bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of 3D printed mouthpieces for musical instruments
Authors: Bacciaglia Antonio , Ceruti Alessandro , Liverani Alfredo
Published: January 2020

Purpose

The purpose of this study is the evaluation of advantages and criticalities related to the application of addtive manufacturing (AM) to the production of parts for musical instruments. A comparison between traditional manufacturing and AM based on different aspects is carried out.

Design/methodology/approach

A set of mouthpieces produced through different AM techniques has been designed, manufactured and evaluated using an end-user satisfaction-oriented approach. A musician has been tasked to play the same classical music piece with different mouthpieces, and the sound has been recorded in a recording studio. The mouthpiece and sound characteristics have been evaluated in a structured methodology.

Findings

The quality of the sound and comfort of 3D printed mouthpieces can be similar to the traditional ones provided that an accurate design and proper materials and technologies are adopted. When personalization and economic issues are considered, AM is superior to mouthpieces produced by traditional techniques.

Research limitations/implications

In this research, a mouthpiece for trombone has been investigated. However, a wider analysis where several musical instruments and related parts are evaluated could provide more data.

Practical implications

The production of mouthpieces with AM techniques is suggested owing to the advantages which can be tackled in terms of customization, manufacturing cost and time reduction.

Originality/value

This research is carried out using a multidisciplinary approach where several data have been considered to evaluate the end user satisfaction of 3D printed mouthpieces.
A case of the blues: depression screenings in a community pharmacy
Authors: Mazzei Matthew J. , Galdo John A.
Published: January 2020

Theoretical basis

This case builds on elements of project management (PM) – specifically project initiation – including the development of a project charter and stakeholder analysis.

Research methodology

The case was developed from secondary sources as well as first-hand knowledge of the project by one of the authors. This author was on faculty at a private university in the southeastern USA, teaching numerous courses in the pharmacy curriculum while also serving as the Community Practice Residency Director for community pharmacies around the state. While connecting with these organizations, additional revenue requirements and complementary services were frequent topics of attention, leading to a grant to assist pharmacies in building out such services. Through this grant, the author engaged in consultations with community pharmacies around the state, including the pharmacy highlighted via this case. Pseudonyms have been used for the business, and all individuals associated with it, to maintain anonymity. Secondary sources used for additional research include industry reports and related websites.

Case overview/synopsis

Richard has owned and operated a community pharmacy, Our Family Farmacy (OFF), for years. A changing industry climate has forced Richard to diversify the products and services he provides. In addition to the distribution of medicine and front-end sales of consumer goods, Richard is seeking to expand into a larger spectrum of healthcare services. After researching several different types of services, and after dealing with related personal family circumstances, Richard decided that OFF should begin their expansion by offering depression screening services. He turned initiation of the project over to his pharmacy intern, Caitlin.

Complexity academic level

This compact case is geared toward undergraduate- and graduate-level students taking courses in general management and, more specifically, PM. This case might also be used by students with a career focus in the healthcare sector, and could of particular interest for students in a pharmacy program. Classroom application should encompass discussions on the project initiation process group, particularly with the processes regarding the project charter deliverable and the identification and assessment of project stakeholders.
Primary cutaneous γδ T‐cell lymphoma with unusual immunophenotype: A case report and review of published work
Authors: Kamijo Hiroaki , Miyagaki Tomomitsu , Norimatsu Yurie , Awaji Kentaro , Oka Tomonori , Suga Hiraku , Sugaya Makoto , Sato Shinichi
Published: January 2020

Primary cutaneous γδ T‐cell lymphoma (CGD‐TCL) is a rare form of primary cutaneous lymphoma. The histopathological features of CGD‐TCL are still unclear because of its rarity. Here, we report a case of a 77‐year‐old Japanese man who presented with a 9‐month history of erythematous plaques on his left forearm. Skin biopsy specimens revealed the infiltration of atypical medium/large‐sized lymphocytes from the epidermis to the deep dermis. Atypical lymphocytes were positive for CD3, CD5, CD8 and Vδ1, and negative for CD4, CD7, CD56, EBER‐ISH, intracellular antigen‐1, granzyme B and perforin. CD30 was partially expressed. We also reviewed 246 cases of CGD‐TCL from the published work. CD4−CD8− double‐negative cases were 113 of 196 cases (57.6%), followed by CD4−CD8+ cases (52/196, 26.5%). CD5 was expressed in 25.8% of the cases (34/132). At least one cytotoxic molecule marker was expressed in 150 of 160 cases (93.8%). Some cases showed an indolent clinical course, especially in mycosis fungoides‐like CGD‐TCL cases. CD5 positivity and lack of cytotoxic molecule expression could be associated with a better prognosis. In addition, CD30 expression was found in approximately half of CGD‐TCL cases (51/112 cases), suggesting that brentuximab vedotin could be a good treatment option for such patients. Further studies with more cases with detailed clinical and pathological information are necessary to elucidate the etiology and prognostic markers of this entity.
Incorporating known petrophysical model in the seismic full‐waveform inversion using the Gramian constraint
Authors: Malovichko M. , Khokhlov N. , Yavich N. , Zhdanov M. S.
Published: January 2020

In this paper, we develop a general approach to integrating petrophysical models in three‐dimensional seismic full‐waveform inversion based on the Gramian constraints. In the framework of this approach, we present an example of the frequency‐domain P‐wave velocity inversion guided by an electrical conductivity model. In order to introduce a coupling between the two models, we minimize the corresponding Gramian functional, which is included in the Tikhonov parametric functional. We demonstrate that in the case of a single‐physics inversion guided by a model of different physical type, the general expressions of the Gramian functional and its gradients become simple and easy to program. We also prove that the Gramian functional has a non‐negative quadratic form, so it can be easily incorporated in a standard gradient‐based minimization scheme. The developed new approach of seismic inversion guided by the known petrophysical model has been validated by three‐dimensional inversion of synthetic seismic data generated for a realistic three‐dimensional model of the subsurface.
Functional traits that moderate tropical tree recruitment during post‐windstorm secondary succession
Authors: Lai Hao Ran , Chong Kwek Yan , Yee Alex Thiam Koon , Tan Hugh Tiang Wah , van Breugel Michiel
Published: January 2020

Understanding how functional traits moderate species’ demographic responses along environmental gradients is a core pursuit in ecology, often to predict how species abundances will respond to a rapidly changing environment. The latter necessitates species demography, or at least abundance, to be modelled directly as a response; yet, most studies till date use abundance indirectly to calculate and then correlate community‐aggregated trait indices to environmental variables, rendering the prediction of species demographic responses along environmental gradients unfeasible.

Using a hierarchical Bayesian approach that stems from joint species distribution modelling, we modelled the recruitments of 53 woody plant species along windstorm‐generated environmental gradients from twenty‐eight 100‐m2 tropical secondary forest plots censused over 5 years in Singapore, and then examined whether environmental responses across species can be explained and generalized by functional traits.

We found that species recruitment along the light‐availability gradient was moderated by wood density, in that low wood‐density species responded more positively to elevated light conditions by being more responsive in height growth. Seed mass moderated species recruitment along the leaf litter depth gradient, such that large‐seeded species with greater energy reserves recruited more in sites with thicker leaf litter depths than small‐seeded species. Shorter‐ and taller‐statured species recruited more in historically short‐ and tall‐canopied forest sites, respectively, indicating an influence from surrounding parent trees and the importance of considering dispersal limitation in successional studies. Leaf economic traits (specific leaf area, leaf dry‐matter content and lamina thickness) did not moderate recruitment responses across environments, suggesting a weak role of leaf traits during the earlier life stages or their high plasticity.

Synthesis. Wood density, seed mass and adult stature are the main traits that moderate sapling recruitment in our wind‐generated forest gaps. The roles of multiple traits in moderating the shared environmental responses across species may be crucial in the maintenance of coexistence and diversity through niche partitioning. Most importantly, we estimated the strength and direction of trait effects on species responses to environmental changes during succession. These are potentially generalizable results that can directly predict the demographic responses of any species—given its traits—to environmental changes.
Catabolism of biogenic amines in Pseudomonas species
Authors: Luengo José M. , Olivera Elías R.
Published: January 2020

Biogenic amines (BAs; 2‐phenylethylamine, tyramine, dopamine, epinephrine, norepinephrine, octopamine, histamine, tryptamine, serotonin, agmatine, cadaverine, putrescine, spermidine, spermine and certain aliphatic amines) are widely distributed organic molecules that play basic physiological functions in animals, plants and microorganisms. Pseudomonas species can grow in media containing different BAs as carbon and energy sources, a reason why these bacteria are excellent models for studying such catabolic pathways. In this review, we analyse most of the routes used by different species of Pseudomonas (P. putida, P. aeruginosa, P. entomophila and P. fluorescens) to degrade BAs. Analysis of these pathways has led to the identification of a huge number of genes, catabolic enzymes, transport systems and regulators, as well as to understanding of their hierarchy and functional evolution. Knowledge of these pathways has allowed the design and collection of genetically manipulated microbes useful for eliminating BAs from different sources, highlighting the biotechnological applications of these studies.
Monitoring the effects of land transformation on African clawless otters (Aonyx capensis) using fecal glucocorticoid metabolite concentrations as a measure of stress
Authors: MAJELANTLE Tshepiso L. , MCINTYRE Trevor , GANSWINDT Andre
Published: January 2020

In a time of increasing environmental change caused by anthropogenic disturbance, there is a greater need to understand animal adaptations to manmade environments. In this regard, the measurement of stress‐related endocrine markers provides a useful tool to examine the impact of environmental challenges and the physiological consequences for wildlife occupying such space. The aims of the present study were to validate fecal glucocorticoid metabolite (fGCM) concentrations as a measure of stress using samples from a male African clawless otter (Aonyx capensis; n = 1) and to compare fGCM concentrations of otters occurring in a transformed and in 2 natural areas in South Africa. From the 5 different enzyme‐immunoassays (EIA) tested, a cortisol and oxoetiocholanolone (measuring 11,17 dioxoandrostanes) EIA revealed the highest response (74% and 48% increase, respectively) 30 and 24 hours after a stress event (translocation of a captive individual as part of its rehabilitation prior to release), respectively. For both EIAs, fGCM concentrations were comparable for samples collected up to 3 h post‐defecation. Using the cortisol EIA for subsequent analyses, fGCM concentrations of animals from the transformed area (n = 20; mean [± SD]: 0.468 [± 0.539] µg/g dry weight [DW]) were significantly higher (P = 0.013) than those from otters in the natural areas (n = 17; 0.242 [± 0.226] µg/g DW). These preliminary results suggest that African clawless otters may have increased adrenocortical activity that could be due to conditions linked to living in a transformed environment.
Exquisite structure of the lateral line system in eyeless cavefish Sinocyclocheilus tianlinensis contrast to eyed Sinocyclocheilus macrophthalmus (Cypriniformes: Cyprinidae)
Authors: MA Zhiqiang , HERZOG Hendrik , JIANG Yonggang , ZHAO Yahui , ZHANG Deyuan
Published: January 2020

In this study, the lateral line systems in Chinese cavefish eyeless Sinocyclocheilus tianlinensis and eyed Sinocyclocheilus macrophthalmus were investigated to reveal their morphological changes to survive in harsh environments. Compared with the eyed cavefish S. macrophthalmus (atypical), the lateral line system in the eyeless cavefish S. tianlinensis (typical) has certain features to adapt to the dark cave environments: the superficial lateral line system in the eyeless species possesses a higher number of superficial neuromasts and more hair cells within an individual neuromast, and the trunk lateral line canal system in S. tianlinensis exhibits larger canal pores, higher canal diameter and more pronounced constrictions. Fluid–structure interaction analysis suggested that the trunk lateral line canal system in the eyeless S. tianlinensis should be more sensitive than that in the eyed S. macrophthalmus. These morphological features of the lateral line system in the eyeless S. tianlinensis probably enhance the functioning of the lateral line system and compensate for the lack of eyes. The revelation of the form–function relationship in the cavefish lateral line system provides inspiration for the design of sensitive artificial flow sensors.
A Long View of Southern California Water Supply: Perfect Droughts Revisited
Authors: Woodhouse C.A. , Meko D.M. , Bigio E.R.
Published: January 2020

The impact of drought on water resources in arid and semiarid regions can be buffered by water supplies from different source regions. Simultaneous drought in all major source regions — or perfect drought — poses the most serious challenge to water management. We examine perfect droughts relevant to Southern California (SoCal) water resources with instrumental records and tree‐ring reconstructions for the Sacramento and Colorado Rivers, and SoCal. Perfect droughts have occurred five times since 1906, lasting two to three years, except for the most recent event, 2012–2015. This number and duration of perfect droughts is not unusual in the context of the past six centuries. The modern period stands out for the relatively even distribution of perfect droughts and lacks the clusters of perfect drought documented in prior centuries. In comparison, perfect droughts of the 12th Century were both longer (up to nine years) and more widespread. Perfect droughts of the 20th and 21st Centuries have occurred under different oceanic/atmospheric patterns, zonal and meridional flow, and ENSO or non‐ENSO conditions. Multidecadal coherence across the three regions exists, but it has varied over the past six centuries, resulting in irregular intervals of perfect drought. Although the causes of perfect droughts are not clear, given the long‐term natural variability along with projected changes in climate, it is reasonable to expect more frequent and longer perfect droughts in the future.
Estimating the Frequency and Extent of Overbank Flow of a Baseflow‐Dominated Stream Flowing through a Wetland
Authors: Potter Kenneth W. , Boyington T. Matthew
Published: January 2020

River floodplains provide critical habitat for a wide range of animal and plant species and reduce phosphorus and nitrogen loads in streams. It has been observed that baseflow‐dominated streams flowing through wetlands are commonly at or near bankfull and overflow their banks much more frequently than other streams. However, there is very little published quantitative support for this observation. The study focuses on a 1‐km reach of Black Earth Creek, a stream in the Midwestern United States (U.S.). We used one‐dimensional hydraulic modeling to estimate bankfull discharge at evenly spaced stream cross sections, and two‐dimensional modeling to quantitate the extent of wetland inundation as a function of discharge. We then used historical streamflow data from two U.S. Geological Survey gaging stations to quantitate the frequency of wetland inundation. For the with‐sediment case, the frequency of overbank conditions at the 38 cross sections in the wetland ranged from 3 to 85 days per year and averaged 43 days per year. Ten percent of the wetland was inundated for an average of 35 days per year. For the without‐sediment case, the frequency of overbank conditions ranged from 2.6 to 48 days per year and averaged 14 days per year. Also, 10% of the wetland was inundated for an average of 25 days per year. These unusually high rates of floodplain inundation are likely due in part to the very low stream gradient and shallow depths of overbank flow.
Targeted genotyping to identify potential functional variants associated with cholesterol content in bovine milk
Authors: Do D. N. , Schenkel F. , Miglior F. , Zhao X. , Ibeagha‐Awemu E. M.
Published: January 2020

High blood cholesterol concentration, mainly caused by high dietary cholesterol, is a potential risk factor for human health. Dairy products are important sources of human dietary cholesterol intake. Therefore, monitoring bovine milk cholesterol concentration is important for human health benefit. Genetic selection for improvement of cow milk cholesterol content requires understanding of the genetics of milk cholesterol. For this purpose, we performed analyses of additive and dominance effects of 126 potentially functional SNPs within 43 candidate genes with milk cholesterol content [expressed as mg of cholesterol in 100 g of fat (CHL_fat) or in 100 mg of milk (CHL_milk)]. The additive and dominance effects of SNPs rs380643365 in AGPAT1 (P = 0.04) and rs134357240 in SOAT1 (P = 0.035) genes associated significantly with CHL_fat. Moreover, five (rs109326954 and rs523413537 in DGAT1, rs109376747 in LDLR, rs42781651 in FAM198B and rs109967779 in ACAT2) and four (rs137347384 in RBM19, rs109376747 in LDLR, rs42016945 in PPARG and rs110862179 in SCAP) SNPs were significantly associated with CHL_milk (P < 0.05) based on additive and dominance effect analyses respectively. Rs109326954 and rs523413537 in DGAT1 explained a considerable portion of the phenotypic variance of CHL_milk (7.54 and 6.84% respectively), and might be useful in selection programs for reduced milk cholesterol content. Several significantly associated SNPs were in genes (such as ACAT2 and LDLR) involved in cholesterol metabolism in the liver or cholesterol transport, suggesting multiple mechanisms regulating milk cholesterol content. Nine and seven SNPs identified by additive or dominance effect analyses associated significantly with milk yield and fat yield respectively. Further analyses are required to better understand the consequences of these variants and their potential use in genomic selection of the studied traits.
Safety, tolerability, pharmacokinetics and pharmacodynamics of parenterally administered dutogliptin: A prospective dose‐escalating trial
Authors: Buchtele Nina , Schwameis Michael , Schoergenhofer Christian , Derhaschnig Ulla , Firbas Christa , Karch Rudolf , Nix Darrell , Schenk Roman , Jilma Bernd
Published: January 2020

Aims

Animal studies suggest that inhibition of dipeptidyl peptidase 4 (DPP‐IV) may improve heart function and survival after myocardial infarction by increasing cardiac myocytes’ regenerative capacity. Parenterally administered dutogliptin may provide continuous strong DPP‐IV inhibition to translate these results into humans. This trial investigated the safety and tolerability, as well as pharmacokinetics and pharmacodynamics, of parenterally administered dutogliptin after single and repeated doses.

Methods

In an open‐label trial, volunteers received dutogliptin at increasing doses of 30–120 mg subcutaneously or 30 mg intravenously in the single‐dose cohorts. Subjects in the multiple‐dose cohort received 60, 90 or 120 mg dutogliptin subcutaneously once daily on 7 consecutive days.

Results

Forty healthy males were included in the trial. No related serious adverse events occurred. Mild local injection site reactions with no requirement for intervention comprised 147 of 153 (96%) related adverse events. Subcutaneous bioavailability was approximately 100%. Multiple injections at daily intervals did not lead to the accumulation of the study drug. The accumulation ratios based on AUC0‐24h range from 0.90 to 1.03, supporting this argument. All subjects receiving ≥60 mg dutogliptin yielded a maximum DPP‐IV inhibition >90%. The duration of DPP‐IV inhibition over time increased in a dose‐dependent manner and was highest in the 120‐mg multiple‐dosing cohort with a maximum AUEC0‐24h of 342 h % (standard deviation: 73), translating into 86% DPP‐IV inhibition 24 hours after dosing.

Conclusion

Parenteral injection of dutogliptin was safe and subcutaneous bioavailability is excellent. DPP‐IV inhibition increased dose dependently to >86% over 24 hours after multiple doses of 120 mg dutogliptin.
Modelling inter‐individual differences in latent within‐person variation: The confirmatory factor level variability model
Authors: Nestler Steffen
Published: January 2020

Psychological theories often produce hypotheses that pertain to individual differences in within‐person variability. To empirically test the predictions entailed by such hypotheses with longitudinal data, researchers often use multilevel approaches that allow them to model between‐person differences in the mean level of a certain variableandthe residual within‐person variance. Currently, these approaches can be applied only when the data stem from asinglevariable. However, it is common practice in psychology to assess not just a single measure but ratherseveralmeasures of a construct. In this paper we describe a model in which we combine the single‐indicator model with confirmatory factor analysis. The new model allows individual differences in latent mean‐level factors and latent within‐person variability factors to be estimated. Furthermore, we show how the model's parameters can be estimated with a maximum likelihood estimator, and we illustrate the approach using an example that involves intensive longitudinal data.
Claspin overexpression is associated with high‐grade histology and poor prognosis in renal cell carcinoma
Authors: Kobayashi Go , Sentani Kazuhiro , Babasaki Takashi , Sekino Yohei , Shigematsu Yoshinori , Hayashi Tetsutaro , Oue Naohide , Teishima Jun , Matsubara Akio , Sasaki Naomi , Yasui Wataru
Published: January 2020

Renal cell carcinoma (RCC) is one of the most common human cancers. We previously reported that claspin is a key regulator in the progression of gastric cancer, and it likely plays an important role in cancer stem cells of gastric cancer. However, the significance of claspin in RCC has not been examined. First, we analyzed the expression and distribution of claspin in 95 RCC cases by immunohistochemistry. In the nonneoplastic kidney, the staining of claspin was either weak or absent, whereas RCC tissue showed nuclear staining. In total, claspin expression was detected in 45 (47%) of 95 RCC cases. The claspin staining appeared relatively stronger in high nuclear grade RCC than in low nuclear grade RCC. Claspin‐positive RCC cases were associated with higher T grade, tumor stage, nuclear grade, vein invasion, and poorer prognosis. CLSPN siRNA treatment decreased RCC cell proliferation. The levels of phosphorylated Erk and Akt were lower in CLSPN siRNA‐transfected RCC cells than in control cells. In addition, claspin was coexpressed with CD44, epidermal growth factor receptor, p53, and programmed death ligand‐1. These results suggest that claspin plays an important role in tumor progression in RCC and might be a prognostic marker and novel therapeutic target molecule.
Mitochondrial DNA pathogenic mutations in multiple symmetric lipomatosis
Authors: López‐Gallardo Ester , Cammarata‐Scalisi Francisco , Emperador Sonia , Hernández‐Ainsa Carmen , Habbane Mouna , Vela‐Sebastián Ana , Bayona‐Bafaluy María Pilar , Montoya Julio , Ruiz‐Pesini Eduardo
Published: January 2020

The frequency of dermatological manifestations in diseases due to mitochondrial DNA mutations is not well known, although multiple symmetric lipomatosis has been repeatedly associated to mitochondrial DNA mutations. Here, we present a patient suffering from multiple symmetric lipomatosis and other skin signs. We found a new mitochondrial DNA mutation, m.8357T>C, in the tRNALys‐coding gene and, using a cybrid approach, confirmed its pathogenicity. A meta‐analysis of the dermatological signs of the patient shows that they are not common in patients with confirmed mitochondrial DNA mutations and suggests that, in these cases, lipomatosis is not related to the oxidative phosphorylation dysfunction, but to an alteration of an additional function associated to particular mitochondrial tRNAs.
Governance principles for community‐centered conservation in the post‐2020 global biodiversity framework
Authors: Armitage Derek , Mbatha Philile , Muhl Ella‐Kari , Rice Wayne , Sowman Merle
Published: January 2020

Strategies to protect biodiversity in the face of a global crisis must be place‐based and sensitive to context. A failure to consider the socioeconomic and political circumstances, as well as wellbeing needs and lived realities of those most directly reliant upon biodiversity will further undermine progress on Aichi targets and subsequent goals for the post‐2020 framework. How communities experience the benefits or costs of conservation action is influenced in large measure by the principles that guide conservation governance, and the subsequent institutional structures and processes that frame conservation action (at local to global scales). In this article, we define and critically reflect on core principles of community‐centered conservation governance needed to yield desirable and long‐term conservation outcomes—both ecological and social (i.e., equitable and just). In doing so, we emphasize a conception of community‐centered conservation that we argue is relevant to guide implementation of a post‐2020 biodiversity framework, and which is based on a foundation of well‐established evidence. Core principles of community‐centered conservation governance include: (a) building multilevel networks and collaborative relationships needed to coproduce conservation solutions; (b) promoting equity and recognizing the central role of women as agents of positive change in conservation efforts across scales; (c) reframing conservation action through the lens of reconciliation and redress (e.g., responding to injustices from land grabs and territorial enclosures); (d) ensuring a rights‐based approach to conservation action in which community agency, access and decision making autonomy are supported; and (e) revitalizing the customary and local institutions that provide legitimate and adaptive strategies for the stewardship of biodiversity.
Diagnostic performance of endoscopic ultrasound through‐the‐needle microforceps biopsy of pancreatic cystic lesions: Systematic review with meta‐analysis
Authors: Tacelli Matteo , Celsa Ciro , Magro Bianca , Barchiesi Marco , Barresi Luca , Capurso Gabriele , Arcidiacono Paolo Giorgio , Cammà Calogero , Crinò Stefano Francesco
Published: January 2020

Objectives

Endoscopic ultrasound through‐the‐needle biopsy (EUS‐TTNB) is a useful tool for differential diagnosis among pancreatic cystic lesions (PCLs). Cystic fluid cytology (CFC) is recommended by guidelines, but its diagnostic accuracy is about 50%. The aim of this meta‐analysis is to assess the clinical impact of EUS‐TTNB in terms of technical success (TS), histological accuracy (HA) and diagnostic yield (DY).

Methods

Original studies in English language on EUS‐TTNB were searched in MEDLINE and EMBASE until October 2019. Diagnostic accuracy of EUS‐TTNB for identification of mucinous PCLs was calculated using individual diagnostic data of patients who underwent CFC and surgery.

Results

Nine studies, including 454 patients who underwent EUS‐TTNB, met the inclusion criteria for the meta‐analysis. TS and HA of EUS‐TTNB were, respectively, 98.5% (95% Confidence Interval [CI] 97.3%–99.6%) and 86.7% (95%CI 80.1–93.4). DY was 69.5% (95%CI 59.2–79.7) for EUS‐TTNB and 28.7% (95%CI 15.7–41.6) for CFC. Heterogeneity persisted significantly high in most of subgroup analyses. In the multivariate meta‐regression, cyst size was independently associated with higher DY. Sensitivity and specificity for mucinous PCLs were 88.6 and 94.7% for EUS‐TTNB, and 40 and 100% for CFC. Adverse events rate was 8.6% (95%CI 4.0–13.1).

Conclusions

This meta‐analysis shows that EUS‐TTNB is a feasible technique that allows a high rate of adequate specimens to be obtained for histology; in about two‐thirds of patients a specific histotype diagnosis could be assessed. The number of adverse events is slightly higher respect to standard EUS‐FNA, but complications are very rarely severe.
PFKFB4 negatively regulated the expression of histone acetyltransferase GCN5 to mediate the tumorigenesis of thyroid cancer
Authors: Lu Huanquan , Chen Siyuan , You Zhijian , Xie Chuping , Huang Shichuan , Hu Xiarong
Published: January 2020

Thyroid cancer (TC) is the most common malignant endocrine tumor, and its incidence has progressively increased over several decades. Accumulating evidence has suggested that PFKFB4, a critical regulatory enzyme of glycolysis, has been implicated in various solid cancers. However, the exact effect of PFKFB4 on TC remains unclear. Hence, the objective of this work was to investigate the role of PFKFB4 in TC and explore the underlying regulatory mechanisms. Here, we provide evidence that mRNA levels of PFKFB4 were upregulated in TC patients’ thyroids and cell lines. Downregulation of PFKFB4 reduced TC cell viability and inhibited colony formation. In addition, the migration and invasion of TC cells were suppressed by PFKFB4 knockdown, suggesting that PFKFB4 is positively correlated with tumorigenesis of TC. Molecularly, knockdown of PFKFB4 significantly inhibited expression of GCN5 and phosphorylation of PI3K/AKT. Moreover, the suppressive role of shPFKFB4 in TC cell growth was reversed by upregulation of GCN5. Finally, the in vivo experiment indicated that downregulation of PFKF4B suppressed tumor growth in xenografts TC model mice. In total, our results suggested that PFKFB4‐mediated TC tumorigenesis by positively regulating GCN5 and PI3K/AKT signaling. These findings provide new research directions and therapeutic options considering PFKF4B as a novel diagnosis marker and therapeutic target.
State of the art: understanding and integration of the social context in diabetes care
Authors: de Wit M. , Trief P. M. , Huber J. W. , Willaing I.
Published: January 2020

We review the past 25 years of research addressing challenges people living with diabetes experience in their daily lives related to social contexts, i.e. in their family, at work and in society at large, and identify research gaps. We found that young people with diabetes, as they develop through to adulthood, are exposed to considerable risks to their physical and mental health. Family‐system interventions have had mixed outcomes. Research in this area would benefit from attention to ethnic/cultural diversity, and involving fathers and other family members. In adults with diabetes, social support relates to better diabetes outcomes. While family member involvement in care is likely to affect health and psychosocial outcomes of the person with diabetes, key elements and mediators of effective family interventions need to be identified. The challenges of diabetes management at work are under‐researched; distress and intentional hyperglycaemia are common. When depression is comorbid with diabetes, there are increased work‐related risks, e.g. unemployment, sickness absence and reduced income. Research to support people with diabetes at work should involve colleagues and employers to raise awareness and create supportive environments. Stigma and discrimination have been found to be more common than previously acknowledged, affecting self‐care, well‐being and access to health services. Guidance on stigma‐reducing choice of language has been published recently. Resilience, defined as successful adaptation to adversity such as stigma and discrimination, requires studies relevant to the specific challenges of diabetes, whether at diagnosis or subsequently. The importance of the social context for living well with diabetes is now fully recognized, but understanding of many of the challenges, whether at home or work, is still limited, with much work needed to develop successful interventions.
The limiting factor: energy, growth, and divergence, 1820–1913
Authors: Malanima Paolo
Published: January 2020

On the basis of a new series on the consumption of traditional and modern sources of energy between 1820 and 1913, this article addresses the start of modern growth and the great divergence on the world scale. Since the beginning of the nineteenth century, the greater availability of modern energy sources expanded working capacity well beyond the potential of previous agricultural civilizations. Growth of energy consumption rose primarily in western Europe, northern America, and Oceania. As a result, labour productivity rose, leading to an increase in real wages, which was an incentive to replace labour with mechanical engines. The higher energy consumption in these three macro‐areas led to global inequality in productive capacity and technology which peaked on the eve of the First World War.
Sensitivity of primary production to precipitation across the United States
Authors: Maurer Gregory E. , Hallmark Alesia J. , Brown Renée F. , Sala Osvaldo E. , Collins Scott L.
Published: January 2020

Primary production, a key regulator of the global carbon cycle, is highly responsive to variations in climate. Yet, a detailed, continental‐scale risk assessment of climate‐related impacts on primary production is lacking. We combined 16 years of MODIS NDVI data, a remotely sensed proxy for primary production, with observations from 1218 climate stations to derive values of ecosystem sensitivity to precipitation and aridity. For the first time, we produced an empirically‐derived map of ecosystem sensitivity to climate across the conterminous United States. Over this 16‐year period, annual primary production values were most sensitive to precipitation and aridity in dryland and grassland ecosystems. Century‐long trends measured at the climate stations showed intensifying aridity and climatic variability in many of these sensitive regions. Dryland ecosystems in the western US may be particularly vulnerable to reductions in primary production and consequent degradation of ecosystem services as climate change and variability increase in the future.
Off‐label use of midazolam in older inpatients: analysis of prescribing practices in a French hospital (MIDnight study)
Authors: Michelon Hugues , Pons‐Peyneau Cécile , Gourdon Mathilde , Le Dastumer Bruno , Teillet Laurent , Herr Marie
Published: January 2020

Midazolam is a short‐acting benzodiazepine approved for sedation and anesthesia induction. Recent data suggested that midazolam may also be used in off‐label indications such as treatment of behavioral and psychological disturbances in older people. Given the scarcity of published data and a lack of evidence in older people in such indications, midazolam raises concern because it may also cause serious‐related adverse events. To provide a better understanding of its real‐life use in geriatrics, we examined the prescribing practices of midazolam in French older inpatients. Of the 460 patients aged 65 years and over hospitalized at the time of the study, 21 had a prescription of midazolam (5%) which was mainly prescribed for anxiolysis (n = 12), premedication before painful procedures (n = 5), and agitation (n = 4). Midazolam was often prescribed “as required,” and the median duration of prescription was 6 months. This work results in a better knowledge and information about the use of midazolam in older people. These prescribing practices, which are not anecdotal, also plead for age‐specific guidelines for the treatment of behavioral and psychological disturbances.
Drug‐induced hearing loss: a case/non‐case study in the French pharmacovigilance database
Authors: Favrelière Sylvie , Delaunay Paul , Lebreton Jean‐Pascal , Rouby Franck , Atzenhoffer Martine , Lafay‐Chebassier Claire , Pérault‐Pochat Marie Christine
Published: January 2020

Hearing loss is defined as a decrease in the ability to perceive sounds which can occur suddenly or gradually and affects one ear or both. It is related to various etiologies, in particular drugs. The identification of all drugs that could be associated with hearing loss is essential for the patients' life quality. The objective of our study was to identify signals of hearing loss involving drugs approved in the last 20 years. The occurrence in association with drugs known for their ototoxicity was also analyzed. We used a case/non‐case method in the French Pharmacovigilance Database (FPVD). The cases were reports of hearing loss in the FPVD between January 2007 and August 2017. Non‐cases were all reports over the same period. We calculated the reporting odds ratio (ROR) with 95% confidence intervals. Among the 555 reports of hearing loss, significant RORs were found for 68 drugs. The main therapeutic classes implicated were antineoplastic agents (n = 240), systemic anti‐infective agents (n = 182), immunosuppressants (n = 42) loop diuretics (n = 26), and salicylate analgesics (n = 26). We found signals of hearing loss with azacitidine, vaccines and nevirapine, immunosuppressants such as leflunomide, and biotherapies such as panitumumab and vandetanib. Prescribers should be informed about the potential associations with all these drugs. The role of the pathology itself and the known ototoxic drugs that can be associated do not allow to conclude definitively. Audiograms for the early detection of hearing loss induced by drugs known to be ototoxic are rarely carried out. Preventive treatments exist and must be considered.
Experimental fracture investigation of CNT/epoxy nanocomposite under mixed mode II/III loading conditions
Authors: Karami Javane , Ayatollahi Majid Reza , Saboori Behnam
Published: January 2020

For the first time, the brittle fracture of epoxy‐based nanocomposite reinforced with MWCNTs (multi‐walled carbon nanotubes) and subjected to mixed mode II/III loading conditions is investigated. This experimental investigation is carried out using a newly developed test configuration. Araldite LY 5052 epoxy, which is a resin frequently used in aerospace industry, is utilized to fabricate pure epoxy and nanocomposite test specimens with two different MWCNTs contents of 0.1 and 0.5 wt%. The obtained experimental results reveal that adding MWCNTs to epoxy resin up to 0.5 wt% improves the fracture toughness under pure mode II and pure mode III loading with an increasing trend. This is while the improvement under mixed mode II/III loading is reduced by adding nanotubes more than 0.1 wt%. To justify the variations of fracture toughness in terms of nanoparticles content, SEM (scanning electron microscopy) photographs of the fracture surfaces of the specimens in the vicinity of the initial crack front are prepared. Additional fracture mechanisms caused by adding carbon nanotubes are discussed in detail based on the provided SEM images.
Positive biotic interactions in freshwaters: A review and research directive
Authors: Silknetter Samuel , Creed Robert P. , Brown Bryan L. , Frimpong Emmanuel A. , Skelton James , Peoples Brandon K.
Published: January 2020

Positive interspecific interactions such as mutualism, commensalism, and facilitation are globally ubiquitous. Although research on positive interactions in terrestrial and marine systems has progressed over the past few decades, comparatively little is known about them in freshwater ecosystems. However, recent advances have brought the study of positive interactions in freshwater systems to a point where synthesis is warranted.

In this review, we catalogue the variety of direct positive interactions described to date in freshwater ecosystems, discuss factors that could influence prevalence and impact of these interactions, and provide a framework for future research.

In positive interactions, organisms exchange key resources such as nutrients, protection, transportation, or habitat to a net benefit for at least one participant. A few mutualistic relationships have received research attention to date, namely seed‐dispersing fishes, crayfishes and their ectosymbiotic cleaners, and communal‐spawning stream fishes. Similarly, only a handful of commensalisms have been studied, primarily phoretic relationships. Facilitation via ecosystem engineering has received more attention, for example habitat modification by beavers and bioturbation by salmon.

It is well known that interaction outcomes vary with abiotic and biotic context. However, only a few of studies have examined context dependency in positive interactions in freshwater systems. Likewise, positive interactions incur costs as well as benefits; conceptualising interactions in terms of net cost/benefit to participants will help to clarify complex interactions.

It is likely that there are many positive interactions that have yet to be discovered in freshwater systems. To identify these interactions, we encourage inductive natural history studies combined with hypotheses deduced from general ecological models. Research on positive interactions must move beyond small‐scale experiments and observational studies and adopt a cross‐scale approach. Likewise, we must progress from reducing systems to oversimplified pairwise interactions, toward studying positive interactions in broader community contexts. Positive interactions have been greatly overlooked in applied freshwater ecology, but have great potential for conservation, restoration, and aquaculture.
Turbid reefs moderate coral bleaching under climate‐related temperature stress
Authors: Sully Shannon , van Woesik Robert
Published: January 2020

Thermal‐stress events that cause coral bleaching and mortality have recently increased in frequency and severity. Yet few studies have explored conditions that moderate coral bleaching. Given that high light and high ocean temperature together cause coral bleaching, we explore whether corals at turbid localities, with reduced light, are less likely to bleach during thermal‐stress events than corals at other localities. We analyzed coral bleaching, temperature, and turbidity data from 3,694 sites worldwide with a Bayesian model and found that Kd490, a measurement positively related to turbidity, between 0.080 and 0.127 reduced coral bleaching during thermal‐stress events. Approximately 12% of the world's reefs exist within this “moderating turbidity” range, and 30% of reefs that have moderating turbidity are in the Coral Triangle. We suggest that these turbid nearshore environments may provide some refuge through climate change, but these reefs will need high conservation status to sustain them close to dense human populations.
Anthropogenic global shifts in biospheric N and P concentrations and ratios and their impacts on biodiversity, ecosystem productivity, food security, and human health
Authors: Penuelas Josep , Janssens Ivan A. , Ciais Philippe , Obersteiner Michael , Sardans Jordi
Published: January 2020

The availability of carbon (C) from high levels of atmospheric carbon dioxide (CO2) and anthropogenic release of nitrogen (N) is increasing, but these increases are not paralleled by increases in levels of phosphorus (P). The current unstoppable changes in the stoichiometries of C and N relative to P have no historical precedent. We describe changes in P and N fluxes over the last five decades that have led to asymmetrical increases in P and N inputs to the biosphere. We identified widespread and rapid changes in N:P ratios in air, soil, water, and organisms and important consequences to the structure, function, and biodiversity of ecosystems. A mass‐balance approach found that the combined limited availability of P and N was likely to reduce C storage by natural ecosystems during the remainder of the 21st Century, and projected crop yields of the Millennium Ecosystem Assessment indicated an increase in nutrient deficiency in developing regions if access to P fertilizer is limited. Imbalances of the N:P ratio would likely negatively affect human health, food security, and global economic and geopolitical stability, with feedbacks and synergistic effects on drivers of global environmental change, such as increasing levels of CO2, climatic warming, and increasing pollution. We summarize potential solutions for avoiding the negative impacts of global imbalances of N:P ratios on the environment, biodiversity, climate change, food security, and human health.
A substantial role of soil erosion in the land carbon sink and its future changes
Authors: Tan Zeli , Leung L. Ruby , Li Hong‐Yi , Tesfa Teklu , Zhu Qing , Huang Maoyi
Published: January 2020

Realistic representation of land carbon sink in climate models is vital for predicting carbon climate feedbacks in a changing world. Although soil erosion that removes land organic carbon has increased substantially since the onset of agriculture, it is rarely included in the current generation of climate models. Using an Earth system model (ESM) with soil erosion represented, we estimated that on average soil erosion displaces 5% of newly fixed land organic carbon downslope annually in the continental United States. In the lower Mississippi river basin and the Cascades, the fraction can be as large as 40%. About 12% of the eroded organic carbon is eventually exported to inland waters, which is equal to 14% of the simulated net carbon gain by terrestrial ecosystems. By comparing the eroded organic carbon export to rivers with the particulate organic carbon export to oceans, we demonstrated that a large fraction of the carbon export to rivers could have been mineralized in inland waters. Importantly, with a direct comparison of eroded and exported soil organic carbon and land net carbon uptake, we found that ESMs that ignore soil erosion likely offset the erosional carbon loss by increasing heterotrophic respiration implicitly. But as soil erosion and heterotrophic respiration respond differently to a warming climate, this unrealistic compensation would lead to biased predictions of future land carbon sink.