bluuebunny/crossref_metadata_2025 huggingface dataset:
Fewer gastrointestinal bleeds with ticagrelor and prasugrel compared with clopidogrel in patients with acute coronary syndrome following percutaneous coronary intervention
Authors: Abraham Neena S. , Yang Eric H. , Noseworthy Peter A. , Inselman Jonathan , Yao Xiaoxi , Herrin Jeph , Sangaralingham Lindsey R. , Ngufor Che , Shah Nilay D.
Published: July 2020

Background

Gastrointestinal bleeding (GIB) frequently occurs following percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) with the prescription of P2Y12 inhibiting antiplatelet agents. Compared with clopidogrel, the newer P2Y12 inhibitors lower major adverse cardiac events with similar or possibly higher major bleeding events. The comparative GIB rates of these medications remain poorly understood.

Aim

To compare GIB rates associated with clopidogrel, prasugrel and ticagrelor using national medical and pharmacy claims data from privately insured and Medicare Advantage enrollees .

Methods

Propensity score and inverse probability treatment weighting were used to balance baseline characteristics among treatment groups. The 1‐year GIB risk was calculated using weighted Cox proportional hazard models and expressed as hazard ratios (HR) with 95% confidence intervals (CI) and number needed to harm (NNH).

Results

We identified 37 019 patients with ACS (non‐ST elevation ACS [NSTE‐ACS] and ST‐elevation myocardial infarction [STEMI]) within 14 days of a PCI (mean age 63 years and 70% male). Clopidogrel prescription was most common (69%) with prasugrel (16%) and ticagrelor (14%) prescribed less frequently. When compared with clopidogrel, ticagrelor was associated with a 34% risk reduction (HR 0.66; 95% CI: 0.54–0.81) in GIB overall and with NSTE‐ACS, and a 37% GIB risk reduction (HR 0.63; 95% CI: 0.42–0.93) in STEMI patients. When compared with clopidogrel, prasugrel was associated with a 21% risk reduction (HR 0.79; 95% CI: 0.64–0.97) overall, a 36% GIB risk reduction (HR 0.64; 95% CI: 0.49–0.85) in STEMI patients but no reduction of GIB risk in NSTE‐ACS patients.

Conclusions

In the first year following PCI, ticagrelor or prasugrel are associated with fewer GIB events than clopidogrel.
Editorial: which factors influence HBsAg levels in HBV‐infected patients?
Authors: Cornberg Markus , Glebe Dieter
Published: July 2020

LINKED CONTENT

This article is linked to Cavallone et al and Brunetto and Cavallone papers. To view these articles, visit
https://doi.org/10.1111/apt.15753 and https://doi.org/10.1111/apt.15910.
Letter: faecal microbiota transplantation for irritable bowel syndrome. Authors' reply
Authors: Lahtinen Perttu , Jalanka Jonna , Hartikainen Anna , Mattila Eero , Hillilä Markku , Punkkinen Jari , Koskenpato Jari , Anttila Veli‐Jukka , Tillonen Jyrki , Satokari Reetta , Arkkila Perttu
Published: July 2020

LINKED CONTENT

This article is linked to Lahtinen et al and Segal papers. To view these articles, visit
https://doi.org/10.1111/apt.15810 and https://doi.org/10.1111/apt.15824.
Letter: ustekinumab dose intensification for loss of response—should we re‐induce before shortening the dose interval? Author's reply
Authors: Kopylov Uri
Published: July 2020

LINKED CONTENT

This article is linked to Kopylov et al and Srinivansan papers. To view these articles, visit https://doi.org/10.1111/apt.15784 and https://doi.org/10.1111/apt.15883.
Letter: ciclosporin and vedolizumab for steroid‐refractory ulcerative colitis
Authors: Resál Tamás , Pigniczki Daniella , Szántó Kata , Rutka Mariann , Farkas Klaudia , Molnar Tamas
Published: July 2020

LINKED CONTENT

This article is linked to Ollech et al paper. To view this article, visit https://doi.org/10.1111/apt.15616.
Letter: is unrealised adult height resulting from paediatric Crohn’s disease associated with a potential reduction in lifetime earnings? Authors’ reply
Authors: Mouratidou Natalia , Malmborg Petter , Olén Ola
Published: July 2020

LINKED CONTENT

This article is linked to Mouratidou et al and Hron papers. To view these articles, visit
https://doi.org/10.1111/apt.15667 and https://doi.org/10.1111/apt.15828.
Association between healthcare practitioners' beliefs about statins and patients' beliefs and adherence
Authors: Huiskes Victor J.B. , van den Ende Cornelia H.M. , van Dijk Liset , Burger David M. , van den Bemt Bartholomeus J.F.
Published: July 2020

Aims

Adherence to statins ranges from 32% to 79%. Patients' beliefs about medication are associated with adherence. There is lack of insight into the possible association between beliefs of healthcare practitioners (HCPs) about statins and patients' beliefs and adherence. This study aims to examine whether HCPs' beliefs about statins are associated with patients' beliefs and adherence about/to statins.

Methods

Cross‐sectional study in 48 pharmacies and affiliated physicians' practices between 3 September 2014 and 20 March 2015. HCPs' (prescribers and pharmacy staff) and patients' beliefs about statins were assessed with the Beliefs about Medicine Questionnaire (BMQ) specific. Adherence to statins was assessed with the MARS‐5 questionnaire. Multilevel regression analysis was performed to assess the association between HCPs' beliefs and patients' beliefs and adherence.

Results

1504 patients (mean age 66.8 [s.d. ± 9.9] years, 46.5% female) and 734 HCPs (209 physicians, 118 pharmacists and 366 pharmacy technicians) participated in this study. Patients have higher BMQ necessity (16.9 [s.d. ± 4.3]) and BMQ concern (12.3 [s.d. ± 3.9]) scores than HCPs (15.0 [s.d. ± 3.0] and 11.5 [s.d. ± 2.9], P < 0.001). No associations were found between any of the HCPs' BMQ and patients' BMQ scores and adherence to statins. Patients' BMQ necessity, concern and necessity‐concerns (NC)‐differential scores were associated with patients' adherence (MARS‐5) scores. B (95% CI) coefficients were 0.057 (0.035‐0.079), −0.040 (−0.064 to –0.016) and.061 (0.043‐0.079).

Conclusions

Patients have stronger beliefs about medication compared to HCPs. No associations were found between HCPs' BMQ scores on the one hand and patients' BMQ scores and adherence to statins on the other hand.
Why and when suffering increases the perceived likelihood of fortuitous rewards
Authors: Ong How Hwee , Nelissen Rob M. A. , van Beest Ilja
Published: July 2020

Cultural practices and anecdotal accounts suggest that people expect suffering to lead to fortuitous rewards. To shed light on this illusory ‘suffering–reward’ association, we tested why and when this effect manifests. Across three vignette studies in which we manipulated the degree of suffering experienced by the protagonist, we tested a ‘just‐world maintenance’ explanation (suffering deserves to be compensated) and a ‘virtuous suffering’ explanation (suffering indicates virtues, which will be rewarded). Our findings revealed that the illusory ‘suffering–reward’ association (1) could serve as a way for people to cope with just‐world threats posed by the suffering of innocent victims, and (2) manifested when the suffering was not caused by the victim's own behaviour and not readily attributable to bad luck. Taken together, these findings not only provide evidence for the existence of the illusory ‘suffering–reward’ association but also elucidate its psychological underpinnings.
Novel anti‐cancer candidates from a combinatorial peptide library
Authors: Ambaye Nigus D. , Yu Hua E.
Published: July 2020

STAT3 is attractive target for development of anti‐cancer therapeutics as it is implicated in nearly all forms of human tumors. To identify novel leads, we screened a combinatorial peptide library displayed on the surface of M13 bacteriophage. After three rounds of biopanning, a dodecapeptide with the YYVSWPPDMMHY sequence was found to be enriched by 36% while another with a short consensus motif was displayed in 20% of the phages. Binding analysis by isothermal titration calorimetry shows the most displayed peptide interacted with a Kd of 1.79 μM, which on modification of its structure to mimic the natural binding partners of STAT3 brought the affinity to high nanomolar range (Kd = 500 nM). Using a panel of tumor cell lines, we show that the peptides prevented the proliferation of triple‐negative breast cancer cells with a moderate activity (GI50 = 50 μM). Furthermore, gene expression analysis shows the peptide reduced the expression of oncoproteins critical for tumor cell proliferation, angiogenesis, and metastasis. To find novel STAT3‐interacting proteins, we searched the non‐redundant sequences of the National Center for Biotechnology Information database which allowed us to identify potential binding partners of the protein. In sum, our data show the identified agents could serve as useful therapeutics candidates for further development.
UV‐free Texturing using Sparse Voxel DAGs
Authors: Dolonius D. , Sintorn E. , Assarsson U.
Published: July 2020

An application may have to load an unknown 3D model and, for enhanced realistic rendering, precompute values over the surface domain, such as light maps, ambient occlusion, or other global‐illumination parameters. High‐quality uv‐unwrapping has several problems, such as seams, distortions, and wasted texture space. Additionally, procedurally generated scene content, perhaps on the fly, can make manual uv unwrapping impossible. Even when artist manipulation is feasible, good uv layouts can require expertise and be highly labor intensive.

This paper investigates how to use Sparse Voxel DAGs (or DAGs for short) as one alternative to avoid uv mapping. The result is an algorithm enabling high compression ratios of both voxel structure and colors, which can be important for a baked scene to fit in GPU memory. Specifically, we enable practical usage for an automatic system by targeting efficient real‐time mipmap filtering using compressed textures and adding support for individual mesh voxelizations and resolutions in the same DAG. Furthermore, the latter increases the texture‐compression ratios by up to 32% compared to using one global voxelization, DAG compression by 10 – 15% compared to using a DAG per mesh, and reduces color‐bleeding problems for large mipmap filter sizes.

The voxel‐filtering is more costly than standard hardware 2D‐texture filtering. However, for full HD with deferred shading, it is optimized down to 2.5 ± 0.5 ms for a custom multisampling filtering (e.g., targeted for minification of low‐frequency textures) and 5 ± 2 ms for quad‐linear mipmap filtering (e.g., for high‐frequency textures). Multiple textures sharing voxelization can amortize the majority of this cost. Hence, these numbers involve 1–3 textures per pixel (Fig. 1c).
Combinatorial Construction of Seamless Parameter Domains
Authors: Zhou J. , Tu C. , Zorin D. , Campen M.
Published: July 2020

The problem of seamless parametrization of surfaces is of interest in the context of structured quadrilateral mesh generation and spline‐based surface approximation. It has been tackled by a variety of approaches, commonly relying on continuous numerical optimization to ultimately obtain suitable parameter domains. We present a general combinatorial seamless parameter domain construction, free from the potential numerical issues inherent to continuous optimization techniques in practice. The domains are constructed as abstract polygonal complexes which can be embedded in a discrete planar grid space, as unions of unit squares. We ensure that the domain structure matches any prescribed parametrization singularities (cones) and satisfies seamlessness conditions. Surfaces of arbitrary genus are supported. Once a domain suitable for a given surface is constructed, a seamless and locally injective parametrization over this domain can be obtained using existing planar disk mapping techniques, making recourse to Tutte's classical embedding theorem.
Motion Retargetting based on Dilated Convolutions and Skeleton‐specific Loss Functions
Authors: Kim SangBin , Park Inbum , Kwon Seongsu , Han JungHyun
Published: July 2020

Motion retargetting refers to the process of adapting the motion of a source character to a target. This paper presents a motion retargetting model based on temporal dilated convolutions. In an unsupervised manner, the model generates realistic motions for various humanoid characters. The retargetted motions not only preserve the high‐frequency detail of the input motions but also produce natural and stable trajectories despite the skeleton size differences between the source and target. Extensive experiments are made using a 3D character motion dataset and a motion capture dataset. Both qualitative and quantitative comparisons against prior methods demonstrate the effectiveness and robustness of our method.
Simulation of Dendritic Painting
Authors: Canabal José A. , Otaduy Miguel A. , Kim Byungmoon , Echevarria Jose
Published: July 2020

We present a new system for interactive dendritic painting. Dendritic painting is characterized by the unique and intricate branching patterns that grow from the interaction of inks, solvents and medium. Painting sessions thus become very dynamic and experimental. To achieve a compelling simulation of this painting technique we introduce a new Reaction‐Diffusion model with carefully designed terms to allow natural interactions in a painting context. We include additional user control not possible in the real world to guide and constrain the growth of the patterns in expressive ways. Our multi‐field model is able to capture and simulate all these complex phenomena efficiently in real time, expanding the tools available to the digital artist, while producing compelling animations for motion graphics.
Impact of end‐expiratory pressure fluctuation on tidal volume in the trilevel positive airway pressure mode
Authors: Ma Zhi‐xiang , Zhou Tian‐ran , Li Wei , Ma De‐dong
Published: July 2020

Introduction

In noninvasive positive‐pressure ventilation (NPPV), the changes in the expiratory positive airway pressure (EPAP) directly affect the magnitude of the tidal volume.

Objectives

This experimental study aims to verify the precise effects of end‐expiratory fluctuation on the body tidal volume to better assist NPPV in clinical practice.

Methods

We selected the TestChest‐simulated lung simulation of different populations, including healthy subjects (normal group), patients with chronic obstructive pulmonary disease (COPD) with emphysema as their primary phenotype (COPD1 group), and patients with COPD with bronchitis as their primary phenotype (COPD2 group).

Results

Regarding the tidal volume curves of the three groups under various conditions, sixfold charts revealed that the tidal volume changed with the end‐expiratory pressure fluctuations. In addition, regression coefficients for end‐expiratory pressure fluctuations, (IPAP–EPAP) and (IPAP–EEPAP) exhibited a significant contribution to the tidal volume. The two coefficients in the normal, COPD1 and COPD2 groups were 52.294 and 10.414, 46.192 and −8.816, and 11.922 and 17.947, respectively. The circuit simulation results showed that the simulation curve fitted the experimental curve better by changing the coefficient of the descending edge of the expiratory phase.

Conclusions

The study results suggest that the end‐expiratory pressure fluctuation affects the body tidal volume. Compared with the bilevel positive airway pressure (PAP), the trilevel PAP provides additional respiratory support to the body during a respiratory difference in initial respiration and descent.
Papillary fibroelastoma of the right atrial appendage: Is it that rare?
Authors: Pilato Giuseppe , Argirò Alessia , Barletta Giuseppe , Del Bene Maria Riccarda
Published: July 2020

Papillary fibroelastoma (PF) of the right atrium accounts for 2% of nonvalvular cases, and right appendage (RAA) PF was described only once in literature. We present three cases of RAA PF in patients with unrelated symptoms undergoing 3‐dimensional transesophageal echocardiographic examination (3D‐TEE) scheduled for conventional indications. Key to diagnosis in routine practice resides in systematic examination of the right atrium and RAA in live 3D‐TEE imaging with backward and forward navigation of the real‐time pyramidal data. A review of literature is provided. Our experience demonstrates that systematic imaging of all cardiac structures with 3D‐TEE allows refining PF nosology.
Play, but not observing play, engages rat medial prefrontal cortex
Authors: Concha‐Miranda Miguel , Hartmann Konstantin , Reinhold Annika , Brecht Michael , Sanguinetti-Scheck Juan I.
Published: July 2020

Rats have elaborate cognitive capacities for playing Hide & Seek. Playing Hide & Seek strongly engages medial prefrontal cortex and the activity of prefrontal cortex neurons reflects the structure of the game. We wondered if prefrontal neurons would also show a mirroring of play‐related neural activity. Specifically, we asked how does the activity in the rat medial prefrontal cortex differ when the animal plays itself versus when it observes others playing. Consistent with our previous work, when the animal plays itself we observed medial prefrontal cortex activity that was sharply locked to game events. Observing play, however, did not lead to a comparable activation of rat medial prefrontal cortex. Firing rates during observing play were lower than during real play. The modulation of responses in medial prefrontal cortex by game events was strong during playing Hide & Seek, but weak during observing Hide & Seek. We conclude the rat prefrontal cortex does not mirror play events under our experimental conditions.
Roles of cell fusion between mesenchymal stromal/stem cells and malignant cells in tumor growth and metastasis
Authors: Zhang Li‐Na , Zhang Di‐Di , Yang Lei , Gu Yu‐Xuan , Zuo Qiu‐Ping , Wang Hao‐Yi , Xu Jia , Liu Dian‐Xin
Published: July 2020

Invasion and metastasis are the basic characteristics and important markers of malignant tumors, which are also the main cause of death in cancer patients. Epithelial–mesenchymal transition (EMT) is recognized as the first step of tumor invasion and metastasis. Many studies have demonstrated that cell fusion is a common phenomenon and plays a critical role in cancer development and progression. At present, cancer stem cell fusion has been considered as a new mechanism of cancer metastasis. Mesenchymal stromal/stem cell (MSC) is a kind of adult stem cells with high self‐renewal ability and multidifferentiation potential, which is used as a very promising fusogenic candidate in the tumor microenvironment and has a crucial role in cancer progression. Many research results have shown that MSCs are involved in the regulation of tumor growth and metastasis through cell fusion. However, the role of cell fusion between MSCs and malignant cells in tumor growth and metastasis is still controversial. Several studies have demonstrated that MSCs can enhance malignant characteristics, promoting tumor growth and metastasis by fusing with malignant cells, while other conflicting reports believe that MSCs can reduce tumorigenicity upon fusion with malignant cells. In this review, we summarize the recent research on cell fusion events between MSCs and malignant cells in tumor growth and metastasis. The elucidation of the molecular mechanisms between MSC fusion and tumor metastasis may provide an effective strategy for tumor biotherapy.
The response of soil respiration to precipitation change is asymmetric and differs between grasslands and forests
Authors: Du Yue , Wang Ying‐Ping , Su Fanglong , Jiang Jun , Wang Chen , Yu Mengxiao , Yan Junhua
Published: July 2020

Intensification of the Earth's hydrological cycle amplifies the interannual variability of precipitation, which will significantly impact the terrestrial carbon (C) cycle. However, it is still unknown whether previously observed relationship between soil respiration (Rs) and precipitation remains applicable under extreme precipitation change. By analyzing the observations from a much larger dataset of field experiments (248 published papers including 151 grassland studies and 97 forest studies) across a wider range of precipitation manipulation than previous studies, we found that the relationship of Rs response with precipitation change was highly nonlinear or asymmetric, and differed significantly between grasslands and forests, between moderate and extreme precipitation changes. Response of Rs to precipitation change was negatively asymmetric (concave‐down) in grasslands, and double‐asymmetric in forests with a positive asymmetry (concave‐up) under moderate precipitation changes and a negative asymmetry (concave‐down) under extreme precipitation changes. In grasslands, the negative asymmetry in Rs response was attributed to the higher sensitivities of soil moisture, microbial and root activities to decreased precipitation (DPPT) than to increased precipitation (IPPT). In forests, the positive asymmetry was predominantly driven by the significant increase in microbial respiration under moderate IPPT, while the negative asymmetry was caused by the reductions in root biomass and respiration under extreme DPPT. The different asymmetric responses of Rs between grasslands and forests will greatly improve our ability to forecast the C cycle consequences of increased precipitation variability. Specifically, the negative asymmetry of Rs response under extreme precipitation change suggests that the soil C efflux will decrease across grasslands and forests under future precipitation regime with more wet and dry extremes.
Analysis of the impact of school performance on income inequality in the long run: An application to Chilean municipalities
Authors: Leiva Yeycol , Pino Gabriel
Published: July 2020

High income inequality has become a barrier to economic development for emerging economies. Education is commonly seen as a way to decrease income inequality; however, the empirical evidence is not convincing. By focusing on school performance, we take advantage of spatial econometrics to estimate a long‐run relationship showing that income inequality can be reduced by increases in school performance. In particular, our results show that increases in school performance at early stages of educational levels and using mathematics as the subject goal can decrease income inequality in the long run. We use the case of Chile, which presents high income inequality and low school performance compared to similar nations.
Niacinamide mitigates SASP‐related inflammation induced by environmental stressors in human epidermal keratinocytes and skin
Authors: Bierman John C. , Laughlin Timothy , Tamura Makio , Hulette Ben C. , Mack Catherine E. , Sherrill Joseph D. , Tan Christina Y.R. , Morenc Malgorzata , Bellanger Sophie , Oblong John E.
Published: July 2020

Objective

To evaluate whether niacinamide (Nam) can mitigate production of inflammatory and senescence‐related biomarkers induced by environmental stressors.

Methods

Human epidermal keratinocytes were exposed to UVB, urban dust, diesel exhaust and cigarette smoke extract and treated with Nam or vehicle control. Full thickness 3‐D skin organotypic models were exposed to a combination of UVB and PM2.5 and treated with Nam or vehicle control. Quantitation of the SASP‐related inflammatory mediators PGE2, IL‐6 and IL‐8 was performed on cultured media. UVB‐exposed keratinocytes treated with and without Nam were immunostained for the senescence biomarker Lamin B1 (LmnB1). Transcriptomics profiling of cigarette smoke extract effects on keratinocytes was performed. A double‐blind, placebo‐controlled clinical was conducted on 40 female panellists that were pretreated on back sites for two weeks with 5% Nam or vehicle and then exposed to 1.5 minimal erythemal dose (MED) solar‐simulated radiation (SSR). Treated sites were compared with non‐treated exposed sites for erythema and the skin surface IL‐1αRA/IL‐1α inflammatory biomarkers.

Results

Ultraviolet B induced synthesis of PGE2, IL‐8 and IL‐6 and reduced LmnB1 levels in keratinocytes. Urban dust and diesel exhaust only stimulated synthesis of IL‐8 whereas cigarette smoke extract only stimulated levels of PGE2. In all exposures, treatment with Nam significantly mitigated synthesis of the inflammatory mediators and restored levels of UVB‐reduced LmnB1. In the 3D skin equivalent model, Nam reduced IL‐8 levels stimulated by a combination of topical PM2.5 and UV exposure. In a UV challenge clinical, pretreatment with 5% Nam reduced erythema and skin surface IL‐1αRA/IL‐1α inflammatory biomarkers that were induced by SSR.

Conclusion

Since it is known that Nam has anti‐inflammatory properties, we tested whether Nam can inhibit environmental stress‐induced inflammation and senescence‐associated secretory phenotype (SASP) biomarkers. We show Nam can reduce PGE2, IL‐6 and IL‐8 levels induced by environmental stressors. Additionally, in vivo pretreatment with Nam can reduce UV‐induced erythema and skin surface inflammatory biomarkers. These findings add to the body of evidence that Nam can mitigate the skin’s inflammatory response elicited by environmental stressors. This supports Nam can potentially inhibit senescence and premature ageing and thereby maintain skin’s functionality and appearance.
The role of host genetics in the immune response to SARS‐CoV‐2 and COVID‐19 susceptibility and severity
Authors: Ovsyannikova Inna G. , Haralambieva Iana H. , Crooke Stephen N. , Poland Gregory A. , Kennedy Richard B.
Published: July 2020

This article provides a review of studies evaluating the role of host (and viral) genetics (including variation in HLA genes) in the immune response to coronaviruses, as well as the clinical outcome of coronavirus‐mediated disease. The initial sections focus on seasonal coronaviruses, SARS‐CoV, and MERS‐CoV. We then examine the state of the knowledge regarding genetic polymorphisms and SARS‐CoV‐2 and COVID‐19. The article concludes by discussing research areas with current knowledge gaps and proposes several avenues for future scientific exploration in order to develop new insights into the immunology of SARS‐CoV‐2.
The microbiome and cytosolic innate immune receptors
Authors: Liwinski Timur , Zheng Danping , Elinav Eran
Published: July 2020

The discovery of innate immune sensors (pattern recognition receptors, PRRs) has profoundly transformed the notion of innate immunity, in providing a mechanistic basis for host immune interactions with a wealth of environmental signals, leading to a variety of immune‐mediated outcomes including instruction and activation of the adaptive immune arm. As part of this growing understanding of host‐environmental cross talk, an intimate connection has been unveiled between innate immune sensors and signals perceived from the commensal microbiota, which may be regarded as a hub integrating a variety of environmental cues. Among cytosolic PRRs impacting on host homeostasis by interacting with the commensal microbiota are nucleotide‐binding domain, leucine‐rich repeat‐containing protein receptors (NLRs), together with a number of cytosolic DNA sensors and the family of absent in melanoma (AIM)–like receptors (ALRs). NLR sensors have been a particular focus of research, and some NLRs have emerged as key orchestrators of inflammatory responses and host homeostasis. Some NLRs achieve this through the formation of cytoplasmic multiprotein complexes termed inflammasomes. More recently discovered PRRs include retinoic acid‐inducible gene‐I (RIG‐I)–like receptors (RLRs), cyclic GMP‐AMP synthase (cGAS), and STING. In the present review, they summarize recent advancements in knowledge on structure and function of cytosolic PRRs and their roles in host‐microbiota cross talk and immune surveillance. In addition, we discuss their relevance for human health and disease and future therapeutic applications involving modulation of their activation and signaling.
Hypertension burden and challenges across the hypertension treatment cascade among adults enrolled in HIV care in northern Tanzania
Authors: Manavalan Preeti , Madut Deng B. , Hertz Julian T. , Thielman Nathan M. , Okeke Nwora Lance , Mmbaga Blandina T. , Watt Melissa H.
Published: July 2020

Failure to address hypertension among people living with HIV (PLWH) may undermine the significant progress made toward reducing mortality among this high‐risk population in sub‐Saharan Africa (SSA). Here, the authors report hypertension prevalence, diagnosis, and treatment among patients enrolled in HIV care in Tanzania. Patients attending an HIV clinic were consecutively screened for hypertension. Hypertension was defined as follows: a single blood pressure measurement ≥160 mm Hg systolic or ≥100 mm Hg diastolic, two measurements at separate visits ≥140 mm Hg systolic or ≥90 mm Hg diastolic, or self‐reported hypertension diagnosis. The authors screened 555 patients, and 19.6% met hypertension criteria. Among a subset of 91 hypertensive participants, 44 (48.4%) reported previous blood pressure measurements, 32 (35.2%) were aware of diagnosis, 10 (11.0%) reported current antihypertensive use, and none had controlled blood pressure. Addressing barriers along the hypertension treatment cascade must be a top priority to improve cardiovascular outcomes among PLWH in SSA.
Sotrastaurin, a PKC inhibitor, attenuates RANKL‐induced bone resorption and attenuates osteochondral pathologies associated with the development of OA
Authors: Pang Cong , Wen Liangbao , Qin Haikuo , Zhu Bikang , Lu Xuanyuan , Luo Shixing
Published: July 2020

Osteoarthritis (OA) is a common degenerative disease that affects the musculoskeletal structure of the whole joint, which is characterized by progressive destruction of both articular cartilage and subchondral bone. Treatment of the bone pathologies, particularly osteoclast‐mediated subchondral bone loss in the early stages of OA, could prevent subsequent cartilage degeneration and progression of OA. In the present study, the PKC inhibitor, Sotrastaurin, was found to inhibit RANKL‐induced osteoclast formation in vitro in a dose‐ and time‐dependent manner. In particular, SO exerted its anti‐osteoclastic effect predominantly at the early stages of RANKL stimulation, suggesting inhibitory effects on precursor cell fusion. Using mature osteoclasts cultured on bovine bone discs, we showed that SO also exerts anti‐resorptive effects on mature osteoclasts bone resorptive function. Mechanistically, SO attenuates the early activation of the p38, ERK and JNK signalling pathways, leeding to impaired induction of crucial osteoclast transcription factors c‐Jun, c‐Fos and NFATc1. We also showed that SO treatment significantly inhibited the phosphorylation of PKCδ and MARCKS, an upstream regulator of cathepsin K secretion. Finally, in animal studies, SO significantly alleviates the osteochondral pathologies of subchondral bone destruction as well as articular cartilage degeneration following DMM‐induced OA, markedly improving OARSI scores. The reduced subchondral bone loss was associated with marked reductions in TRAP(+) osteoclasts in the subchondral bone tissue. Collectively, our data provide evidence for the protective effects of SO against OA by preventing aberrant subchondral bone and articular cartilage changes. Thus, SO demonstrates potential for further development as an alternative therapeutic option against OA.
Ageing‐associated increase in SGLT2 disrupts mitochondrial/sarcoplasmic reticulum Ca2+ homeostasis and promotes cardiac dysfunction
Authors: Olgar Yusuf , Tuncay Erkan , Degirmenci Sinan , Billur Deniz , Dhingra Rimpy , Kirshenbaum Lorrie , Turan Belma
Published: July 2020

The prevalence of death from cardiovascular disease is significantly higher in elderly populations; the underlying factors that contribute to the age‐associated decline in cardiac performance are poorly understood. Herein, we identify the involvement of sodium/glucose co‐transporter gene (SGLT2) in disrupted cellular Ca2+‐homeostasis, and mitochondrial dysfunction in age‐associated cardiac dysfunction. In contrast to younger rats (6‐month of age), older rats (24‐month of age) exhibited severe cardiac ultrastructural defects, including deformed, fragmented mitochondria with high electron densities. Cardiomyocytes isolated from aged rats demonstrated increased reactive oxygen species (ROS), loss of mitochondrial membrane potential and altered mitochondrial dynamics, compared with younger controls. Moreover, mitochondrial defects were accompanied by mitochondrial and cytosolic Ca2+ ([Ca2+]i) overload, indicative of disrupted cellular Ca2+‐homeostasis. Interestingly, increased [Ca2+]i coincided with decreased phosphorylation of phospholamban (PLB) and contractility. Aged‐cardiomyocytes also displayed high Na+/Ca2+‐exchanger (NCX) activity and blood glucose levels compared with young‐controls. Interestingly, the protein level of SGLT2 was dramatically increased in the aged cardiomyocytes. Moreover, SGLT2 inhibition was sufficient to restore age‐associated defects in [Ca2+]i‐homeostasis, PLB phosphorylation, NCX activity and mitochondrial Ca2+‐loading. Hence, the present data suggest that deregulated SGLT2 during ageing disrupts mitochondrial function and cardiac contractility through a mechanism that impinges upon [Ca2+]i‐homeostasis. Our studies support the notion that interventions that modulate SGLT2‐activity can provide benefits in maintaining [Ca2+]i and cardiac function with advanced age.
MiR‐101 promotes pain hypersensitivity in rats with chronic constriction injury via the MKP‐1 mediated MAPK pathway
Authors: Qiu Shuang , Liu Benjuan , Mo Yanshuai , Wang Xueqin , Zhong Lina , Han Xiao , Mi Fuli
Published: July 2020

This study was performed to characterize the effect of microRNA‐101 (miR‐101) on the pain hypersensitivity in CCI rat models with the involvement of mitogen‐activated protein kinase phosphatase 1 (MKP‐1) in spinal cord microglial cells. The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) in the developed CCI models were determined to assess the hypersensitivity of rats to mechanical stimulation and thermal pain. To assess inflammation, the levels of interleukin (IL)‐1β, IL‐6 and tumour necrosis factor‐α (TNF‐α) in the spinal dorsal horns of CCI rats and lipopolysaccharide (LPS)‐activated microglial cells were examined. miR‐101 and MKP‐1 gain‐ and loss‐of‐function experiments were conducted in in vivo and in vitro settings to examine the roles of miR‐101 and MKP‐1 in CCI hypersensitivity and inflammation. The results showed that miR‐101 was highly expressed in the spinal dorsal horn and microglial cells of CCI rat models. Furthermore, overexpression of miR‐101 promoted the pain hypersensitivity in CCI rat models by reducing MWT and TWL. The overexpression of miR‐101 also promoted inflammation in LPS‐exposed microglial cells, as indicated by increased levels of IL‐1β, IL‐6 and TNF‐α. MiR‐101 was shown to target MKP‐1, inhibiting its expression. Moreover, miR‐101 promoted pain hypersensitivity in CCI rat models by inhibiting MKP‐1 expression and activating the mitogen‐activated protein kinase (MAPK) signalling pathway. Taken together, miR‐101 could potentially promote hypersensitivity and inflammatory response of microglial cells and aggravate neuropathic pain in CCI rat models by inhibiting MKP‐1 in the MAPK signalling pathway.
Dichloroacetate reveals the presence of metabolic inertia at the start of exercise in rainbow trout (Oncorhynchus mykiss, Walbaum 1792)
Authors: Wood Chris M. , Pane Eric F. , Heigenhauser George J. F.
Published: July 2020

A lag in the increase in oxygen consumption (MO2) occurs at the start of sustainable exercise in trout. Waterborne dichloroacetate (0.58 and 3.49 mmol l−1), a compound which activates pyruvate dehydrogenase (PDH) by inhibiting PDH kinase in muscle, accelerates the increase in MO2 during the first 10 min of sustainable exercise when velocity is elevated to 75% critical swimming speed in a swim tunnel. There are no effects on MO2 thereafter or at rest. This indicates that a delay in PDH activation (“metabolic inertia”) contributes to the lag phenomenon.
Cancer survival statistics for patients and healthcare professionals – a tutorial of real‐world data analysis
Authors: Eloranta S. , Smedby K. E. , Dickman P. W. , Andersson T. M.
Published: July 2020

Monitoring survival of cancer patients using data collected by population‐based cancer registries is an important component of cancer control. In this setting, patient survival is often summarized using net survival, that is survival from cancer if there were no other possible causes of death. Although net survival is the gold standard for comparing survival between groups or over time, it is less relevant for understanding the anticipated real‐world prognosis of patients. In this review, we explain statistical concepts targeted towards patients, clinicians and healthcare professionals that summarize cancer patient survival under the assumption that other causes of death exist. Specifically, we explain the appropriate use, interpretation and assumptions behind statistical methods for competing risks, loss in life expectancy due to cancer and conditional survival. These concepts are relevant when producing statistics for risk communication between physicians and patients, planning for use of healthcare resources, or other applications when consideration of both cancer outcomes and the competing risks of death is required. To reinforce the concepts, we use Swedish population‐based data of patients diagnosed with cancer of the breast, prostate, colon and chronic myeloid leukaemia. We conclude that when choosing between summary measures of survival it is critical to characterize the purpose of the study and to determine the nature of the hypothesis under investigation. The choice of terminology and style of reporting should be carefully adapted to the target audience and may range from summaries for specialist readers of scientific publications to interactive online tools aimed towards lay persons.
Are Denture Adhesives Safe for Oral Cells?
Authors: López‐García Sergio , Pecci‐Lloret María P. , García‐Bernal David , Guerrero‐Gironés Julia , Pecci‐Lloret Miguel R. , Rodríguez‐Lozano Francisco J.
Published: July 2020

Purpose

To compare the cytotoxicity of six commercially available denture adhesives on human gingival cells: Poligrip Flavour Free Fixative Cream, Fixodent Pro Duo Protection, Novafix cream, FittyDent, Polident Total Action, and Fixodent Pro Plus Duo Protection.

Material and Methods

Eluates of denture adhesives were brought into contact with human gingival cells and compared to untreated cells (w/o any dental adhesive elute). Cell toxicity was assessed by measuring cell viability (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) (MTT) assays), cell morphology (immunofluorescence assays), induction of apoptosis/necrosis and production of reactive oxygen species (ROS) (flow cytometry assays). In addition, the pH of each sample was determined. Data were analyzed using one‐way analysis of variance (ANOVA) followed by Dunnett's multiple comparisons test.

Results

All denture adhesives tested led to a reduction in pH, especially Fixodent Pro Duo Protection and Fixodent Pro Plus Duo Protection. The cell viability assays showed that Fixodent Pro Duo Protection (1:1 72 hours, p = 3.04 × 10−6; 1:2 72 hours, p = 2.07 × 10−6; 1:4 72 hours, p = 2.04 × 10−6) and Fixodent Pro Plus Duo Protection (1:1 72 hours, p = 2.01 × 10−6; 1:2 72 hours, p = 3.03 × 10−6; 1:4 72 hours, p = 2.02 × 10−6) significantly decreased cell viability at all dilutions. Compared to the control group and the rest of the adhesives, Poligrip Flavour Free Fixative Cream (PFF 1:1 72 hours, p = 2.24 × 10−6; 1:2 72 hours, p = 2.44 × 10−6; 1:4 72 hours, p = 2.04 × 10−6) showed a significantly higher cell viability score at all dilutions. Fixodent Pro Duo Protection and Fixodent Pro Plus Duo Protection, both adhesives containing zinc salts in their composition, were responsible for necrosis, and the number of cells was much reduced, with aberrant morphology and pyknotic nucleus. Finally, Fixodent (1:2, p = 2.04 × 10−6, 1:4, p = 0.00036; 1:2, p = 8.82 × 10−6, 1:4, p = 2.30 × 10−6) products significantly promoted ROS production in gingival cells.

Conclusions

The results suggest that denture adhesives containing zinc in their composition could be responsible of the decrease of cell viability, ROS production, aberrant cell morphology, and induction of apoptosis and cell death. However, other possible additional cytotoxic factors must be considered. Thus, more studies are necessary to confirm this hypothesis.
A retrospective study on prescribing pattern and cost analysis of proton-pump inhibitors used among adults of Saudi Arabia
Authors: Ali Mohammad Daud , Ahmad Ayaz
Published: July 2020

Objective

To evaluate the use of proton-pump inhibitors (PPIs) for treatment of different gastric disease in Saudi population and their related administration cost.

Materials and methods

It was a cross-sectional retrospective drug utilization study. The utilization rates and cost analysis of each PPIs class of drugs were compared. Study data were obtained from pharmacy database. Data between 1 January 2019 and 31 December 2019 were investigated, including incidence, prevalence and duration of use of proton-pump inhibitors among adults of Saudi Arabia.

Key findings

We observed 26 798 (4.27%) prescription of PPIs were dispensed in the in-patient and out-patient pharmacy department of Al-Mana Group of Hospital (AGH) Al khobar. Among all the PPIs user, more than the half ((53.01%, n = 14 208), 95% CI (52.42–53.62)) were male. 30–40 years age patients (24.57%, 95% CI (24.06–25.09) (n = 6585)) were highest number of PPI users. Nearly, equal number of PPI users belongs between 51–60 years ((20.88%, n = 5596), 95% CI (20.40–21.37)) and >60 years ((20.36%, n = 5456), 95% CI (19.8–20.85)). Among all the dispensed PPIs drugs, Pantoprazole is dispensed to the highest number of patients (79.09% (95% CI, 78.61–79.58) (n = 21 197)) while their average duration of therapy was 18.86 days. Among all PPIs, pantoprazole average unit wise cost was highest SR 8.83 (USD 2.35) in comparison to other PPIs.

Conclusion

In our study, among all the PPIs Pantoprazole was prescribed to the highest number of patients also it was costliest; hence, their safe and effective use must be warranted. Current study will also help in to develop nation database regarding utilization of proton-pump inhibitors.
Diet diversity was limited in Malawi resulting in stunting despite availability of foods in markets
Authors: Adachi Motoi , Urabe Daisaku
Published: July 2020

Background

Stunting, the most common type of malnutrition, has been a big burden for developing countries such as the Republic of Malawi. The state of malnutrition and the eating behavior of children were surveyed at the border between Malawi and Zambia using anthropometrical measurements and Household Diet Diversity Scores.

Methods

Two rural sites were chosen to compare the impact of empowering communities with nutritional knowledge. Children between 6 months and 5 years old were randomly recruited to evaluate nutritional status. Their caregivers were interviewed to collect Household Dietary Diversity Scores.

Results

Nutritional knowledge at the site where intervention had occurred was higher than at the site where intervention had not yet occurred. However, stunting prevalence at the site where intervention occurred was not statistically lower than site that had not experienced intervention. The Household Dietary Diversity Scores study revealed that some kinds of food groups were almost absent such as organ meat (kidney, liver, and heart), and dairy products but that cereals, spices, and other vegetables were almost 100% taken at both sites, and distance from market was not associated with diet diversity.

Conclusions

The fact that food diversity was not associated with distance from market would explain the limited food accessibility and poor utilization. Although animal resource foods are available at market, they were not been consumed. The profound challenge lays in their accessibility and utilization. A successful project would aim to introduce vitamin A‐rich vegetables and would explore the sustainable production of animal resource foods in the community.
Distributed Renewable Power Generation and Implications for Capacity Investment and Electricity Prices
Authors: Angelus Alexandar
Published: July 2020

Renewable energy generation at the point of consumption (i.e., distributed generation) reduces consumer's electricity expenditure, and eliminates the cost, complexity, and inefficiency associated with power transmission and distribution. In this study, we address the problem of how a consumer should invest in distributed renewable generation to minimize the total expected cost of meeting his electricity demand. In contrast to the existing literature that focuses on grid‐connected, large‐scale investments in renewable power generation in the wholesale electricity market, we address investment in stand‐alone, distributed renewable energy by an individual consumer who participates in a regulated, retail electricity market. We formulate an infinite‐horizon, continuous‐time model in which the utility moves first, and announces a retail electricity rate. Each consumer then acts strategically in deciding if, when, and how much distributed generation capacity to install. We find the subgame‐perfect Nash equilibrium of this dynamic Stackelberg game by first deriving the consumer's optimal investment time and the resulting optimal capacity of his installed distributed generation. Using those results, we quantify the ensuing cost savings to the consumer, which average over 22% across a range of model parameters. Next, we evaluate the impact of consumer's investment in renewable energy on the revenue of his electric utility, and arrive at the structure of the pricing policy that maximizes that revenue. We quantify the revenue increase available to the utility from following this revenue‐maximizing pricing when serving either a single consumer or multiple heterogeneous consumers, and find that it averages over 10% in our numerical studies.
Optimising the foliar uptake of zinc oxide nanoparticles: Do leaf surface properties and particle coating affect absorption?
Authors: Read Thea Lund , Doolette Casey Louise , Li Cui , Schjoerring Jan Kofod , Kopittke Peter Martin , Donner Erica , Lombi Enzo
Published: July 2020

Foliar absorption of zinc (Zn) is limited by several barriers, the first of which is the leaf cuticle. In this study, we investigated the absorption of Zn from Zn oxide nanoparticles (ZnO‐NPs) in wheat (Triticum aestivum cv Gladius) and sunflower (Helianthus annuus cv Hyoleic 41) to determine the importance of NP surface coating for Zn absorption. Fourier transform infrared (FTIR) spectroscopy showed a higher polysaccharide content in the wheat cuticle than sunflower, indicated by a more pronounced glycosidic bond at 1020 cm−1, but wax and cutin content were similar. Scanning electron microscopy (SEM) revealed that trichome density was twice as high in wheat (3600 ± 900 cm−2) as in sunflower (1600 cm−2) and stomatal density four times higher in sunflower (6400 ± 800 cm−2 in wheat and 22 900 cm−2 in sunflower). Suspensions of ZnO‐NPs with coatings of different hydrophobicity were applied to leaves to compare Zn absorption using X‐ray fluorescence microscopy (XFM) and inductively coupled plasma mass spectroscopy (ICP‐MS). Absorption of Zn was similar between wheat and sunflower when Zn was applied at 1000 mg Zn l−1, but much less Zn was absorbed from all ZnO products than from soluble Zn fertiliser. Particle coating did not affect Zn absorption, but it may facilitate particle adhesion to leaves, providing a longer‐term source of resupply of Zn ions to the leaves. Differences in leaf surface characteristics did not affect Zn absorption, indicating that the cuticle is the main pathway of absorption under these conditions.
Characterization of a new HLA‐A allele, HLA‐A*29:128, in a Spanish individual
Authors: Sánchez‐Gordo Francisco P.
Published: July 2020

HLA‐A*29:128 differs from A*29:02:01:01 by one nucleotide mutation in codon 94.