tbuckley/cabot-search huggingface dataset:
A multicenter yearlong randomized controlled trial of different exercise modalities in prostate cancer survivors on androgen deprivation therapy.
Authors: Daniel Abido Galvao, Dennis R Taaffe, Prue Cormie, Nigel Spry, David John Joseph, Suzanne K Chambers, Robert Alexander Gardiner, Kate Bolam, Bradley Alan Wall, Robert Usher Newton
Journal: Journal of Clinical Oncology (2014)

5037 Background: It is well recognized that androgen deprivation therapy (ADT) for prostate cancer is associated with a number of substantial adverse effects including a reduction in muscle mass and strength, increased fat mass and poorer physical function. Recently, undertaking purposeful physical exercise has been proposed as an effective strategy to counter many of these ADT-related adverse effects. The purpose of this multi-centre, year-long randomized controlled trial was to extend these findings by assessing the effects of two varying exercise regimens, one targeting the musculoskeletal system (impact loading + resistance training; ILRT) and the other the cardiovascular and muscular systems (aerobic + resistance training; ART), on body composition, lower body muscle strength and physical function in men currently undertaking ADT. Methods: One hundred and sixty three men aged 42-90 years with a BMI of 24.8 kg/m2 completed baseline testing and were randomized to ILRT (n=58), ART (n=54) or delayed exercise (CON, n=51) for 12 months. Training was undertaken for ~1 hour twice weekly under supervision at a moderate-to-high intensity. Lean and fat mass were determined by DXA, muscle strength by the 1-RM test, and lower body physical function by a battery of tests (6-m walk, 6-m backwards walk, 400-m walk, chair rise, stair climb). Results: There were no differences among the groups for any variable at baseline. Between pre and post-intervention, lean mass increased in ILRT by 1.4 kg (p<0.001) and 0.6 kg (p=0.030) in ART with no change in CON. Fat mass also increased in ILRT and CON by1.1 kg (p<0.001) with no significant change in ART (0.6 kg, p=0.156). Upper and lower body muscle strength increased by 17-45% in ILRT which was greater than that in ART and CON (p<0.001). Compared to pre-intervention, ILRT and ART generally improved in most physical function tasks (p<0.050). Conclusions: The combination of impact loading and resistance training produced superior gains in lean mass and muscle strength compared to aerobic plus resistance exercise in prostate cancer survivors on ADT. Strategies to implement this novel training protocol are warranted. Clinical trial information: ACTRN12609000200280.
Adenocarcinoma of the lung and venous thromboembolic events: a monoinstitutional, retrospective evaluation.
Authors: Angelo Delmonte, Marita Mariotti, Emanuela Scarpi, Paola Ulivi, Giampaolo Gavelli, Daniele Calistri, Marco Angelo Burgio, Angela Ragazzini, Lucio Crino, Dino Amadori
Journal: Journal of Clinical Oncology (2015)

e19149 Background: the association of venous thromboembolic events (VTE) and lung cancer has a high prevalence. Limited data are available in the adenocarcinoma subtype population especially in relation to platinum based therapy and presence of driver mutations. We evaluated these aspects in our retrospective series. Methods: we evaluated data of patients treated for advanced adenocarcinoma from January 2003 to July 2014 in our Institution. We conducted a subgroup analysis according to EGFR, KRAS and BRAF status defined by MassArray (Sequonom). Presence of EML4-ALK translocation was evaluated by FISH. Overall Survival (OS) and 95% Confidence Interval (95% CI) was estimated by Kaplan-Meier method and compared by logrank test. Results: among 289 evaluable patients, 62 (21.5%) experienced VTE. Median OS was 17 months (14.6-22.3): OS in VTE patients was 14.5 months (10.8-17.1) while in non VTE patients was 21.6 months (15.3-27.1) (p = 0.036). Forty-three (21%) of the 202 patients who received chemotherapy containing platinum in any line of treatment (188 in first line) developed TVE; a similar percentage of VTE was seen in those patients who never received platinum compounds. Among VTE patients, 45 (72.6%) didn’t show driver mutations (p = 0.408). In the group of patients with driver mutations, 12 of 49 (24.5%) with EGFR mutation (p = 0.706) had VTE. Only 131 patients were evaluated for KRAS status: 50 presented KRAS mutation of which only 3 (6%) had VTE; occurrence of VTE was significantly higher in KRAS wild type patients (p = 0.032). Of 110 patients evaluated for EML4-ALK status only 2 of 6 (33%) with translocation had VTE (p = 0.276). No VTE were seen in 5 BRAF mutated patients. Conclusions: Occurrence of VTE in lung adenocarcinoma in our series was higher than that reported in historical control of literature and is related with worsening of prognosis. No clear statistically significant relationship was seen between VTE and platinum based chemotherapy or presence of driver mutations. In particular the KRAS mutation seems to be not related with VTE. Prospective data in larger population are needed to confirm these findings.
Low-Dose Paclitaxel–Coated Versus Uncoated Percutaneous Transluminal Balloon Angioplasty for Femoropopliteal Peripheral Artery Disease
Authors: Henrik Schroeder, Martin Werner, Dirk-Roelfs Meyer, Peter Reimer, Karsten Krüger, Michael R. Jaff, Marianne Brodmann
Journal: Circulation (2017)

Numerous studies have reported favorable outcomes using drug-coated balloons (DCBs) for treatment of symptomatic peripheral artery disease of the superficial femoral and popliteal arteries. However, the treatment effect compared with an uncoated balloon has differed greatly among the randomized trials, with better outcomes observed with higher-dose DCBs. This European trial was designed to assess the safety and effectiveness of a next-generation low-dose (2-µg/mm2 surface dose of paclitaxel) DCB.This was a prospective, randomized, multicenter, single-blinded trial. Patients were randomized (3:1) to treatment with a low-dose DCB or an uncoated percutaneous transluminal angioplasty (PTA) balloon. The primary safety end point was a composite of freedom from device- and procedure-related death through 30 days after the procedure and freedom from target limb major amputation and clinically driven target lesion revascularization through 12 months after the procedure. The primary effectiveness end point was primary patency at 12 months.Patients were randomized to treatment with a DCB (222 patients, 254 lesions) or uncoated PTA balloon (72 patients, 79 lesions) after successful predilatation. Mean lesion length was 7.2 and 7.1 cm, and 19.2% and 19.0% of lesions represented total occlusions, respectively. The primary safety end point was met, and superiority was demonstrated; freedom from a primary safety event was 94.1% (193 of 205) with DCB and 83.3% (50 of 60) with PTA, for a difference of 10.8% (95% confidence interval, 0.9%-23.0%). The primary effectiveness end point was met, and superiority of DCB over PTA was achieved (83.9% [188 of 224] versus 60.6% [40 of 66]; P<0.001). Outcomes with DCB were also superior to PTA per the Kaplan-Meier estimate for primary patency (89.0% versus 65.0% at 365 days; log-rank P<0.001) and for rates of clinically driven target lesion revascularization (5.9% versus 16.7%; P=0.014).Superiority with a low-dose DCB for femoropopliteal interventions was demonstrated over PTA for both the safety and effectiveness end points.URL: http://www.clinicaltrials.gov. Unique identifier: NCT01858363.
TCTAP C-166 Embolization of the Atrial Septal Occluder Device : Why Was This Device Dislodged
Authors: Sang Yeub Lee, Dae-Whan Bae, Sangmin Kim, Ju-Hee Lee, Jang-Whan Bae, Myeong-Chan Cho
Journal: Journal of the American College of Cardiology (2017)
Eradication of Tumors through Simultaneous Ablation of CD276/B7-H3-Positive Tumor Cells and Tumor Vasculature
Authors: Steven Seaman, Zhongyu Zhu, Saurabh Saha, Xiaoyan M. Zhang, Mi Young Yang, Mary Beth Hilton, Karen Morris, Christopher Szot, Holly Morris, Deborah A. Swing, Lino Tessarollo, Sean W. Smith, Sylvia Degrado, Dmitry Borkin, Nareshkumar Jain, Julia Scheiermann, Yang Feng, Yanping Wang, Jinyu Li, Dean Welsch, Gary DeCrescenzo, Amit Chaudhary, Enrique Zudaire, Kimberly D. Klarmann, Jonathan R. Keller, Dimiter S. Dimitrov, Brad St. Croix
Journal: Cancer Cell (2017)
Type I interferon responses drive intrahepatic T cells to promote metabolic syndrome
Authors: Magar Ghazarian, Xavier S. Revelo, Mark K. Nøhr, Helen Luck, Kejing Zeng, Helena Lei, Sue Tsai, Stephanie A. Schroer, Yoo Jin Park, Melissa Hui Yen Chng, Lei Shen, June Ann D’Angelo, Peter Horton, William C. Chapman, Diane Brockmeier, Minna Woo, Edgar G. Engleman, Oyedele Adeyi, Naoto Hirano, Tianru Jin, Adam J. Gehring, Shawn Winer, Daniel A. Winer
Journal: Science Immunology (2017)

Obesity-related insulin resistance correlates with type I interferon–driven activation and expansion of intrahepatic T cells. See the related Focus by Ma et al .
Transdiagnostic Behavioral Therapies in Pediatric Primary Care
Authors: John T. Walkup, Tara Mathews, Cori Meredith Green
Journal: JAMA Psychiatry (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
Cell Therapy Trials in Congenital Heart Disease
Authors: Hidemasa Oh
Journal: Circulation Research (2017)

Dramatic evolution in medical and catheter interventions and complex surgeries to treat children with congenital heart disease (CHD) has led to a growing number of patients with a multitude of long-term complications associated with morbidity and mortality. Heart failure in patients with hypoplastic left heart syndrome predicated by functional single ventricle lesions is associated with an increase in CHD prevalence and remains a significant challenge. Pathophysiological mechanisms contributing to the progression of CHD, including single ventricle lesions and dilated cardiomyopathy, and adult heart disease may inevitably differ. Although therapeutic options for advanced cardiac failure are restricted to heart transplantation or mechanical circulatory support, there is a strong impetus to develop novel therapeutic strategies. As lower vertebrates, such as the newt and zebrafish, have a remarkable ability to replace lost cardiac tissue, this intrinsic self-repair machinery at the early postnatal stage in mice was confirmed by partial ventricular resection. Although the underlying mechanistic insights might differ among the species, mammalian heart regeneration occurs even in humans, with the highest degree occurring in early childhood and gradually declining with age in adulthood, suggesting the advantage of stem cell therapy to ameliorate ventricular dysfunction in patients with CHD. Although effective clinical translation by a variety of stem cells in adult heart disease remains inconclusive with respect to the improvement of cardiac function, case reports and clinical trials based on stem cell therapies in patients with CHD may be invaluable for the next stage of therapeutic development. Dissecting the differential mechanisms underlying progressive ventricular dysfunction in children and adults may lead us to identify a novel regenerative therapy. Future regenerative technologies to treat patients with CHD are exciting prospects for heart regeneration in general practice.
In Reply
Authors: Aman U. Buzdar, Richard L. Theriault, Kelly K. Hunt, Gabriel N. Hortobagyi
Journal: Journal of Clinical Oncology (2005)

due to the small size of the study, but we agree with the authors that additional clinical and laboratory research is warranted to evaluate the significance of this finding.Although some might argue with the decision of the trial's Data Monitoring Committee to stop the study, we feel that this was the right decision from the ethical standpoint.The drawback was that we might never be able to establish, in a prospective way, the real long-term safety and efficacy of this regimen.In conclusion, though the results of this study are encouraging, the addition of trastuzumab to anthracycline-based chemotherapy should not be used on a routine basis for the treatment of operable breast cancer.Further research is required, in particular, to further establish the long-term cardiac safety of this regimen.
Phosphorylation of Akt isoforms induces resistance to cisplatin, doxorubicin and paclitaxel in human uterine cancer cells
Authors: Véronique Gagnon, Eric Asselin
Journal: Cancer Research (2005)

5943  Endometrial cancer is the leading type of gynecological cancer and is the fourth in importance among all type of cancer in women. While most patients with disease recurrence after primary therapy are incurable, there is a subset of patients treated with surgery only who have recurrence confined to the pelvis that may be cured with appropriate radical pelvic irradiation. However, a major difficulty in chemotherapy is cellular resistance to chemotherapeutic drugs and the mechanisms involved remain to be elucidated. Serine/threonine protein kinase Akt activity has been shown to suppress apoptosis in cancer cells. To date, three isoforms of Akt have been identified: Akt1, Akt2, Akt3. Akt isoforms are expressed and regulated differently in normal and cancer cells but their specific roles remain to be clarified. Objective of this study was to investigate the possible involvement of Akt activity in the resistance of human endometrial cancer cells to cisplatin, doxorubicin and paclitaxel. In the present study, one endometrial (KLE), one cervical (Hela) cancer cell lines known as wild-type PTEN (tumor suppressor phosphatase tensin homologue, a lipid phosphatase involved in the regulation of Akt phosphorylation) and one mutated-PTEN (Ishikawa) were used. Basal levels of Akt1, Akt2, Akt3 and PTEN mRNAs were determined by real time quantitative RT-PCR and Western blot analyses were carried out to determine protein abundance. Akt1 mRNA and protein were present in all cell lines studied. Akt2 and Akt3 mRNAs and proteins were strongly expressed in KLE cells. Surprisingly, Akt phosphorylation was found in KLE cells. Cisplatin, doxorubicin and paclitaxel induced cell death in Ishikawa and Hela cells but KLE cells expressing Akt2 and Akt3 remained resistant to these chemotherapeutic agents. We have found that overexpression of Akt using a constitutively active expression vector resulted in an up-regulation of cIAP-1 expression, an inhibitor of caspase activity. Moreover, transfection of constitutively active Akt vector reduced cisplatin sensitivity whereas Akt1, Akt2 and Akt3 knockdown by siRNA had the opposite effect and amplified the action of cisplatin on cell death induction. These findings suggest that Akt, particularly Akt2 and Akt3, may be involved in chemoresistance to cisplatin, doxorubicin and paclitaxel and that cIAP-1, or other member of IAP family, may be involved in the process of chemoresistance in uterine cancers. Supported by CIHR (MOP-66987).
Endoscopic advanced imaging of the respiratory tract: exploring probe-based confocal laser endomicroscopy in emphysema
Authors: J Yserbyt, C Dooms, W Janssens, G M Verleden
Journal: Thorax (2017)

Probe-based confocal laser endomicroscopy (pCLE) was performed in 15 patients with emphysema and 15 healthy subjects to visualise small airways in a direct and dynamic way. Morphometry shows that the median cross-sectional area of the alveolar openings at the level of the alveolar ducts is significantly larger in emphysema (7.2×10 4 µm 2 ) as compared with healthy subjects (5.2×10 4 µm 2 ) (p=0.0002). Normalised autofluorescence intensity histograms show a decrease in median autofluorescence intensity (mAFI) in emphysema (p=0.001). mAFI correlates well with Tiffeneau index (r=0.66, p=0.007, 95% CI 0.21 to 0.88). Autofluorescence intensity in emphysema correlates with corresponding data of CT-based quantification. pCLE-based morphometry and autofluorescence intensity analysis in emphysema is able to detect regional changes inside the ‘quiet zone’. Trial registration number Results, NCT01204970 .
Effects of preoperative abiraterone acetate (AA) plus enzalutamide (E) and leuprolide acetate (LHRHa) versus AA and LHRHa in localized high-risk prostate cancer (LHRPC).
Authors: Eleni Efstathiou, Patricia Troncoso, Elsa Li Ning Tapia, John W. Davis, Mark Anton Titus, Anh Hoang, Ina N. Prokhorova, Sijin Wen, Christopher Logothetis
Journal: Journal of Clinical Oncology (2015)

5061 Background: High degree of heterogeneity in cytoreduction has been observed in LHRPC following AA+LHRHa and LHRHa (Taplin et al, J Clin Oncol 2014;32:3705; Efstathiou et al, J Clin Oncol2012:30 (suppl; abs 4556). Rationale exists for AA+E combination and promising efficacy is reported in mCRPC. This study aims to determine effects of AA+E vs AA and modulation of androgen signaling in LHRPC. Methods: Single-institution preoperative study of 24 wks of 1 g AA + 160 mg E + 5 mg prednisone (P) QD + LHRHa (Arm A) vs AA/P+LHRHa (Arm B) (randomized 2:1) in LHRPC pts (clinical stage T1c/T2; biopsy Gleason score ≥ 8, or ≥ T2b with Gleason ≥ 7 and PSA > 10 ng/mL). Safety and treatment effect on pathology stage, androgen metabolites, cellular density (% epithelial component of tumor volume), and link between molecular markers (by IHC) with clinical, pathology, and cellular response were assessed. Results: Study accrued 66 pts; 39 completed 24 wks therapy and had robot-assisted laparoscopic prostatectomy. Preliminary observations in evaluable pts: no perioperative ≥ Gr 3 adverse events (AEs); on-treatment Gr 3 AEs: liver function test elevation (7 Arm A, 2 Arm B), hypertension (5 Arm A, 1 Arm B), hypokalemia (1 Arm A), cognitive disturbance (1 Arm A), pulmonary embolism (1 Arm A), fatigue (1 Arm A). Fatigue Gr 1/2 in 38/55 evaluable pts (29/38 [76%] Arm A and 9/17 [53%] Arm B). Preoperative PSA was ≤ 0.1 ng/mL in 23/26 (89%) Arm A pts vs 10/11 (91%) Arm B pts; (p = ns). To date pathologic downstaging ( ≤ ypT2N0) occurred in 11/27 (41%) in Arm A vs 7/12 (58%) in Arm B (p = ns); pCR (2 Arm A, 1 Arm B). Tumors segregated by low ( ≤ 30%) (range 0-30%, median 5%) vs high ( ≥ 45%) (range 45-80%, median 55%) cellular density; low density in 63% Arm A and 77% Arm B. Preoperative testosterone was undetectable in 33/39; when detectable (range 1-10 pg/mL). Tumors with pathology stage ≤ ypT2N0 had higher AR-N terminal expression (85% vs 58% and AR-C/AR-N ratio; p = 0.008). Conclusions: Tumor cytoreduction is dichotomised despite universal serum PSA decline at 6 ms preoperative treatment. Planned Comprehensive molecular characterization of androgen biosynthesis will inform marker-driven LHRPC treatment strategy. Clinical trial information: NCT01946165.
The role of infection models and PK/PD modelling for optimising care of critically ill patients with severe infections
Authors: T. Tängdén, V. Ramos Martín, T. W. Felton, E. I. Nielsen, S. Marchand, R. J. Brüggemann, J. B. Bulitta, M. Bassetti, U. Theuretzbacher, B. T. Tsuji, D. W. Wareham, L. E. Friberg, J. J. De Waele, V. H. Tam, Jason A. Roberts
Journal: Intensive Care Medicine (2017)
INFLUENCE OF FATIGUE ON HAMSTRING MUSCLE FUNCTION DURING REPEATED SPRINTS
Authors: Pascal EDOUARD, Philippe GIMENEZ, Pierrick ARNAL, Pedro JIMENEZ-REYES, Pierre SAMOZINO, MENDIGUCHIA Jurdan, Matt BRUGHELLI, Jean-Benoît MORIN
Journal: British Journal of Sports Medicine (2017)

Background The hamstring muscles are the most injured muscles in athletes practicing sprints. In addition, they seem greatly contributing to the production of horizontal force, a key element in the sprint acceleration performance. Objective To experimentally analyse the relationship between horizontal force production and hamstrings strength during maximum-velocity treadmill sprints with and without fatigue. Design Descriptive cross-sectional study. Setting Laboratory study on competitor-level athletes. Participants 14 healthy male athletes trained for sprint running. Main Outcome Measurements Comparison analyses of the following parameters before and after 12 6-seconds sprints separated by 44 seconds of recovery on an instrumented treadmill sprint: horizontal ground force production, EMG activity of the vastus lateralis, rectus biceps femoris and gluteus muscles, maximum isokinetic strength of the flexors and extensors of the hip and knee measured at 120°/s in concentric and eccentric before and just after the 12 sprints. Results For the best performance sprint, the multiple linear regression analysis showed a significant relationship (p=0.02) between the horizontal force and the combination of EMG activity of the biceps femoris in late swing phase of the stride and the eccentric isokinetic strength of the knee flexors. After the 12 sprints, there was a significant decrease (p&lt;0.05) in sprint performance (−6.6%), horizontal force (−8.6%), isokinetic strength (−5.8 to -11.9%) and muscle activity (−5.0 to −38.9%), and there was a significant correlation between the horizontal force and eccentric strength of the knee extensors (r=0.640; p&lt;0.02), and concentric strength of hip extensors (r=0.676; p&lt;0.01). Conclusions For a high-performance acceleration, it would seem necessary to be able both to strongly activate the hamstrings just before ground contact and have a great capacity eccentric strength of the hamstrings. In fatigue conditions, horizontal force reduction would seem not only related to the strength of decreased hamstring, but with the knee extensors eccentric strength decrease.
<i>‘WNT-er is coming’</i>: WNT signalling in chronic lung diseases
Authors: H A Baarsma, M Königshoff
Journal: Thorax (2017)

Chronic lung diseases represent a major public health problem with only limited therapeutic options. An important unmet need is to identify compounds and drugs that target key molecular pathways involved in the pathogenesis of chronic lung diseases. Over the last decade, there has been extensive interest in investigating Wingless/integrase-1 (WNT) signalling pathways; and WNT signal alterations have been linked to pulmonary disease pathogenesis and progression. Here, we comprehensively review the cumulative evidence for WNT pathway alterations in chronic lung pathologies, including idiopathic pulmonary fibrosis, pulmonary arterial hypertension, asthma and COPD. While many studies have focused on the canonical WNT/β-catenin signalling pathway, recent reports highlight that non-canonical WNT signalling may also significantly contribute to chronic lung pathologies; these studies will be particularly featured in this review. We further discuss recent advances uncovering the role of WNT signalling early in life, the potential of pharmaceutically modulating WNT signalling pathways and highlight (pre)clinical studies describing promising new therapies for chronic lung diseases.
Prognostic significance of estrogen receptors (ER), determined by two different methods, in breast cancer (b.c.).
Authors: A.Molino Amolino, F.Bonetti Fbonetti, A.Bonetti Abonetti, M.Turazza Mturazza, P.Capelli Pcapelli, E.Piazzola Epiazzola, G.Martignoni Gmartignoni, G.Pollini Gpollini, S.Modena Smodena, R.Nortilli Rnortilli, R.Pradella Rpradella, A.Corgnati Acorgnati, Q.Piubello Qpiubello, G.L.Cetto Glcetto
Journal: Annals of Oncology (1990)