tbuckley/cabot-search huggingface dataset:
S100-SPECT uncovers cellular and molecular events of pre-metastatic niche formation and following organ-specific cancer metastasis
Authors: Masakiyo Sakaguchi
Journal: Theranostics (2017)

Great progress has been made in in vivo imaging for cancer metastasis.Eisenblaetter et al. developed an innovative S100A8/A9-specific single photon emission computed tomography (SPECT) probe for imaging and succeeded in detecting the metastatic organ favored by the cancer before the cancer arrival.By utilizing this advanced method, researchers have also found that cancer-derived monocytes are the main source of the abundant production of S100A8/A9 in the pre-metastatic area.The CCL2-CCR2 axis is associated with S100A8/A9 production.Clinical establishment of this technique is expected to enable accurate prediction and monitoring of cancer metastasis during therapy.
Ten-year overall and prostate cancer (PCa)-specific mortality in high-risk patients after high-dose-rate brachytherapy combined with external beam radiation therapy (HDR-BT/EBRT) compared with EBRT alone.
Authors: Trude Baastad Wedde, Sophie Fosså, Sigmund Brabrand, Stein Kaasa, Kjell Magne Russnes, Taran Poulsen Hellebust, Gunnar Tafjord, Wolfgang Lilleby
Journal: Journal of Clinical Oncology (2017)

5059 Background: The effect of dose-escalation with HDR-BT boost for high-risk PCa is not known. The objective is to compare 10-year PCa-specific mortality (PCSM) and overall mortality (OM) in non-metastatic patients treated with HDR-BT/EBRT (2004-2010) to EBRT alone (historical RCT, SPCG-7, 1996-2003). Methods: HDR-BT boosts (10 Gy x 2) were given 2 weeks apart followed by 50 Gy conformal EBRT (2 Gy x 25) to the prostate and seminal vesicles (assuming alpha/beta ratio of 3, EQD2 = 102 Gy). The HDR-BT/EBRT group (N:325) received Androgen Deprivation Therapy (ADT) for a total of 2 years. Patients in the control group (N:296) received 70 Gy (2Gy x 35) to the prostate and seminal vesicles with lifelong Anti-Androgen Treatment (AA). cT1-cT2 vs cT3 tumours and Gleason score 6-7 vs 8-10 were analysed. For each treatment group PCSM and OM were established by Kaplan-Meier (KM) analyses, and inter-treatment differences were tested by the logrank tests. Cox regression analysis evaluated the significance of available pre-treatment variables. Significance level p &lt; 0.05. Results: In both groups the median age was 66 years. Median follow-up was 104 (range 13-120) and 120 (range 3-120) months for the HDR-BT/EBRT and EBRT groups respectively. KM plots revealed an 1.8% risk of PCSM in the HDR-BT/EBRT patient group and an 8.4% risk in the EBRT cohort (p = 0.001). For OM, the figures were 12.3% in the HDR-BT/EBRT group compared to 23.3% in the EBRT group (p = 0.014). In the Cox regression analysis, treatment (HR = 3.9, CI95% 1.8-8.3) and Gleason score (HR = 3.2, CI95% 1.8-5.9) were significantly associated with PCSM whilst T-stage, age and PSA levels were not. Treatment (HR = 1.7, CI95% = 1.1-2.6) was the only factor significantly associated with OM. Conclusions: In men with high-risk PCa dose-escalation with HDR-BT/EBRT compared to EBRT alone resulted in a significantly decreased risk of 10-year PCSM and OM despite shorter length of hormonal therapy. PCSM was significantly influenced by both Gleason score and type of treatment, whereas treatment remained the only significant covariate for OM.
A phase II study of temsirolimus added to low-dose weekly carboplatin and paclitaxel for patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC)
Authors: L.A. Dunn, M.G. Fury, H. Xiao, S.S. Baxi, E.J. Sherman, S. Korte, C. Pfister, S. Haque, N. Katabi, A.L. Ho, D.G. Pfister
Journal: Annals of Oncology (2017)
Low-Dose Decitabine Combined with Modified Bucy Is More Effective Conditioning Regimen for High-Risk Patients with Acute Myeloid Leukaemia/Myelodysplastic Syndrome
Authors: Xiaowen Tang, Jing Cao, Xiaojing Shi, Ling Ge, Aining Sun, Xiaming Zhu, Huiying Qiu, Zhengming Jin, Miao Miao, Chengcheng Fu, Xiao Ma, Feng Chen, Shengli Xue, Yue Han, Mengxing Xue, Xinliang Mao, Depei Wu
Journal: Blood (2016)
Type 1 Diabetes: Urinary Proteomics and Protein Network Analysis Support Perturbation of Lysosomal Function
Authors: Harinder Singh, Yanbao Yu, Moo-Jin Suh, Manolito G Torralba, Robert D. Stenzel, Andrey Tovchigrechko, Vishal Thovarai, Derek M. Harkins, Seesandra V. Rajagopala, Whitney Osborne, Fran R. Cogen, Paul B. Kaplowitz, Karen E. Nelson, Ramana Madupu, Rembert Pieper
Journal: Theranostics (2017)

While insulin replacement therapy restores the health and prevents the onset of diabetic complications (DC) for many decades, some T1D patients have elevated hemoglobin A1c values suggesting poor glycemic control, a risk factor of DC.We surveyed the stool microbiome and urinary proteome of a cohort of 220 adolescents and children, half of which had lived with T1D for an average of 7 years and half of which were healthy siblings.Phylogenetic analysis of the 16S rRNA gene did not reveal significant differences in gut microbial alpha-diversity comparing the two cohorts.The urinary proteome of T1D patients revealed increased abundances of several lysosomal proteins that correlated with elevated HbA1c values.In silico protein network analysis linked such proteins to extracellular matrix components and the glycoprotein LRG1.LRG1 is a prominent inflammation and neovascularization biomarker.We hypothesize that these changes implicate aberrant glycation of macromolecules that alter lysosomal function and metabolism in renal tubular epithelial cells, cells that line part of the upper urinary tract.
Quality and Equitable Health Care Gaps for Women
Authors: Leslee J. Shaw, Carl J. Pepine, Joe Xie, Puja K. Mehta, Alanna A. Morris, Neal W. Dickert, Keith C. Ferdinand, Martha Gulati, Harmony Reynolds, Sharonne N. Hayes, Dipti Itchhaporia, Jennifer H. Mieres, Elizabeth Ofili, Nanette K. Wenger, C. Noel Bairey Merz
Journal: Journal of the American College of Cardiology (2017)
Intensive Glycemic Control and the Prevention of Cardiovascular Events: Implications of the ACCORD, ADVANCE, and VA Diabetes Trials
Authors: Jay S. Skyler, Richard Bergenstal, Robert O. Bonow, John Buse, Prakash Deedwania, Edwin A.M. Gale, Barbara V. Howard, M. Sue Kirkman, Mikhail Kosiborod, Peter Reaven, Robert S. Sherwin
Journal: Circulation (2008)

D iabetes is defined by its association with hyperglycemia- specific microvascular complications; however, it also imparts a 2-to 4-fold risk of cardiovascular disease (CVD).Although microvascular complications can lead to significant morbidity and premature mortality, by far the greatest cause of death in people with diabetes is CVD.4][5] In the Diabetes Control and Complications Trial (DCCT), there was an Ϸ60% reduction in the development or progression of diabetic retinopathy, nephropathy, and neuropathy between the intensively treated group (goal A 1c , Ͻ6.05%; mean achieved A 1c , Ϸ7%) and the standard group (A 1c , Ϸ9%) over an average of 6.5 years.The relationship between glucose control (as reflected by the mean on-study A 1c value) and risk of complications was log-linear and extended down to the normal A 1c range (Ͻ6%) with no threshold noted.In the UK Prospective Diabetes Study (UKPDS), participants newly diagnosed with type 2 diabetes were followed up for 10 years, and intensive control (median A 1c , 7.0%) was found to reduce the overall microvascular complication rate by 25% compared with conventional treatment (median A 1c , 7.9%).Here, too, secondary analyses showed a continuous relationship between the risk of microvascular complications and glycemia extending into the normal range of A 1c , with no glycemic threshold.
Mannose-Binding Lectin Levels Could Predict Prognosis in IgA Nephropathy
Authors: Wei-yi Guo, Li Zhu, Si-jun Meng, Su-fang Shi, Li-jun Liu, Ji-cheng Lv, Hong Zhang
Journal: Journal of the American Society of Nephrology (2017)

IgA nephropathy (IgAN) is characterized by infections followed by episodic gross hematuria. Deficiency of mannose-binding lectin (MBL) is associated with recurrent infection in many diseases, but controversy exists regarding the role of MBL in IgAN. Here, we measured MBL2 variants and MBL levels in 749 patients with IgAN and 489 healthy controls. Overall, 5.2% (39 of 749) of patients with IgAN had MBL deficiency (MBL levels <100 ng/ml), among whom LYPB/LYPB and LXPA/LYPB were the predominant MBL2 haplotypes (82%; 32 of 39). We found a nonlinear association between MBL levels and renal outcome in IgAN. Patients with IgAN and MBL deficiency had a higher incidence of prodromic infections and gross hematuria than those with sufficient MBL levels (100-3540 ng/ml). Moreover, MBL deficiency independently associated with poor renal outcome in IgAN after multiple adjustments (hazard ratio, 5.18; 95% confidence interval, 2.50 to 10.72; P<0.001). Patients with high MBL levels (>3540 ng/ml) had more severe proteinuria and a higher proportion of crescents, although the association with IgAN progression did not reach statistical significance after adjustments. In conclusion, MBL deficiency and MBL excess may both have deleterious effects on IgAN progression, which suggests that MBL contributes to IgAN pathogenesis through multiple mechanisms.
Acute Porphyria
Authors: A. Goldberg, A. C. Macdonald, C. Rimington
Journal: BMJ (1952)

In six cases E.E.G. studies were carried out to ascertain if the phenomena described by Roth as occurring in the electric shock treatment of depression would occur.The change was seen in one case out of six, and at the point when a striking clinical improvement occurred in a woman suffering from.obsessionalillness.With this unpromising material it was possible to obtain a much closer emotional rapport than by using other forms of abreaction.The patients would show great emotion, and discuss previously repressed material relating to their conflicts in the frankest manner and with great emotion.In some cases the patients were able to free themselves from antisocial sexual habits of a criminal character.In cases in which horrific war experiences had been a causal factor the patient relived the incident with marked emotional expression of fear and rage.A strong abreaction was of favourable prognostic significance.Thirty-eight (76%) patients stated that they had received immediate emotional relief from the treatment.Twenty-five (50%) have shown an improvement lasting from six months to two years.Illustrative cases are given.The treatment has been found valuable in conjunction with psychotherapy in treating chronic cases of neurosis and behaviour disorder, and may be superior to other methods of abreactive therapy.One of us (A.C.) is grateful to the Dan Mason Research Foundation for a grant to carry out work of which the present study forms a part.We
Synergy between the Host Immune System and Bacteriophage Is Essential for Successful Phage Therapy against an Acute Respiratory Pathogen
Authors: Dwayne R. Roach, Chung Yin Leung, Marine Henry, Eric Morello, Devika Singh, James P. Di Santo, Joshua S. Weitz, Laurent Debarbieux
Journal: Cell Host & Microbe (2017)
Tivo-3: A phase 3, randomized, controlled, multi-center, open-label study to compare tivozanib hydrochloride to sorafenib in subjects with refractory advanced renal cell carcinoma (RCC).
Authors: Brian I. Rini, Michael B. Atkins, Bernard J. Escudier, Thomas E. Hutson, Piotr Koralewski, David F. McDermott, Sumanta K. Pal, Michael N. Needle, Camillo Porta
Journal: Journal of Clinical Oncology (2017)

TPS4600 Background: Tivozanib is a biochemically potent and selective VEGF tyrosine kinase inhibitor in clinical development in RCC. Other agents used for treatment of RCC inhibit multiple tyrosine kinases in addition to the VEGF receptor tyrosine kinase, leading to off-target toxicities such as fatigue, hand-foot syndrome, stomatitis, and neutropenia. The adverse event (AE) profile of tivozanib demonstrates minimal off-target toxicities. TIVO-1 (AV-951-09-301) was an open-label, randomized, controlled, multi-national, multi-center, parallel-arm trial comparing tivozanib to sorafenib in patients with advanced RCC. The blinded independent radiological assessment showed the median progression free survival (mPFS) in the tivozanib arm to be 11.9 months (95% confidence interval (CI) [9.3, 14.7]), compared with 9.1 months (95% CI [7.3, 9.5]) in the sorafenib arm (p = 0.042, HR = 0.797). Overall survival had a negative trend, most likely due to a one-way crossover for patients randomized to sorafenib. This study is designed, in part, to demonstrate that the negative trend in OS was an artifact. Methods: Subjects with metastatic RCC who have failed 2 or 3 prior systemic regimens, one of which includes a VEGFR TKI other than sorafenib or tivozanib, will be randomized in a 1:1 ratio stratified by the IMDC risk category (favorable; intermediate; poor) and prior therapy (two VEGFR TKIs; a prior checkpoint inhibitor plus a prior VEGFR TKI; a prior VEGFR TKI plus any other systemic agent). The primary objective is to compare the progression-free survival (PFS) of subjects randomized to tivozanib with those randomized to sorafenib as assessed by blinded independent radiological review (IRR). Secondary endpoints are overall survival, objective response rate, and duration of response. Clinical trial information: NCT02627963.
Association Between Contemporary Trends in Inferior Vena Cava Filter Placement and the 2010 US Food and Drug Administration Advisory
Authors: Satyajit Reddy, Vladimir Lakhter, Chad J. Zack, Huaqing Zhao, Saurav Chatterjee, Riyaz Bashir
Journal: JAMA Internal Medicine (2017)

This study uses the National Inpatient Sample database to assess the association between rates of inferior vena cava filter placement in the United States and the 2010 US FDA device safety warning.
Chemotherapy-related adverse events among breast cancer patients: A retrospective analysis of the SEER-Medicare database
Authors: J. J. Doyle, D. L. Hershman, A. I. Neugut, L. S. Stern, L. M. Katz, M. Dolgitser
Journal: Journal of Clinical Oncology (2006)

10634 Background: Systemic chemotherapy is a common treatment option for female breast cancer (BC) patients. Chemotherapeutic agents often cause myelosuppression events (MEs), which may be costly and severe. Methods: Women ≥ 65 years of age diagnosed with stage I - III breast cancer from 1/1/92–12/31/99 within The Surveillance, Epidemiology and End Results (SEER)-Medicare database were analyzed. Using our extensive previous work with this BC cohort, a retrospective cohort study was conducted to assess the incidence and costs of MEs in chemotherapy-treated BC patients. Chemotherapies were captured using HCPCS codes; hospitalizations related to ME events (identified with ICD-9 diagnosis codes for anemia, thrombocytopenia, or leukopenia) were detected anytime after index date (date of first BC diagnosis). Total inpatient charges after index date were calculated. Results: 31,748 female BC patients were identified, 17.6% of whom received chemotherapy during follow-up. The mean age for these patients was 75.6 years (SD = 6.6, Range: 66–107). ME-related hospitalizations were significantly more likely in chemotherapy than non-chemotherapy patients, with 12.1% and 1.8%, respectively [OR = 2.3 (2.0–2.5)]; anemia in 8.6% and 5.1%, respectively [OR = 1.8 (1.6–1.0)], thrombocytopenia in 2.0% and 0.7%, respectively [OR = 2.9 (2.3–3.7)], and leukopenia in 4.4% and 0.5%, respectively [OR = 9.7 (7.8–12.1)]. Chemotherapy patients had significantly higher inpatient charges than patients without chemotherapy. Among chemotherapy patients, significantly higher inpatient charges were found in those with MEs than without ($15,297 vs. $4,211, p &lt; 0.0001). Conclusion: Chemotherapy-related MEs were common among Medicare BC patients and led to substantial hospital charge increases. No significant financial relationships to disclose.
Abstract 054: Deficiency Of Nuclear Receptor Interaction Protein Causes Cardiac Hypertrophy
Authors: Show-Li Chen
Journal: Circulation Research (2013)

Previously, we demonstrate a novel gene, nuclear receptor interaction protein (NRIP, also named as DCAF6 or IQWD1). We also identify NRIP as a Ca2+- dependent calmodulin binding protein that activates calcineurin phosphatase activity. To investigate insights into in vivo function of NRIP, we generated NRIP-null mice and found that loss of NRIP impairs cardiac function and lead to cardiac hypertrophy progressively. Furthermore, NRIP-/- mice display weaker muscle strength, reduced cardiac function, and cardiac fibrosis compared with WT. To verify the regulation mechanism, we found that α-actinin-2 (ACTN2), which is a biomarker of muscular Z-disc complex, is one of NRIP-interacting proteins from the yeast two-hybrid system. ACTN2 cross-links with actin filament to stabilize sarcomeric structure and muscle contraction, which is an essential constituent of sarcomere. Through the in vitro and in vivo binding assays, we further confirm the interaction and define the interacting domains between NRIP and ACTN2. Plus co-localization of NRIP and ACTN2 is discovered in cardiac tissue by immunofluorescence assays, we firstly define NRIP as a Z-disc protein. Although the Z-disc has been viewed as a passive constituent of the sarcomere traditionally, increasing numbers of mutations in Z-disc proteins leading to disruption and malfunction of the contractile apparatus have been shown to cause cardiomyopathies and/or muscular dystrophies. Hence, we analyzed the sarcomeric structure of NRIP-/- cardiomyocytes and found reduction of I-band width and extension of Z-disc. Besides, we know that NRIP is a Ca2+- dependent calmodulin binding protein. In cardiomyocytes, calmodulin interacts with multiple calcium ion channels or proteins to directly or indirectly regulate the variation of calcium concentration during muscle contraction. Therefore, we isolated and measured the calcium transient of cardiomyocytes. Then, we found that deficiency of NRIP decreases the amplitude of calcium transient. In a conclusion, we speculated that loss of NRIP impairs the structure of sarcomere, the amplitude of calcium transient during muscle contraction and the function of muscle contraction resulting in cardiomyopathy.
Outcome of Patients with Second Cancer after Hematopoietic Stem Cell Transplantation: On Behalf of the Complications and Quality of Life Working Party of the EBMT
Authors: André Tichelli, Eric Beohou, Myriam Labopin, Gérard Socié, Alicia Rovó, Manuela Badoglio, Anja van Biezen, Grzegorz Basak, Rafael F. Duarte, Nina Salooja
Journal: Blood (2016)
Validation of a novel imaging approach using multi-slice CT and cone-beam CT to follow-up on condylar remodeling after bimaxillary surgery
Authors: Laura Ferreira Pinheiro Nicolielo, Jeroen Van Dessel, Eman Shaheen, Carolina Letelier, Marina Codari, Constantinus Politis, Ivo Lambrichts, Reinhilde Jacobs
Journal: International Journal of Oral Science (2017)

The main goal of this study was to introduce a novel three-dimensional procedure to objectively quantify both inner and outer condylar remodelling on preoperative multi-slice computed tomography (MSCT) and postoperative cone-beam computed tomography (CBCT) images. Second, the reliability and accuracy of this condylar volume quantification method was assessed. The mandibles of 20 patients (11 female and 9 male) who underwent bimaxillary surgery were semi-automatically extracted from MSCT/CBCT scans and rendered in 3D. The resulting condyles were spatially matched by using an anatomical landmark-based registration procedure. A standardized sphere was created around each condyle, and the condylar bone volume within this selected region of interest was automatically calculated. To investigate the reproducibility of the method, inter- and intra-observer reliability was calculated for assessments made by two experienced radiologists twice five months apart in a set of ten randomly selected patients. To test the accuracy of the bone segmentation, the inner and outer bone structures of one dry mandible, scanned according to the clinical set-up, were compared with the gold standard, micro-CT. Thirty-eight condyles showed a significant (P<0.05) mean bone volume decrease of 26.4%±11.4% (502.9 mm3±268.1 mm3). No significant effects of side, sex or age were found. Good to excellent (ICC>0.6) intra- and inter-observer reliability was observed for both MSCT and CBCT. Moreover, the bone segmentation accuracy was less than one voxel (0.4 mm) for MSCT (0.3 mm±0.2 mm) and CBCT (0.4 mm±0.3 mm), thus indicating the clinical potential of this method for objective follow-up in pathological condylar resorption.
Multidimensional Evidence Generation and FDA Regulatory Decision Making
Authors: Jonathan P. Jarow, Lisa LaVange, Janet Woodcock
Journal: JAMA (2017)

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Effect of Cytochrome P450 Metabolites of Arachidonic Acid in Nephrology
Authors: Fan Fan, Richard J. Roman
Journal: Journal of the American Society of Nephrology (2017)

Thirty-five years ago, a third pathway for the metabolism of arachidonic acid by cytochrome P450 enzymes emerged. Subsequent work revealed that 20-hydroxyeicosatetraenoic and epoxyeicosatrienoic acids formed by these pathways have essential roles in the regulation of renal tubular and vascular function. Sequence variants in the genes that produce 20-hydroxyeicosatetraenoic acid are associated with hypertension in humans, whereas the evidence supporting a role for variants in the genes that alter levels of epoxyeicosatrienoic acids is less convincing. Studies in animal models suggest that changes in the production of cytochrome P450 eicosanoids alter BP. However, the mechanisms involved remain controversial, especially for 20-hydroxyeicosatetraenoic acid, which has both vasoconstrictive and natriuretic actions. Epoxyeicosatrienoic acids are vasodilators with anti-inflammatory properties that oppose the development of hypertension and CKD; 20-hydroxyeicosatetraenoic acid levels are elevated after renal ischemia and may protect against injury. Levels of this eicosanoid are also elevated in polycystic kidney disease and may contribute to cyst formation. Our review summarizes the emerging evidence that cytochrome P450 eicosanoids have a role in the pathogenesis of hypertension, polycystic kidney disease, AKI, and CKD.