bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low Dose, High Frequency Movement Based Dilator Therapy for Dyspareunia: Retrospective Analysis of 26 Cases
Authors: Miles Katherine , Miles Shana 
Published: May 2021

Abstract

Introduction
While two-thirds of women will experience dyspareunia and vaginal dilators are often used to treat dyspareunia, outside of a single case report, no study has investigated the potential of low-dose, high frequency movement-based dilator therapy for dyspareunia in premenopausal female patients.

Aim
To determine the utility of low-dose, high frequency movement-based dilator use for dyspareunia in premenopausal female patients.

Methods
Retrospective study of women presenting to outpatient hospital-based pelvic floor physical therapy office in a tertiary care center. All adult premenopausal female patients who were referred to pelvic floor physical therapy for dyspareunia and completed movement-based dilator therapy (MBDT) and met study criteria (n = 26) were included for analysis.

Main Outcome Measure
Patient change in pain level status using Numeric Pain Rating Scale with intercourse was compared between initial evaluation and time of discharge from pelvic floor physical therapy.

Results
Among the 26 women who met criteria for this study, the average pain score decreased from 8.3 (SD 2.2) before treatment to 1.3 (SD 2.0) after treatment and was statistically significant (P&lt; .001). Complete resolution of dyspareunia was reported in 58% of patients. Patients completed between 2 and 6 total pelvic floor physical therapy visits (average 3.7, SD1.5), over 0–44 weeks (mean 9.6 weeks, SD 8.3).

Conclusion
Low-dose, high frequency, movement-based dilator therapy significantly reduced or resolved the experience of pain with penetrative vaginal intercourse with dyspareunia. Future prospective studies with larger samples and the inclusion of sexual functional status should be considered to explore the full potential of this modality in treatment of premenopausal patients with dyspareunia.
DO WEAK OR STRONG ACIDS REMOVE CARBONATE CONTAMINATION FROM ANCIENT TOOTH ENAMEL MORE EFFECTIVELY? THE EFFECT OF ACID PRETREATMENT ON RADIOCARBON AND δ13C ANALYSES
Authors: Wood Rachel , Fleury Andre Barros Curado , Fallon Stewart , Nguyen Thi Mai Huong , Nguyen Anh Tuan 
Published: May 2021

ABSTRACTIn hot environments, collagen, which is normally targeted when radiocarbon (14C) dating bone, rapidly degrades. With little other skeletal material suitable for 14C dating, it can be impossible to obtain dates directly on skeletal materials. A small amount of carbonate occurs in hydroxyapatite, the mineral phase of bone and tooth enamel, and has been used as an alternative to collagen. Unfortunately, the mineral phase is often heavily contaminated with exogenous carbonate causing 14C dates to underestimate the true age of a sample. Although tooth enamel, with its larger, more stable crystals and lower porosity, is likely to be more robust to diagenesis than bone, little work has been undertaken to investigate how exogenous carbonate can be effectively removed prior to 14C dating. Typically, acid is used to dissolve calcite and etch the surface of the enamel, but it is unclear which acid is most effective. This study repeats and extends earlier work using a wider range of samples and acids and chelating agents (hydrochloric, lactic, acetic and propionic acids, and EDTA). We find that weaker acids remove carbonate contaminants more effectively than stronger acids, and acetic acid is the most effective. However, accurate dates cannot always be obtained.
Bedaquiline, an FDA-approved drug, inhibits mitochondrial ATP production and metastasis in vivo, by targeting the gamma subunit (ATP5F1C) of the ATP synthase
Authors: Fiorillo Marco , Scatena Cristian , Naccarato Antonio Giuseppe , Sotgia Federica , Lisanti Michael P. 
Published: May 2021

AbstractHere, we provide evidence that high ATP production by the mitochondrial ATP-synthase is a new therapeutic target for anticancer therapy, especially for preventing tumor progression. More specifically, we isolated a subpopulation of ATP-high cancer cells which are phenotypically aggressive and demonstrate increases in proliferation, stemness, anchorage-independence, cell migration, invasion and multi-drug resistance, as well as high antioxidant capacity. Clinically, these findings have important implications for understanding treatment failure and cancer cell dormancy. Using bioinformatic analysis of patient samples, we defined a mitochondrial-related gene signature for metastasis, which features the gamma-subunit of the mitochondrial ATP-synthase (ATP5F1C). The relationship between ATP5F1C protein expression and metastasis was indeed confirmed by immunohistochemistry. Next, we used MDA-MB-231 cells as a model system to functionally validate these findings. Importantly, ATP-high MDA-MB-231 cells showed a nearly fivefold increase in metastatic capacity in vivo. Consistent with these observations, ATP-high cells overexpressed (i) components of mitochondrial complexes I–V, including ATP5F1C, and (ii) markers associated with circulating tumor cells (CTCs) and metastasis, such as EpCAM and VCAM1. Knockdown of ATP5F1C expression significantly reduced ATP-production, anchorage-independent growth, and cell migration, as predicted. Similarly, therapeutic administration of the FDA-approved drug, Bedaquiline, downregulated ATP5F1C expression in vitro and prevented spontaneous metastasis in vivo. In contrast, Bedaquiline had no effect on the growth of non-tumorigenic mammary epithelial cells (MCF10A) or primary tumors in vivo. Taken together, our results suggest that mitochondrial ATP depletion is a new therapeutic strategy for metastasis prophylaxis, to avoid treatment failure. In summary, we conclude that mitochondrial ATP5F1C is a promising new biomarker and molecular target for future drug development, for the prevention of metastatic disease progression.
Kartogenin prevents cartilage degradation and alleviates osteoarthritis progression in mice via the miR-146a/NRF2 axis
Authors: Hou Mingzhuang , Zhang Yijian , Zhou Xinfeng , Liu Tao , Yang Huilin , Chen Xi , He Fan , Zhu Xuesong 
Published: May 2021

AbstractOsteoarthritis (OA) is a common articular degenerative disease characterized by loss of cartilage matrix and subchondral bone sclerosis. Kartogenin (KGN) has been reported to improve chondrogenic differentiation of mesenchymal stem cells. However, the therapeutic effect of KGN on OA-induced cartilage degeneration was still unclear. This study aimed to explore the protective effects and underlying mechanisms of KGN on articular cartilage degradation using mice with post-traumatic OA. To mimic the in vivo arthritic environment, in vitro cultured chondrocytes were exposed to interleukin-1β (IL-1β). We found that KGN barely affected the cell proliferation of chondrocytes; however, KGN significantly enhanced the synthesis of cartilage matrix components such as type II collagen and aggrecan in a dose-dependent manner. Meanwhile, KGN markedly suppressed the expression of matrix degradation enzymes such as MMP13 and ADAMTS5. In vivo experiments showed that intra-articular administration of KGN ameliorated cartilage degeneration and inhibited subchondral bone sclerosis in an experimental OA mouse model. Molecular biology experiments revealed that KGN modulated intracellular reactive oxygen species in IL-1β-stimulated chondrocytes by up-regulating nuclear factor erythroid 2-related factor 2 (NRF2), while barely affecting its mRNA expression. Microarray analysis further revealed that IL-1β significantly up-regulated miR-146a that played a critical role in regulating the protein levels of NRF2. KGN treatment showed a strong inhibitory effect on the expression of miR-146a in IL-1β-stimulated chondrocytes. Over-expression of miR-146a abolished the anti-arthritic effects of KGN not only by down-regulating the protein levels of NRF2 but also by up-regulating the expression of matrix degradation enzymes. Our findings demonstrate, for the first time, that KGN exerts anti-arthritic effects via activation of the miR-146a-NRF2 axis and KGN is a promising heterocyclic molecule to prevent OA-induced cartilage degeneration.
Stepwise ABC system for classification of any type of genetic variant
Authors: Houge Gunnar , Laner Andreas , Cirak Sebahattin , de Leeuw Nicole , Scheffer Hans , den Dunnen Johan T. 
Published: May 2021

AbstractThe American College of Medical Genetics and Genomicsand the Association for Molecular Pathology (ACMG-AMP) system for variant classification is score based with five classes: benign, likely benign, variant of unknown significance (VUS), likely pathogenic, and pathogenic. Here, we present a variant classification model that can be an add-on or alternative to ACMG classification: A stepwise system that can classify any type of genetic variant (e.g., hypomorphic alleles, imprinted alleles, copy number variants, runs of homozygosity, enhancer variants, and variants related to traits). We call it the ABC system because classification is first functional (A), then clinical (B), and optionally a standard comment that fits the clinical question is selected (C). Both steps A and B have 1–5 grading when knowledge is sufficient, if not, class “zero” is assigned. Functional grading (A) only concerns biological consequences with the stages normal function (1), likely normal function (2), hypothetical functional effect (3), likely functional effect (4), and proven functional effect (5). Clinical grading (B) is genotype–phenotype focused with the stages “right type of gene” (1), risk factor (2), and pathogenic (3–5, depending on penetrance). Both grades are listed for each variant and combined to generate a joint class ranging from A to F. Importantly, the A–F classes are linked to standard comments, reflecting laboratory or national policy. In step A, the VUS class is split into class 0 (true unknown) and class 3 (hypothetical functional effect based on molecular predictions or de novo occurrence), providing a rationale for variant-of-interest reporting when the clinical picture could fit the finding. The system gives clinicians a better guide to variant significance.
Oxygen vacancy-induced topological nanodomains in ultrathin ferroelectric films
Authors: Peng Wei , Mun Junsik , Xie Qidong , Chen Jingsheng , Wang Lingfei , Kim Miyoung , Noh Tae Won 
Published: May 2021

AbstractOxygen vacancy in oxide ferroelectrics can be strongly coupled to the polar order via local strain and electric fields, thus holding the capability of producing and stabilizing exotic polarization patterns. However, despite intense theoretical studies, an explicit microscopic picture to correlate the polarization pattern and the distribution of oxygen vacancies remains absent in experiments. Here we show that in a high-quality, uniaxial ferroelectric system, i.e., compressively strained BaTiO3 ultrathin films (below 10 nm), nanoscale polarization structures can be created by intentionally introducing oxygen vacancies in the film while maintaining structure integrity (namely no extended lattice defects). Using scanning transmission electron microscopy, we reveal that the nanodomain is composed of swirling electric dipoles in the vicinity of clustered oxygen vacancies. This finding opens a new path toward the creation and understanding of the long-sought topological polar objects such as vortices and skyrmions.
Development of P301S tau seeded organotypic hippocampal slice cultures to study potential therapeutics
Authors: McCarthy James M. , Virdee Jasmeet , Brown Jessica , Ursu Daniel , Ahmed Zeshan , Cavallini Annalisa , Nuthall Hugh N. 
Published: May 2021

AbstractIntracellular tau inclusions are a pathological hallmark of Alzheimer's disease, progressive supranuclear palsy, corticobasal degeneration and other sporadic neurodegenerative tauopathies. Recent in vitro and in vivo studies have shown that tau aggregates may spread to neighbouring cells and functionally connected brain regions, where they can seed further tau aggregation. This process is referred to as tau propagation. Here we describe an ex vivo system using organotypic hippocampal slice cultures (OHCs) which recapitulates aspects of this phenomenon. OHCs are explants of hippocampal tissue which may be maintained in culture for months. They maintain their synaptic connections and multicellular 3D architecture whilst also permitting direct control of the environment and direct access for various analysis types. We inoculated OHCs prepared from P301S mouse pups with brain homogenate from terminally ill P301S mice and then examined the slices for viability and the production and localization of insoluble phosphorylated tau. We show that following seeding, phosphorylated insoluble tau accumulate in a time and concentration dependent manner within OHCs. Furthermore, we show the ability of the conformation dependent anti-tau antibody, MC1, to compromise tau accrual in OHCs, thus showcasing the potential of this therapeutic approach and the utility of OHCs as an ex vivo model system for assessing such therapeutics.
Strongly masked content retained in memory made accessible through repetition
Authors: Pang Damian K. F. , Elntib Stamatis 
Published: May 2021

AbstractA growing body of evidence indicates that information can be stored even in the absence of conscious awareness. Despite these findings, unconscious memory is still poorly understood with limited evidence for unconscious iconic memory storage. Here we show that strongly masked visual data can be stored and accumulate to elicit clear perception. We used a repetition method across a wide range of conditions (Experiment 1) and a more focused follow-up experiment with enhanced masking conditions (Experiment 2). Information was stored despite being masked, demonstrating that masking did not erase or overwrite memory traces but limited perception. We examined the temporal properties and found that stored information followed a gradual but rapid decay. Extraction of meaningful information was severely impaired after 300 ms, and most data was lost after 700 ms. Our findings are congruent with theories of consciousness that are based on an integration of subliminal information and support theoretical predictions based on the global workspace theory of consciousness, especially the existence of an implicit iconic memory buffer store.
Positive effect of timed blue-enriched white light on sleep and cognition in patients with mild and moderate Alzheimer’s disease
Authors: Kim Seong Jae , Lee Sun Hee , Suh In Bum , Jang Jae-Won , Jhoo Jin Hyeong , Lee Jung Hie 
Published: May 2021

AbstractConflicting results have been reported regarding the effectiveness of light treatment (LT) in patients with Alzheimer’s disease (AD). We investigated the effectiveness of blue-enriched white LT on sleep, cognition, mood and behavior in patients with mild and moderate AD. The treatment group (n = 14) sat about 60 cm away from a small (136 × 73 × 16 mm) LED light box for 1 h each morning for 2 weeks. The control group (n = 11) wore dark, blue-attenuating sunglasses during the 1 h exposures. The morning light started 9–10 h after each individual’s dim light melatonin onset (DLMO). Assessments were done at baseline (T0), immediate post-treatment (T1), and 4 weeks after the end of the 2 weeks of LT (T2). Sleep was measured by actigraphy. Blue-enriched LT had a significantly better effect on the Pittsburgh Sleep Quality Index at T2 compared to blue-attenuated LT, and a trend of better effectiveness on total sleep time at T2. There was a significant increase in Mini-Mental State Examination score at T2 after blue-enriched LT than that at T0. Our findings suggest that morning blue-enriched LT has a benefit in improving sleep and cognitive function in AD patients.
CMM-Net: Contextual multi-scale multi-level network for efficient biomedical image segmentation
Authors: Al-masni Mohammed A. , Kim Dong-Hyun 
Published: May 2021

AbstractMedical image segmentation of tissue abnormalities, key organs, or blood vascular system is of great significance for any computerized diagnostic system. However, automatic segmentation in medical image analysis is a challenging task since it requires sophisticated knowledge of the target organ anatomy. This paper develops an end-to-end deep learning segmentation method called Contextual Multi-Scale Multi-Level Network (CMM-Net). The main idea is to fuse the global contextual features of multiple spatial scales at every contracting convolutional network level in the U-Net. Also, we re-exploit the dilated convolution module that enables an expansion of the receptive field with different rates depending on the size of feature maps throughout the networks. In addition, an augmented testing scheme referred to as Inversion Recovery (IR) which uses logical “OR” and “AND” operators is developed. The proposed segmentation network is evaluated on three medical imaging datasets, namely ISIC 2017 for skin lesions segmentation from dermoscopy images, DRIVE for retinal blood vessels segmentation from fundus images, and BraTS 2018 for brain gliomas segmentation from MR scans. The experimental results showed superior state-of-the-art performance with overall dice similarity coefficients of 85.78%, 80.27%, and 88.96% on the segmentation of skin lesions, retinal blood vessels, and brain tumors, respectively. The proposed CMM-Net is inherently general and could be efficiently applied as a robust tool for various medical image segmentations.
Genetic dissection of heterosis of indica–japonica by introgression line, recombinant inbred line and their testcross populations
Authors: Yang Wenqing , Zhang Fan , Zafar Sundus , Wang Junmin , Lu Huajin , Naveed Shahzad , Lou Jue , Xu Jianlong 
Published: May 2021

AbstractThe successful implementation of heterosis in rice has significantly enhanced rice productivity, but the genetic basis of heterosis in rice remains unclear. To understand the genetic basis of heterosis in rice, main-effect and epistatic quantitative trait loci (QTLs) associated with heterosis for grain yield-related traits in the four related rice mapping populations derived from Xiushui09 (XS09) (japonica) and IR2061 (indica), were dissected using single nucleotide polymorphism bin maps and replicated phenotyping experiments under two locations. Most mid-parent heterosis of testcross F1s (TCF1s) of XS09 background introgression lines (XSILs) with Peiai64S were significantly higher than those of TCF1s of recombinant inbred lines (RILs) with PA64S at two locations, suggesting that the effects of heterosis was influenced by the proportion of introgression of IR2061’s genome into XS09 background. A total of 81 main-effect QTLs (M-QTLs) and 41 epistatic QTLs were identified for the phenotypic variations of four traits of RILs and XSILs, TCF1s and absolute mid-parent heterosis in two locations. Furthermore, overdominance and underdominance were detected to play predominant effects on most traits in this study, suggesting overdominance and underdominance as well as epistasis are the main genetic bases of heterosis in rice. Some M-QTLs exhibiting positive overdominance effects such as qPN1.2, qPN1.5 and qPN4.3 for increased panicle number per plant, qGYP9 and qGYP12.1 for increased grain yield per plant, and qTGW3.4 and qTGW8.2 for enhanced 1000-grain weight would be highly valuable for breeding to enhance grain yield of hybrid rice by marker-assisted selection.
Successful elimination of bilirubin in critically ill patients with acute liver dysfunction using a cytokine adsorber and albumin dialysis: a pilot study
Authors: Scharf Christina , Liebchen Uwe , Paal Michael , Becker-Pennrich Andrea , Irlbeck Michael , Zoller Michael , Schroeder Ines 
Published: May 2021

AbstractThere are different methods of artificial liver support for patients with acute liver dysfunction (ALD). However, CytoSorb (CS) might be a new approved option for those patients. Question of interest is whether the elimination performance of CS was comparable to that of advanced organ support (ADVOS). Patients, treated with CS (integrated into high-flux dialysis) or ADVOS and a total bilirubin > 10 mg/dl were included. Laboratory parameters were evaluated before starting therapy (d0) and 12–24 h thereafter (d1). The Wilcoxon-test with associated samples was used for statistical analysis. Thirty-nine patients (33 CS, 6 ADVOS) were included. The median bilirubin at d0 was 16.9 and 17.7 mg/dl and at d1 was 13.2 and 15.9 mg/dl, in the CS and ADVOS group, respectively. There was a significant bilirubin reduction as well in the CS group (p < 0.001, median relative reduction: 22.5%) as in the ADVOS group (p = 0.028, median relative reduction: 22.8%). There was no significant difference in the relative bilirubin reduction between CS and ADVOS therapies. The use of CytoSorb and ADVOS in patients with ALD led to a significant and comparable decrease in total bilirubin. The easy use of CS might be an advantage compared to other procedures.
Articulatory Correlates of Stress Pattern Disturbances in Talkers With Dysarthria
Authors: Kim Daniel , Kuruvilla-Dugdale Mili , de Riesthal Michael , Jones Robin , Bagnato Francesca , Mefferd Antje 
Published: May 2021

Purpose
Reduced stress commonly occurs in talkers with Parkinson's disease (PD), whereas excessive and equal stress is frequently associated with dysarthria of talkers with amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). This study sought to identify articulatory impairment patterns that underlie these two impaired stress patterns. We further aimed to determine if talkers with the same stress pattern disturbance but different diseases (ALS and MS) exhibit disease-specific articulatory deficits.

Method

Fifty-seven talkers participated in the study—33 talkers with dysarthria and 24 controls. Talkers with dysarthria were grouped based on their medical diagnosis: PD (
n
= 15), ALS (
n
= 10), MS (
n
= 8). Participants repeated target words embedded in a carrier phrase. Kinematic data were recorded using electromagnetic articulography. Duration, displacement, peak speed, stiffness, time-to-peak speed, and parameter c were extracted for the initial lower lip opening stroke of each target word, which was either stressed or unstressed.

Results
Stress effects were significant for all kinematic measures across groups except for stiffness and time-to-peak speed, which were nonsignificant in ALS. For comparisons with controls, more kinematic measures significantly differed in the ALS group than in the PD and MS groups. Additionally, ALS and MS showed mostly similar articulatory impairment patterns.

Conclusions
In general, significant stress effects were observed in talkers with dysarthria. However, stress-specific between-group differences in articulatory performance, particularly displacement, may explain the perceptual impression of disturbed stress patterns. Furthermore, similar findings for ALS and MS suggest that articulatory deficits underlying similar stress pattern disturbances are not disease-specific.