Miracle-dz/UniFAR-FTUs huggingface dataset:
Biophysical and morphological changes in inner hair cells and their efferent innervation in the ageing mouse cochlea

Age‐related hearing loss is a progressive hearing loss involving environmental and genetic factors, leading to a decrease in hearing sensitivity, threshold and speech discrimination. We compared age‐related changes in inner hair cells (IHCs) between four mouse strains with different levels of progressive hearing loss. The surface area of apical coil IHCs (9–12 kHz cochlear region) decreases by about 30–40% with age. The number of BK channels progressively decreases with age in the IHCs from most mouse strains, but the basolateral membrane current profile remains unchanged. The mechanoelectrical transducer current is smaller in mice harbouring the hypomorphic Cdh23 allele Cdh23ahl (C57BL/6J; C57BL/6NTac), but not in Cdh23‐repaired mice (C57BL/6NTacCdh23+), indicating that it could contribute to the different progression of hearing loss among mouse strains. The degree of efferent rewiring onto aged IHCs, most likely coming from the lateral olivocochlea fibres, was correlated with hearing loss in the different mouse strains.
Sleep Tests in the Non-Contact Era of the COVID-19 Pandemic: Home Sleep Tests Versus In-Laboratory Polysomnography

Copyright © 2020 by Korean Society of Otorhinolaryngology-Head and Neck Surgery. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Clinical and Experimental Otorhinolaryngology Vol. 13, No. 4: 318-319, November 2020 https://doi.org/10.21053/ceo.2020. 01599
Attosecond metrology in a continuous-beam transmission electron microscope

Electron microscopy is advanced to attosecond resolution by modulating the beam with the field cycles of a continuous-wave laser. Electron microscopy can visualize the structure of complex materials with atomic and subatomic resolution, but investigations of reaction dynamics and light-matter interaction call for time resolution as well, ideally on a level below the oscillation period of light. Here, we report the use of the optical cycles of a continuous-wave laser to bunch the electron beam inside a transmission electron microscope into electron pulses that are shorter than half a cycle of light. The pulses arrive at the target at almost the full average brightness of the electron source and in synchrony to the optical cycles, providing attosecond time resolution of spectroscopic features. The necessary modifications are simple and can turn almost any electron microscope into an attosecond instrument that may be useful for visualizing the inner workings of light-matter interaction on the basis of the atoms and the cycles of light.
Assessment of dental implant stability using resonance frequency analysis and quantitative ultrasound methods.

PURPOSE Quantitative ultrasound (QUS) and resonance frequency analyses (RFA) are promising methods to assess the stability of dental implants. The aim of this in vivo preclinical study is to compare the results obtained with these two techniques with the bone-implant contact (BIC) ratio, which is the gold standard to assess dental implant stability. METHODS Twenty-two identical dental implants were inserted in the tibia and femur of 12 rabbits, which were sacrificed after different healing durations (0, 4, 8 and 13 weeks). For each implant, the ultrasonic indicator (UI) and the implant stability quotient (ISQ) were retrieved just before the animal sacrifice using the QUS and RFA techniques, respectively. Histomorphometric analyses were carried out to estimate the bone-implant contact ratio. RESULTS UI values were found to be better correlated to BIC values (R²=0.47) compared to ISQ values (R²=0.39 for measurements in one direction and R²=0.18 for the other direction), which were shown to be dependent on the direction of measurements. Errors realized on the UI were around 3.3 times lower to the ones realized on the ISQ. CONCLUSIONS QUS provide a better estimation of dental implant stability compared to RFA. This study paves the way for the future clinical development of a medical device aiming at assessing dental implant stability in a patient-specific manner. Clinical studies should confirm these results in the future.
Impact of Medium Cut-Off Dialyzers on Patient-Reported Outcomes: COREXH Registry

Introduction: A new generation of hemodialysis (HD) membranes called medium cut-off (MCO) membranes possesses enhanced capacities for middle molecule clearance, which have been associated with adverse outcomes in this population. These improvements could potentially positively impact patient-reported outcomes (PROs). Objective: The objective of this study was to evaluate the impact of MCO membranes on PROs in a cohort of HD patients in Colombia. Methods: This was a prospective, multicenter, observational cohort study of 992 patients from 12 renal clinics in Colombia who were switched from high-flux HD to MCO therapy and observed for 12 months. Changes in Kidney Disease Quality of Life 36-Item Short Form Survey (KDQoL-SF36) domains, Dialysis Symptom Index (DSI), and restless legs syndrome (RLS) 12 months after switching to MCO membranes were compared with time on high-flux membranes. Repeated measures of ANOVA were used to evaluate changes in KDQoL-SF36 scores; severity scoring was used to assess DSI changes over time; Cochran’s Q test was used to evaluate changes in frequency of diagnostic criteria of RLS. Results: During 12 months of follow-up, 3 of 5 KDQoL-SF36 domains improved compared with baseline: symptoms (p < 0.0001), effects of kidney disease (p < 0.0001), and burden of kidney disease (p < 0.001). The proportion of patients diagnosed with RLS significantly decreased from 22.1% at baseline to 10% at 12 months (p < 0.0001). No significant differences in the number of symptoms (DSI, p = 0.1) were observed, although their severity decreased (p = 0.009). Conclusions: In conventional HD patients, the expanded clearance of large middle molecules with MCO-HD membranes was associated with higher health-related quality of life scores and a decrease in the prevalence of RLS.
Molecular characteristics of eae-positive clinical Shiga toxin-producing Escherichia coli in Sweden

ABSTRACT Shiga toxin (Stx)-producing Escherichia coli (STEC) can cause a wide range of symptoms from asymptomatic carriage, mild diarrhea to bloody diarrhea (BD) and hemolytic uremic syndrome (HUS). Intimin, encoded by the eae gene, also plays a critical role in STEC pathogenesis. Herein, we investigated the prevalence and genetic diversity of eae among clinical STEC isolates from patients with diarrhea, BD, HUS as well as from asymptomatic STEC-positive individuals in Sweden with whole-genome sequencing. We found that 173 out of 239 (72.4%) of clinical STEC strains were eae positive. Six eae subtypes (ϵ1, γ1, β3, θ, ζ and ρ) were identified eae and its subtype γ1 were significantly overrepresented in O157:H7 strains isolated from BD and HUS patients. ϵ1 was associated with O121:H19 and O103:H2 strains, and β3 to O26:H11 strains. The combination of eae subtype γ1 and stx subtype (stx 2 or stx 1+stx 2) is more likely to cause severe disease, suggesting the possibility of using eae genotypes in risk assessment of STEC infection. In summary, this study demonstrated a high prevalence of eae in clinical STEC strains and considerable genetic diversity of eae in STEC strains in Sweden from 1994 through 2018, and revealed association between eae subtypes and disease severity.
Circulating microtranscriptome profiles reveal distinct expression of microRNAs in severe leptospirosis

Biomarkers to predict the severity of leptospirosis are still lacking. This study aimed to identify and validate microRNAs in patients with severe leptospirosis, that could potentially be used as biomarkers for predicting an unfavorable outcome. Serum samples were collected from participants with definite diagnosis of leptospirosis. The participants were divided into two groups, non-severe and severe leptospirosis, as defined by the Specific Organ Sequential Organ Failure (SOFA) Score of more than two in any organ. Microtranscriptome analysis was performed using the NanoString miRNA Expression Assay. The expression level of candidate miRNAs was then validated by quantitative RT-PCR. Based on the NanoString, the microtranscriptome profile of the severe group was significantly different from that of the non-severe group. Upregulation of miR155-5p, miR362-3p, miR502-5p, miR601, miR1323, and miR630 in the severe group were identified, and further investigated. A total of 119 participants were enrolled in the validation cohort. Serum miR155-5p and miR630 levels were significantly higher in the severe group compared to the non-severe group. The combined use of miR155-5p or miR-630 with serum bicarbonate levels had an AUC of 0.79 (95%CI; 0.69–0.89, p<0.001) in identifying the severity of the disease. This data provides the first evidence that the microtranscriptome profiles of patients with severe leptospirosis were different from the non-severe group. Serum miR155-5p and miR630 levels might be novel biomarkers for identifying severe leptospirosis.
Therapeutic Potential of Tpl2 (Tumor Progression Locus 2) Inhibition on Diabetic Vasculopathy Through the Blockage of the Inflammasome Complex

Supplemental Digital Content is available in the text. Objective: Diabetic retinopathy, one of retinal vasculopathy, is characterized by retinal inflammation, vascular leakage, blood-retinal barrier breakdown, and neovascularization. However, the molecular mechanisms that contribute to diabetic retinopathy progression remain unclear. Approach and Results: Tpl2 (tumor progression locus 2) is a protein kinase implicated in inflammation and pathological vascular angiogenesis. Nε-carboxymethyllysine (CML) and inflammatory cytokines levels in human sera and in several diabetic murine models were detected by ELISA, whereas liquid chromatography–tandem mass spectrometry analysis was used for whole eye tissues. The CML and p-Tpl2 expressions on the human retinal pigment epithelium (RPE) cells were determined by immunofluorescence. Intravitreal injection of pharmacological inhibitor or NA (neutralizing antibody) was used in a diabetic rat model. Retinal leukostasis, optical coherence tomography, and H&E staining were used to observe pathological features. Sera of diabetic retinopathy patients had significantly increased CML levels that positively correlated with diabetic retinopathy severity and foveal thickness. CML and p-Tpl2 expressions also significantly increased in the RPE of both T1DM and T2DM diabetes animal models. Mechanistic studies on RPE revealed that CML-induced Tpl2 activation and NADPH oxidase, and inflammasome complex activation were all effectively attenuated by Tpl2 inhibition. Tpl2 inhibition by NA also effectively reduced inflammatory/angiogenic factors, retinal leukostasis in streptozotocin-induced diabetic rats, and RPE secretion of inflammatory cytokines. The attenuated release of angiogenic factors led to inhibited vascular abnormalities in the diabetic animal model. Conclusions: The inhibition of Tpl2 can block the inflammasome signaling pathway in RPE and has potential clinical and therapeutic implications in diabetes-associated retinal microvascular dysfunction.
Modification of diet, exercise and lifestyle (MODEL) study: a randomised controlled trial protocol

Introduction Most cardiovascular disease (CVD)-related events could be prevented or substantially delayed with improved diet and lifestyle. Providing information on structural vascular disease may improve CVD risk factor management, but its impact on lifestyle change remains unclear. This study aims to determine whether providing visualisation and pictorial representation of structural vascular disease (abdominal aortic calcification (AAC)) can result in healthful diet and lifestyle change. Methods and analysis This study, including men and women aged 60–80 years, is a 12-week, two-arm, multisite randomised controlled trial. At baseline, all participants will have AAC assessed from a lateral spine image captured using a bone densitometer. Participants will then be randomised to receive their AAC results at baseline (intervention group) or a usual care control group that will receive their results at 12 weeks. All participants will receive information about routinely assessed CVD risk factors and standardised (video) diet and lifestyle advice with three simple goals: (1) increase fruit and vegetable (FV) intake by at least one serve per day, (2) improve other aspects of the diet and (3) reduce sitting time and increase physical activity. Clinical assessments will be performed at baseline and 12 weeks. Outcomes The primary outcome is a change in serum carotenoid concentrations as an objective measure of FV intake. The study design, procedures and treatment of data will adhere to Standard Protocol Items for Randomized Trials guidelines. Ethics and dissemination Ethics approval for this study has been granted by the Edith Cowan University and the Deakin University Human Research Ethics Committees (Project Numbers: 20513 HODGSON and 2019-220, respectively). Results of this study will be published in peer-reviewed academic journals and presented in scientific meetings and conferences. Information regarding consent, confidentiality, access to data, ancillary and post-trial care and dissemination policy has been disclosed in the participant information form. Trial registration number Australian New Zealand Clinical Trial Registry (ACTRN12618001087246).
Mesothelin-targeted CAR-T cell therapy for solid tumors

ABSTRACT Introduction: Mesothelin (MSLN) is a tumor differentiation antigen normally restricted to the body’s mesothelial surfaces, but significantly overexpressed in a broad range of solid tumors. For this reason, MSLN has emerged as an important target for the development of novel immunotherapies. This review focuses on anti-MSLN chimeric antigen receptor (CAR) T cell immunotherapy approaches. Areas covered: A brief overview of MSLN as a therapeutic target and existing anti-MSLN antibody-based drugs and vaccines is provided. A detailed account of anti-MSLN CAR-T cell approaches utilized in preclinical models is presented. Finally, a comprehensive summary of currently ongoing and completed anti-MSLN CAR-T cell clinical trials is discussed. Expert opinion: Initial trials using anti-MSLN CAR-T cells have been safe, but efficacy has been limited. Employing regional routes of delivery, introducing novel modifications leading to enhanced tumor infiltration and persistence, and improved safety profiles and combining anti-MSLN CAR-T cells with standard therapies, could render them more efficacious in the treatment of solid malignancies.
Production et traitement de données omiques hétérogènes en vue de l'étude de la plasticité de la paroi chez des écotypes de la plante modèle Arabidopsis thaliana provenant d'altitudes contrastées

Le rechauffement climatique constitue une problematique d'actualite tres preoccupante en raison de ses effets potentiels sur la biodiversite et le secteur agricole. Mieux comprendre l'adaptation des plantes face a ce phenomene recent represente donc un interet majeur pour la science et la societe. L'etude de populations naturelles provenant d'un gradient d'altitude permet de correler l'impact d'un ensemble de conditions climatiques (temperature, humidite, radiation, etc.) a des traits phenotypiques. Ces differentes populations sont dites adaptees a leurs conditions climatiques in natura. En cultivant ces plantes dans des conditions standardisees de laboratoire (intensite lumineuse, substrat, temperature, arrosage, etc.), la variabilite phenotypique observee, est alors due essentiellement a la variabilite genetique intrinseque a chaque plante, donc a son genotype. La mise en culture de ces memes plantes en changeant une seule variable, par exemple la temperature, permet de mettre en evidence un phenotype caracteristique. Ce phenotype observe peut etre une reponse d'acclimatation d'un genome adapte. Le projet WallOmics vise a caracteriser l'adaptation des plantes a l'altitude par l'etude de populations naturelles d'Arabidopsis thaliana provenant des Pyrenees. Les acteurs moleculaires de l'adaptation des plantes au climat sont encore mal connus mais il apparait que la paroi des cellules vegetales pourrait avoir un role important dans ce processus. En effet, celle-ci represente le squelette des plantes et leur confere une rigidite tout en representant une barriere externe sensible et dynamique face aux changements environnementaux. Sa structure et sa composition peuvent etre modifiees a tout moment. Il est d'ailleurs possible de dire que cette paroi vegetale donne la forme generale de la plante (taille, forme, densite, etc.), son phenotype observable. Ce projet se consacrera principalement a l'etude des parois des cellules vegetales. Les nouvelles technologies ont permis l'emergence des donnees dites "omiques", c'est-a-dire de vastes ensembles de donnees provenant de niveaux biologiques multiples, comme des donnees ecologiques, de phenotypages, biochimiques, proteomiques, transcriptomiques et genomiques. L'etude et la mise en relation de ces donnees ont favorise le developpement d'approches globales qui visent a etablir une reponse a plusieurs echelles. C'est justement par ce type d'approche non mecanistique que le projet WallOmics a contribue a etablir les bases moleculaires des modifications des parois face aux changements climatiques.
Biting rhythm and demographic attributes of Aedes albopictus (Skuse) females from different urbanized settings in Penang Island, Malaysia under uncontrolled laboratory conditions

Urbanization could potentially modify Aedes albopictus’ ecology by changing the dynamics of the species, and affecting their breeding sites due to environmental changes, and thus contribute to dengue outbreaks. Thus, this study was conducted to evaluate the biting rhythm, fecundity and longevity of adult female Ae. albopictus in relation to urbanization strata; urban, suburban and rural areas in Penang Island, Malaysia. The experiments were done in comparison to a laboratory strain. Twenty-four hours biting activity of all the mosquito strains showed a clear bimodal biting activity, with morning and evening twilight peaks. The interaction effect between biting time and mosquito strains was not significant. Meanwhile, differences in fecundity among mosquito strains were statistically significant (F(3,442) = 10.559, P < 0.05) with urban areas having higher mean number of eggs (mean = 107.69, standard error = 3.98) than suburban (mean = 94.48, standard error = 5.18), and rural areas (mean = 72.52, standard error = 3.87). Longevity of adult females were significantly higher (F(3,441) = 31.259, P < 0.05) for mosquito strains from urban areas compared to the other strains. These findings would provide crucial information for the planning of control programs in Malaysia, particularly Penang.
Alternative splicing patterns of doublesex reveal a missing link between Nix and doublesex in the sex determination cascade of Aedes albopictus

Sexual development in insects is regulated by a complicated hierarchical cascade of sex determination. The primary signals are diverse, whereas the central nexus doublesex (dsx) gene is relatively conserved within the pathway. Aedes (Stegomyia) albopictus is an important vector with an extensive worldwide distribution. We previously reported that Ae. albopictus dsx (Aalbdsx) yields one male‐ (AalbdsxM) and three female‐specific isoforms (AalbdsxF1‐3); however, the spatiotemporal expression profiles and mechanisms regulating sex‐specific alternative splicing require further investigation. In this study, we demonstrated that the AalbdsxM messenger RNA (mRNA) represents the default pattern when analyzed in human foreskin fibroblasts and HeLa cells. We combined reverse transcription polymerase chain reaction with RNA immunoprecipitation using specific antibodies against tagged Ae. albopictus male‐determining factor AalNix and confirmed that AalNix indirectly regulates dsx pre‐mRNA and regulates its alternative splicing. During the early embryo stage (0–2 and 4–8 h), maternal dsxF and default splicing dsxM were detected in both sexes; the expression of dsxM then decreased until sufficient AalNix transcripts accumulated in male embryos at 20–24 h. These findings suggest that one or more potential dsx splicing enhancers can shift dsxM to dsxF in both sexes; however, the presence of Nix influences the function of this unknown splicing enhancer and ultimately leads to the formation of dsxM in males. Finally, our results provide important insight into the regulatory mechanism of dsx alternative splicing in the mosquito.
Pleurotus highking mushrooms potentiate antiproliferative and antimigratory activity against triple-negative breast cancer cells by suppressing Akt signaling

In this study, we evaluated the antiproliferative and antimetastatic effects of the Pleurotus highking mushroom on the human triple-negative breast cancer cell lines MDA-MB-231 and HCC-1937 and attempted to elucidate the underlying molecular mechanisms. The antiproliferative effects of P. highking purified fraction-III (PEF-III) were investigated using colony formation and MTS assays. The antimigratory effects of PEF-III were determined by wound healing, transwell migration, and matrigel cell invasion assays. The protein expression levels were evaluated using Western blot analysis. The effect of PEF-III on tumor-sphere formation was examined in a 3D sphere-forming medium, and the mRNA expressions of proliferation- and migration-related genes in the cells from the tumor spheres were determined using RT-qPCR. PEF-III treatment caused a potent and concentration-dependent decrease in the numbers of colonies and viable cells. It also remarkably suppressed the migratory ability of the cells. Mechanistically, PEF-III treatment reduced the expression of pAkt, matrix metallopeptidase-9 (MMP-9), and vimentin. Furthermore, PEF-III reduced the number and size of the tumor spheres in the 3D culture system. It also significantly reduced the mRNA expression of Ki-67, MMP-9, and vimentin in the PEF-III-treated tumor-sphere cells. PEF-III exerted promising antiproliferative and antimigratory effects in triple-negative breast cancer cell lines by suppressing Akt signaling. Therefore, P. highking mushrooms may be considered a potential source for the development of potent anticancer drug(s) for the treatment of breast cancer.
Nanoencapsulation of Plant Volatile Organic Compounds to Improve Their Biological Activities

Abstract Plant volatile organic compounds (volatiles) are secondary plant metabolites that play crucial roles in the reproduction, defence, and interactions with other vegetation. They have been shown to exhibit a broad range of biological properties and have been investigated for antimicrobial and anticancer activities. In addition, they are thought be more environmentally friendly than many other synthetic chemicals 1. Despite these facts, their applications in the medical, food, and agricultural fields are considerably restricted due to their volatilities, instabilities, and aqueous insolubilities. Nanoparticle encapsulation of plant volatile organic compounds is regarded as one of the best strategies that could lead to the enhancement of the bioavailability and biological activity of the volatile compounds by overcoming their physical limitations and promoting their controlled release and cellular absorption. In this review, we will discuss the biosynthesis and analysis of plant volatile organic compounds, their biological activities, and limitations. Furthermore, different types of nanoparticle platforms used to encapsulate the volatiles and the biological efficacies of nanoencapsulated volatile organic compounds will be covered.