bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prostate MRI evolution in clinical practice: Audit of tumour detection and staging versus prostatectomy with staged introduction of multiparametric MRI and Prostate Imaging Reporting and Data System v2 reporting
Authors: Raeside Mitchell , Low Andrew , Cohen Penelope , Sutherland Peter , Gormly Kirsten 
Published: April 2019

AbstractIntroductionWe conducted a retrospective audit to compare dominant nodule detection and local staging before and after the introduction of functional sequences and PI‐RADS v2 reporting to MRI prostate scans in routine private practice.MethodsA retrospective audit was performed of 245 patients in four separate groups undergoing robotic prostatectomy for prostate cancer by a single urologist between 2009 and 2017. The initial 100 consecutive patients had T2 imaging only. The next 43 patients had T2 and DWI. 52 subsequent patients had T2, DWI and DCE sequences (mpMRI). A final 50 consecutive patients had mpMRI using PI‐RADS v2 reporting. Preoperative MRI reports were compared with prostatectomy histopathology to determine the sensitivity of MRI in detecting dominant tumour nodule and T3 extension.ResultsThe addition of DWI and DCE sequences improved sensitivity for detection of dominant tumour nodule, with a significant further increase using PI‐RADS v2 reporting (38% for T2 vs. 62% for T2/DWI vs. 67% for mpMRI vs 91% for PI‐RADS v2). The accuracy of detecting T3 disease was initially very low. The use of additional imaging techniques did not significantly influence this, but the use of a three category likelihood of extraprostatic extension in the PI‐RADS v2 group had a significant increase in detection of T3 disease (sensitivity 27% vs. 23% vs. 38% vs 63%).ConclusionThis audit tracks the significant improvements in MRI detection of prostate cancer dominant tumour nodule and T3 extension in patients undergoing prostatectomy with changing techniques and reporting standards in routine clinical practice.
Contour variation is a primary source of error when delivering post prostatectomy radiotherapy: Results of the Trans‐Tasman Radiation Oncology Group 08.03 Radiotherapy Adjuvant Versus Early Salvage (RAVES) benchmarking exercise
Authors: Cloak Kirrily , Jameson Michael G , Paneghel Andrea , Wiltshire Kirsty , Kneebone Andrew , Pearse Maria , Sidhom Mark , Tang Colin , Fraser‐Browne Carol , Holloway Lois C , Haworth Annette 
Published: April 2019

AbstractIntroductionVariation in target volume delineation from clinical trial protocols has been shown to contribute to poorer patient outcomes. A clinical trial quality assurance framework can support compliance with trial protocol. Results of the TROG 08.03 RAVES benchmarking exercise considering variation from protocol, inter‐observer variability and impact on dosimetry are reported in this paper.MethodsClinicians were required to contour and plan a benchmarking case according to trial protocol. Geometric pjmirometers including volume, Hausdorff Distance, Mean Distance to Agreement and DICE similarity coefficient were analysed for targets and organs at risk. Submitted volumes were compared to a STAPLE and consensus ‘reference’ volume for each structure. Dosimetric analysis was performed using dose volume histogram data.ResultsBenchmarking exercise submissions were received from 96 clinicians. In total 205 protocol variations were identified. The most common variation was inadequate contouring of the CTV in 84/205 (41%). The CTV volume ranged from 65.3 to 193.1 cm3 with a median of 113.2 cm3. The most common dosimetric protocol variation related to rectal dosimetry. The mean submitted rectal volume receiving 40 Gy and 60 Gy, respectively, was 56.14% ± 5.55% and 30.25% ± 6.15%. When corrected to the protocol defined length the mean rectal volume receiving 40 Gy was 60.8% ± 7.92%, while the volume receiving 60 Gy was 33.86% ± 8.21%.ConclusionVariations from protocol were found in the RAVES benchmarking exercise, most notably in CTV and rectum delineation. Inter‐observer variability was evident. Incorrect delineation of the rectum impacted on dosimetric compliance with protocol.
Comparison of a combination of chemotherapy and immune checkpoint inhibitors and immune checkpoint inhibitors alone for the treatment of advanced and metastatic non‐small cell lung cancer
Authors: Kuo Chih‐Hsi Scott , Wang Chin‐Chou , Huang Yu‐Chen , Pavlidis Stelios , Liu Chien‐Ying , Ko How‐Wen , Chung Fu‐Tsai , Lin Tin‐Yu , Wang Chih‐Liang , Guo Yi‐Ke , Yang Cheng‐Ta 
Published: April 2019

BackgroundSingle agent immune checkpoint inhibitors (ICIs) improve survival outcomes compared to chemotherapy for advanced non‐small cell lung cancer (NSCLC), but treatment efficacy widely varies. The combination of ICIs with chemotherapy has shown promising efficacy over chemotherapy alone; however, whether this strategy is superior to single agent ICIs for the treatment of advanced NSCLC remains unknown.MethodsThe records of 109 patients with advanced NSCLC who were administered at least one cycle of ICIs were retrospectively reviewed. Patients were grouped based on the presence or absence of a chemotherapy treatment combination. Efficacy and survival outcomes were analyzed.ResultSixty‐nine (58.0%) patients received single agent ICIs (ICI group) and 50 (42.0%) received ICIs and chemotherapy (ICC group). The median (3.2 vs. 3.0 months; P = 0.025) and one‐year (34.5 vs. 9.6%; P = 0.026) progression‐free survival (PFS) rates were significantly better in the ICC than in the ICI group. The superior efficacy of ICC remained in the propensity score matched pairs (median PFS 3.2 vs. 2.6 months, P = 0.032; 1‐year PFS 35.2 vs. 7.6%; P = 0.035). Eastern Cooperative Oncology Group performance status 0–1 (HR 0.37, 95% CI 0.22–0.62; P < 0.001) and the ICC group (HR 0.56, 95% CI 0.34–0.94; P = 0.028) were predictive of PFS. Subgroup‐to‐chemotherapy interaction revealed improved risk reduction for adenocarcinoma and EGFR mutation.ConclusionCombing chemotherapy with ICIs improved treatment efficacy over ICIs alone. The additional efficacy of chemotherapy may differ between histological subtypes and EGFR mutation status.
Effects of IGF‐1 isoforms on muscle growth and sarcopenia
Authors: Ascenzi Francesca , Barberi Laura , Dobrowolny Gabriella , Villa Nova Bacurau Aline , Nicoletti Carmine , Rizzuto Emanuele , Rosenthal Nadia , Scicchitano Bianca Maria , Musarò Antonio 
Published: April 2019

AbstractThe decline in skeletal muscle mass and strength occurring in aging, referred as sarcopenia, is the result of many factors including an imbalance between protein synthesis and degradation, changes in metabolic/hormonal status, and in circulating levels of inflammatory mediators. Thus, factors that increase muscle mass and promote anabolic pathways might be of therapeutic benefit to counteract sarcopenia. Among these, the insulin‐like growth factor‐1 (IGF‐1) has been implicated in many anabolic pathways in skeletal muscle. IGF‐1 exists in different isoforms that might exert different role in skeletal muscle. Here we study the effects of two full propeptides IGF‐1Ea and IGF‐1Eb in skeletal muscle, with the aim to define whether and through which mechanisms their overexpression impacts muscle aging. We report that only IGF‐1Ea expression promotes a pronounced hypertrophic phenotype in young mice, which is maintained in aged mice. Nevertheless, examination of aged transgenic mice revealed that the local expression of either IGF‐1Ea or IGF‐1Eb transgenes was protective against age‐related loss of muscle mass and force. At molecular level, both isoforms activate the autophagy/lysosome system, normally altered during aging, and increase PGC1‐α expression, modulating mitochondrial function, ROS detoxification, and the basal inflammatory state occurring at old age. Moreover, morphological integrity of neuromuscular junctions was maintained and preserved in both MLC/IGF‐1Ea and MLC/IGF‐1Eb mice during aging. These data suggest that IGF‐1 is a promising therapeutic agent in staving off advancing muscle weakness.
Maintenance of World Health Organization Risk Drinking Level Reductions and Posttreatment Functioning Following a Large Alcohol Use Disorder Clinical Trial
Authors: Witkiewitz Katie , Falk Daniel E. , Litten Raye Z. , Hasin Deborah S. , Kranzler Henry R. , Mann Karl F. , O'Malley Stephanie S. , Anton Raymond F. 
Published: April 2019

BackgroundReductions in the World Health Organization (WHO) risk drinking levels have been proposed as an alternative primary outcome for alcohol clinical trials. Yet, little is known about whether reductions in WHO risk drinking levels can be maintained over time. The current study examined whether reductions in WHO risk drinking levels were maintained for up to 1 year following treatment, and whether reductions over time were associated with improvements in functioning.MethodsSecondary data analysis of individuals with alcohol dependence (n = 1,226) enrolled in the COMBINE study, a multisite, randomized, placebo‐controlled clinical trial. Logistic regression was used to examine the maintenance of end‐of‐treatment WHO risk level reductions and WHO risk level reductions at the 1‐year follow‐up. Repeated‐measures mixed models were used to examine the association between WHO risk level reductions and functional outcomes over time.ResultsAchieving at least a 1‐ or 2‐level reduction in risk by the end of treatment was significantly associated with WHO risk level reductions at the 1‐year follow‐up assessment (p < 0.001). Among individuals who achieved at least a 1‐level reduction by the end of treatment, 85.5% reported at least a 1‐level reduction at the 1‐year follow‐up. Among individuals who achieved at least a 2‐level reduction by the end of treatment, 77.8% reported at least a 2‐level reduction at the 1‐year follow‐up. WHO risk level reductions were associated with significantly lower alcohol consumption, better physical health (p < 0.01), and fewer alcohol‐related consequences (p < 0.001) up to 1 year following treatment.ConclusionsOne‐ and 2‐level reductions in WHO risk levels during alcohol treatment were maintained after treatment and associated with better functioning over time. These findings support the use of the WHO risk level reductions as an outcome measure that reflects clinically significant improvement in how individuals seeking treatment for alcohol use disorder feel and function.
Severe childhood trauma and clinical and neurocognitive features in schizotypal personality disorder
Authors: Velikonja T. , Velthorst E. , McClure M. M. , Rutter S. , Calabrese W. R. , Rosell D. , Koenigsberg H. W. , Goodman M. , New A. S. , Hazlett E. A. , Perez‐Rodriguez M. M. 
Published: April 2019

ObjectiveLiterature suggests that childhood trauma increases vulnerability for schizophrenia‐spectrum disorders, including schizotypal personality disorder (SPD). Yet, it remains unexplored whether childhood trauma predicts symptom load and the level of neurocognitive functioning in SPD.MethodWe included 225 individuals with SPD and 127 healthy controls. Childhood trauma was evaluated using the Childhood Trauma Questionnaire, and schizotypal traits were assessed using the Schizotypal Personality Questionnaire. Standard neurocognitive assessments covered six cognitive domains.ResultsAll types of reported childhood trauma were significantly associated with SPD, in a linear fashion. Severe sexual abuse showed the greatest magnitude of association with higher cognitive–perceptual load (e.g., ideas of reference, odd belief or magical thinking); severe emotional neglect was associated with interpersonal scores (e.g., excessive social anxiety, constricted affect) within the SPD group. SPD individuals who reported severe trauma showed worse cognitive functioning (i.e., working memory, verbal/visual learning and memory, as well as verbal fluency).ConclusionsParticular severe childhood trauma types were associated with higher cognitive–perceptual and interpersonal symptoms in SPD, along with worse cognitive functioning. These findings highlight the need for clinicians to enquire about childhood trauma in SPD patients, since unaddressed early adverse experiences may carry long‐term negative consequences.
DNMT3a in the hippocampal CA1 is crucial in the acquisition of morphine self‐administration in rats
Authors: Zhang Jian‐Jun , Jiang Feng‐Ze , Zheng Wei , Duan Ying , Jin Shu‐Bo , Shen Fang , Liang Jing , Li Ming , Sui Nan 
Published: April 2019

AbstractDrug‐reinforced excessive operant responding is one fundamental feature of long‐lasting addiction‐like behaviors and relapse in animals. However, the transcriptional regulatory mechanisms responsible for the persistent drug‐specific (not natural rewards) operant behavior are not entirely clear. In this study, we demonstrate a key role for one of the de novo DNA methyltransferase, DNMT3a, in the acquisition of morphine self‐administration (SA) in rats. The expression of DNMT3a in the hippocampal CA1 region but not in the nucleus accumbens shell was significantly up‐regulated after 1‐ and 7‐day morphine SA (0.3 mg/kg/infusion) but not after the yoked morphine injection. On the other hand, saccharin SA did not affect the expression of DNMT3a or DNMT3b. DNMT inhibitor 5‐aza‐2‐deoxycytidine (5‐aza) microinjected into the hippocampal CA1 significantly attenuated the acquisition of morphine SA. Knockdown of DNMT3a also impaired the ability to acquire the morphine SA. Overall, these findings suggest that DNMT3a in the hippocampus plays an important role in the acquisition of morphine SA and may be a valid target to prevent the development of morphine addiction.
Inhibitory effects of Shati/Nat8l overexpression in the medial prefrontal cortex on methamphetamine‐induced conditioned place preference in mice
Authors: Haddar Meriem , Uno Kyosuke , Azuma Katsunori , Muramatsu Shin‐ichi , Nitta Atsumi 
Published: April 2019

AbstractShati/Nat8l is a novel N‐acetyltransferase identified in the brain of mice treated with methamphetamine (METH). Shati/Nat8l mRNA is expressed in various brain areas, including the prefrontal cortex (PFC), where the expression level is higher than that in other brain regions. Shati/Nat8l overexpression in the nucleus accumbens (NAc) attenuates the pharmacological response to METH via mGluR3. Meanwhile, dopamine (DA) and glutamate dysregulations have been reported in the medial prefrontal cortex (mPFC) and NAc after METH self‐administration and during reinstatement. However, the mechanism, the reward system, and function of Shati/Nat8l in the mPFC is unclear. Here, we injected an adeno‐associated virus (AAV) vector containing Shati/Nat8l into the mPFC of mice, to overexpress Shati/Nat8l in the mPFC (mPFC‐Shati/Nat8l). Interestingly, the METH‐induced conditioned place preference (CPP) was attenuated in the mPFC‐Shati/Nat8l mice, but locomotor activity was not. Additionally, immunohistochemical results from mice that were injected with AAV‐GFP showed fluorescence in the mPFC and other brain regions, mainly the NAc, indicating an mPFC‐NAc top‐down connection. Finally, in vivo microdialysis experiments revealed that Shati/Nat8l overexpression in the mPFC reduced extracellular DA levels and suppressed the METH‐induced DA increase in the NAc. Moreover, decreased extracellular glutamate levels were observed in the NAc. These results indicate that Shati/Nat8l overexpression in the mPFC attenuates METH‐induced CPP by decreasing extracellular DA in the NAc. In contrast, Shati/Nat8l‐mPFC overexpression did not alter METH‐induced hyperlocomotion. This study demonstrates that Shati/Nat8l in the mPFC attenuates METH reward‐seeking behaviour but not the psychomotor activity of METH.
Understanding the assistive technology needs of people over 55: The future of mobility aids
Authors: Moxham Lorna J. , Stutchbury Tamantha K. , Spinks Geoffrey , de Vet Eliza , Ikutegbe Victoria , Traynor Victoria , Taylor Leanne , Michielin Nicole 
Published: April 2019

ObjectiveTo understand mobility issues not adequately serviced by assistive technology (AT).MethodsA two‐stage mixed‐methods research project that forms the basis of future AT design and manufacture. Stage 1: a focus group comprising 46 participants (people aged 55 years or older with mobility issue/s) and their support networks. Stage 2: a sample of 413 people over 55 completed a purpose‐designed survey informed by stage 1, regarding mobility issues and perceived desirability of suggested AT mobility aids.ResultsTwo core themes emerged: (a) functionality issues relating to existing AT designs and (b) identified mobility issues encountered during activities of daily living that could potentially be resolved by developing new AT. Importance was placed on certain features of AT mobility aids with cost, transportability and aesthetics being primary issues.ConclusionConsulting end‐users and their networks ensures valuable insight into how future AT can better address and target mobility needs.
Prevalence and outcomes of overweight and obesity among pregnant women in rural Queensland
Authors: Cochrane Lynsey , Brumpton Kay , Winter Sacha , Bell Katrina , Burnham Harriet , Wadwell Kristen , Kitchener Scott 
Published: April 2019

AbstractObjectiveTo assess the prevalence of overweight and obese women in the antenatal and perinatal periods, in rural hospitals; and to evaluate neonatal and maternal outcomes, including transfer to larger birthing centres.DesignA retrospective clinical chart audit.SettingRural maternity services in five Queensland rural hospitals.ParticipantsData were collected from 250 women presenting to participating rural hospitals, with an estimated due date in 2016.Main outcome measuresObstetric and neonatal data, whether transfer occurred, mode of delivery and any complications, and neonatal outcomes including birth weight and complications were collected. Demographic information collected included maternal age, gravidity and parity, race, smoking status and pre‐pregnancy body mass index. The main outcome measures of interest were birth weight, Caesarean rate, transfer rate and diagnosis of gestational diabetes in relation to the body mass index.ResultsOver 50% of women were overweight or obese while entering pregnancy, with 5.2% of mothers in the morbidly obese category. There was an increase in the birth weight of mothers with a body mass index of more than 25. The increasing body mass index was associated with an increased likelihood of transfer, diagnosis of gestational diabetes, elective and, especially, emergency Caesareans performed at the hospital. Twenty‐four percent of women continued to smoke throughout pregnancy.ConclusionA high prevalence of obesity was found in the rural obstetric population. As the body mass index increases, so too does birth weight, gestational diabetes, transfer rate and Caesarean section rate. The rates of smoking throughout pregnancy were higher than the average metropolitan rates. These findings have implications not just for rural hospital operation and resources, but also for preventive health activities in rural communities.
Toward clinically applicable biomarkers for asthma: An EAACI position paper
Authors: Diamant Zuzana , Vijverberg Susanne , Alving Kjell , Bakirtas Arzu , Bjermer Leif , Custovic Adnan , Dahlen Sven‐Erik , Gaga Mina , Gerth van Wijk Roy , Del Giacco Stefano , Hamelmann Eckard , Heaney Liam G. , Heffler Enrico , Kalayci Ömer , Kostikas Konstantinos , Lutter Rene , Olin Anna‐Carin , Sergejeva Svetlana , Simpson Angela , Sterk Peter J. , Tufvesson Ellen , Agache Ioana , Seys Sven F. 
Published: April 2019

AbstractInflammation, structural, and functional abnormalities within the airways are key features of asthma. Although these processes are well documented, their expression varies across the heterogeneous spectrum of asthma. Type 2 inflammatory responses are characterized by increased levels of eosinophils, FeNO, and type 2 cytokines in blood and/or airways. Presently, type 2 asthma is the best‐defined endotype, typically found in patients with allergic asthma, but surprisingly also in nonallergic patients with (severe) asthma. The etiology of asthma with non‐type 2 inflammation is less clear. During the past decade, targeted therapies, including biologicals and small molecules, have been increasingly integrated into treatment strategies of severe asthma. These treatments block specific inflammatory pathways or single mediators. Single or composite biomarkers help to identify patients who will benefit from these treatments. So far, only a few inflammatory biomarkers have been validated for clinical application. The European Academy of Allergy & Clinical Immunology Task Force on Biomarkers in Asthma was initiated to review different biomarker sampling methods and to investigate clinical applicability of new and existing inflammatory biomarkers (point‐of‐care) to support diagnosis, targeted treatment, and monitoring of severe asthma. Subsequently, we discuss existing and novel targeted therapies for asthma as well as applicable biomarkers.
Intra‐operative analgesia with remifentanil vs. dexmedetomidine: a systematic review and meta‐analysis with trial sequential analysis
Authors: Grape S. , Kirkham K. R. , Frauenknecht J. , Albrecht E. 
Published: April 2019

SummaryIntra‐operative remifentanil is associated with increased postoperative analgesic requirements and opioid consumption. Dexmedetomidine has characteristics suggesting it may substitute for intra‐operative remifentanil during general anaesthesia, but existing literature has reported conflicting results. We undertook this meta‐analysis to investigate whether general anaesthesia including dexmedetomidine would result in less postoperative pain than general anaesthesia including remifentanil. The MEDLINE and PubMed electronic databases were searched up to October 2018. Only randomised trials including patients receiving general anaesthesia and comparing dexmedetomidine with remifentanil administration were included. Meta‐analyses were performed mostly employing a random effects model. The primary outcome was pain score at rest (visual analogue scale, 0–10) at two postoperative hours. The secondary outcomes included: pain score at rest at 24 postoperative hours; opioid consumption at 2 and 24 postoperative hours; and rates of hypotension, bradycardia, shivering and postoperative nausea and vomiting. Twenty‐one randomised trials, including 1309 patients, were identified. Pain scores at rest at two postoperative hours were lower in the dexmedetomidine group, with a mean difference (95%CI) of −0.7 (−1.2 to −0.2), I2 = 85%, p = 0.004, and a moderate quality of evidence. Secondary pain outcomes were also significantly better in the dexmedetomidine group. Rates of hypotension, shivering and postoperative nausea and vomiting were at least twice as frequent in patients who received remifentanil. Time to analgesia request was longer, and use of postoperative morphine and rescue analgesia were less, with dexmedetomidine, whereas episodes of bradycardia were similar between groups. There is moderate evidence that intra‐operative dexmedetomidine during general anaesthesia improves pain outcomes during the first 24 postoperative hours, when compared with remifentanil, with fewer side effects.