bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and Validation of the Craving Automated Scale for Alcohol
Authors: Vollstädt‐Klein Sabine , Leménager Tagrid , Jorde Anne , Kiefer Falk , Nakovics Helmut 
Published: February 2015

BackgroundAlcohol consumption has been suggested to be associated with a dysregulation in habit formation and execution in dependent patients. Although there are established craving questionnaires assessing various components of craving, to our knowledge, no questionnaire exists to assess habitual and automated substance intake. In this study, we present and validate the “Craving Automated Scale for Alcohol” (CAS‐A), a newly developed questionnaire assessing craving and other components of automated addictive behavior.MethodsForty‐three recently detoxified alcohol‐dependent patients were examined in an inpatient setting using a cross‐sectional design. TheCAS‐A, a self‐report questionnaire, was applied. According to classical test theory, we conducted principal component analyses (PCAs) to identify the components ofCAS‐A, after which we validated it using established craving questionnaires. Thirty‐two healthy participants served as a control group.ResultsOur first‐order PCA identified a 5‐factor solution. A second‐order analysis then identified 2 general factors. These factors were partially associated with established craving measures and with the severity of dependence.ConclusionsOur findings suggest thatCAS‐A assesses additional components of addictive behavior compared to established measures. We interpret the 5CAS‐A factors as “only aware in hindsight,” “no deliberate decision,” “contrary to intention,” “no perception,” and “no control.” We suggest the 2 general factors be interpreted as “unaware” and “nonvolitional.” Our results indicate that theCAS‐A indeed assesses some components of automated craving and automated drinking behavior in a more sophisticated way than established questionnaires. TheCAS‐A as a retrospective questionnaire can be considered to be a trait rather than a state measure.
Cognitive Regulation of Craving in Alcohol‐Dependent and Social Drinkers
Authors: Naqvi Nasir H. , Ochsner Kevin N. , Kober Hedy , Kuerbis Alexis , Feng Tianshu , Wall Melanie , Morgenstern Jon 
Published: February 2015

BackgroundHelping alcohol‐dependent individuals to cope with, or regulate, cue‐induced craving using cognitive strategies is a therapeutic goal of cognitive behavioral therapy (CBT) for alcohol dependence. An assumption that underlies this approach is that alcohol dependence is associated with deficits in such cognitive regulation abilities. To date, however, the ability to utilize such strategies for regulation of craving has never been tested in a laboratory setting.MethodsHere we compared 19 non‐treatment‐seeking, alcohol‐dependent drinkers (AD) to 21 social drinkers (SD), using a laboratory task that measured the ability to reduce cue‐induced alcohol craving by thinking about long‐term negative consequences of drinking, which is a specific cognitive regulation strategy that is taught in CBT. The task also assessed the ability to reduce food craving elicited by high‐calorie food cues using a similar strategy.ResultsThe reduction in craving when using this cognitive regulation strategy was approximately double in SD, compared to AD, for both alcohol and food cues. Furthermore, in SD but not AD, the ability to regulate cue‐induced alcohol craving was correlated with the ability to regulate food craving. There were no significant correlations found between the ability to regulate cue‐induced alcohol craving and a number of self‐report measures related to severity of alcohol dependence, baseline craving, impulsivity, and general self‐regulation ability, for either AD or SD.ConclusionsThe results suggest that alcohol dependence is associated with deficits in cognitive regulation of cue‐induced craving and that these deficits are not specific to the regulation of alcohol craving, but generalize to the regulation of other appetitive states, such as food craving. Future studies may use similar procedures to address the neural and cognitive processes that underlie such regulation deficits, as well as the effects of treatments such as CBT on these processes.
Cholinergic receptor activation on epithelia protects against cytokine‐induced barrier dysfunction
Authors: Dhawan S. , Hiemstra I. H. , Verseijden C. , Hilbers F. W. , te Velde A. A. , Willemsen L. E. M. , Stap J. , den Haan J. M. , de Jonge W. J. 
Published: February 2015

AbstractAimVarious types of cholinergic receptors are expressed on intestinal epithelia. Their function is not completely understood. We hypothesize that cholinergic receptor activation on epithelium may serve a protective function in cytokine‐induced barrier dysfunction.MethodsThe effect of cholinergic receptor activation on cellular barrier function in epithelial cells was assessed by measuring electrical impedance, and by determining para‐cellular transport in transwell experiments. Cell lysates treated with cytokine and/or cholinergic agonists were analysed for cyto‐ and chemokine production, and tight junction (TJ) protein rearrangement was assessed. Primary colonic epithelial cells were isolated from surgically resected colon tissue of patients with inflammatory bowel disease.ResultsIL‐1β induced production of chemokines (CXCL‐1, CXCL‐10, IL‐8, CCL‐7) and led to a rearrangement of TJ proteins (occludin and ZO‐1). This response was inhibited by pre‐treatment with muscarinic, rather than nicotinic, acetylcholine receptor agonists. Treatment with IL‐1β enhanced paracellular permeability (4kD dextran) and reduced impedance across the monolayer, which was counteracted by pre‐incubation with acetylcholine, or muscarinic receptor agonist bethanechol. The protective effect of acetylcholine was antagonized by atropine, underscoring muscarinic receptor involvement. IL‐1β induced transcription of myosin light chain kinase and phosphorylation of myosin light chain, and this cytokine‐induced phosphorylation of MLC was inhibited by muscarinic receptor agonists. Furthermore, in epithelial cells from resection material of patients with Crohn's disease and ulcerative colitis, high expression of CXCL‐8 was associated with a reduced choline acetyl transferase expression, suggesting an aberrant epithelial production of ACh in inflammatory context.ConclusionAcetylcholine acts on muscarinic receptors on epithelial cells to maintain epithelial barrier function under inflammatory conditions.
T lymphocytes possess the machinery for 5‐HT synthesis, storage, degradation and release
Authors: Chen Y. , Leon‐Ponte M. , Pingle S. C. , O'Connell P. J. , Ahern G. P. 
Published: February 2015

AbstractAimAlthough activated T lymphocytes express tryptophan hydroxylase 1 and produce 5‐HT, the metabolic fate and cellular handling of this 5‐HT is unclear. Here, we investigated key proteins in T cells linked to 5‐HT metabolism and storage and compare differences in 5‐HT synthesis and metabolism between T‐cell subsets.MethodsWe cultured human Jurkat T cells and mouse splenic CD3+, CD4+ and CD8+ T cells with or without T‐cell activators (phorbol ester/ionomycin, concavalin A or plate‐bound anti‐CD3 antibody). Subsequently, we measured mRNA and/or protein for monoamine oxidase A and B, vesicular monoamine transporter 1 and 2, N‐acetyl transferase and tryptophan hydroxylase 1. In addition, we measured the release of exogenously loaded [3H]5‐HT and endogenously synthesized 5‐HT from CD4+ and CD8+ T‐cell subsets.ResultsHuman and mouse T cells selectively express monoamine oxidase A. Following T‐cell activation, mRNA levels of MAO‐A increase robustly in parallel with tryptophan hydroxylase 1. Concomitant with these changes, T cells increase the expression of the type 1 vesicular monoamine transporter. Raised intracellular [Ca2+] rapidly releases preloaded [3H]5‐HT from CD4+ and CD8+ T cells indicating that these cells have the capacity for the storage and regulated secretion of 5‐HT. Notably, both the expression of tryptophan hydroxylase 1 and monoamine oxidase A, and 5‐HT production are significantly greater in CD8+ compared with CD4+ T cells.ConclusionThese data reveal coordinated changes in 5‐HT production, metabolism and storage that may optimize 5‐HT secretion from the CD8+ T cell subset in response to activation stimuli.
Purinergic receptors in tubulointerstitial inflammatory cells: a pathophysiological mechanism of salt‐sensitive hypertension
Authors: Franco M. , Bautista‐Pérez R. , Pérez‐Méndez O. 
Published: February 2015

AbstractRecent studies have suggested that both the tubulointerstitial inflammatory cells and the activation of purinergic receptors integrate common mechanisms that result in salt‐sensitive hypertension. The basis of this hypothesis is that renal endothelial cells release ATP in response to shear stress in the setting of hypertension. It has been demonstrated that the over‐expression and activation of the P2X7, P2Y12 and P2X1 receptors favour the elevation of blood pressure induced by high‐salt intake. In addition, the release of interleukins and inflammatory mediators in the tubulointerstitial area appears to be related to the activation of these receptors. Renal vasoconstriction and tubulointerstitial injury develop as a result, which increase sodium reabsorption by epithelial cells. Consistent with these effects, the reduction of tubulointerstitial inflammation caused by immunosuppressants, such as mycophenolate mofetil, prevents the development of salt‐sensitive hypertension. Also, P2X7‐receptor knockout mice develop minor renal injury when hypertension is induced via the administration of deoxycorticosterone acetate and a high‐salt diet. In the setting of angiotensin II‐induced hypertension, which is an early stage in the development of salt‐sensitive hypertension, an acute blockade with the specific, non‐selective P2 antagonist pyridoxalphosphate‐6‐azophenyl‐2’,4’‐disulfonic acid prevented the renal vasoconstriction induced by angiotensin II. In addition, it normalized glomerular haemodynamics and restored sodium excretion to control values. These findings suggest that chronic administration of P2 purinergic antagonists may prevent the deleterious effects of purinergic receptors during the development of salt‐sensitive hypertension.
Phase Ib/II trial of CYKLONE (cyclophosphamide, carfilzomib, thalidomide and dexamethasone) for newly diagnosed myeloma
Authors: Mikhael Joseph R. , Reeder Craig B. , Libby Edward N. , Costa Luciano J. , Bergsagel P. Leif , Buadi Francis , Mayo Angela , Nagi Reddy Sravan K. , Gano Katherine , Dueck Amylou C. , Stewart A. Keith 
Published: February 2015

SummarySixty‐four transplant‐eligible patients with newly diagnosed multiple myeloma (NDMM) received carfilzomib (days 1, 2, 8, 9, 15, 16), 300 mg/m2 cyclophosphamide (days 1, 8, 15), 100 mg thalidomide (days 1–28) and 40 mg dexamethasone (days 1, 8, 15, 22) in 28‐day cycles (CYKLONE regimen). Carfilzomib was dose‐escalated to 15/20, 20/27, 20/36 and 20/45 mg/m2 to determine the maximum tolerated dose (MTD), which was 20/36 mg/m2. Regardless of attribution, common Grade 3 or higher adverse events were lymphopenia (38%), neutropenia (23%) and anaemia (20%). All peripheral neuropathy (31%) was Grade 1 and considered most likely to be thalidomide‐related. Common cardiac or pulmonary events of any grade in ≥5% of patients included dyspnoea (20%) and cough (6%). Overall (N = 64), 91% of patients achieved a best response of partial response or better across all cycles of treatment, including five patients with complete responses. At the MTD (n = 29), 59% of patients achieved a very good partial response or better after four cycles (primary end point). Stem cell collection was successful in all patients in whom it was attempted (n = 42). Progression‐free survival and overall survival at 24 months was 76% and 96%, respectively (median follow‐up of 17·5 months). CYKLONE appears highly efficacious in NDMM patients, with manageable toxicities.
Outcome of aplastic anaemia in children. A study by the severe aplastic anaemia and paediatric disease working parties of the European group blood and bone marrow transplant
Authors: Dufour Carlo , Pillon Marta , Sociè Gerard , Rovò Alicia , Carraro Elisa , Bacigalupo Andrea , Oneto Rosi , Passweg Jakob , Risitano Antonio , Tichelli Andrè , Peffault de Latour Regis , Schrezenmeier Hubert , Hocshmann Britta , Peters Christina , Kulasekararaj Austin , Van Biezen Anja , Samarasinghe Sujith , Hussein Ayad Ahmed , Ayas Mouhab , Aljurf Mahmoud , Marsh Judith 
Published: February 2015

SummaryThis study analysed the outcome of 563 Aplastic Anaemia (AA) children aged 0–12 years reported to the Severe Aplastic Anaemia Working Party database of the European Society for Blood and Marrow Transplantation, according to treatment received. Overall survival (OS) after upfront human leucocyte antigen‐matched family donor (MFD) haematopoietic stem cell transplantation (HSCT) or immunosuppressive treatment (IST) was 91% vs. 87% (P 0·18). Event‐free survival (EFS) after upfront MFD HSCT or IST was 87% vs. 33% (P 0·001). Ninety‐one of 167 patients (55%) failed front‐line IST and underwent rescue HSCT. The OS of this rescue group was 83% compared with 91% for upfront MFD HSCT patients and 97% for those who did not fail IST up‐front (P 0·017). Rejection was 2% for MFD HSCT and HSCT post‐IST failure (P 0·73). Acute graft‐versus‐host disease (GVHD) grade II‐IV was 8% in MFD graft vs. 25% for HSCT post‐IST failure (P < 0·0001). Chronic GVHD was 6% in MFD HSCT vs. 20% in HSCT post‐IST failure (P < 0·0001). MFD HSCT is an excellent therapy for children with AA. IST has a high failure rate, but remains a reasonable first‐line choice if MFD HSCT is not available because high OS enables access to HSCT, which is a very good rescue option.
Management and controversies of classical Hodgkin lymphoma in pregnancy
Authors: Eyre Toby A. , Lau I‐Jun , Mackillop Lucy , Collins Graham P. 
Published: February 2015

SummaryThe goal of managing classical Hodgkin lymphoma (cHL) in pregnancy is to obtain good long‐term outcomes for both the mother and fetus. Given the excellent outcomes outside of pregnancy, the goal of treatment should remain curative. There remains a tension and debate regarding the timing of chemotherapy, the curative nature of such treatment and the timing of delivery. Moreover, the aim during pregnancy should be to minimize fetal toxicity and optimize perinatal outcomes. The management of cHL within pregnancy was covered within the excellent recent British Committee for Standards in Haematology guidelines, but with necessary brevity. By reviewing the literature over the last 30 years, herein we discuss the options for management during each trimester. Critical organogenesis occurs between 2 and 8 weeks post‐conception; during which time the immature fetus is vulnerable to cytotoxic exposure. We discuss the evidence for using ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) and single agent vinblastine in the first trimester. cHL presenting in pregnancy raises complex and difficult ethical dilemmas that can cause anxiety for patients, families and physicians. Decision‐making must be multi‐disciplinary and holistic, taking into account the patient's wishes, psycho‐social and religious beliefs and personal circumstances. Clear communication between the haemato‐oncologist, medical obstetrician, nurse specialists, midwives and neonatologists is paramount to a successful outcome.
Utility and significance of ureteric frozen section analysis during radical cystectomy
Authors: Satkunasivam Raj , Hu Brian , Metcalfe Charles , Ghodoussipour Saum B. , Aron Manju , Cai Jie , Miranda Gus , Gill Inderbir , Daneshmand Siamak 
Published: February 2015

ObjectiveTo assess the utility of routine frozen section analysis of ureters at the time of radical cystectomy (RC) for urothelial cancer (UC), and the long‐term outcomes of adverse ureteric pathology.Patients and MethodsPathological data on 2 047 patients undergoing RC for UC with routine frozen section analysis of ureters (January 1971 to December 2009) were analysed. Univariate and multivariable logistic and Cox proportional hazards models were used to determine the risk of upper tract UC (UTUC) recurrence, local recurrence and overall survival in those identified as having adverse pathology (severe atypia/carcinoma in situ [CIS] or UC) at time of frozen section analysis.ResultsAdverse pathology was identified by frozen section analysis in 178 patients (8.6%). Frozen section analysis was found to have poor sensitivity in identifying adverse pathology (59.1%), which was improved in patients with preoperative CIS (68.0%). After a median (interquartile range) follow‐up of 12.4 (1.9–10.1) years, 28 patients (1.4%) developed UTUC recurrence. There were no uretero‐enteric anastomotic recurrences. Adverse pathology on frozen section analysis was associated with UTUC recurrence on univariate analysis (hazard ratio [HR] 6.2, 95% confidence interval [CI] 2.9–13.5), but 15/28 patients (54%) with UTUC recurrence had benign ureteric frozen section analysis on initial sectioning. Adverse pathology on frozen section analysis was not independently associated with the risk of local recurrence (HR 1.08, 95% CI 0.61–1.89) or overall survival (HR 1.12, 95% CI 0.94–1.35) in multivariate models.ConclusionsUreteric frozen section analysis has poor sensitivity and may be marginally improved in pre‐existing CIS. UTUC recurrence is rare and can occur despite negative frozen section analysis. Our data question the utility of routine frozen section analysis of the distal ureteric margin at the time of RC.
Does the addition of targeted prostate biopsies to standard systemic biopsies influence treatment management for radiation oncologists?
Authors: Kamrava Mitchell , Hegde John V. , Abgaryan Narine , Chang Edward , Le Jesse D. , Wang Jason , Kupelian Patrick A. , Marks Leonard S. 
Published: February 2015

ObjectivesTo study the management impact that magnetic resonance imaging (MRI)‐guided targeted prostate biopsies could provide relative to using only non‐targeted systematic biopsies in men with clinically localized prostate cancer (PCa).Patients and MethodsA consecutive series of untreated men undergoing Artemis (MRI‐ultrasonography fusion) biopsies between March 2010 and June 2013 was evaluated in this retrospective, institutional review board‐approved study. Fusion biopsy included MRI‐targeted and systematic sampling at the same session. 3‐Tesla multiparametric MRI was performed at a median of 2 weeks before biopsy. Patients were included if ≥1 systematic core was found to harbour PCa. The impact of the information obtained from targeted vs systematic biopsies was studied with regard to the following: Gleason score (GS), National Comprehensive Cancer Network (NCCN) risk reclassification, cancer core length, percentage of core positive for tumour involvement, and percentage of positive biopsy cores.ResultsThe study sample included 215 men (mean ± sd age 66 ± 8 years). The median (range) prostate‐specific antigen (PSA) was 6.0 (0.7–181) ng/mL. The mean number of total biopsy samples was 18 (12 systematic and six targeted samples). Of 215 men, 34 (16%) had a higher GS on targeted vs systematic biopsy. A total of 21/183 men (12%) were stratified into a higher NCCN risk group when incorporating targeted biopsy GS results and 18/101 men (18%) were upgraded to intermediate‐ or high‐risk from the low‐risk group. Among the 34 men whose cancer severity was upgraded, increases in cancer core length, percentage of tumour involvement and percentage of cores involved were all statistically significant (P < 0.01).ConclusionTargeted prostate biopsy provided information about GS, NCCN risk and tumour volume beyond that obtained in systematic biopsies, specifically increasing the proportions of men in the intermediate‐ and high‐risk groups. Such men may be recommended for additional treatments (pelvic nodal irradiation or hormonal therapy). The appropriateness of changing treatment because of targeted biopsy results is still unclear.
Serum luteinizing hormone concentration is significantly associated with recovery of urinary function after radical prostatectomy
Authors: Namiki Shunichi , Mitsuzuka Koji , Kaiho Yasuhiro , Yamada Shigeyuki , Adachi Hisanobu , Yamashita Shinichi , Saito Hideo , Ito Akihiro , Nakagawa Haruo , Takegami Misa , Arai Yoichi 
Published: February 2015

ObjectiveTo perform a longitudinal investigation of the correlation between functional recovery and sex hormone concentrations after radical prostatectomy (RP).Patients and MethodsA total of 72 consecutive patients undergoing RP between January 2012 and June 2013 were prospectively included and serially followed after surgery for comparative analysis. Their luteinizing hormone (LH) and total testosterone (TT) concentrations were measured before surgery and 3 and 12 months after surgery. They also filled out a health‐related quality of life questionnaire before and at 1, 3, 6 and 12 months after surgery.ResultsThe mean LH concentration increased from 4.28 U/L at baseline to 5.53 U/L at 3 months and remained high at 12 months after RP (both P < 0.001). There were no significant changes in the TT concentration after RP. LH at baseline was negatively correlated with the urinary function (UF) score at 3 and 12 months after RP (P = 0.030 and 0.032, respectively). After RP, subjects with high baseline LH (n = 37) were more likely than those with low LH concentrations to report lower UF scores (P = 0.014). Multivariate analysis of variance in an interaction of time × LH concentration for UF scores indicated a significant relationship between changes in UF score and LH concentration (P = 0.004).ConclusionsRadical prostatectomy affects sex hormones by increasing LH concentrations, while TT concentrations remain stable after surgery. Baseline LH concentrations are significantly associated with the recovery of urinary outcomes after RP.
Outcomes of robotic‐assisted laparoscopic upper urinary tract reconstruction: 250 consecutive patients
Authors: Marien Tracy , Bjurlin Marc A. , Wynia Blake , Bilbily Matthew , Rao Gaurav , Zhao Lee C. , Shah Ojas , Stifelman Michael D. 
Published: February 2015

ObjectiveTo evaluate the long‐term outcomes of robotic‐assisted laparoscopic (RAL) upper urinary tract (UUT) reconstruction performed at a tertiary referral centre.Materials and MethodsData from 250 consecutive patients undergoing RAL UUT reconstruction, including pyeloplasty with or without stone extraction, ureterolysis, uretero‐ureterostomy, ureterocalicostomy, ureteropyelostomy, ureteric reimplantation and buccal mucosa graft ureteroplasty, were collected at a tertiary referral centre between March 2003 and December 2013. The primary outcomes were symptomatic and radiographic improvement of obstruction and complication rate. The mean follow‐up was 17.1 months.ResultsRadiographic and symptomatic success rates ranged from 85% to 100% for each procedure, with a 98% radiographic success rate and 97% symptomatic success rate for the entire series. There were a total of 34 complications, none greater than Clavien grade 3.ConclusionRobotic‐assisted laparoscopic UUT can be performed with few complications, with durable long‐term success, and is a reasonable alternative to the open procedure in experienced robotic surgeons.