bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long‐term safety and efficacy of lanreotide autogel in Japanese patients with neuroendocrine tumors: Final results of a phase II open‐label extension study
Authors: Ito Tetsuhide , Fujimori Nao , Honma Yoshitaka , Kudo Atsushi , Hijioka Susumu , Katsushima Shinji , Kimura Yasutoshi , Fukutomi Akira , Hisamatsu Seiichi , Nakajima Akihiro , Shimatsu Akira 
Published: August 2020

AbstractAimThe aim of this study was to describe the long‐term safety and efficacy of lanreotide in Japanese patients with neuroendocrine tumors.MethodsThe final analyses of a 48‐week open‐label phase II study (n = 32) and its extension study (n = 17) were conducted. Patients received 4‐weekly subcutaneous injections of lanreotide autogel 120 mg. Safety was evaluated by adverse events. Efficacy endpoints included tumor response by RECIST and change in tumor size. Post hoc analyses including tumor growth rate were performed.ResultsThe median (range) of lanreotide exposure in the safety analysis set (n = 17) and efficacy analysis set (n = 28) were 151.4 (52–181) and 52.7 (12–181) weeks, respectively. Sixteen patients developed adverse drug reaction; of these, upper abdominal pain and urticaria were not reported before 48 weeks. No patient discontinued lanreotide or died from an adverse event. Two serious events of bile duct stones in one patient were drug‐related. Partial response was observed in 2 patients (7.1%; at 60 and 108 weeks), stable disease in 20 (71.4%) and progressive disease in 6 (21.4%). The mean of the greatest change from baseline in the sum of diameters of target lesions was −5.5%. The mean (standard deviation) tumor growth rate before treatment and from baseline to last observation was 25.3% (35.7%)/month and 6.4% (9.6%)/month, respectively.ConclusionLanreotide treatment had an acceptable safety profile and was effective over long‐term treatment in Japanese patients with neuroendocrine tumors. No unexpected serious adverse events developed during prolonged use of lanreotide.
The changing paradigm of managing Merkel cell carcinoma in Australia: An expert commentary
Authors: Kok David L. , Wang Annie , Xu Wen , Chua Margaret S. T. , Guminski Alexander , Veness Michael , Howle Julie , Tothill Richard , Kichendasse Ganessan , Poulsen Michael , Sandhu Shahneen , Fogarty Gerald 
Published: August 2020

AbstractMerkel cell carcinoma (MCC) is a highly aggressive neuroendocrine tumor of the skin with an estimated disease‐associated mortality of 15–33%. Australia has a higher incidence of MCC compared to the rest of the world, thought to be due to a higher ultraviolet index. The Australian MCC population is distinct from the MCC population of the Northern hemisphere, characterized by a predominantly viral negative etiology with high tumor mutational burden. The optimal management of MCC and the choice of treatment modality vary significantly across the world and even between institutions within Australia. Historically, the treatment for MCC has been resection followed by radiotherapy (RT), though definitive RT is an alternative treatment used commonly in Australia. The arrival of immune checkpoint inhibitors and the mounting evidence that MCC is a highly immunogenic disease is transforming the treatment landscape for MCC. Australia is playing a key role in the further development of treatment options for MCC with two upcoming Australian/New Zealand investigator‐initiated clinical trials that will explore the interplay of RT and immunotherapy in the treatment of early and late stage MCC.
C‐reactive protein trajectory in the first 48 hours predicts the need for intervention in conservative management of acute diverticulitis
Authors: Ahmadi Nima , Ravindran Praveen , Kim Taejun , Ayoubi Salah E. , Byrne Christopher M. , Young Christopher J. 
Published: August 2020

AbstractBackgroundC‐reactive protein (CRP) is a useful marker for monitoring response to treatment in sepsis. The aim of this study was to examine the use of CRP trajectory in predicting the need for intervention in conservatively managed patients with acute diverticulitis (AD).MethodsA retrospective review of patients with AD who were managed conservatively was performed. They were divided into four groups based on CRP relative to the median at day 0 and 2: ‘Low rise’ (levels below median at day 0 and 2), ‘High rise’ (levels above median at day 0 and 2), ‘Rapid rise’ (levels below median at day 0 but above median at day 2) and ‘Decline’ (levels above median at day 0 but below median at day 2).ResultsIntervention was required in 64 of 456 (14%) with 30 (48%) of these performed after day 2 of admission. There were 150 patients (54%) in the ‘Low rise’, 76 (27%) in the ‘Decline’, 26 patients (9%) in the ‘Rapid rise’ and 25 patients (9%) in the ‘High rise’ groups. Within these groups 5%, 8%, 19% and 32% of patients required intervention (P = 0.001). On multivariate analysis, patients with a pelvic abscess were more likely to need intervention (odds ratio 19.1 (confidence interval 6.2–59.4), P < 0.0001).ConclusionThe CRP trajectory during the initial 48 h of admission can predict the need for intervention in AD patients being managed conservatively. Patients with a ‘Rapid rise’ or ‘High rise’ in CRP from day 0 to 2 are more likely to need intervention.
The low‐expression programming of 11β‐HSD2 mediates osteoporosis susceptibility induced by prenatal caffeine exposure in male offspring rats
Authors: Xiao Hao , Wu Zhixin , Li Bin , Shangguan Yangfan , Stoltz Jean‐François , Magdalou Jacques , Chen Liaobin , Wang Hui 
Published: August 2020

Background and PurposePrenatal caffeine exposure (PCE) can cause developmental toxicity of long bones in offspring, but the long‐term effects and the underlying mechanism have not been fully clarified. Here, we investigated the effects of PCE peak bone mass accumulation and osteoporosis susceptibility in offspring and its intrauterine programming mechanism.Experimental ApproachPregnant Wistar rats were administrated intragastrically with saline or caffeine (120 mg·kg−1·day−1) on gestational days 9–20. The serum and bone samples were collected from the fetal and postnatal offspring for bone mass, genes expression and corticosterone analysis. Then, rat bone marrow mesenchymal stem cells (BMSCs) were treated with corticosterone in vitro to confirm the molecular mechanism.Key ResultsPCE caused fetal bone dysplasia in male and female offspring. In adulthood, PCE reduced peak bone mass and increased osteoporosis susceptibility in male offspring but not in females. Meanwhile, PCE only decreased the H3K9ac and expression levels of 11β‐hydroxysteroid dehydrogenase 2 (11β‐HSD2) before and after birth in the male offspring but not in the females. Moreover, the high level of corticosterone induced by PCE down‐regulated the H3K9ac and expression levels of 11β‐HSD2 through promoting glucocorticoid receptor (GR; NR3C1) into the nucleus of bone marrow mesenchymal stem cells (BMSCs) and recruiting histone deacetylase 11 (HDAC11) binding to 11β‐HSD2 promoter region, which further enhanced the effect of corticosterone on suppressing osteogenic function of BMSCs.Conclusion and ImplicationsPCE caused osteoporosis susceptibility in male adult offspring, which attributed to the low‐functional programming of 11β‐HSD2 induced by corticosterone via GR/HDAC11 signalling.
IoT cloud platform for information processing in smart city
Authors: Chen Xiangcong , Zhang Shuqing , Ding Xiaohui , Kadry Seifedine Nimer , Hsu Ching‐Hsien 
Published: August 2020

AbstractThe construction of a sustainable transport network for people or goods will gain and harm mobility depending on their nature and implementation, using new technology and business models. The regular mobile handoff and replacement of connections allow the efficient mobility management of asynchronous wireless transfer mode (ATM) networks. Hence, the design of the broad spectrum usability network architecture for public ATM systems has been given considerable attention in the literature. Since it has been done on the critical subject of estimating user mobility and the prediction, which aims to improve communication efficiency and the bandwidth efficiency of the underlying system architecture, this article addresses the problem by developing the impact of hierarchical framework of service on transportation and traffic pattern (HFSTTP). The growth in mobile Internet and the use of mobile devices over the last decade allowed for omnipresent information on traffic. With the growing use of unique mobile apps, the number of routing users has evolved to be sufficiently large to interrupt the traffic flow pattern. Modern carriage systems and urban logistics improve the efficiency of the transport of goods and slow down the use of road infrastructure. Numerical examples of vehicle traffic include proof of ties between the network traffic and the routing decision‐making layer. The partnership between a cooperative control layer and a lower control layer to optimize freight transport is a second example. The congestion price in all over the world shows how to incorporate the social plan layer in future mobility services.
Optimal Use of Echocardiography in Management of Thrombosis After Anterior Myocardial Infarction
Authors: Barbieri Andrea , Mantovani Francesca , Bursi Francesca , Faggiano Andrea , Boriani Giuseppe , Faggiano Pompilio 
Published: August 2020

AbstractDespite advancement in therapy and management, left ventricular thrombus (LVT) after anterior myocardial infarction (MI) is sporadically encountered and remains associated with a very high risk of major cardiovascular events and mortality. Cardiac magnetic resonance (CMR) is considered the gold standard technique for LVT detection, but it is a time‐consuming and expensive test not available in all centers, especially when repeated examinations are necessary. Transthoracic echocardiography represents a useful tool to screen for LVT and to identify predictors of high risk of developing LVT. The advances in ultrasound technology and the use of contrast agents may potentially help clinicians to identify LVT and the use of sequential echocardiography for each patient with acute MI complicated by LVT may provide an opportunity to quantify regression and its correlation with outcomes to tailor the management of these patients. Hence, this narrative review focuses on the added value of echocardiographic‐guided LVT management in patients with recent anterior MI to reduce mortality and morbidity excess related to LVT based on current evidence.
Degree of left ventricular dilatation at end‐diastole: Correlation and prognostic utility of quantitative volumes by 2D‐echocardiography versus linear dimensions in patients with asymptomatic aortic regurgitation
Authors: Barbieri Andrea , Benfari Giovanni , Giubertoni Elisa , Manicardi Marcella , Bursi Francesca , Rossi Andrea , Maritan Luca , Venturi Gabriele , Boriani Giuseppe 
Published: August 2020

AbstractBackgroundGuideline recommendations for aortic valve replacement (AVR) in asymptomatic patients with chronic aortic regurgitation (AR) have historically focused on linear dimensions without normalization for the body surface area (BSA). Values for grading the severity of end‐diastolic volume dilatation by 2D echocardiography remain to be established.Methods and ResultsWe retrospectively analyzed 543 consecutive asymptomatic patients with pure chronic moderate/severe AR (mean age 66 ± 17 years, 37.7% males). Applying the ASE/EACVI guidelines, BSA‐indexed LV end‐diastolic volume (LVEDVi) and indexed LV end‐diastolic diameter (LVEDDi) were assessed. Then, we identified 192 patients with at least mild LV end‐diastolic dilatation by volumetric or linear measurements. The outcome endpoint was the combination of cardiac death, hospitalization for acute heart failure or AVR during a median follow‐up of 4.5 ± 3.6 years. Multivariable Cox regression analyses including age, LV ejection fraction (EF) and AR severity showed an independent prognostic value of the LVEDDi and LVEDVi (P < .001 and P < .01, respectively). Congruent severe LVEDDi and LVEDVi dilatation was associated with a higher event rate compared to discordant severe LV end‐diastolic dilatation or nonsevere LV dilatation (P = .001) even after landmark analysis (P = .02). In patients with EF > 50%, only the LVEDVi showed and independent prognostic value (P < .001).ConclusionsIn a cohort of asymptomatic patients with AR, the presence of severe LV volume and diameter dilatation on the basis of the cutoff values proposed by current recommendations and normalized for BSA may be instrumental in the identification of patients at increased risk of clinical progression regardless of EF.
Feedback‐dependent neuronal properties make focal dystonias so focal
Authors: Sedov Alexey , Usova Svetlana , Popov Valentin , Tomskiy Alexey , Jinnah Hyder A. , Shaikh Aasef G. 
Published: August 2020

AbstractFocal dystonia, by definition, affects a specific body part; however, it may have a widespread neural substrate. We tested this hypothesis by examining the intrinsic behaviour and the neuronal properties that are modulated by changes in the physiological behaviour of their connections, that is feedback dependence, of the isolated pallidal neurons. During deep brain stimulation surgery in 12 patients with isolated cervical dystonia (without hand involvement), we measured spontaneous as well as evoked single‐unit properties in response to fist making (hand movement) or shoulder shrug (neck movements). We measured the activity of isolated neurons that were only sensitive to the neck movements, hand movement, or not responsive to hand or neck movements. The spontaneous firing behaviour, such as the instantaneous firing rate and its regularity, was comparable in all three types of neurons. The neck movement‐sensitive neurons had prominent bursting behaviour in comparison with the hand neurons. The feedback dependence of the neck movement‐sensitive neurons was also significantly impaired when compared to hand movement‐sensitive neurons. Motor‐evoked change in firing rate of neck movement‐sensitive neurons rapidly declined; the decay time constant was much shorter compared to hand movement‐sensitive neurons. These results suggest that in isolated cervical dystonia, at the resolution of single neurons, the deficits are much widespread, affecting the neurons that drive the neck movement as well as the hand movements. We speculate that clinically discernable dystonia occurs when additional abnormality is added to baseline dysfunctional network, and one source of such abnormality may involve feedback.
A guide to measuring phagosomal dynamics
Authors: Levin‐Konigsberg Roni , Mantegazza Adriana R. 
Published: August 2020

Phagocytosis is an essential mechanism for immunity and homeostasis, performed by a subset of cells known as phagocytes. Upon target engulfment, de novo formation of specialized compartments termed phagosomes takes place. Phagosomes then undergo a series of fusion and fission events as they interact with the endolysosomal system and other organelles, in a dynamic process known as phagosome maturation. Because phagocytes play a key role in tissue patrolling and immune surveillance, phagosome maturation is associated with signaling pathways that link phagocytosis to antigen presentation and the development of adaptive immune responses. In addition, and depending on the nature of the cargo, phagosome integrity may be compromised, triggering additional cellular mechanisms including inflammation and autophagy. Upon completion of maturation, phagosomes enter a recently described phase: phagosome resolution, where catabolites from degraded cargo are metabolized, phagosomes are resorbed, and vesicles of phagosomal origin are recycled. Finally, phagocytes return to homeostasis and become ready for a new round of phagocytosis. Altogether, phagosome maturation and resolution encompass a series of dynamic events and organelle crosstalk that can be measured by biochemical, imaging, photoluminescence, cytometric, and immune‐based assays that will be described in this guide.
The politics of social assistance in South Africa: How protests and electoral politics shape the Child Support Grant
Authors: Yörük Erdem , Gençer Alper Şükrü 
Published: August 2020

AbstractSince the 1990s, South Africa, like many other countries from the Global South, has provided extensive social assistance for the poor. The literature on these policies, however, is largely dominated by structuralist accounts, and it largely overlooks political factors. We conducted quantitative analyses regarding the South African flagship Child Support Grant (CSG) program and investigated how contentious and electoral political dynamics jointly shape the provision of this program. Based on a logistic regression analysis, we measured the effect of protest participation, voting preference, and their interaction on the likelihood of CSG receipt. Our analysis showed that CSG receipt is much higher among “uncontentious supporters” of ANC and “contentious nonsupporters,” as well as those who join violent protests. This lends support for our argument that CSG is being used as a tool for electoral politics and containment of unrest, providing fresh evidence for political mediation theories of social policy.
Development and content validation of the percutaneous nephrolithotomy assessment score
Authors: Quirke Kate , Aydın Abdullatif , Bultitude Matthew , Sarıca Kemal , Glass Jonathan , Khan Azhar , Marsh Howard , Al‐Hayek Samih , Wiseman Oliver , Patterson Jake , Makanjuola Jonathan , Skolarikos Andreas , Somani Bhaskar , Khan Muhammad Shamim , Dasgupta Prokar , Ahmed Kamran 
Published: August 2020

ObjectivesTo develop and content validate a percutaneous nephrolithotomy assessment score, taking into consideration the procedure‐specific risks.MethodsThis prospective international study utilized the Healthcare Failure Mode and Effect Analysis to systematically outline percutaneous nephrolithotomy and failure modes for each step. A total of 25 h was spent observing percutaneous nephrolithotomy carried out by six expert surgeons. Hazard analysis scoring was carried out by 11 experts. It was determined if the steps were single point weaknesses. Single point weaknesses and those assigned a hazard score ≥4 were included in the percutaneous nephrolithotomy assessment score. The tool was then content validated by 16 experts from 10 countries.ResultsApplication of the Healthcare Failure Mode and Effect Analysis identified 64 failure modes; 37 failure modes had a hazard score ≥4. After adaptations based on expert feedback the final percutaneous nephrolithotomy assessment score was developed containing 10 phases, 21 processes and 47 subprocesses. All participants agreed that the tool contained pertinent procedural steps.ConclusionsThis study has developed and shown the international content validity of a novel percutaneous nephrolithotomy assessment score. The tool can be utilized in modular operating room training to quantify operator progress, and can be used in conjunction with other modules as part of a complete percutaneous nephrolithotomy curriculum for trainees.
Outcomes and costs of skilled support for people with severe or profound intellectual disability and complex needs
Authors: Beadle‐Brown Julie , Beecham Jennifer , Leigh Jennifer , Whelton Rebecca , Richardson Lisa 
Published: August 2020

AbstractBackgroundWith increasing reductions in funding for social care across many countries, the need to ensure that resources are used to best effect is becoming increasingly important, in particular for those with severe and complex needs.MethodsIn order to explore the outcomes and costs of skilled support for this group of people, quality of life was assessed for 110 people in 35 services in England. Information on costs was also collected.ResultsPeople who received consistently good active support experienced better outcomes in terms of several quality of life domains. Good support did not require significantly more staff time, and there was no evidence of higher total costs for those receiving good support.ConclusionsThe inclusion of active support in government guidance and local commissioning practices related to people with severe intellectual disabilities is likely to improve user outcomes. Observation should be an important element in measuring service quality.
Immediate versus delayed temporization at posterior single implant sites: A randomized controlled trial
Authors: Wang Joseph , Lerman Gila , Bittner Nurit , Fan Weijia , Lalla Evanthia , Papapanou Panos N. 
Published: August 2020

AbstractAimsWe conducted a randomized controlled trial to assess the clinical outcomes of two loading protocols involving either immediate or delayed prosthetic temporization of single implants placed at posterior, healed sites.Materials and MethodsForty‐nine patients in need of single implants at premolar or molar sites were randomized to receive a temporary crown either immediately after implant placement or 3 months later. Randomization was stratified by sex, implant location (premolar/molar) and arch (maxilla/mandible). Final implant screw‐retained zirconia crowns with angulated screw channels were delivered at 5 months after surgery. Radiographic bone levels (primary outcome), peri‐implant mucosal margin levels and peri‐implant probing depths were recorded at baseline, 6 and 12 months after surgery.ResultsBoth treatment arms showed similar patterns of soft tissue and bone re‐modelling from the implant platform over 12 months [mean bone level change 1.6 mm (SD 1.0 mm) in the delayed, and 1.2 mm (SD 1.3 mm) in the immediate temporization group], with the majority of changes occurring within the first 6 months.ConclusionsImmediate or delayed temporization of single implants placed at posterior healed sites resulted in largely similar 1‐year outcomes with respect to peri‐implant bone levels and soft tissue changes.
Identification of truncated C‐terminal fragments of the Alzheimer’s disease amyloid protein precursor derived from sequential proteolytic pathways
Authors: Mosser Sebastien , Gerber Hermeto , Fraering Patrick C. 
Published: August 2020

AbstractRecent evidence supports the emerging hypothesis that the amyloid‐β precursor protein C‐terminal fragments (APP‐CTFs) and dysregulations in both their qualitative and quantitative productions may actively and directly contribute to the neuronal toxicity in early phases of Alzheimer's disease (AD). These new findings revealed the urgent needs and gaps in better understanding the metabolism and full spectrum of APP‐CTFs. In this study, we characterized by mass spectrometry the full patterns of APP‐CTFs in different cell types and in the brain of an AD APPPS1 mouse model. In these systems, we first discovered a series of 71–80 amino acids long N‐terminally truncated APP‐CTFs of unknown functions. We next demonstrated that these N‐terminally truncated APP‐CTFs are sequentially produced by the proteolytic processing of APP‐C80, by an as yet unidentified protease. Finally, these N‐terminally truncated APP‐CTFs are likely protein substrates recognized and processed by the γ‐secretase complex, leading to the production of N‐terminally truncated Aβ peptides. Together, our findings provide new insights into the metabolism of APP and offer potential new strategies to modulate the production of toxic Aβ peptides in AD.
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