bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abdominal massage for the alleviation of constipation symptoms in people with multiple sclerosis: a randomized controlled feasibility study
Authors: McClurg Doreen , Hagen Suzanne , Hawkins Stanley , Lowe-Strong Andrea 
Published: October 2010

Background: Constipation affects many people with multiple sclerosis (MS), negatively impacting on their quality of life. The use of abdominal massage has been reported in several populations and has been shown to increase the frequency of defaecation. Objective: The objective of this study was to determine the feasibility of undertaking abdominal massage in people with MS. Methods: Following ethical approval, 30 patients with MS and constipation were recruited. After providing informed written consent and completion of baseline outcome measures, participants were randomly allocated to a massage group or a control group. The massage group participants were provided with advice on bowel management, and they or their carers were taught how to deliver abdominal massage and were recommended to perform it daily during the 4-week intervention period. The control group received bowel management advice only. Outcomes were measured pre (Week 0) and post treatment (Week 4), and at Week 8 and included: the Constipation Scoring System (CSS) (primary outcome), the Neurogenic Bowel Dysfunction Score, and a bowel diary. Results: Both groups demonstrated a decrease in CSS score from Week 0 to Week 4, indicating an improvement in constipation symptoms; however, the massage group improved significantly more than the control groups (mean difference between groups in score change −5.0 (SD 1.5), 95% CI −8.1, −1.8; t = −3.28, df = 28, p = 0.003). Conclusion: The results of this small study suggest a positive effect of the intervention on the symptoms of constipation, and support the feasibility of a substantive trial of abdominal massage for the alleviation of the symptoms of constipation in people with MS.
A potential role for α-actinin in inside-out αIIbβ3 signaling
Authors: Tadokoro Seiji , Nakazawa Tsuyoshi , Kamae Tsuyoshi , Kiyomizu Kazunobu , Kashiwagi Hirokazu , Honda Shigenori , Kanakura Yuzuru , Tomiyama Yoshiaki 
Published: October 2010

AbstractMany different biochemical signaling pathways regulate integrin activation through the integrin cytoplasmic tail. Here, we describe a new role for α-actinin in inside-out integrin activation. In resting human platelets, α-actinin was associated with αIIbβ3, whereas inside-out signaling (αIIbβ3 activation signals) from protease-activated receptors (PARs) dephosphorylated and dissociated α-actinin from αIIbβ3. We evaluated the time-dependent changes of the αIIbβ3 activation state by measuring PAC-1 binding velocity. The initial velocity analysis clearly showed that PAR1-activating peptide stimulation induced only transient αIIbβ3 activation, whereas PAR4-activating peptide induced long-lasting αIIbβ3 activation. When αIIbβ3 activation signaling dwindled, α-actinin became rephosphorylated and reassociated with αIIbβ3. Compared with control platelets, the dissociation of α-actinin from αIIbβ3 was only transient in PAR4-stimulated P2Y12-deficient platelets in which the sustained αIIbβ3 activation was markedly impaired. Overexpression of wild-type α-actinin, but not the mutant Y12F α-actinin, increased its binding to αIIbβ3 and inhibited PAR1-induced initial αIIbβ3 activation in the human megakaryoblastic cell line, CMK. In contrast, knockdown of α-actinin augmented PAR-induced αIIbβ3 activation in CMK. These observations suggest that α-actinin might play a potential role in setting integrins to a default low-affinity ligand-binding state in resting platelets and regulating αIIbβ3 activation by inside-out signaling.
Silent cerebral infarcts occur despite regular blood transfusion therapy after first strokes in children with sickle cell disease
Authors: Hulbert Monica L. , McKinstry Robert C. , Lacey JoAnne L. , Moran Christopher J. , Panepinto Julie A. , Thompson Alexis A. , Sarnaik Sharada A. , Woods Gerald M. , Casella James F. , Inusa Baba , Howard Jo , Kirkham Fenella J. , Anie Kofi A. , Mullin Jonathan E. , Ichord Rebecca , Noetzel Michael , Yan Yan , Rodeghier Mark , DeBaun Michael R. 
Published: October 2010

AbstractChildren with sickle cell disease (SCD) and strokes receive blood transfusion therapy for secondary stroke prevention; despite this, approximately 20% experience second overt strokes. Given this rate of second overt strokes and the clinical significance of silent cerebral infarcts, we tested the hypothesis that silent cerebral infarcts occur among children with SCD being transfused for secondary stroke prevention. A prospective cohort enrolled children with SCD and overt strokes at 7 academic centers. Magnetic resonance imaging and magnetic resonance angiography of the brain were scheduled approximately every 1 to 2 years; studies were reviewed by a panel of neuroradiologists. Eligibility criteria included regularly scheduled blood transfusion therapy. Forty children were included; mean pretransfusion hemoglobin S concentration was 29%. Progressive cerebral infarcts occurred in 45% (18 of 40 children) while receiving chronic blood transfusion therapy; 7 had second overt strokes and 11 had new silent cerebral infarcts. Worsening cerebral vasculopathy was associated with new cerebral infarction (overt or silent; relative risk = 12.7; 95% confidence interval, 2.65-60.5, P = .001). Children with SCD and overt strokes receiving regular blood transfusion therapy experience silent cerebral infarcts at a higher rate than previously recognized. Additional therapies are needed for secondary stroke prevention in children with SCD.
The phylogenetic position of Acoela as revealed by the complete mitochondrial genome of Symsagittifera roscoffensis
Authors: Mwinyi Adina , Bailly Xavier , Bourlat Sarah J , Jondelius Ulf , Littlewood D Timothy J , Podsiadlowski Lars 
Published: October 2010

Abstract

Background
Acoels are simply organized unsegmented worms, lacking hindgut and anus. Several publications over recent years challenge the long-held view that acoels are early offshoots of the flatworms. Instead a basal position as sister group to all other bilaterian animals was suggested, mainly based on molecular evidence. This led to the view that features of acoels might reflect those of the last common ancestor of Bilateria, and resulted in several evo-devo studies trying to interpret bilaterian evolution using acoels as a proxy model for the "Urbilateria".

Results
We describe the first complete mitochondrial genome sequence of a member of the Acoela, Symsagittifera roscoffensis. Gene content and circular organization of the mitochondrial genome does not significantly differ from other bilaterian animals. However, gene order shows no similarity to any other mitochondrial genome within the Metazoa. Phylogenetic analyses of concatenated alignments of amino acid sequences from protein coding genes support a position of Acoela and Nemertodermatida as the sister group to all other Bilateria. Our data provided no support for a sister group relationship between Xenoturbellida and Acoela or Acoelomorpha. The phylogenetic position of Xenoturbella bocki as sister group to or part of the deuterostomes was also unstable.

Conclusions
Our phylogenetic analysis supports the view that acoels and nemertodermatids are the earliest divergent extant lineage of Bilateria. As such they remain a valid source for seeking primitive characters present in the last common ancestor of Bilateria. Gene order of mitochondrial genomes seems to be very variable among Acoela and Nemertodermatida and the groundplan for the metazoan mitochondrial genome remains elusive. More data are needed to interpret mitochondrial genome evolution at the base of Bilateria.
Association between the Cytotoxic T-Lymphocyte Antigen 4 +49G > A polymorphism and cancer risk: a meta-analysis
Authors: Zheng Jian , Yu Xiao , Jiang Lan , Xiao Mang , Bai Bing , Lu Jiachun , Zhou Yifeng 
Published: October 2010

AbstractBackgroundAs a key gene in the immunosurveillance of cell malignancy, Cytotoxic T-lymphocyte antigen 4 (CTLA-4 is an important negative regulator of T cell activation and proliferation. The CTLA-4 +49G > A polymorphism is one of the most commonly studied polymorphisms in this gene due to its association with cancer risks, but previous results have been conflicting.MethodsWe preformed a meta-analysis using 22 eligible case-control studies (including 32 datasets) with a total of 11,273 patients and 13,179 controls to summarize the existing data on the association between theCTLA-4+49G > A polymorphism and cancer risk.ResultsCompared with the commonCTLA-4+49G > A GG genotype, the carriers of variant genotypes (CTLA-4+49 GC/CC) had a 1.24-fold elevated risk of cancer (95% CI = 1.18-1.32,P< 0.05) under the dominant genetic model, as estimated using a fixed effect model. The effect of theCTLA-4+49G > A polymorphism was further evaluated using stratification analysis. In four breast cancer studies, patients with the variant genotypes had a significantly increased risk of breast cancer (OR = 1.31, 95% CI = 1.17-1.48,P< 0.00001). A similar result was found in three skin cancer studies (OR = 1.30, 95% CI = 1.10-1.52,P= 0.001). In 26 solid tumor studies, subjects with the variant genotypes had a significantly higher risk of developing solid tumors (OR = 1.25, 95% CI = 1.18-1.33,P< 0.00001) compared with the 6 non-solid tumor studies (OR = 1.08, 95% CI = 0.79-1.48,P= 0.62). Patients with variant genotypes had significantly increased risk of non-epithelial tumors and epithelial tumors, with ORs of 1.23 (95% CI = 1.14-1.32,P< 0.00001) and 1.29 (95% CI = 1.17-1.41,P< 0.00001), respectively. It was also demonstrated that the increased risk of cancer associated withCTLA-4+49G > A variant genotypes was more pronounced in Caucasians (OR = 1.29, 95% CI = 1.13-1.47,P= 0.0002), Asians (OR = 1.23, 95% CI = 1.16-1.32,P< 0.00001) and Chinese (OR = 1.23, 95% CI = 1.15-1.31,P< 0.00001).ConclusionOur meta-analysis suggests that theCTLA-4+49G > A polymorphism genotypes (GA + AA) might be associated with an increased risk of cancer, especially in Caucasians and Chinese.
The serine protease inhibitor serpinE2 is a novel target of ERK signaling involved in human colorectal tumorigenesis
Authors: Bergeron Sébastien , Lemieux Etienne , Durand Véronique , Cagnol Sébastien , Carrier Julie C , Lussier Jacques G , Boucher Marie-Josée , Rivard Nathalie 
Published: October 2010

Abstract

Background
Among the most harmful of all genetic abnormalities that appear in colorectal cancer (CRC) development are mutations of KRAS and its downstream effector BRAF as they result in abnormal extracellular signal-related kinase (ERK) signaling. In a previous report, we had shown that expression of a constitutive active mutant of MEK1 (caMEK) in normal rat intestinal epithelial cells (IECs) induced morphological transformation associated with epithelial to mesenchymal transition, growth in soft agar, invasion and metastases in nude mice. Results from microarrays comparing control to caMEK-expressing IECs identified the gene encoding for serpinE2, a serine protease inhibitor, as a potential target of activated MEK1.

Results
1- RT-PCR and western blot analyses confirmed the strong up-regulation of serpinE2 expression and secretion by IECs expressing oncogenic MEK, Ras or BRAF. 2- Interestingly, serpinE2 mRNA and protein were also markedly enhanced in human CRC cells exhibiting mutation in KRAS and BRAF. 3- RNAi directed against serpinE2 in caMEK-transformed rat IECs or in human CRC cell lines HCT116 and LoVo markedly decreased foci formation, anchorage-independent growth in soft agarose, cell migration and tumor formation in nude mice. 4- Treatment of CRC cell lines with U0126 markedly reduced serpinE2 mRNA levels, indicating that expression of serpinE2 is likely dependent of ERK activity. 5- Finally, Q-PCR analyses demonstrated that mRNA levels of serpinE2 were markedly increased in human adenomas in comparison to healthy adjacent tissues and in colorectal tumors, regardless of tumor stage and grade.

Conclusions
Our data indicate that serpinE2 is up-regulated by oncogenic activation of Ras, BRAF and MEK1 and contributes to pro-neoplastic actions of ERK signaling in intestinal epithelial cells. Hence, serpinE2 may be a potential therapeutic target for colorectal cancer treatment.
Screening for Distress in Lung and Breast Cancer Outpatients: A Randomized Controlled Trial
Authors: Carlson Linda E. , Groff Shannon L. , Maciejewski Olga , Bultz Barry D. 
Published: October 2010

Purpose Distress has been recognized as the sixth vital sign in cancer care and several guidelines recommend routine screening. Despite this, screening for distress is rarely conducted and infrequently evaluated. Methods A program of routine online screening for distress was implemented for new patients with breast and lung cancer. Patients were randomly assigned to one of three conditions: (1) minimal screening: the distress thermometer (DT) only plus usual care; (2) full screening: DT, problem checklist, Psychological Screen for Cancer part C measuring anxiety and depression, a personalized report summarizing concerns and the report on the medical file; or (3) triage: full screening plus optional personalized phone triage with referral to resources. Patients in all conditions received an information packet and were reassessed 3 months later with the full screening battery. Results Five hundred eighty-five patients with breast cancer and 549 patients with lung cancer were assessed at baseline (89% of all patients), and 75.5% retained for follow-up. High prevalence of baseline distress was found across patients. Twenty percent fewer patients with lung cancer in triage continued to have high distress at follow-up compared to those in the other two groups, and patients with breast cancer in the full screening and triage conditions showed lower distress at follow-up than those in minimal screening. The best predictor of decreased anxiety and depression in full screening and triage conditions was receiving a referral to psychosocial services. Conclusion Routine online screening is feasible in a large cancer center and may help to reduce future distress levels, particularly when coupled with uptake of appropriate resources.
Bortezomib-Melphalan-Prednisone-Thalidomide Followed by Maintenance With Bortezomib-Thalidomide Compared With Bortezomib-Melphalan-Prednisone for Initial Treatment of Multiple Myeloma: A Randomized Controlled Trial
Authors: Palumbo Antonio , Bringhen Sara , Rossi Davide , Cavalli Maide , Larocca Alessandra , Ria Roberto , Offidani Massimo , Patriarca Francesca , Nozzoli Chiara , Guglielmelli Tommasina , Benevolo Giulia , Callea Vincenzo , Baldini Luca , Morabito Fortunato , Grasso Mariella , Leonardi Giovanna , Rizzo Manuela , Pia Falcone Antonietta , Gottardi Daniela , Montefusco Vittorio , Musto Pellegrino , Petrucci Maria Teresa , Ciccone Giovannino , Boccadoro Mario 
Published: October 2010

PurposeThe combination of bortezomib-melphalan-prednisone (VMP) is a new standard of care for newly diagnosed multiple myeloma. This phase III study examined the efficacy of the four-drug combination of bortezomib-melphalan-prednisone-thalidomide (VMPT) followed by maintenance with bortezomib-thalidomide (VMPT-VT) compared with VMP treatment alone in untreated multiple myeloma patients who are ineligible for autologous stem-cell transplantation.Patients and MethodsA total of 511 patients were randomly assigned to receive nine cycles of VMPT followed by continuous VT as maintenance, or nine cycles of VMP at the same doses with no additional therapy. The primary end point was progression-free survival.ResultsThe 3-year estimates of progression-free survival were 56% in patients receiving VMPT-VT and 41% in those receiving VMP (hazard ratio [HR], 0.67; 95% CI, 0.50 to 0.90; P = .008). At 3 years, the cumulative proportions of patients who did not go on to the next therapy were 72% with VMPT-VT and 60% with VMP (HR, 0.58; 95% CI, 0.50 to 0.90; P = .007). Complete response rates were 38% in the VMPT-VT group and 24% in the VMP group (P < .001). The 3-year overall survival was 89% with VMPT-VT and 87% with VMP (HR, 0.92; 95% CI, 0.53 to 1.60; P = .77). Grade 3 to 4 neutropenia (38% v 28%; P = .02), cardiologic events (10% v 5%; P = .04), and thromboembolic events (5% v 2%; P = .08) were more frequent among patients assigned to the VMPT-VT group than among those assigned to the VMP group; treatment-related deaths were 4% with VMPT-VT and 3% with VMP.ConclusionVMPT followed by VT as maintenance was superior to VMP alone in patients with multiple myeloma who are ineligible for autologous stem-cell transplantation.
Phase III Trial Assessing Bevacizumab in Stages II and III Carcinoma of the Colon: Results of NSABP Protocol C-08
Authors: Allegra Carmen J. , Yothers Greg , O'Connell Michael J. , Sharif Saima , Petrelli Nicholas J. , Colangelo Linda H. , Atkins James N. , Seay Thomas E. , Fehrenbacher Louis , Goldberg Richard M. , O'Reilly Seamus , Chu Luis , Azar Catherine A. , Lopa Samia , Wolmark Norman 
Published: October 2010

PurposeThe National Surgical Adjuvant Breast and Bowel Project C-08 trial was designed to investigate the safety and efficacy of adding bevacizumab to modified FOLFOX6 (mFOLFOX6; ie, infusional/bolus fluorouracil, leucovorin, and oxaliplatin) for the adjuvant treatment of patients with stages II to III colon cancer.MethodsPatients received mFOLFOX6 every 2 weeks for 26 weeks alone or modified as FOLFOX6 + bevacizumab (5 mg/kg every 2 weeks for 52 weeks [ie, experimental group]). The primary end point was disease-free survival (DFS).ResultsAmong 2,672 analyzed patients, demographic factors were well balanced by treatment. With a median follow-up of 35.6 months, the addition of bevacizumab to mFOLFOX6 did not result in an overall significant increase in DFS (hazard ratio [HR], 0.89; 95% CI, 0.76 to 1.04; P = .15). The point estimates for 3-year DFS for the overall population were 77.4% and 75.5% for the experimental and control arms, respectively. For patients with stages II and III diseases, these same estimates were 87.4% and 84.7%, respectively, for stage II and 74.2% and 72.4%, respectively, for stage III. Exploratory analyses found that the effect of bevacizumab on DFS was different before and after a 15-month landmark (time-by-treatment interaction P value < .0001). Bevacizumab had a strong effect before the landmark (HR, 0.61; 95% CI, 0.48 to 0.78; P < .001) but no significant effect after (HR, 1.22; 95% CI, 0.98 to 1.52; P = .076).ConclusionBevacizumab for 1 year with mFOLFOX6 does not significantly prolong DFS in stages II and III colon cancer. However, a significant but transient effect during bevacizumab exposure was observed in the experimental arm. We postulate that this observation reflects a biologic effect during bevacizumab exposure. Given the lack of improvement in DFS, the use of bevacizumab cannot be recommended for use in the adjuvant treatment of patients with colon cancer.
Cinacalcet HCl Reduces Hypercalcemia in Primary Hyperparathyroidism across a Wide Spectrum of Disease Severity
Authors: Peacock Munro , Bilezikian J. P. , Bolognese M. A. , Borofsky Michael , Scumpia Simona , Sterling L. R. , Cheng Sunfa , Shoback Dolores 
Published: October 2010

Context: Primary hyperparathyroidism (PHPT) is characterized by elevated serum calcium (Ca) and increased PTH concentrations.
Objective: The objective of the investigation was to establish the efficacy of cinacalcet in reducing serum Ca in patients with PHPT across a wide spectrum of disease severity.
Design and Setting: The study was a pooled analysis of data from three multicenter clinical trials of cinacalcet in PHPT.
Patients : Patients were grouped into three disease categories for analysis based on the following: 1) history of failed parathyroidectomy (n = 29); 2) meeting one or more criteria for parathyroidectomy but without prior surgery (n = 37); and 3) mild asymptomatic PHPT without meeting criteria for either above category (n = 15).
Intervention: The intervention in this study was treatment with cinacalcet for up to 4.5 yr.
Outcomes: Measurements in the study included serum Ca, PTH, phosphate, and bone-specific alkaline phosphatase, and areal bone mineral density (aBMD). Vital signs, safety biochemical and hematological indices, and adverse events were monitored throughout the study period.
Results: The extent of cinacalcet-induced serum Ca reduction, proportion of patients achieving normal serum Ca (≤10.3 mg/dl), reduction in serum PTH, and increase in serum phosphate were similar across all three categories. Except for decreased aBMD at the total femur indicated for parathyroidectomy group at 1 yr, no significant changes in aBMD occurred. The efficacy of cinacalcet was maintained for up to 4.5 yr of follow-up. AEs were mild and similar across the three categories.
Conclusions: Cinacalcet is equally effective in the medical management of PHPT patients across a broad spectrum of disease severity, and overall cinacalcet is well tolerated.
Familial Focal Congenital Hyperinsulinism
Authors: Ismail Dunia , Smith Virpi V. , de Lonlay Pascale , Ribeiro Maria-Joao , Rahier Jacques , Blankenstein Oliver , Flanagan Sarah E. , Bellanné-Chantelot Christine , Verkarre Virginie , Aigrain Yves , Pierro Agostino , Ellard Sian , Hussain Khalid 
Published: October 2010

Background:Congenital hyperinsulinism (CHI) is a cause of persistent hypoglycemia. Histologically, there are two subgroups, diffuse and focal. Focal CHI is a consequence of two independent events, inheritance of a paternal mutation in ABCC8/KCNJ11 and paternal uniparental isodisomy of chromosome 11p15 within the embryonic pancreas, leading to an imbalance in the expression of imprinted genes. The probability of both events occurring within siblings is rare.Aim:We describe the first familial form of focal CHI in two siblings.Patients and Methods:The proband presented with medically unresponsive CHI. He underwent pancreatic venous sampling and Fluorine-18-L-dihydroxyphenylalanine positron emission tomography scan, which localized a 5-mm focal lesion in the isthmus of the pancreas. The sibling presented 8 yr later also with medically unresponsive CHI. An Fluorine-18-L-dihydroxyphenylalanine positron emission-computerised tomography scan showed a 7-mm focal lesion in the posterior section of the head of the pancreas. Both siblings were found to be heterozygous for two paternally inherited ABCC8 mutations, A355T and R1494W. Surgical removal of the focal lesions in both siblings cured the Hyperinsulinaemic hypoglycaemia.Conclusion:This is the first report of focal CHI occurring in siblings. Genetic counseling for families of patients with focal CHI should be recommended, despite the rare risk of recurrence of this disease.