tbuckley/cabot-search huggingface dataset:
Inspiratory muscle training reduces respiratory neural drive (RND) during exercise in patients with COPD
Authors: Daniel Langer, Casey Ciavaglia, Kathy Webb, Megan Preston, J. Alberto Neder, Rik Gosselink, Denis O'Donnell
Journal: European Respiratory Journal (2014)

Mechanisms for improvements in dyspnea after inspiratory muscle training (IMT) have not been systematically studied. We investigated whether this might be ascribed to reductions in RND.  Ten clinically stable patients with COPD (FEV 1 :61±20%pred.) with activity related dyspnea (Baseline Dyspnea Index:6.0±1.3) and inspiratory muscle weakness (Pi,max: 61±12cmH 2 O) were randomized into an intervention group (n=7), or a control group (n=3). Before and after an 8-week daily IMT program, an endurance cycling test was performed at 75% peak work rate. Patients rated dyspnea during exercise an a Borg CR-10 scale and diaphragm electromyography (EMGdi) was assessed with a multipair esophageal electrode catheter (Luo, Y.M. et al. Clin Sci 2008;115:233-44). IMT intensity either increased from 68±11% to 123±21% baseline Pi,max (intervention) or remained constant at 8±2% baseline Pi,max (control). Larger increases in Pi,max (28±13 vs 10±3cmH 2 O; p=0.009) and reductions in RND (-12±6% vs 3±11% EMGdimax; p=0.023; Figure) at standardized ventilation were observed in the intervention group. This was associated with larger improvements in endurance time (356±265sec vs 17±38sec; p=0.014; Figure) and dyspnea at standardized ventilation (-3.3±2.6 vs -0.3±0.6 Borg units; p=0.023).  IMT decreases RND during exercise and this might be mechanistically related to improvements in dyspnea and exercise tolerance in selected patients with COPD.
Osteolytic lesions, cytogenetic features and bone marrow levels of cytokines and chemokines in multiple myeloma patients: Role of chemokine (C-C motif) ligand 20
Authors: B Dalla Palma, D Guasco, M Pedrazzoni, M Bolzoni, F Accardi, F Costa, G Sammarelli, L Craviotto, M De Filippo, L Ruffini, P Omedè, R Ria, F Aversa, N Giuliani
Journal: Leukemia (2015)
Hemodynamic and Cardiac Effects of the Selective T-Type and L-Type Calcium Channel Blocking Agent Mibefradil in Patients With Varying Degrees of Left Ventricular Systolic Dysfunction11This work was supported in part by a grant from Hoffmann-La Roche, Basel, Switzerland. It was presented in part at the 67th Scientific Sessions of the American Heart Association, Dallas, Texas, November 1994.
Authors: MICHEL F ROUSSEAU, WATARU HAYASHIDA, CHRISTIAN van EYLL, OTTO M HESS, CLAUDE R BENEDICT, FRÉDÉRIC CHAPELLE, ISAAC KOBRIN, HUBERT POULEUR
Journal: Journal of the American College of Cardiology (1996)
Spine pruning drives antipsychotic-sensitive locomotion via circuit control of striatal dopamine
Authors: Il Hwan Kim, Mark A Rossi, Dipendra K Aryal, Bence Racz, Namsoo Kim, Akiyoshi Uezu, Fan Wang, William C Wetsel, Richard J Weinberg, Henry Yin, Scott H Soderling
Journal: Nature Neuroscience (2015)
Molecular mechanisms of cancer cell invasion and plasticity
Authors: Katarina Wolf, Peter Friedl
Journal: British Journal of Dermatology (2006)

Cancer cell interactions with the extracellular matrix and the migration therein involve the function of adhesion receptors of the integrin family, a dynamic cytoskeleton, as well as proteolytic mechanisms to overcome tissue barriers. Recent progress in investigating tumour cell migration and associated matrix remodelling was made using three‐dimensional (3D) dermis equivalents such as 3D collagen lattices or dermal explant cultures, prompting new concepts in molecular tumour invasion mechanisms and related adaptation responses. Mesenchymal HT‐1080 fibrosarcoma cells as a model line migrate in an integrin‐dependent manner and proteolytically cleave extracellular matrix structures. After interference with integrin and protease function, however, cancer cells can switch migration programs and thereby rescue migration by alternative mechanisms. Depending on the context of invasion, treatment with protease inhibitors or integrin antagonists can cause the mesenchymal–amoeboid transition and the collective–amoeboid transition, both generating sustained dissemination of single cells. These adaptation responses show an unexpected degree of plasticity resulting in migratory 'escape' strategies after pharmacotherapeutic intervention by prompting alternative mechanisms of cancer cell dissemination in tissues.
Phase II study of neoadjuvant gemcitabine (GC), pegylated liposomal doxorubicin (DX) and docetaxel (TT) in locally advanced breast cancer
Authors: G. Cartei, L. Borgato, G. Lombardi, A. Cappetta, F. Bozza, S. Zovato, G. Zavagno, S. Mocellin, G. Artioli
Journal: Journal of Clinical Oncology (2008)

606 Background: Neoadjuvant chemotherapy is currently the standard of care for the management of locally advanced breast cancer, as it improves both disease-free and overall survival. Methods: Patients with histologic confirmation of locally advanced breast cancer, age >18 years, left ventricular ejection fraction >50%, good performance status and adequate bone marrow, negative chest and abdominal CT scan, renal and hepatic function were included in the study. Prior systemic therapy and radiotherapy and the presence of metastases were not allowed. The treatment schedule was as follows: GC: 1,250 mg/m2 (day 1); GC 1,000 mg/m2 plus TT 75 mg/m2 plus DX 30 mg/m2 (day 8). Pegfilgrastim was routinely administered as primary prophylaxis against febrile neutropenia. Courses were repeated each 21 days for 4–6 cycles. This study was aimed to assess the activity of GC, DX and TT in locally advanced breast cancer. Results: Fifty patients were enrolled and treated. Median age was 51 years (range: 34–73), 27 (54%) being postmenopausal patients. Infiltrating ductal carcinoma was diagnosed in 84% of cases. Tumor size was as follows: T1 (n=2, 4%), T2 (n= 31, 62%), T3 (n=14, 28%), T4 (n=2, 4%). G3 grading was found in 28% of cases. Median tumor size was 4 cm (range: 2–10). Tumors were ER+, PR+ and c-Erb-B2+ in 34 (68%), 31(62%) and 27 (54%) cases, respectively. Surgery was performed in 47 (94%) patients: 12 (26%) pathologic complete response, 24 (51%) partial response and 9 (19%) stable disease were observed resulting in a pathologic overall response rate of 77%. Logistic regression analysis revealed that larger tumor size, Mib1 higher expression and higher number of cycles were independently associated with better tumor response rates. Conclusions: This combination chemotherapy can yield a high tumor response rate. Correlation analysis suggests that this neoadjuvant regimen might be more effective in patients with larger tumors expressing Mib1, particularly if full treatment can be administered. No significant financial relationships to disclose.
A randomized trial of standard chemotherapy v a high-dose chemotherapy regimen in the treatment of poor prognosis nonseminomatous germ-cell tumors.
Authors: R F Ozols, D C Ihde, W M Linehan, J Jacob, Y Ostchega, R C Young
Journal: Journal of Clinical Oncology (1988)

We performed a prospective randomized trial of a high-dose chemotherapy regimen v standard cisplatin-based chemotherapy in poor prognosis nonseminomatous germ-cell cancer patients. The high-dose regimen consisting of twice the standard dose of cisplatin (P), along with vinblastine (Ve), bleomycin (B), and the epipodophylotoxin etoposide (VP-16) (V) (PVeBV) was compared to the classic regimen with normal dose cisplatin, vinblastine, and bleomycin (PVeB). Eligibility criteria included large abdominal masses, liver metastases, multiple pulmonary metastases, brain metastases, marked elevations in serum tumor markers (alpha-fetoprotein greater than 1,000 ng/mL or the beta-subunit of human chorionic gonadotropin greater than 10,000 mIU), unfavorable histology (pure choriocarcinoma), or extragonadal germ-cell tumors. Fifty-two consecutive patients with poor prognostic features were randomized to receive either PVeBV or PVeB. The median follow-up is 4 years. Treatment with the high-dose regimen increased the complete remission rate (88% v 67%, P = .14) and was associated with a lower relapse rate (17% v 41%, P = .2). The median survival of patients receiving standard therapy was 30 months, while the median survival for patients receiving the high-dose regimen has not been reached. Actuarial 5-year survival for patients treated with the high-dose regimen is 78%, compared with 48% for patients receiving standard therapy (two-sided Mantel-Cox test = .06). Disease-free survival was also superior for patients randomized to PVeBV (P = .03). Sixty-eight percent of patients (23 of 34) randomized to PVeBV are alive and continuously disease-free, compared with 33% (six of 18) for PVeB (P = .02). The major difference in toxicity between the high-dose regimen and standard therapy was the severity of myelosuppression and the incidence of severe hearing loss. Ninety-one percent of patients treated with PVeBV had a WBC count less than 1,000/microL, compared with 50% of patients receiving PVeB (P less than .05). Hearing aids were recommended for 12 patients who received PVeBV and two who received PVeB. The increased effectiveness of the PVeBV regimen in poor prognosis germ-cell cancer patients may relate to the double-dose cisplatin, the addition of VP-16, or to a synergistic effect of these two drugs.
Identification of proteins potentially involved in the formation of Lafora bodies, a hallmark of Lafora disease
Authors: Elham Schokraie, Oliver Kötting, Matthew S Gentry
Journal: Molecular Neurodegeneration (2013)

Background Lafora Disease (LD) is a fatal teenage-onset progressive myoclonus epilepsy. It is characterized by the formation of Lafora bodies (LBs), deposits of abnormally branched, insoluble, hyperphosphorylated glycogen-like polymers that are generally believed to trigger the development of the clinical symptoms of LD. 58% and 35% of the LD cases are caused by mutations in EPM2A (laforin) and EPM2B (malin), respectively. However, little is known about their function in LB formation. Two different mechanisms have been proposed to explain the accumulation of insoluble LBs: first, excessive glycogen phosphorylation and, second, an imbalance between glycogen synthesizing enzymes. The present study aims at the identification of proteins involved in the molecular mechanisms leading to LB formation and appearance of LD and the phosphorylation of glycogen.
HFE and alcoholic liver disease Reply
Authors: D K GEORGE, L W POWELL, C P DAY
Journal: Gut (1999)

Peripheral arthropathies in inflammatory bowel diseaseEDITOR,-We read with interest the paper by Orchard et al (Gut 1998;42:387-91) describing peripheral arthropathy in inflammatory bowel disease (IBD).However their study concentrated upon those patients with joint swelling or eVusion, classifying them as either pauciarticular (type 1) or polyarticular (type 2).We were interested to note the low prevalence of arthralgia in their patients (14.3% for Crohn's disease), and that these patients were disregarded from further study.This report is in the context of a wide variation in the published prevalence of peripheral arthropathy in Crohn's disease (0.4 to 23%). 1 In our own retrospective study of 102 patients with Crohn's disease we found a higher prevalence of joint symptoms (53%).Ankylosing spondylitis was present in 4% of patients, 9% had peripheral arthritis, and 24% had peripheral arthralgia without joint swelling or eVusion.The remainder of patients had degenerative joint disease or seropositive arthritis.Figure 1 shows the joint distribution of the peripheral arthropathies.This demonstrates a prediliction for arthritis to aVect the wrist and joints of the hands when compared with patients with arthralgia, significantly so in the wrists (p<0.05).Both the patients with peripheral arthralgia and peripheral arthritis had a significantly greater prevalence of mucocutaneous manifestations of IBD (i.e.oral ulceration, erythema nodosum, pyoderma gangrenosum, and uveitis) when compared with patients without joint symptoms (p<0.01 and p<0.05, respectively).This pattern is similar in some respects to that of the type 1 peripheral arthropathy described by Orchard et al.We also noted that patients with peripheral arthropathy were less likely to have perianal disease than those without peripheral arthropathy (p<0.05),although there was no diVerence in fistulating disease.In contrast to Orchard et al, we found no association between peripheral arthralgia and colonic disease or the requirement for surgery.Non-steroidal anti-inflammatory
Paclitaxel and Cisplatin as First-Line Therapy in Recurrent or Advanced Squamous Cell Carcinoma of the Cervix: A Gynecologic Oncology Group Study
Authors: Peter G. Rose, John A. Blessing, David M. Gershenson, Ramon McGehee
Journal: Journal of Clinical Oncology (1999)

On the basis of the activity of paclitaxel as a single agent in chemotherapy-naive squamous cell carcinoma of the cervix in a prior Gynecologic Oncology Group (GOG) trial, a phase II study of paclitaxel and cisplatin as first-line therapy was conducted by the GOG.Eligibility included squamous cell cancer of the cervix not curable by surgery or radiation, measurable disease, WBC count > or = 3,000/microL, platelet count > or = 100, 000/microL, serum creatinine > or = 2 mg/100 mL, and adequate hepatic function. The starting dose was paclitaxel 135 mg/m(2) infused over 24 hours followed by cisplatin 75 mg/m(2) every 21 days. On the basis of toxicity, a dose escalation of paclitaxel to a maximum dose of 170 mg/m(2)/d was prescribed.Forty-seven patients were enrolled onto this study; 44 patients were assessable for toxicity and 41 for response. Forty (90.9%) had received prior radiation therapy. A median of six courses of chemotherapy was given (range, one to 10 courses). Neutropenia grade 3 (15.9%) and 4 (61.4%) was the most frequent severe adverse effect and was associated with fever in 13 patients (27.7%). Two patients (4.5%) died from neutropenic sepsis. Grade 4 thrombocytopenia occurred in 6.8% of patients. Of 41 assessable patients, five (12.2%) had complete responses and 14 (34.1%) had partial responses for an overall response rate of 46.3% (95% confidence interval, 30.7% to 62.6%). The median progression-free interval, was 5.4+ months (range, 0.3 to 22+ months) with a median survival of 10.0+ months (range, 0.9 to 22. 2 months). Response was more frequent in patients with disease in nonirradiated sites (70% v 23%, P =.008).This regimen seems highly active in advanced and recurrent squamous cell carcinoma of the cervix and is currently being evaluated by the GOG in a phase III randomized study comparing the combination of paclitaxel and cisplatin with cisplatin alone.
Transthoracic chest ultrasound in critically ill patients: Comparison with bedside chest radiography
Authors: Gamal Agmy, Sherif Mohamed, Yasser Gad
Journal: European Respiratory Journal (2014)

PURPOSE:   To compare the diagnostic performance of transthoracic ultrasound (TUS) and bedside chest radiography (CXR) for the detection of various pathological abnormalities in critically ill patients, using computed tomography (CT) as a gold standard.   METHODS:   Two hundred mechanically ventilated patients scheduled for CT and CXR were prospectively studied with a modified TUS protocol. Four pathological entities were evaluated: pleural effusion, pneumothorax, consolidation and interstitial syndrome.   RESULTS:   All patients were evaluated by the three imaging techniques. The sensitivity, specificity, and diagnostic accuracy of CXR were 55, 84, and 65% for pleural effusion, 40, 96, and 88% for pneumothorax, 40, 85, and 50% for consolidation and 42, 82, and 60% for interstitial syndrome respectively. The corresponding values for TUS were 100, 100, and 100% for pleural effusion, 100, 100, and 100% for pneumothorax, 100, 87, and 95% for consolidation, 95, 95, and 95% for interstitial syndrome respectively.   CONCLUSIONS:   In our ICU population TUS has a considerably better diagnostic performance than CXR for the diagnosis of common pathological disorders and may be used as an alternative to thoracic CT.   Clinical Implication:   Clinician-performed ultrasonography is a reliable tool in the diagnosis of common chest pathological entities. It has the advantage of portability, simplicity, rapidity, and similar sensitivity and specificity compared with CT.
mRNA biomarker screening in pulmonary tumors showing neuroendocrine differentiation
Authors: Robert Fred Henry Walter, Fabian Dominik Mairinger, Robert Werner, Saskia Ting, Thomas Hager, Claudia Vollbrecht, Daniel Christoph, Kurt Werner Schmid, Jeremias Wohlschlaeger
Journal: European Respiratory Journal (2013)

Neuroendocrine tumors of the lung comprise more than 25% of all lung tumors. Typical and atypical carcinoids, large cell neuroendocrine and small cell neuroendocrine carcinomas belong to this subgroup of lung cancer. Until now most of the neuroendocrine tumors exhibit poor survival rates due to a lack of treatment strategies, diagnostic, prognostic and predictive biomarkers. The aim of this study is to identify key biomarkers that could help to overcome these limitations.  201 patients with lung tumors with neuroendocrine differentiation were chosen for the study. 80 patients with diagnostically verified entity were used for NanoString nCounter expression analysis with a custom CodeSet. A total of 91 genes were investigated targeting genes of SOX signaling, MET, MTOR signaling, angiogenesis, apoptosis, neuroendocrine differentiation, folate synthesis, DNA-repair, cell cycle regulation, tumormileu and miscellaneous. Statistical analysis was done using the R statistical program.  CDK6, CDKN2A, CHGA, FOLR1, SOX4, SYP and TYMS exhibited most significant values for tumor type and grade. Additional 28 genes correlated significantly with tumor grade and 41 with tumor type. Highly significant correlations were found for PAX6 regarding overall survival. GABBR2, OCT4 and PCDHB9 were found to be most significant for progression free survival. Additional significant correlations were found for tyrosine kinase inhibitor targets, TNM-staging, tumor size and further tumor characteristics.  Expression analysis of distinct neuroendocrine tumor entities exhibited several significant biomarkers that could enhance tumor subgroup classification, treatment strategies, prediction and prognosis in routine clinical settings.
Some 400 million people lack access to essential health services
Authors: A. Gulland
Journal: BMJ (2015)

As many as 400 million people around the world do not have access to essential health services, a report by the World Health Organization and World Bank has found.1

The report looked at access to family planning, antenatal care, skilled birth attendance, childhood vaccinations, antiretroviral treatment, treatment of tuberculosis, and clean water and sanitation. It found that although good progress had been made in some areas, such as childhood vaccinations, in others not enough headway had been made. For example, in 2013 84% of infants received the required three doses of the diphtheria, tetanus, and pertussis vaccination. However, in the same year just 37% of people infected with HIV received antiretrovirals.

Treatment of …
Re‐evaluation of hepatitis B virus clinical phases by systems biology identifies unappreciated roles for the innate immune response and B cells
Authors: Thomas Vanwolleghem, Jun Hou, Gertine van Oord, Arno C. Andeweg, A.D.M.E. Osterhaus, Suzan D. Pas, Harry L.A. Janssen, Andre Boonstra
Journal: Hepatology (2015)

To identify immunological mechanisms that govern distinct clinical phases of a chronic hepatitis B virus (HBV) infection—immune tolerant (IT), immune active (IA), inactive carrier (IC), and hepatitis B e antigen (HBeAg)‐negative (ENEG) hepatitis phases—we performed a systems biology study. Serum samples from untreated chronic HBV patients (n = 71) were used for multiplex cytokine measurements, quantitative hepatitis B surface antigen (HBsAg), HBeAg levels, HBV genotype, and mutant analysis. Leukocytes were phenotyped using multicolor flow cytometry, and whole‐blood transcriptome profiles were generated. The latter were compared with liver biopsy transcriptomes from IA (n = 16) and IT (n = 3) patients. HBV viral load as well as HBeAg and HBsAg levels ( P &lt; 0.001), but not leukocyte composition, differed significantly between distinct phases. Serum macrophage chemotactic protein 1, interleukin‐12p40, interferon (IFN)‐gamma‐inducible protein 10, and macrophage inflammatory protein 1 beta levels were different between two or more clinical phases ( P &lt; 0.05). Comparison of blood transcriptomes identified 64 differentially expressed genes. The gene signature distinguishing IA from IT and IC patients was predominantly composed of highly up‐regulated immunoglobulin‐encoding genes. Modular repertoire analysis using gene sets clustered according to similar expression patterns corroborated the abundant expression of B‐cell function‐related genes in IA patients and pointed toward increased (ISG) transcript levels in IT patients, compared to subsequent phases. Natural killer cell activities were clustered in clinical phases with biochemical liver damage (IA and ENEG phases), whereas T‐cell activities were higher in all phases, compared to IT patients. B‐cell‐related transcripts proved to be higher in biopsies from IA versus IT patients. Conclusion : HBV clinical phases are characterized by distinct blood gene signatures. Innate IFN and B‐cell responses are highly active during the IT and IA phases, respectively. This suggests that the presumed immune tolerance in chronic HBV infections needs to be redefined. (H epatology 2015;62:87‐100)
High-dose busulfan and cyclophosphamide with autologous bone marrow transplantation support in advanced malignancies in children: a phase II study.
Authors: O Hartmann, E Benhamou, F Beaujean, J L Pico, C Kalifa, C Patte, F Flamant, J Lemerle
Journal: Journal of Clinical Oncology (1986)

Twenty children with advanced, nonleukemic malignancies entered a phase II study of high-dose busulfan-cyclophosphamide followed by bone marrow transplantation (BMT). All had disease refractory to conventional and/or high-dose chemotherapy (HDC). There were ten neuroblastoma patients, six non-Hodgkin's lymphoma, three Ewing's sarcoma, and one rhabdomyosarcoma. Eight had primarily resistant disease, ten were in second progressive relapse, and two in third progressive relapse. One patient was not evaluable for response. Among the 19 evaluable patients the responses observed were complete response (CR), seven; partial response (PR), three; objective effect, five; and failure, four. However, survival was poor: 15 patients died, two are alive with disease, and three are alive with no evidence of disease (NED) at 8+, 11+, 14+ months post-BMT. Toxicity was high but considered as acceptable, taking into account the terminal state of these patients. Seven treatment-related deaths were observed. This combination therapy proved to be highly effective, with a response rate of 50%, and its value for eradication of residual disease in less advanced patients should be investigated.