control and reduce relapse post allo-HCT. Methods: Patients received In- Zevalin on day -21 followed by 90 Y- Zevalin 0.4mCi/kg on day -14, flu 25 mg/m 2 daily on days -9 to -5 and mel 140 mg/m 2 on day -4. Rituximab (R) level was measured on Day -22 and -15 and if the level was ≥ 10 μg/ml, R was not given prior to In-Zevalin or 90 Y- Zevalin to enhance biodistribution. Tacrolimus and sirolimus was used for GVHD prophylaxis. Between 10/2007 and 11/2011, 31 were treated. Median age 55 (range 27-67), median regimen =3 (range 2-8). Median time from diagnosis to HCT was 20 mo (range 5-105). Histology: DLBCL (including transformed lymphoma)=14 (45%), MCL=7 (23%), FL=5 (16%) and SLL/CLL=5 (16%). Disease status at HCT: 1CR=7, Relapse=9, ≥2CR=5, primary refractory =10. Fifteen had chemoresistant and 19 had FDG PET+ at HCT. Donors: sib=13, URD=18. Results: All patients engrafted with the median time to ANC ≥500 and platelet ≥ 20,000 was 14 (range 10-28) and 13.5 days (range 11-28), respectively. There were 10 deaths from disease progression (2) infection (5) GVHD (1) and multi-organ failure (2). TRM at day +100 and at 1 yr was 6.5% and 17%, Five with DLBCL relapsed between 3-7 mos. Grade II-IV acute GVHD was 65%, Grade III-IV was 16%, chronic GVHD was 65%. Fifteen became PET- at day +100 while 4 remained PET+ and relapsed. Twenty-one are alive at a median followup of 24 mos (range 2-46). The 2 yrs OS and PFS was 65% (95% CI, 51-75%) and 57% (95% CI, 46-67%), respectively. Univariate analysis identified disease status predict for OS and PFS while histology predict for PFS. Conclusions: This study demonstrates the feasibility of adding Zevalin to flu/mel in the allo-HCT setting for B-cell NHL and suggest that this approach could be used to provide early disease control before GVL effect takes place. Innovative approaches should be explored in DLBCL.
New Insights into Podocyte Biology in Glomerular Health and Disease
Authors: Suheir Assady, Nicola Wanner, Karl L. Skorecki, Tobias B. Huber
Journal: Journal of the American Society of Nephrology (2017)

Podocyte and glomerular research is center stage for the development of improved preventive and therapeutic strategies for chronic progressive kidney diseases. Held April 3–6, 2016, the 11th International Podocyte Conference took place in Haifa and Jerusalem, Israel, where participants from all over the world presented their work on new developments in podocyte research. In this review, we briefly highlight the advances made in characterizing the mechanisms involved in podocyte development, metabolism, acquired injury, and repair, including progress in determining the roles of genetic variants and microRNA in particular, as well as the advances made in diagnostic techniques and therapeutics.
Spatiotemporal Evolution of the Wound Repairing Process in a 3D Human Dermis Equivalent
Authors: Bernadette Lombardi, Costantino Casale, Giorgia Imparato, Francesco Urciuolo, Paolo Antonio Netti
Journal: Advanced Healthcare Materials (2017)

Several skin equivalent models have been developed to investigate in vitro the re-epithelialization process occurring during wound healing. Although these models recapitulate closure dynamics of epithelial cells, they fail to capture how a wounded connective tissue rebuilds its 3D architecture until the evolution in a scar. Here, the in vitro tissue repair dynamics of a connective tissue is replicated by using a 3D human dermis equivalent (3D-HDE) model composed of fibroblasts embedded in their own extracellular matrix (ECM). After inducing a physical damage, 3D-HDE undergoes a series of cellular and extracellular events quite similar to those occurring in the native dermis. In particular, fibroblasts differentiation toward myofibroblasts phenotype and neosynthesis of hyaluronic acid, fibronectin, and collagen during the repair process are assessed. Moreover, tissue reorganization after physical damage is investigated by measuring the diameter of bundles and the orientation of fibers of the newly formed ECM network. Finally, the ultimate formation of a scar-like tissue as physiological consequence of the repair and closure process is demonstrated. Taking together, the results highlight that the presence of cell-assembled and responsive stromal components enables quantitative and qualitative in vitro evaluation of the processes involved in scarring during wound healing.
Vaccination with inhibin-α provides effective immunotherapy against testicular stromal cell tumors
Authors: Robert Aguilar, Justin M. Johnson, Patrick Barrett, Vincent K. Tuohy
Journal: Journal for ImmunoTherapy of Cancer (2017)

Testicular cancer is the most common male neoplasm occurring in men between the ages of 20 and 34. Although germ-line testicular tumors respond favorably to current standard of care, testicular stromal cell (TSC) tumors derived from Sertoli cells or Leydig cells often fail to respond to chemotherapy or radiation therapy and have a 5-year overall survival significantly lower than the more common and more treatable germ line testicular tumors.To improve outcomes for TSC cancer, we have developed a therapeutic vaccine targeting inhibin-α, a protein produced by normal Sertoli and Leydig cells of the testes and expressed in the majority of TSC tumors.We found that vaccination against recombinant mouse inhibin-α provides protection and therapy against transplantable I-10 mouse TSC tumors in male BALB/c mice. Similarly, we found that vaccination with the immunodominant p215-234 peptide of inhibin-α (Inα 215-234) inhibits the growth of autochthonous TSC tumors occurring in male SJL.AMH-SV40Tag transgenic mice. The tumor immunity and enhanced overall survival induced by inhibin-α vaccination may be passively transferred into naive male BALB/c recipients with either CD4+ T cells, B220+ B cells, or sera from inhibin-α primed mice.Considering the lack of any alternative effective treatment for chemo- and radiation-resistant TSC tumors, our results provide for the first time a rational basis for immune-mediated control of these aggressive and lethal variants of testicular cancer.
Abstract 398: Histone Demethylase Kdm6a Contributes To X Chromosome Dependent Ischemia/reperfusion Injury Via Epigenetic Regulation
Authors: Jingyuan Li, Yuichiro Itoh, Xuqi Chen, Arthur Arnold, Mansoureh Eghbali
Journal: Circulation Research (2015)

Introduction: Sex differences in susceptibility to ischemia/reperfusion (I/R) injury have been mostly attributed to sex hormones. Recently we examined the role of sex chromosomes in sex differences in myocardial I/R injury. We discovered that gonadectomized mice with two X chromosomes (XX or XXY) have ~50% larger infarct size after I/R injury, compared to mice with one X chromosome (XY or XO). Only few X genes escape X inactivation and are expressed higher in XX than XY individuals. Here we examined the role of “X escapee” histone demethylase Kdm6a which is important in cardiac development. Methods: Female mice with a heterozygous global knockout of Kdm6a (Kdm6a+/-) and with 2 copies of Kdm6a (Kdm6a+/+, regular WT) were used. Isolated mouse hearts were subjected to 30 min global normothermic ischemia followed by 60 min reperfusion. RNA-Seq analysis was performed by comparing gene expression in hearts of Kdm6a+/+ vs. Kdm6a+/- females at baseline before ischemia. We calculated an unbiased composite score of relevance in which the level of significance of the Kdm6a effect on expression (p value) was integrated with the size of the KDM6A effect on expression (fold change), and with the amount of H3K27me3 mark found on the genes in the heart based on online ChIP-Seq data. Two way ANOVA was used for statistical analysis. P&lt;0.05 was considered statistically significant. Values are expressed as mean± SE. Results: Kdm6a+/+ female mice had significantly lower heart functional recovery compared to their littermate Kdm6a+/- (LVDP: 46.7±9.8% vs. 79.8±3.5%; RPP: 44.1±10.5% vs. 76.2±8.5%, n=6-8 mice/group, p&lt;0.01). The integration of our RNA-Seq data using the hearts of female mice with 2 vs. 1 copy of Kdm6a (n=4 samples per group) with online datasets measuring the H3K27me3 mark, sex differences in expression in humans and mice, and involvement in ischemic heart failure, revealed carbonic anhydrase-3 (Car3) as the most interesting candidate (upregulated ~7 fold in the hearts of Kdm6a+/+ vs. Kdm6a+/- female mice) at baseline. Car3 encodes one isoform of carbonic anhydrase, involved in pH regulation, which is a critical part of I/R injury. Conclusion: Histone demethylase KDM6A contributes to X chromosome dependent I/R injury via epigenetic regulation
Multifunctional Telodendrimer Nanocarriers Restore Synergy of Bortezomib and Doxorubicin in Ovarian Cancer Treatment
Authors: Lili Wang, Changying Shi, Forrest A. Wright, Dandan Guo, Xu Wang, Dongliang Wang, Richard J.H. Wojcikiewicz, Juntao Luo
Journal: Cancer Research (2017)

Abstract We have developed multifunctional nanoparticles for codelivery of bortezomib and doxorubicin to synchronize their pharmacokinetic profiles and synergize their activities in solid tumor treatment, a need still unmet in the clinic. Micellar nanoparticles were formed by a spatially segregated, linear-dendritic telodendrimer containing three segments: a hydrophilic polyethylene glycol (PEG), a bortezomib-conjugating intermediate, and a dendritic doxorubicin-affinitive interior. Bortezomib-conjugated telodendrimers, together with doxorubicin, self-assembled into monodispersed micelles [NP(BTZ-DOX)] with small particle sizes (20–30 nm) for dual drug delivery. NP(BTZ-DOX) displayed excellent drug-loading capacity and stability, which minimized premature drug leakage and synchronized drug release profiles. Bortezomib release was accelerated significantly by acidic pH, facilitating drug availability in the acidic tumor microenvironment. Synergistic anticancer effects of combined bortezomib and doxorubicin were observed in vitro against both multiple myeloma and ovarian cancer cells. NP(BTZ-DOX) prolonged payload circulation and targeted tumors in vivo efficiently with superior signal ratios of tumor to normal organs. In vitro and in vivo proteasome inhibition analysis and biodistribution studies revealed decreased toxicity and efficient intratumoral bortezomib and doxorubicin delivery by nanoformulation. NP(BTZ-DOX) exhibited significantly improved ovarian cancer treatment in SKOV-3 xenograft mouse models in comparison with free drugs and their combinations, including bortezomib and Doxil. In summary, tumor-targeted and synchronized delivery system elicits enhanced anticancer effects and merits further development in the clinical setting. Cancer Res; 77(12); 3293–305. ©2017 AACR.
Decreased Rates of Severe CRS Seen with Early Intervention Strategies for CD19 CAR-T Cell Toxicity Management
Authors: Rebecca Gardner, Kasey J Leger, Colleen E. Annesley, Corinne Summers, Julie Rivers, Juliane Gust, Katherine Tarlock, Todd M Cooper, Navin R. Pinto, Olivia Finney, Hannah Smithers, Assaf Oron, Daniel Li, Julie R Park, Michael C Jensen
Journal: Blood (2016)
DEEMATITLS HERPETIFORMIS IN AN INFANT
Authors: D. R. EVANS
Journal: British Journal of Dermatology (1949)

Journal Article DEEMATITLS HERPETIFORMIS IN AN INFANT Get access D. R. EVANS, M.C., M.R.C.S., L.R.C.P. D. R. EVANS, M.C., M.R.C.S., L.R.C.P. Clinical Assistant, Skin Department, The London Hospital Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 61, Issue 3, 1 March 1949, Pages 89–94, https://doi.org/10.1111/j.1365-2133.1949.tb11062.x Published: 01 March 1949
DECISION-MAKING AND TECHNIQUE: EVIDENCE FOR INCREASED HEAD INJURY RISK DURING TACKLING IN RUGBY UNION
Authors: Ross Tucker
Journal: British Journal of Sports Medicine (2017)

Background The tackle is the most injurious game event in Rugby Union. We recently found that tackles account for 76% of head injury events in professional rugby. Specific analysis of the tackle is required to understand how interventions such as law change or educational programmes can minimize head-injury risk from tackles. Objective Analyze tackles to identify high risk situations and behaviors. Design Prospective cohort study. Setting 1,516 Rugby matches in six professional tournaments. Participants Head injury cases resulting from tackles. Assessment of Risk Factors A professional video analyst evaluated every tackle-induced head injury event. Propensity was calculated for various tackle characteristics. Main Outcome Measurements Head-injury propensity for tackles, focused on tackle type, player's speeds and body positions. Results 464 Head Injury Events (HIEs) occurred during tackles, with a propensity of 1.94 HIEs/1000 tackles. For body position, the greatest risk was for falling ball carriers (9.8 HIEs/1000 tackles), or for upright tacklers (2.44 HIEs/1000 tackles). In combination, risk was highest when both players were upright, particularly for active shoulder tackles (17.4 HIEs/1000 tackles). Regardless of the tackler position, the lowest risk was for a ball carrier bent at the waist (1.15 HIEs/1000 tackles). Regarding speed, for static or low-speed tacklers, HIE risk increased with ball-carrier speed. However, when the tackler was at high speed, HIE risk decreased from 6.1 HIEs/1000 tackles for a static ball-carrier to 3.3 HIEs/1000 tackles for a high-speed tackler. Conclusions Complex interplay exists between tackle type, body position and speeds. The ability to anticipate and protect oneself in a tackle is crucial for reduced risk, as is the correct selection of tackle type and direction based on relative speeds. The execution of higher force tackles to avoid high risk head impacts is also critical. Decision-making and tackle execution offer potential areas for intervention to reduce HIE risk.
CD73 on T Cells Orchestrates Cardiac Wound Healing After Myocardial Infarction by Purinergic Metabolic Reprogramming
Authors: Nadine Borg, Christina Alter, Nicole Görldt, Christoph Jacoby, Zhaoping Ding, Bodo Steckel, Christine Quast, Florian Bönner, Daniela Friebe, Sebastian Temme, Ulrich Flögel, Jürgen Schrader
Journal: Circulation (2017)

T cells are required for proper healing after myocardial infarction. The mechanism of their beneficial action, however, is unknown. The proinflammatory danger signal ATP, released from damaged cells, is degraded by the ectonucleotidases CD39 and CD73 to the anti-inflammatory mediator adenosine. Here, we investigate the contribution of CD73-derived adenosine produced by T cells to cardiac remodeling after ischemia/reperfusion and define its mechanism of action.Myocardial ischemia (50 minutes followed by reperfusion) was induced in global CD73-/- and CD4-CD73-/- mice. Tissue injury, T-cell purinergic signaling, cytokines, and cardiac function (magnetic resonance tomography at 9.4 T over 4 weeks) were analyzed.Changes in functional parameters of CD4-CD73-/- mice were identical to those in global CD73 knockouts (KOs). T cells infiltrating the injured heart significantly upregulated at the gene (quantitative polymerase chain reaction) and protein (enzymatic activity) levels critical transporters and enzymes (connexin43, connexin37, pannexin-1, equilibrative nucleoside transporter 1, CD39, CD73, ecto-nucleotide pyrophosphatase/phosphodiesterases 1 and 3, CD157, CD38) for the accelerated release and hydrolysis of ATP, cAMP, AMP, and NAD to adenosine. It is surprising that a lack of CD39 on T cells (from CD39-/- mice) did not alter ATP hydrolysis and very likely involves pyrophosphatases (ecto-nucleotide pyrophosphatase/phosphodiesterases 1 and 3). Circulating T cells predominantly expressed A2a receptor (A2aR) transcripts. After myocardial infarction, A2b receptor (A2bR) transcription was induced in both T cells and myeloid cells in the heart. Thus, A2aR and A2bR signaling may contribute to myocardial responses after myocardial infarction. In the case of T cells, this was associated with an accelerated secretion of proinflammatory and profibrotic cytokines (interleukin-2, interferon-γ, and interleukin-17) when CD73 was lacking. Cytokine production by T cells from peripheral lymph nodes was inhibited by A2aR activation (CGS-21680). The A2bR agonist BAY 60-6583 showed off-target effects. The adenosine receptor agonist NECA inhibited interferon-γ and stimulated interleukin-6 production, each of which was antagonized by a specific A2bR antagonist (PSB-603).This work demonstrates that CD73 on T cells plays a crucial role in the cardiac wound healing process after myocardial infarction. The underlying mechanism involves a profound increase in the hydrolysis of ATP/NAD and AMP, resulting primarily from the upregulation of pyrophosphatases and CD73. We also define A2bR/A2aR-mediated autacoid feedback inhibition of proinflammatory/profibrotic cytokines by T cell-derived CD73.
The Cognitive Neuroscience of Placebo Effects: Concepts, Predictions, and Physiology
Authors: Stephan Geuter, Leonie Koban, Tor D. Wager
Journal: Annual Review of Neuroscience (2017)

Placebos have been used ubiquitously throughout the history of medicine. Expectations and associative learning processes are important psychological determinants of placebo effects, but their underlying brain mechanisms are only beginning to be understood. We examine the brain systems underlying placebo effects on pain, autonomic, and immune responses. The ventromedial prefrontal cortex (vmPFC), insula, amygdala, hypothalamus, and periaqueductal gray emerge as central brain structures underlying placebo effects. We argue that the vmPFC is a core element of a network that represents structured relationships among concepts, providing a substrate for expectations and a conception of the situation-the self in context-that is crucial for placebo effects. Such situational representations enable multidimensional predictions, or priors, that are combined with incoming sensory information to construct percepts and shape motivated behavior. They influence experience and physiology via descending pathways to physiological effector systems, including the spinal cord and other peripheral organs.
Lenalidomide-Induced Cytopenias: Relationship to Hematologic Improvement in Patients with Myelodysplastic Syndromes (MDS).
Authors: Mikkael A. Sekeres, Jaroslaw P. Maciejewski, Aristoteles Giagounidis, Kenton Wride, Robert D. Knight, Azra Raza, Alan F. List
Journal: Blood (2007)
TCTAP C-203 Post Bentall's Periconduit Aneurysm, Severe Paraconduit Leak, Aorta to Periconduit Fistula Periconduit to RA Fistula- a Challenging Successful Multiple Device Closures: Clinical-imaging-autopsy Correlation
Authors: Nagaraja Moorthy, Rajiv Ananthakrishna, Dattatreya PV, S.R. Kalpana, C.N. Manjunath
Journal: Journal of the American College of Cardiology (2017)
MyPathway: An open-label phase IIa study of trastuzumab/pertuzumab, erlotinib, vemurafenib, and vismodegib in patients who have advanced solid tumors with mutations or gene expression abnormalities targeted by these agents.
Authors: Howard A. Burris, Herbert Hurwitz, Edith A. Perez, David Spigel, Charles Swanton, John D. Hainsworth, Larry Leon, Mary Beattie, Melissa Brammer, Christopher Sweeney
Journal: Journal of Clinical Oncology (2015)

TPS11111 Background: While many targeted agents are approved for specific cancers, molecular profiling has increasingly led to the identification of genetic abnormalities in tumor types for which targeted agents are not currently approved. MyPathway explores the activity and safety of therapies that target HER2, EGFR, BRAF, and Hedgehog pathways in cancers for which these treatments are not FDA-approved. Methods: MyPathway (trial registration NCT02091141) is a multicenter, non-randomized, phase IIa study of patients with advanced solid tumors that have progressed following standard therapy or for which there is no approved treatment. Eligible patients have a tumor with a potentially actionable genetic alteration, as determined by a Clinical Laboratory Improvement Amendments-certified laboratory. Patients with > 1 mutation are treated based on the mutation considered most critical by the investigator; they may later enroll based on a different mutation, if initial therapy fails. For each pathway, treatments are dosed based on the approved regimen. Patients are evaluated for response after 2 cycles of therapy; those with an objective response or stable disease may continue therapy until tumor progression or unacceptable toxicity. Safety is monitored in real time and reviewed every 3–6 mos. The primary outcome is response rate. Secondary outcomes are disease control rate, progression-free survival, and 1-year survival. Outcomes will be studied by tumor type and pathway (tumor-pathway cohorts). Sample sizes for tumor-pathway cohorts are based on Simon’s 2-stage design procedure. Use of the master protocol will allow possible future exploration of additional pathways as new agents become available. Evidence of activity in this trial may be studied in larger dedicated trials. Clinical trial information: NCT02091141. Pathway Molecular alteration Treatment(s) HER2 Overexpression of HER2 or activating mutation Trastuzumab and pertuzumab EGFR EGFR-activating mutation Erlotinib BRAF BRAF-activating mutation (V600E and others) Vemurafenib Hedgehog SMO-activating mutation, PTCH-1 loss-of-function mutation Vismodegib