bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of Fenfluramine hydrochloride for the treatment of seizures in Dravet syndrome: A real‐world study
Authors: Specchio Nicola , Pietrafusa Nicola , Doccini Viola , Trivisano Marina , Darra Francesca , Ragona Francesca , Cossu Alberto , Spolverato Silvia , Battaglia Domenica , Quintiliani Michela , Luigia Gambardella Maria , Rosati Anna , Mei Davide , Granata Tiziana , Dalla Bernardina Bernardo , Vigevano Federico , Guerrini Renzo 
Published: September 2020

AbstractObjectiveDravet syndrome (DS) is a drug‐resistant, infantile onset epilepsy syndrome with multiple seizure types and developmental delay. In recently published randomized controlled trials, fenfluramine (FFA) proved to be safe and effective in DS.MethodsDS patients were treated with FFA in the Zogenix Early Access Program at four Italian pediatric epilepsy centers. FFA was administered as add‐on, twice daily at an initial dose of 0.2 mg/kg/d up to 0.7 mg/kg/d. Seizures were recorded in a diary. Adverse events and cardiac safety (with Doppler echocardiography) were investigated every 3 to 6 months.ResultsFifty‐two patients were enrolled, with a median age of 8.6 years (interquartile range [IQR] = 4.1‐13.9). Forty‐five (86.5%) patients completed the efficacy analysis. The median follow‐up was 9.0 months (IQR = 3.2‐9.5). At last follow‐up visit, there was a 77.4% median reduction in convulsive seizures. Thirty‐two patients (71.1%) had a ≥50% reduction of convulsive seizures, 24 (53.3%) had a ≥75% reduction, and five (11.1%) were seizure‐free. The most common adverse event was decreased appetite (n = 7, 13.4%). No echocardiographic signs of cardiac valvulopathy or pulmonary hypertension were observed. There was no correlation between type of genetic variants and response to FFA.SignificanceIn this real‐world study, FFA provided a clinically meaningful reduction in convulsive seizure frequency in the majority of patients with DS and was well tolerated.
Glutathione affects rheology and water distribution of wheat dough by changing gluten conformation and protein depolymerisation
Authors: Guo Lunan , Fang Fang , Zhang Yao , Xu Dan , Jin Zhengyu , Xu Xueming 
Published: September 2020

SummaryThe effects of reduced glutathione (GSH) on dough rheology, water state and distribution, gluten conformation, and protein molecular weight distribution were investigated. Addition of GSH (0.02−0.04%) resulted in a more viscous and less elastic dough with decreased G′ and increased tanδ values, which suggested decreased cross‐links in gluten network and a weakened dough structure. The molecular weight of proteins was reduced by the GSH‐induced cleavage of intermolecular disulphide bonds. Fourier transform infrared spectroscopy showed a high fraction of β‐sheet formation at the expense of α‐helix and β‐turns, indicating a destabilised secondary structure and protein depolymerisation. GSH increased water release from the gluten network in dough resulting in an increase in freezable water content and caused water redistributed from bound water to weakly bound water. This study provided insights into correlation between wheat dough rheological properties and gluten structure influenced by GSH.
In vitro and in vivo effects of carrot on human blood platelet aggregation
Authors: Herath Thanuja D. , Paturi Gunaranjan , Butts Christine A. , Sansom Catherine E. , Morgenstern Marco P. 
Published: September 2020

SummaryCarrots are a good source of essential nutrients and bioactive phytochemicals including carotenoids, phenolic compounds and polyacetylenes such as falcarinol. In this study, we investigated the inhibitory effect of a carrot extract on blood platelet aggregation in vitro and the effect of raw diced or juiced carrots on platelet aggregation in a human study. Carrot extract significantly reduced the platelet aggregation in vitro in blood obtained from healthy donors. In a randomised crossover human study, healthy volunteers consumed either 100 g of freshly diced carrots or 100 mL of freshly juiced carrots (with pulp). There was no significant effect on blood platelet aggregation in the participants at 2, 5, 8 and 24 h after the carrot meal due to wide interindividual variations. Further research is required to understand diet, genetics and lifestyle factors that may impact the physiological effects of falcarinol on platelet aggregation and blood flow.
Clusterin regulates macrophage expansion, polarization and phagocytic activity in response to inflammation in the kidneys
Authors: Weng Xiaodong , Zhao Haimei , Guan Qiunong , Shi Ganggang , Feng Shijian , Gleave Martin E , Nguan Christopher CY , Du Caigan 
Published: September 2020

AbstractClusterin (CLU) is a multifunctional protein localized extracellularly and intracellularly. Although CLU‐knockout (KO) mice are more susceptible to renal ischemia‐reperfusion injury (IRI), the mechanisms underlying the actions of CLU in IRI are not fully understood. Macrophages are key regulators of IRI severity and tissue repair. Therefore, we investigated the role of CLU in macrophage polarization and phagocytosis. Renal IRI was induced in wild‐type (WT) or CLU‐KO C57BL/6 mice by clamping the renal pedicles for 30 min at 32°C. Peritoneal macrophages were activated via an intraperitoneal injection of lipopolysaccharide (LPS). Renal tissue damage was examined using histology, whereas leukocyte phenotypes were assessed using flow cytometry and immunohistochemistry. We found that monocytes/macrophages expressed the CLU protein that was upregulated by hypoxia. The percentages of macrophages (F4/80+, CD11b+ or MAC3+) infiltrating the kidneys of WT mice were significantly less than those in CLU‐KO mice after IRI. The M1/M2 phenotype ratio of the macrophages in WT kidneys decreased at day 7 post‐IRI when the injury was repaired, whereas that in KO kidneys increased consistently as tissue injury persisted. In response to LPS stimulation, WT mice produced fewer M1 macrophages, but not M2, than the control did. Phagocytosis was stimulated by CLU expression in macrophages compared with the CLU null controls and by the exogenous CLU protein. In conclusion, CLU suppresses macrophage infiltration and proinflammatory M1 polarization during the recovery period following IRI, and enhances phagocytic activity, which may be partly responsible for tissue repair in the kidneys of WT mice after injury.
miR‐34a‐5p Attenuates EMT through targeting SMAD4 in silica‐induced pulmonary fibrosis
Authors: Qi Yuanmeng , Zhao Ahui , Yang Peiyan , Jin Luheng , Hao Changfu 
Published: September 2020

AbstractSilicosis is an incurable occupational disease, and its pathological feature is diffuse pulmonary fibrosis. Pulmonary epithelial‐mesenchymal transition (EMT) is one of the important events in the pathogenesis of silicosis. Previous studies found that abnormal expression of various microRNAs (miRNAs) involved in the development of lung fibrosis. However, their roles in silicosis have not been elucidated. To research the biological effects of miR‐34a in EMT process in silica‐induced lung fibrosis, we established the silicosis model in mouse and miR‐34a intervention in a cell model of TGF‐β1 stimulated lung epithelial cells (A549). The results showed that miR‐34a expression was down‐regulated in the fibrotic lung tissue after silica treatment, and it was similarly expressed in A549 cells stimulated by TGF‐β1. Meanwhile, silica‐induced EMT process can increase expression of two mesenchymal markers, α‐SMA and vimentin. Furthermore, overexpression miR‐34a markedly inhibited EMT stimulated by TGF‐β1. Mechanistically, SMAD4 was identified as the target of miR‐34a. SMAD4 levels decreased in mRNA and protein levels in A549 cells upon miR‐34a overexpression. In addition, the knockdown of SMAD4 blocked the EMT process. Taken together, miR‐34a regulated EMT, which might be partially realized by targeting SMAD4. Our data might provide new insight into treatment targets for silica‐induced pulmonary fibrosis.
MFGE8 is down‐regulated in cardiac fibrosis and attenuates endothelial‐mesenchymal transition through Smad2/3‐Snail signalling pathway
Authors: Wang Bo , Ge Zhuowang , Wu Yan , Zha Yafang , Zhang Xuan , Yan Yexiang , Xie Yuquan 
Published: September 2020

AbstractEndothelial‐mesenchymal transition (EndMT) is a major source of transformed cardiac fibroblasts, which is reported to play a key role in cardiac fibrosis (CF), a pathogenesis of cardiovascular diseases such as heart failure, myocardial infarction and atrial fibrillation. Nonetheless, the specific mechanism underlying the progression of EndMT to CF is still largely unknown. In this study, we aimed to investigate the role of milk fat globule‐EGF factor 8 (MFGE8), a kind of soluble glycoprotein, in TGF‐β1‐induced EndMT. In animal experiments, the expression of MFGE8 was found down‐regulated in the left ventricle and aorta of rats after transverse aortic constriction (TAC) compared with the sham group, especially in endothelial cells (ECs). In in vitro cultured ECs, silencing MFGE8 with small interfering RNA (siRNA) was found to promote the process of TGF‐β1‐induced EndMT, whereas administration of recombinant human MFGE8 (rh‐MFGE8) attenuated the process. Moreover, activated Smad2/3 signalling pathway after TGF‐β1 treatment and EndMT‐related transcription factors, such as Snail, Twist and Slug, was potentiated by MFGE8 knock‐down but inhibited by rh‐MFGE8. In conclusion, our experiments indicate that MFGE8 might play a protective role in TGF‐β1‐induced EndMT and might be a potential therapeutic target for cardiac fibrosis.
Glucocorticoid levels are linked to lifetime reproductive success and survival of adult barn owls
Authors: Béziers Paul , Korner‐Nievergelt Fränzi , Jenni Lukas , Roulin Alexandre , Almasi Bettina 
Published: September 2020

AbstractGlucocorticoid hormones, such as corticosterone, are crucial in regulating daily life metabolism and energy expenditure, as well as promoting short‐term physiological and behavioural responses to unpredictable environmental challenges. Therefore, glucocorticoids are considered to mediate trade‐offs between survival and reproduction. Relatively little is known about how selection has shaped glucocorticoid levels. We used 15 years of capture–recapture and dead recovery data combined with 13 years of corticosterone and breeding success data taken on breeding barn owls (Tyto alba) to investigate such trade‐offs. We found that survival was positively correlated with stress‐induced corticosterone levels in both sexes, whereas annual and lifetime reproductive success (i.e. the sum of young successfully fledged during the entire reproductive career) was positively correlated with both baseline and stress‐induced corticosterone levels in females only. Our results suggest that, in the barn owl, the stress‐induced corticosterone response is a good proxy for adult survival and lifetime reproductive success. However, selection pressure appears to act differently on corticosterone levels of males and females.
Preoperative Depressive Symptoms Associated with Poor Functional Recovery after Surgery
Authors: Tang Victoria L. , Cenzer Irena , McCulloch Charles E. , Finlayson Emily , Cooper Zara , Silvestrini Molly , Ngo Sarah , Schmitt Eva M. , Inouye Sharon K. 
Published: September 2020

BACKGROUND/OBJECTIVESDepression screening and treatment for older adults are recommended in Age‐Friendly Health Systems. Few studies have evaluated the association between depressive symptoms and postoperative functioning. We aimed to determine the association between varying levels of depressive symptoms in the preoperative setting with postoperative functional recovery.DESIGNProspective cohort study.SETTINGTwo academic hospitals in Boston, Massachusetts.PARTICIPANTSSurgical patients aged 70 and older (N = 560).MEASUREMENTSParticipants were assessed preoperatively and 1 year postoperatively. Preoperative evaluation included the 15‐item short‐form Geriatric Depression Scale (GDS). Results were categorized as low (GDS = 0–1), moderate (2–5), or high (6–15) symptom burden. Primary outcome was 1‐year instrumental activities of daily living functional decline. Secondary outcomes included hospital stay longer than 5 days, discharge to post‐acute care (PAC) facility, and readmission within 30 days.RESULTSMean participant age was 76.6 ± 5 years, 58% were women, 81% underwent an orthopedic operation, 13% gastrointestinal, 6% vascular; 13% had functional decline at 1 year after their operation (by symptom burden: low = 5.5%; moderate = 14.8%, and high = 38.6%). After adjusting for age, sex, and comorbidity, those with moderate or high depressive symptoms demonstrated greater odds of functional decline at 1 year compared with those with a low symptom burden (moderate: adjusted odds ratio [AOR] = 2.7; 95% confidence interval [CI] = 1.3–5.3; high: AOR = 9.3; 95% CI = 4.2–20.6), discharge to PAC facility (moderate: AOR = 1.7; 95%CI = 1.2–2.6; high: AOR = 2.7; 95% CI = 1.4–5.1) but demonstrated no significant association with 30‐day readmission or hospital length of stay longer than 5 days.CONCLUSIONGreater burden of preoperative depressive symptoms is associated with increased likelihood of functional decline at 1 year after surgery and of discharge to PAC facility. Preoperative assessment of the burden of depressive symptoms in older adults undergoing elective surgery may be helpful in identifying patients at high risk of poor outcomes.
Full‐face effects of temporal volumizing and temporal lifting techniques
Authors: Casabona Gabriela , Frank Konstantin , Moellhoff Nicholas , Gavril Diana L. , Swift Arthur , Freytag David L. , Kaiser Antonia , Green Jeremy B. , Nikolis Andreas , Cotofana Sebastian 
Published: September 2020

AbstractBackgroundMost injection techniques utilizing hyaluronic acid–based soft tissue fillers have predictable outcomes at the location injected. However, the temporal region has been identified to have aesthetic effects beyond the temple.AimsTo identify and quantify the panfacial aesthetic effects of three different temporal injection techniques.Patients/MethodsThe medical records of nine female and five male Caucasian patients with a mean age of 50.9 ± 11.9 years were retrospectively reviewed for the effects of these techniques: supraperiosteal, interfascial, and subdermal. Panfacial effects were evaluated by the semiquantitative assessment of aesthetic scores for the temple volume, the temporal crest visibility, the lateral orbital rim visibility, the position of the eyebrows, the severity of lateral canthal lines, the midfacial volume, and the contour of the jawline.ResultsThe supraperiosteal injection technique had the greatest influence on improving the temporal volume (25.0%), the temporal crest (33.3%), and the lateral orbital rim visibility (31.0%) scales but had no effects in other facial regions. The interfascial injection technique revealed good effects on improving temporal hollowing (23.3%) but had an even greater effect on the crow's feet (26.8%) and on the position of the eyebrow (33.3%). The subdermal injection technique had its greatest effects in the lower face by improving the contour of the jawline (26.8%) followed by the improvement of the lower cheek fullness scale (14.3%).ConclusionFuture injection algorithms could utilize all three injection techniques together as one multi‐layer injection approach with a tailored proportion of each technique based on the aesthetic needs of the patient.
Salicylic acid regulates PIN2 auxin transporter hyperclustering and root gravitropic growth via Remorin‐dependent lipid nanodomain organisation in Arabidopsis thaliana
Authors: Ke Meiyu , Ma Zhiming , Wang Deyan , Sun Yanbiao , Wen Chenjin , Huang Dingquan , Chen Zichen , Yang Liang , Tan Shutang , Li Ruixi , Friml Jiří , Miao Yansong , Chen Xu 
Published: September 2020

Summary

To adapt to the diverse array of biotic and abiotic cues, plants have evolved sophisticated mechanisms to sense changes in environmental conditions and modulate their growth. Growth‐promoting hormones and defence signalling fine tune plant development antagonistically. During host–pathogen interactions, this defence–growth trade‐off is mediated by the counteractive effects of the defence hormone salicylic acid (SA) and the growth hormone auxin.

Here we revealed an underlying mechanism of SA regulating auxin signalling by constraining the plasma membrane dynamics of PIN2 auxin efflux transporter in Arabidopsis thaliana roots.

The lateral diffusion of PIN2 proteins is constrained by SA signalling, during which PIN2 proteins are condensed into hyperclusters depending on REM1.2‐mediated nanodomain compartmentalisation. Furthermore, membrane nanodomain compartmentalisation by SA or Remorin (REM) assembly significantly suppressed clathrin‐mediated endocytosis. Consequently, SA‐induced heterogeneous surface condensation disrupted asymmetric auxin distribution and the resultant gravitropic response.

Our results demonstrated a defence–growth trade‐off mechanism by which SA signalling crosstalked with auxin transport by concentrating membrane‐resident PIN2 into heterogeneous compartments.
Endogenous activated small interfering RNAs in virus‐infected Brassicaceae crops show a common host gene‐silencing pattern affecting photosynthesis and stress response
Authors: Leonetti Paola , Ghasemzadeh Aysan , Consiglio Arianna , Gursinsky Torsten , Behrens Sven‐Erik , Pantaleo Vitantonio 
Published: September 2020

Summary

Viral infections are accompanied by a massive production of small interfering RNAs (siRNAs) of plant origin, such as virus‐activated (va)siRNAs, which drive the widespread silencing of host gene expression, and whose effects in plant pathogen interactions remain unknown.

By combining phenotyping and molecular analyses, we characterized vasiRNAs that are associated with typical mosaic symptoms of cauliflower mosaic virus infection in two crops, turnip (Brassica rapa) and oilseed rape (Brassica napus), and the reference plant Arabidopsis thaliana.

We identified 15 loci in the three infected plant species, whose transcripts originate vasiRNAs. These loci appear to be generally affected by virus infections in Brassicaceae and encode factors that are centrally involved in photosynthesis and stress response, such as Rubisco activase (RCA), senescence‐associated protein, heat shock protein HSP70, light harvesting complex, and membrane‐related protein CP5. During infection, the expression of these factors is significantly downregulated, suggesting that their silencing is a central component of the plant’s response to virus infections. Further findings indicate an important role for 22 nt long vasiRNAs in the plant’s endogenous RNA silencing response.

Our study considerably enhances knowledge about the new class of vasiRNAs that are triggered in virus‐infected plants and will help to advance strategies for the engineering of gene clusters involved in the development of crop diseases.
Surface disinfection and protective masks for SARS‐CoV‐2 and other respiratory viruses: A review by SIdP COVID‐19 task force
Authors: Barbato Luigi , Bernardelli Francesco , Braga Giovanni , Clementini Marco , Di Gioia Claudio , Littarru Crisitnano , Oreglia Francesco , Raspini Mario , Brambilla Eugenio , Iavicoli Ivo , Pinchi Vilma , Landi Luca , Sforza Nicola Marco , Cavalcanti Raffaele , Crea Alessandro , Cairo Francesco 
Published: September 2020

AbstractObjectivesPrimary focused question for this systematic review (SR) was “Which is the evidence about surfaces decontamination and protection masks for SARS‐Cov‐2 in dental practice?” Secondary question was “Which is the evidence about surfaces decontamination and protection masks against airborne pathogens and directly transmitted viral pathogens causing respiratory infections?”Materials and MethodsPRISMA guidelines were used. Studies on surface decontamination and protective masks for SARS‐CoV‐2 in dental practice were considered. Studies on other respiratory viruses were considered for the secondary question.ResultsNo studies are available for SARS‐CoV‐2. Four studies on surface disinfection against respiratory viruses were included. Ethanol 70% and sodium hypochlorite 0,5% seem to be effective in reducing infectivity by > 3log TCID. Four RCTs compared different types of masks on HCW. The single studies reported no difference for laboratory‐diagnosed influenza, laboratory‐diagnosed respiratory infection, and influenza‐like illness. A meta‐analysis was not considered appropriate.ConclusionsThere is lack of evidence on the efficacy of surface disinfection and protective masks to reduce the spread of SARS‐CoV‐2 or other respiratory viruses in dentistry. However, the consistent use of respirator and routine surface disinfection is strongly suggested. There is urgent need of data on the efficacy of specific protection protocols for dental HCW against viral infections.
Canine mammary tumours: Size matters–a progression from low to highly malignant subtypes
Authors: Gedon Julia , Wehrend Axel , Failing Klaus , Kessler Martin 
Published: September 2020

AbstractThe purpose of this study was to evaluate a possible association between mammary tumour size and increasing degree of malignancy. Data of 625 dogs with a total of 1459 mammary tumours were analysed retrospectively. 80.3% dogs were intact, mean age at diagnosis was 9.7 ± 2.5 years, 75.8% were pure breed dogs. Median body weight was 20.0 kg. Malignant tumours (n = 580) were significantly larger than their benign counterparts (1.94 cm vs 0.90 cm in mean, respectively; P ≤ .0001), resulting in a positive correlation between increasing tumour size and a change from benign to malignant (P ≤ .0001; rs = 0.214). When malignant tumours were grouped into four degrees of increasing malignancy (complex/simple/solid/anaplastic carcinomas) a significant positive correlation between increasing tumour size and more malignant tumour degree (P ≤ .0001; rs = 0.195) could be demonstrated. In a number of cases, highly malignant tumours were found to arise within less malignant lesions, supporting the concept of a further progression within the malignant tumour subtypes. In patients with multiple tumours, mean tumour sizes for malignant tumours were significantly smaller compared to patients with only one tumour (1.67 vs 2.71 cm in mean, respectively; P < .0001). These findings suggest that mammary tumours progress not only from benign to malignant but also from low to highly malignant. An increase in diameter of only a few millimetres may therefore have a big impact on the patient's outcome.