tbuckley/cabot-search huggingface dataset:
The Psychosomatic Perspective
Authors: Fiammetta Cosci
Journal: Psychotherapy and Psychosomatics (2019)

Background: Fibromyalgia (FM) is a chronic pain condition characterized by widespread pain, fatigue, sleep disorder and psychological distress.Although the efficacy of psychological interventions such as cognitive-behavioural therapy is well-known, there are few studies investigating the efficacy of brief psychodynamic therapy (BPT) in FM.Therefore, we conducted a randomized controlled trial comparing an individual BPT, inspired on the Brief Dynamic Interpersonal Therapy model, versus an individual cognitive therapy (CT).Methods: Thirty female patients with FM were recruited in an Italian hospital setting and randomized to receive either BPT (16 sessions, 1 session/week) or CT (16 sessions, 1 session/week).Outcome measures, administered before (T0) and after the psychotherapy treatment (T1), included the Fibromyalgia Impact Questionnaire-Revised (FIQ-R), the Hospital Anxiety and Depression Scale (HADS), the Metacognitive Functions Screening Scale (MFSS), the Toronto Alexithymia Scale (TAS-20), the Relationships Questionnaire (RQ) and the health-related quality of life (SF-36).Results: Both treatments were equally effective in reducing the FIQ-R (p=0.018) and the HADS total score (p=0.015) and in improving the health-related quality of life, both in the mental (p=0.001) and physical (p=0.004)component of the SF-36.No significant changes emerged, instead, in the MFSS, RQ and TAS-20 questionnaires after the treatments. Conclusions:The brief psychodynamic therapy showed to be equally effective as the individual cognitive therapy in lowering the psychological distress level, and in improving fibromyalgia-related symptoms and patients' health-related quality of life.
Noninvasive Imaging Biomarker Identifies Small Airway Damage in Severe Chronic Obstructive Pulmonary Disease
Authors: Dragoş M. Vasilescu, Fernando J. Martinez, Nathaniel Marchetti, Craig J. Galbán, Charles Hatt, Catherine A. Meldrum, Chandra Dass, Naoya Tanabe, Rishindra M. Reddy, Amir Lagstein, Brian D. Ross, Wassim W. Labaki, Susan Murray, Xia Meng, Jeffrey L. Curtis, Tillie L. Hackett, Ella A. Kazerooni, Gerard J. Criner, James C. Hogg, MeiLan K. Han
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Rationale: Evidence suggests damage to small airways is a key pathologic lesion in chronic obstructive pulmonary disease (COPD). Computed tomography densitometry has been demonstrated to identify emphysema, but no such studies have been performed linking an imaging metric to small airway abnormality.Objectives: To correlate ex vivo parametric response mapping (PRM) analysis to in vivo lung tissue measurements of patients with severe COPD treated by lung transplantation and control subjects.Methods: Resected lungs were inflated, frozen, and systematically sampled, generating 33 COPD (n = 11 subjects) and 22 control tissue samples (n = 3 subjects) for micro–computed tomography analysis of terminal bronchioles (TBs; last generation of conducting airways) and emphysema.Measurements and Main Results: PRM analysis was conducted to differentiate functional small airways disease (PRMfSAD) from emphysema (PRMEmph). In COPD lungs, TB numbers were reduced (P = 0.01); surviving TBs had increased wall area percentage (P < 0.001), decreased circularity (P < 0.001), reduced cross-sectional luminal area (P < 0.001), and greater airway obstruction (P = 0.008). COPD lungs had increased airspace size (P < 0.001) and decreased alveolar surface area (P < 0.001). Regression analyses demonstrated unique correlations between PRMfSAD and TBs, with decreased circularity (P < 0.001), decreased luminal area (P < 0.001), and complete obstruction (P = 0.008). PRMEmph correlated with increased airspace size (P < 0.001), decreased alveolar surface area (P = 0.003), and fewer alveolar attachments per TB (P = 0.01).Conclusions: PRMfSAD identifies areas of lung tissue with TB loss, luminal narrowing, and obstruction. This is the first confirmation that an imaging biomarker can identify terminal bronchial pathology in established COPD and provides a noninvasive imaging methodology to identify small airway damage in COPD.
Abstract 13265: What Extent of Early Reverse Remodeling is Clinically Relevant After Restrictive Mitral Annuloplasty in Patients With Non-Ischemic Dilated Cardiomyopathy and Functional Mitral Regurgitation?
Authors: Koji Takeda, Taichi Sakaguchi, Shigeru Miyagawa, Yasushi Yoshikawa, Takashi Yamauchi, Yasuhiro Shudo, Kazuhiro Taniguchi, Yoshiki Sawa
Journal: Circulation (2010)

Objective: Restrictive mitral annuloplasty (RMA) can improve heart failure symptoms and induce left ventricular (LV) reverse remodeling in patients with non-ischemic dilated cardiomyopathy (DCM) an...
Abstract P394: Impact of Caffeinated Versus Decaffeinated Energy Shots on Blood Pressure
Authors: Sachin A Shah, Abby Kurtz, Jessica Leong, Anthony E Dargush
Journal: Circulation (2013)

Introduction: Energy drinks are commonly used to boost cognitive performance. However, this is paralleled with a significant increase in systolic and diastolic blood pressures. No studies have evaluated these changes with energy “shots” and whether these effects are driven solely by the caffeine component in energy drinks or a multitude of ingredients remains unknown. The purpose of this study was to determine if the effects of regular (caffeinated) 5-Hour Energy® shot differ from that of decaffeinated 5-Hour Energy® (decaf) shot as assessed by changes in systolic (SBP) and diastolic blood pressure (DBP). Methods: This was a randomized, double-blind, crossover study conducted at a university campus. Healthy subjects, between 18-40 years of age with a blood pressure less than 140/90 and not on any medications were eligible for inclusion. Participants were randomized into either the regular 5-Hour Energy® drink or the decaf 5-Hour Energy® drink study arms with blood pressure recorded at baseline, 1, 3 and 5 hours. Following a washout period of at least 6 days, the same was performed giving the alternate study drink. Additionally, heart rate, adverse events and energy score (1-5 scale) were also assessed. Results: Ten males and 10 females were enrolled in the study with 90% (18 of 20) being of Asian race. Average age was 23.3±2.7 years, weighing 149.1±31.7 pounds with SBP of 114±11.3 mmHg and DBP of 69.5±7.6 mmHg. Baseline coffee consumption was less than 2 cups per week in 11 subjects and at least 1 cup per day in the remainder. The maximum SBP increase from baseline in the regular arm was 7.8±6.5 mmHg versus 2.8±5.6 mmHg in the decaf arm (p = 0.046). Maximum DBP increase was 6.3±3.7mmHg and 1.0±5.4 mmHg (p = 0.003) in the regular and decaf arms, respectively. Significant increases in systolic and diastolic pressures were evident at 1 and 3 hours post consumption (p ≤ 0.027) but not at 5 hours. Maximum heart rate or energy levels between the two groups were not significantly different (p ≥ 0.436). In subgroup analysis, regular energy drinks invoked a significantly higher increase in systolic and diastolic blood pressures (p ≤ 0.003) 1 hour post consumption in caffeine naïve subjects (n=11). Conclusion: Regular energy drinks available in the form of a “shot” increase both systolic and diastolic blood pressures by approximately 5mmHg. This effect appears to be exaggerated in caffeine naïve subjects.
Preclinical study of adoptive immunotherapy with natural killer cells in metastatic colorectal cancer.
Authors: Silvia Brugnatelli, Ilaria Turin, Mariangela Manzoni, Marcello Maestri, Enrica Montini, Laura Caliogna, Marco Paulli, Paolo Dionigi, Andrea Pietrabissa, Sara Delfanti, Bianca Rovati, Sara Mariucci, Rita Maccario, Paolo Pedrazzoli, Daniela Montagna
Journal: Journal of Clinical Oncology (2012)

e13103 Background: Several immune-based approaches for treatment of metastatic colorectal cancer (mCRC) are currently under investigation. Aims of our study were to grow and characterize tumor cells (TC) obtained from mCRC patients, and to investigate their susceptibility to autologous natural killer (NK) cell recognition and killing in vitro. Methods: Tumor samples and peripheral blood mononuclear cells from 10 mCRC patients undergoing surgery were collected. Establishment of TC lines that are representative of the original tumor and could be expanded in vitro for a significant number of passage was performed according with our previously described method (Turin I et al, Cytotherapy 2007). CD56+CD3- NK cells were incubated overnight with medium alone or activated with IL-2 (100U/ml) or IL-15 (20ng/ml) and tested against 51Cr-labeled primary TC in NK assay or in ADCC assay after pre-coating of TC with anti-EGFR monoclonal antibody cetuximab. Results: Eight stable mCRC lines have been obtained and characterized to confirm their neoplastic origin. Patient NK cells display low capacity to lyse autologous TC (median 12%, range 5%-17%). IL-2 and IL-15 incubation significantly potentiate NK cytotoxic capacity (median18%, range 6%-62% and median 35%, range 28%-65%, respectively). These results refer to an effector:target ratio of 25:1. ADCC assay has shown that cetuximab pre-coating of TC results on an increasing of their susceptibility to NK-mediated lysis. Phenotypical and molecular analysis of activating NK receptors and their ligands present on surface of TC are currently under evaluation. Conclusions: NK cells derived from mCRC patients display measurable cytotoxic activity against autologous primary TC. Susceptibility of NK-mediated lysis is strongly enhanced by pre-incubation of NK cell with cytokines and by pre-coating of TC with cetuximab. These findings, presented upon approval by the study’s data monitoring committee and undergoing confirmation in a larger series, may support a pilot study of NK cells pre-activated ex vivo for treatment of mCRC patients.
B cell superantigens in the human intestinal microbiota
Authors: Jeffrey J. Bunker, Christoph Drees, Andrea R. Watson, Catherine H. Plunkett, Cathryn R. Nagler, Olaf Schneewind, A. Murat Eren, Albert Bendelac
Journal: Science Translational Medicine (2019)

IgA is prominently secreted at mucosal surfaces and coats a fraction of the commensal microbiota, a process that is critical for intestinal homeostasis. However, the mechanisms of IgA induction and the molecular targets of these antibodies remain poorly understood, particularly in humans. Here, we demonstrate that microbiota from a subset of human individuals encode two protein "superantigens" expressed on the surface of commensal bacteria of the family Lachnospiraceae such as Ruminococcus gnavus that bind IgA variable regions and stimulate potent IgA responses in mice. These superantigens stimulate B cells expressing human VH3 or murine VH5/6/7 variable regions and subsequently bind their antibodies, allowing these microbial organisms to become highly coated with IgA in vivo. These findings demonstrate a previously unappreciated role for commensal superantigens in host-microbiota interactions. Furthermore, as superantigen-expressing strains show an uneven distribution across human populations, they should be systematically considered in studies evaluating human B cell responses and microbiota during homeostasis and disease.
P147 Treatment with ustekinumab in psoriasic arthritis in conditions of real clinical practice
Authors: J Uceda, R Hernandez, JL Marenco
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Assistant. <h3>Introduction</h3> Psoriatic arthritis (PsA) belongs to the family of spondyloarthritis, with an incidence of 6 cases per 1 00 000 inhabitants. Ustekinumab is an inhibitor of IL 12/13 approved for patients with PsA who do not respond to disease modifying anti-rheumatic drugs (DMARDs). This drug has been shown to be effective and safe in different clinical trials. <h3>Objectives</h3> The primary objective was to assess the effectiveness and safety of Ustekinumab in a cohort of patients with PsA, in follow-up in the Rheumatology Unit of the Valme University Hospital, under conditions of real clinical practice.We have also studied the survival of the drug as well as treatment interruptions and their causes. <h3>Methods</h3> We conducted an observational, descriptive, longitudinal and retrospective study of a cohort of 16 patients diagnosed with PsA, according to CASPAR criteria, who receive or have received treatment with Ustekinumab from January 1, 2015 to February 1, 2018. The effectiveness of the drug was assessed by changing the DAS 28 at 3 and 6 months. We recorded the sociodemographic characteristics of the patients and the characteristics of the disease. Also we recorded previous treatment with anti TNF alpha, and concomitant treatment with DMARDs. We evaluated the suspension of the drug and its reasons. Adverse reactions were recorded too. <h3>Results</h3> 16 patients were studied, 56.3% women. The average age at diagnosis was 41.38 years ±8.5 SD. 62.5% presented polyarticular form, 12.5% oligoarticular, 6.3% axial and 18.8% axial and peripheral arthritis. 87.5% had rheumatoid factor (RF) and antipeptide-citrullinated antibodies (ACPA) negative. 87.55% had received prior treatment with at least one anti-TNF alpha. 81% of the sample received Ustekinumab in combination with a DMARs, being methotrexate the most used. The mean of DAS 28 at the start of treatment with Ustekinumab was 4.51±1.07 SD. The mean of DAS28 was 3.11±1.39 SD and 2.93±1.58 SD after 3 months and 6 months of treatment. The average survival of ustekinumab in the period analyzed (January 1, 2015 to January 1, 2018) was 29.1 months ±3.7 SD. 5 patients of our sample discontinued the treatment: 4 due to ineffectiveness and 1 due to an adverse effect that consisted of a bronchospasm crisis, resolving itself after drug suspension and not requiring hospital admission. There has been no cases of tuberculosis, neoplasia, demyelinating disease or death. <h3>Conclusions</h3> Ustekinumab is an effective drug for psoriatic arthritis since three months of treatment. In our study Ustekinumab presented a high survival and a good safety profile in real clinical practice. <h3>Disclosure of Interest</h3> None declared.
Smoothelin as a marker of muscularis propria in biopsies of colorectal carcinomas.
Authors: Peter E. Stoemmer, Patricia Torres-Galea
Journal: Journal of Clinical Oncology (2012)

e14076 Background: Preoperative staging is of eminent importance for the treatment of colorectal carcinomas (CRCs). Especially the distinction of carcinoma in situ (not permigrating the muscularis mucosae (MM)), the pT1 stage (limited to the submucosa) and pT2 and above, infiltrating the muscularis propria(MP) in endoscopic biopsies could change the therapeutic regimen. Smoothelin (SMT) is a robust marker of the MP in normal colon, which is not expressed in MM; therefore, we analysed its expression in biopsies and resections of CRCs, to test its predictive value in staging of CRCs. Methods: 50 CRCs, diagnosed in biopsy particles and staged in the surgical specimens were analysed by IHC for expression of smoothelin (MoAb R4A, DCS Hamburg), Desmin and smooth muscle antigen SMA (all DAKO ) in MP and MM in the vicinity of invading carcinoma cells and in distance to the tumor. Semiquantitative grading REMMELE. Results: Desmin and SMA were consistently expressed in the smooth muscle cells of MM and MP near and distant to carcinoma cells. SMT showed no or little expression in the muscle cells of MM. The penetration of the MM by tumorcells did not alter their reactivity. In the MP however, the invasion by carcinoma cells caused a total or subtotal loss of SMT in the cytoplasm of the smooth muscle cells. The diameter of the nucleus and the longitudinal axis in SMT-deprivated cells did not change, but the transversal diameters of the cells were decreased. Reducing the mechanical stress of smooth muscle cells diminishes also the expression of SMT. No predictive correlation between biopsy-estimated depth and real depth of tumorinfiltration was seen. Conclusions: Expression of SMT correlates to functional status of the cells. The reliable difference in the IHC-expression of SMT in MM and MP in normal colon is not seen in the colon near carcinomas: the muscle cells of MP also lose their STM expression. Thus, negativity for SMT in smooth muscle cells near tumorcells does not necessarely proof, that this will be MM; as well, it could be SMT-deprivated cells of the MP. To rely upon SMT in biopsies for the determination of the depth of invasion is highly dangerous.
Promoter hypermethylation of GPX3 as a predictor for chemoresistance and survival in head and neck cancer patients
Authors: Z. Guo, Z. Chen, Z. Yang, L. Schumaker, K. J. Cullen
Journal: Journal of Clinical Oncology (2007)

6027 Background: Resistance of cancer cells to cisplatin and its analogues is the major limitation in clinical application of cisplatin-based chemotherapy. The mechanisms by which cancer cells develop resistance to the drugs are still unclear, and there is no way currently to predict the drug resistance of individual tumors. By genome-wide scanning of hypermethylated genes on head and neck cancer cells, we identified glutathione peroxidase 3 (GPX3) as one of the strong candidates whose promoter hypermethylation may be associated with head and neck chemoresistance. In this study, we investigated the potential predictive value of GPX3 methylation for head and neck cancer chemoresistance and patient prognosis. Methods: Promoter methylation and expression of GPX3 gene in head and neck cancer cell lines were examined by plasmid cloning, bisulfite DNA sequencing, reverse transcription-PCR and Western blot. GPX3 methylation in primary cancer tissues was assessed by real-time methylation-specific PCR (MSP). Forty-six head and neck cancer cases, for which chemotherapy response and survival were known, were selected for analysis. Correlation of GPX3 methylation and chemoresistance was tested using two-sided Fisher’s Exact Test and its prediction for patient survival was assessed using Kaplan-Meier survival analysis. Results: Loss of GPX3 expression was observed in 4 of 8 head and neck cancer cell lines and was consistent with cisplatin resistance. Demethylating treatment of the cell lines negative for GPX3 expression significantly restored its expression. Bisulfite DNA sequencing showed that the 5’ flanking promoter region of GPX3 was heavily hypermethylated in all cell lines with expression-silencing of the gene. In the 46 head and neck cancer cases analyzed by MSP, 15 of 23 non-responding cases (65%) showed GPX3 methylation, while 4 of 23 complete and partial response cases (17%) contained low levels of GPX3 methylation (Relative Risk 3.343, two sided Fisher’s exact test, P=0.002). Kaplan-Meier survival analysis showed a relative risk of death of 1.942 in patients with GPX3 methylation. Conclusions: Our findings suggest that GPX3 methylation is a strong candidate predictor for chemoresistance and prognosis of head and neck cancer patients. No significant financial relationships to disclose.
Nimotuzumab combined with radiotherapy on esophageal cancer: Preliminary study of a phase II clinical trial.
Authors: Jun Liang, Luhua Wang, Mingyan E, Wu Gang, Lujun Zhao, Xia Li, Xia Xiu, Ning Li, Bo Chen, Zhouguang Hui, Jima Lv, Hui Fang, Yu Tang, Nan Bi, Wenqing Wang, Yirui Zhai, Tao Li, Dongfu Chen, Shuangmei Zou, Ning Lu
Journal: Journal of Clinical Oncology (2012)

e14511 Background: To evaluate the safety and therapeutic effect of Nimotuzumab (h-R3) in combination with radiotherapy on esophageal cancer. Methods: 42 patients with stage II (Inoperable or refused surgery) to IV (Supraclavicular lymph node metastasis only)were assigned to the phase II clinical trial during Nov. 2008 to Jul. 2010. Histopathological classification of all patients was squamous cell carcinoma. All patients received 50-70 Gy of three-dimensional conformal radiotherapy. 200mg of Nimotuzumab was administered once a week during radiotherapy. Results: There were 9, 25 and 8 patients with stage II, III and IV esophageal cancer, respectively. All patients received 50-70 Gy of radiation therapy except two. 37 patients (88.1%) received Nimotuzumab for more than 5 times. The recorded grade III toxicities (21.4% of all adverse events) included gastrointestinal toxicity, esophagitis, dermatology toxicity and hematological toxicity. Complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) were observed in 0, 22 (52.4%), 17 (40.5%) and 3 (7.1%) patients in one month after treatment. EGFR over-expression rate was 95.2%. Median survival time (MST) was 14 months. One-year and 2-year overall survival (OS) and progression-free survival (PFS) were 54.8%, 36.8% and 39.4, 33.3%, respectively. After a median follow-up time of 17 months, the local recurrence and distant metastases were observed in 18 (42.9%) and 14 (33.3%) patients, respectively. Conclusions: Nimotuzumab combined with radiotherapy were well-tolerated in patients with esophageal cancer. The incidence of grade III toxicity was 21.4%, no grade IV toxicity was observed. EGFR over-expression was found higher than in previous studies. One-year and 2-year OS and PFS were 54.8%, 36.8% and 39.4, 33.3%, respectively. Further study is needed to confirm the therapeutic efficacy of Nimotuzumab in esophageal cancer.
Cell-Autonomous Hedgehog Signaling Is Not Required for Cyst Formation in Autosomal Dominant Polycystic Kidney Disease
Authors: Ming Ma, Emilie Legué, Xin Tian, Stefan Somlo, Karel F. Liem
Journal: Journal of the American Society of Nephrology (2019)

PKD1 or PKD2, the two main causal genes for autosomal dominant polycystic kidney disease (ADPKD), encode the multipass transmembrane proteins polycystin-1 (PC1) and polycystin-2 (PC2), respectively. Polycystins localize to the primary cilium, an organelle essential for cell signaling, including signal transduction of the Hedgehog pathway. Mutations in ciliary genes that build and maintain the cilium also cause renal cystic disease through unknown pathways. Although recent studies have found alterations in Hedgehog signaling in ADPKD-related models and tissues, the relationship between Hedgehog and polycystic kidney disease is not known.To examine the potential role of cell-autonomous Hedgehog signaling in regulating kidney cyst formation in vivo in both early- and adult-onset mouse models of ADPKD, we used conditional inactivation of Pkd1 combined with conditional modulation of Hedgehog signaling components in renal epithelial cells, where mutations in Pkd1 initiate cyst formation. After increasing or decreasing levels of Hedgehog signaling in cells that underwent inactivation of Pkd1, we evaluated the effects of these genetic manipulations on quantitative parameters of polycystic kidney disease severity.We found that in Pkd1 conditional mutant mouse kidneys, neither downregulation nor activation of the Hedgehog pathway in epithelial cells along the nephron significantly influenced the severity of the polycystic kidney phenotype in mouse models of developmental or adult-onset of ADPKD.These data suggest that loss of Pkd1 function results in kidney cysts through pathways that are not affected by the activity of the Hedgehog pathway.
A 3-LncRNA Risk Scoring System for Prognosis of Adult Acute Myeloid Leukemia
Authors: Yuandong Feng, Yachun Jia, Ying Shen, Hongli Chen, Yue Peng, Ru Zhang, Yun Yang, Jian-Li Wang, Ju Bai, Fang-Xia Wang, Yan Xu, Aili He
Journal: Blood (2018)