bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmaceutical payments to physicians may increase prescribing for opioids
Authors: Nguyen Thuy D. , Bradford W. David , Simon Kosali I. 
Published: January 2019

AbstractBackground and AimsGiven the recent complete suspension of opioid‐related promotional activities aimed at physicians, interest has renewed in understanding the role of promotion in the US opioid crisis. The present analysis aimed to measure associations between such interactions and opioid prescribing.DesignData on all promotions by pharmaceutical companies directly to physicians were linked to physician‐level data on opioid prescriptions filled in a federal insurance program and analyzed using multivariate regression.SettingUnited States.ParticipantsA total of 865 347 US physicians, with prescriptions filled in Medicare Part D, that might receive payments from pharmaceutical promotional activities from 2014 to 2016.MeasurementsThe outcome variable was days’ supply dispensed by each prescriber, by year, for all opioids (collectively) and separately for the following opioid classes: hydrocodone, oxycodone, fentanyl, tapentadol, morphine and a catch‐all ‘other opioids’. The independent variables were receipt of any payments and dollar amounts of payments received by each prescriber by year for all opioids and separately for opioid categories.FindingsPrescribers who received opioid‐specific payments prescribed 8784 opioid daily doses per year more than their peers who did not receive any such payments (P < 0.001). Recipient of hydrocodone‐related payments was associated with 5161 additional daily doses of hydrocodone (P < 0.001). Recipient of oxycodone‐related payments was associated with 3624 additional daily doses of oxycodone (P < 0.001). Prescribers receiving any fentanyl‐specific payments prescribed 1124 daily doses per year more than their peers (P < 0.001). Among recipients of opioid‐specific payments (63 062 physicians), a 1% increase in amount of payments was associated with 50 daily doses of opioid prescription (P < 0.001).ConclusionsIn the United States, physicians who receive direct payments from providers for opioid prescribing tend to prescribe substantially larger quantities, particularly for hydrocodone and oxycodone.
The ethics of biobanking: Assessing the right to control problem for broad consent
Authors: Manson Neil C. 
Published: January 2019

AbstractThe biobank consent debate is one with deeply held convictions on both the ‘broad’ and ‘specific’ side with little sign of resolution. Recently, Thomas Ploug and Soren Holm have developed an alternative to both specific and broad consent: a meta‐consent framework. The aim here is to consider whether meta‐consent provides a ‘solution’ to the biobank consent debate. We clarify what ‘meta‐consent’ actually is (arguing that the label is a misnomer and ‘consent à la carte’ is more accurate). We identify problems with Ploug and Holm's arguments, and some challenges for meta‐consent. We focus on whether there is any ethical obligation to provide consent à la carte. There may seem to be so, especially if we draw upon an unclear appeal to the ethical significance of ‘respect for autonomy’. Similarly, there might seem to be an intuitive inference from the fact that ethically legitimate research requires informed consent to the conclusion that it thereby requires consent à la carte. It is shown that this line of inference is mistaken.
Changes in ostracod assemblages and morphologies during lake‐level variations of Lago Cardiel (49°S), Patagonia, Argentina, over the last 15.6 ka
Authors: Ramos Lorena , Alperin Marta , Schwalb Antje , Markgraf Vera , Ariztegui Daniel , Cusminsky Gabriela 
Published: January 2019

Changes in the ostracod assemblages from two sediment cores collected from Lago Cardiel in southeastern Patagonia (49°S) reflect the main regional abrupt climatic changes over the last 15.6 cal. kaBP. Shifts in species abundance and switches in dominances suggest that these were mainly driven by variable salinity. During the Late Pleistocene,Limnocythere rionegroensiswas abundant and dominant, indicating waters with high salinity and prevalence of evaporative processes. Between 12.6 and 10.8 cal. kaBP, Lago Cardiel expanded markedly and reached an Early Holocene highstand of +55 m above present lake level. A major change in ostracod assemblage in whichLimnocythere patagonicaappears as the dominant species in parallel with the disappearance ofL. rionegroensisandEucyprisaff.cecryphaliummirrored this transitional period between the cold and dry Late Pleistocene and the humid and warm Early Holocene. Over the last 4 cal. kaBP,L. rionegroensisreturned to the species assemblage andRiocypris whatleyiincreased its abundance pointing towards increasing salinities. The variations in size, shape and ornamentation ofL. rionegroensisandR. whatleyifossil valves were examined using geometric morphometric techniques and further compared to those of modern Patagonian sites.Limnocythere rionegroensisspecimens displayed high morphological variability during the evolution of Lago Cardiel. More specifically, the switch in reproductive mode – from sexual to parthenogenetic– and the increase in valve ornamentation around 12.7 cal. kaBPsuggest that these changes were promoted by the hydrological alteration that occurred in the Late Pleistocene. This exercise provides a robust range of morphological variation for these proxies, which will be useful in further taxonomic and palaeoenvironmental studies adding more information about different factors influencing the observed morphological trends.
Vegetation and climate during the penultimate interglacial of the northeastern Russian Arctic: the Lake El'gygytgyn pollen record
Authors: Zhao Wenwei , Andreev Andrei A. , Tarasov Pavel E. , Wennrich Volker , Melles Martin 
Published: January 2019

We present a high‐resolution reconstruction of the vegetation and climate dynamics during the penultimate interglacial, corresponding with Marine Isotope Stage (MIS) 7, based on detailed palynological analyses of lacustrine sediments from Lake El'gygytgyn, northeastern Siberia. The analysed sediments were deposited between 246 and 181 ka ago (late MIS 8 to early MIS 6.6). The interglacial vegetation was characterized by herb and shrub (mainly alder and birch) dominated plant communities. Pollen‐based biome reconstruction shows a dominance of the tundra (TUND) biome, thus indicating rather open vegetation. Warmer intervals (MIS 7.5, 7.3 and 7.1) were marked by an increase in the cold deciduous forest (CLDE) biome scores and a synchronous decrease in the cold steppe (STEP) biome scores. The thermal maximum occurred during MIS 7.1, as indicated by the highest CLDE biome scores occurring in this period, and lasted ~10 ka, possibly favoured by the high precession‐related summer insolation and the legacy of the preceding mild and dry stadial (MIS 7.2). In contrast, MIS 7.3 and 7.5 were characterized by shorter durations (~4 ka) and lower summer temperatures. The preceding cold glacial and stadial (MIS 8 and 7.4, respectively) might have led to an extensive distribution of permafrost that hindered vegetation development during the subsequent warm intervals. MIS 7.4 and 6.6 were cold and wet, probably triggered by low obliquity values and coevally low precession‐related summer insolation. As a result, these periods were marked by significantly reduced summer temperatures and an enhanced snow‐ice albedo feedback. The obtained reconstructions provide potential scenarios for future climate changes and allow a better understanding of the relationship between vegetation, climate and external/internal forcings in the high latitudes.
Maintenance of long remission in adult T‐cell leukemia by Tax‐targeted vaccine: A hope for disease‐preventive therapy
Authors: Kannagi Mari , Hasegawa Atsuhiko , Nagano Yoshiko , Iino Tadafumi , Okamura Jun , Suehiro Youko 
Published: January 2019

Adult T‐cell leukemia/lymphoma (ATL) is an aggressive lymphoproliferative disease caused by human T‐cell leukemia virus type 1 (HTLV‐1). Multi‐agent chemotherapy can reduce ATL cells but frequently allows relapses within a short period of time. Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) following chemotherapy is now a standard therapy for ATL in Japan as it can achieve long‐term remission in approximately one‐third of recipient ATL patients; however, it also has a risk of treatment‐related mortality. Allo‐HSCT often induces HTLV‐1 Tax‐specific cytotoxic T cells (CTL) as well as graft‐versus‐host (GVH) response in ATL patients. This observation led to development of a new therapeutic vaccine to activate Tax‐specific CTL, anticipating anti‐ATL effects without GVH response. The newly developed Tax‐DC vaccine consists of autologous dendritic cells pulsed with Tax peptides corresponding to CTL epitopes that have been identified in post‐allo‐HSCT ATL patients. In a pilot study of Tax‐DC therapy in three ATL patients after various initial therapies, two patients survived for more than 4 years after vaccination without severe adverse effects (UMIN000011423). The Tax‐DC vaccine is currently under phase I trial, showing a promising clinical outcome so far. These findings indicate the importance of patients’ own HTLV‐1‐specific T‐cell responses in maintaining remission and provide a new approach to anti‐ATL immunotherapy targeting Tax. Although Tax‐targeted vaccination is ineffective against Tax‐negative ATL cells, it can be a safe alternative maintenance therapy for Tax‐positive ATL and may be further applicable for treatment of indolent ATL or even prophylaxis of ATL development among HTLV‐1‐carriers.
Comparison of inducible nitric oxide synthase mRNA expression in different airway portions and association with nitric oxide parameters from patients with asthma
Authors: Sato Yoko , Chibana Kazuyuki , Horigane Yukiko , Uchida Nobuhiko , Masawa Meitetsu , Koike Ryosuke , Nakamura Yusuke , Watanabe Taiji , Shiobara Taichi , Arai Ryo , Shimizu Yasuo , Takemasa Akihiro , Ishii Yoshiki 
Published: January 2019

AbstractBackgroundFractional exhaled nitric oxide concentration (FeNO) is widely used to support diagnosis and monitoring of bronchial asthma (BA). Tsoukias and George proposed a two‐compartment model (2CM) for assessing the alveolar concentration of NO, referred to as CANO(2CM), while Condorelli et al proposed a model based on the trumpet shape of the airway tree and axial diffusion (TMAD), referred to as CANO(TMAD). In addition, Högman et al proposed non‐linear model, referred to as CANO(non‐linear).ObjectiveWe examined associations between the expression of inducible nitric oxide synthase (iNOS) mRNA in airway cells (ACs) by bronchoscopy and NO‐parameters calculated by the three methods and identified which of them accurately reflected expression of iNOS mRNA from different airway portions.MethodsWe retrospectively analysed data of 18 patients with stable, mild‐moderate asthma, including 10 steroid‐naïve BA (snBA) patients. Samples were obtained from airway brushings and bronchoalveolar lavage (BAL). Expressions of iNOS protein in tissue samples were evaluated by immunostaining. The iNOS mRNA in ACs was measured by qPCR. NO‐parameters calculated by the three methods above and evaluated whether they were associated with iNOS mRNA in ACs derived from proximal (2nd carina), distal (10‐15th) airways and alveolar regions.ResultsImmunostaining revealed expression of iNOS proteins mainly in epithelial cells in the airways, while it was mainly expressed in macrophages in the alveolar region in the snBA group. The iNOS mRNA expression was increased in both proximal and distal ACs in the snBA group compared with steroid‐treated BA group (stBA). CANO(2CM) negatively associated with FEV1 (%predicted) and also associated with iNOS mRNA in distal ACs significantly. However, CANO(TMAD) and CANO(non‐linear) showed no correlation with lung function nor iNOS mRNA expression in any portions of ACs.ConclusionsThese results suggested that CANO(2CM) reflected distal airway inflammation in steroid‐naïve asthma.
LncRNA Riken‐201 and Riken‐203 modulates neural development by regulating the Sox6 through sequestering miRNAs
Authors: Zhang Lei , Xue Zhenyu , Yan Jia , Wang Jie , Liu Qidong , Jiang Hong 
Published: January 2019

AbstractObjectivesLong non‐coding RNAs (LncRNAs) play important roles in epigenetic regulatory function during the development processes. In this study, we found that through alternative splicing, LncRNA C130071C03Riken variants Riken‐201 (Riken‐201) and Riken‐203 (Riken‐203) are both expressed highly in brain, and increase gradually during neural differentiation. However, the function of Rik‐201 and Rik‐203 is unknown.Materials and methodsEmbryonic stem cells (ESCs); RNA sequencing; gene expression of mRNAs, LncRNAs and miRNAs; over‐expression and RNA interference of genes; flow cytometry; real‐time quantity PCR; and Western blot were used in the studies. RNA pull‐down assay and PCR were employed to detect any miRNA that attached to Rik‐201 and Rik‐203. The binding of miRNA with mRNA of Sox6 was presented by the luciferase assay.ResultsRepression of Rik‐201 and Rik‐203 inhibited neural differentiation from mouse embryonic stem cells. Moreover, Rik‐201 and Rik‐203 functioned as the competing endogenous RNA (ceRNA) to repress the function of miR‐96 and miR‐467a‐3p, respectively, and modulate the expression of Sox6 to further regulate neural differentiation. Knockout of the Rik‐203 and Rik‐201 induced high ratio of brain developmental retardation. Further we found that C/EBPβ might potentially activated the transcription of Rik‐201 and Rik‐203.ConclusionsThese findings identify the functional role of Rik‐201 and Rik‐203 in facilitating neural differentiation and further brain development, and elucidate the underlying miRNAs‐Sox6‐associated molecular mechanisms.
Expression of p15 in a spectrum of spitzoid melanocytic neoplasms
Authors: Ma Sophia A. , O'Day Conor P. , Dentchev Tzvete , Takeshita Junko , Ridky Todd W. , Seykora John T. , Chu Emily Y. 
Published: January 2019

BackgroundAccurate classification of spitzoid melanocytic lesions is difficult due to overlapping clinical and histopathologic features between Spitz nevi, atypical Spitz tumors (ASTs), and spitzoid melanomas. Expression of p16 (CDKN2A) has been used as a marker of spitzoid lesions. However, its expression may be variable. p15 is a tumor suppressor encoded by CDKN2B, loss of which has been recently shown to promote transition from nevus to melanoma. We sought to determine whether p15 is a useful immunohistochemical marker to distinguish Spitz nevi from spitzoid melanomas and to compare p15 and p16 staining in this population.MethodsImmunohistochemistry for p15 and p16 was performed on Spitz nevi (n = 19), ASTs (n = 41), and spitzoid melanomas (n = 17). Immunoexpression was categorized by a four‐tiered system: 0 (negative), 1+ (weak), 2+ (moderate), 3+ (strong).Results3+/strong p15 staining was observed in 68.4% of Spitz nevi, 34.2% of ASTs, and 17.7% of spitzoid melanomas. By contrast, we observed 3+ p16 staining in roughly equivalent percentages of Spitz nevi (57.9%), ASTs (56.1%), and spitzoid melanomas (58.8%).ConclusionThese data illustrate that p15 may be more useful than p16 as a biomarker to help distinguish benign from malignant spitzoid lesions.
Geographical scale, industrial diversity, and regional economic stability
Authors: Chen Jing 
Published: January 2019

AbstractThis paper compares the empirical relationship between industrial diversity and economic stability across different geographical scales, including counties, states, Economic Areas, and Metropolitan Statistical Areas, in the contiguous U.S. between 2000 and 2014. It is found that this relationship varies greatly when it is analyzed across these four geographical scales. Meanwhile, several scale‐related problems, such as the modifiable areal unit problem and the small population problem, are introduced to economic diversity literature and further discussed with this variability of the diversity–stability relationship. This paper concludes that the spatial scale problem as well as the optimal unit can be study dependent. Thus, when choosing analytical units to quantify regional economic structure for a specific study, future research should pay attention to scale‐related problems.
The inverted appendix – a potentially problematic diagnosis: clinicopathologic analysis of 21 cases
Authors: Birkness Jacqueline , Lam‐Himlin Dora , Byrnes Kathleen , Wood Laura , Voltaggio Lysandra 
Published: January 2019

AimsInverted appendices are rare, but have the potential to cause diagnostic confusion among endoscopists and pathologists. The aim of this study was to describe the clinicopathological features of inverted appendices seen at our institution over the last 30 years.Methods and resultsTwenty‐one inverted appendices were identified and the clinical and pathological features reviewed. Patients were predominantly middle‐aged women. Most cases were detected incidentally on colonoscopy. Endoscopically, inverted appendices appeared polypoid in the proximal caecum. All resections featured associated pathological processes, including endometriosis (n = 3), inflammatory mucocoele (n = 1), low‐grade appendiceal mucinous neoplasm (n = 2), traditional serrated adenoma (n = 1) and inflammatory fibroid polyp (n = 1). Five cases were endoscopically mischaracterised as caecal polyps and removed via polypectomy; initial pathological impressions were erroneous in most cases. All polypectomies featured a dome‐like configuration covered by mucosa on the convex surface; the majority had aggregates of ganglion cells and neural plexi embedded in muscularis propria. The vast majority of cases, regardless of the procedure, showed lymphoid aggregates. Among post‐polypectomy patients with follow‐up, none experienced perforation‐associated morbidity despite the histological presence of muscularis propria.ConclusionsThe diagnosis of an inverted appendix should be considered in polypectomy specimens from the caecum or appendiceal orifice with (i) dome‐like tissue configuration covered by mucosa on the convex surface, (ii) a deep, robust smooth muscle component with ganglion cells (muscularis propria) and (iii) associated lymphoid aggregates. Prompt recognition on H&E will avoid unnecessary time and resource investment.
Comparison between gallium‐68 citrate positron emission tomography‐computed tomography and gallium‐67 citrate scintigraphy for infection imaging
Authors: Segard Tatiana , Morandeau Laurence M. J. A. , Dunne Marina L. , Robinson James O. , Murray Ronan J. , Geelhoed Elizabeth A. , Francis Roslyn J. 
Published: January 2019

AbstractBackgroundPreliminary studies have reported promising results for the utility of gallium‐68 (Ga‐68) citrate positron emission tomography‐computed tomography (PET–CT) for infection imaging. This technique offers reduced radiation dose to patients, shorter time between injection and imaging and reduced time for image acquisition compared to the ‘gold standard’ nuclear imaging technique: gallium‐67 (Ga‐67) citrate scintigraphy.AimsTo compare the two imaging modalities to ascertain whether Ga‐68 citrate PET–CT is of equivalent diagnostic efficacy for bone and joint infection or pyrexia of unknown origin (PUO) and to assess image quality and reporter confidence.MethodsPatients with PUO and suspected bone or joint infection underwent Ga‐67 citrate scintigraphy and Ga‐68 citrate PET–CT. Participants were followed up for 3 months to record subsequent treatment, investigations and outcome.Results60 patients were recruited to this multicentre prospective study: 32 for bone and joint infection, 28 for PUO. The results show a sensitivity of 81% for Ga‐67 citrate scintigraphy and 69% for Ga‐68 citrate PET–CT, a specificity of 79% for Ga‐67 citrate and 67% for Ga‐68 citrate and were concordant for 76% of the participants. The reporting physician confidence was significantly lower for Ga‐68 citrate (P < 0.05), frequently due to prominent physiologic blood pool activity adjacent to the site of infection.ConclusionThe sensitivity and specificity of Ga‐68 citrate PET–CT were found to be consistently lower than Ga‐67 citrate scintigraphy. Additionally, due to the insufficient level of confidence of the reporting physicians for the Ga‐68 citrate PET–CT, this modality could not currently be recommended to replace Ga‐67 citrate scintigraphy for routine clinical use.
Attenuation of interferon regulatory factor 7 activity in local infectious sites of trachea and lung for preventing the development of acute lung injury caused by influenza A virus
Authors: Yang Lei , Tu Liqun , Zhao Peiyan , Wang Ying , Wang Shengnan , Lu Wenting , Wang Yangyang , Li Xin , Yu Yongli , Hua Shucheng , Wang Liying 
Published: January 2019

SummaryThe excessive activation of interferon regulatory factor 7 (IRF7) promotes the development of acute lung injury (ALI) caused by influenza A virus (IAV). However, the deficiency of IRF7 increases the susceptibility to deadly IAV infection in both humans and mice. To test whether the attenuation rather than the abolishment of IRF7 activity in local infectious sites could alleviate IAV‐induced ALI, we established IAV‐infected mouse model and trachea/lung‐tissue culture systems, and designed two IRF7‐interfering oligodeoxynucleotides, IRF7‐rODN M1 and IRF7‐rODN A1, based on the mouse and human consensus sequences of IRF7‐binding sites of Ifna/IFNA genes, respectively. In the model mice, we found a close relationship between the IAV‐induced ALI and the level/activity of IRF7 in local infectious sites, and also found that the reduced IRF7 level or activity in the lungs of mice treated with IRF7‐rODN M1 led to decreased mRNA levels of Ifna genes, reduced neutrophil infiltration in the lungs and prolonged survival of mice. Furthermore, we found that the effects of IRF7‐rODN M1 on alleviating IAV‐induced ALI could be correlated to the reduced translocation of IRF7, caused by the IRF7‐rODN M1, from cytosol to nucleus in IAV‐infected cells. These data suggest that the proper attenuation of IRF7 activity in local infectious sites could be a novel approach for treating IAV‐induced ALI.
Feasibility and development of a cariogenic diet scale for epidemiological research
Authors: Amezdroz Emily , Carpenter Lauren , Johnson Shae , Flood Victoria , Dashper Stuart G. , Calache Hanny , Gussy Mark , Waters Elizabeth 
Published: January 2019

BackgroundDiet cariogenicity plays a major role as both a protective and risk factor in the development of early childhood caries (ECC).AimDevelop a scale measuring the cariogenicity of foods and beverages and employ it to describe the cariogenicity of young children's diets and predict dental caries outcomes.DesignScores of cariogenicity and consumption frequency were applied to food frequency questionnaire (FFQ) collected from an Australian children's cohort study with three time‐points of data. One‐way ANOVA, with post hoc Tukey test compared mean cariogenic scale measured at 18 months between the subsample of children with caries classification at age 5 years.ResultsAt 6 months, children's mean cariogenic score was 10.05, increasing to 34.18 at 12 and 50.00 at 18 months. Mean cariogenic scale score at 18 months was significantly higher in children with advanced disease at 5 years (mean scale score: 59.0 ± 15.9) compared to those that were healthy (mean score 47.7 ± 17.5, P = 0.007) or had mild‐moderate disease (mean score 48.2 ± 17.3, P = 0.008).ConclusionsThe cariogenic diet scale provides a useful indication of the increasing cariogenicity of children's diets with age and highlights the incorporation of discretionary choice foods and beverages into the diets of young children much earlier than nutritionally recommended.