Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison of Light Condition-Dependent Differences in the Accumulation and Subcellular Localization of Glutathione in Arabidopsis and Wheat

This study aimed to clarify whether the light condition-dependent changes in the redox state and subcellular distribution of glutathione were similar in the dicotyledonous model plant Arabidopsis (wild-type, ascorbate- and glutathione-deficient mutants) and the monocotyledonous crop species wheat (Chinese Spring variety). With increasing light intensity, the amount of its reduced (GSH) and oxidized (GSSG) form and the GSSG/GSH ratio increased in the leaf extracts of both species including all genotypes, while far-red light increased these parameters only in wheat except for GSH in the GSH-deficient Arabidopsis mutant. Based on the expression changes of the glutathione metabolism-related genes, light intensity influences the size and redox state of the glutathione pool at the transcriptional level in wheat but not in Arabidopsis. In line with the results in leaf extracts, a similar inducing effect of both light intensity and far-red light was found on the total glutathione content at the subcellular level in wheat. In contrast to the leaf extracts, the inducing influence of light intensity on glutathione level was only found in the cell compartments of the GSH-deficient Arabidopsis mutant, and far-red light increased it in both mutants. The observed general and genotype-specific, light-dependent changes in the accumulation and subcellular distribution of glutathione participate in adjusting the redox-dependent metabolism to the actual environmental conditions.
Is Religious Self-Regulation a Risk or Protective Factor for Men’s Intimate Partner Violence Perpetration?

Recent research has indicated that religiosity has multiple dimensions and that religious self-regulation may be a more effective predictor of intimate partner violence (IPV) perpetration than other measures of religiosity, such as frequency of prayer or church attendance. Nonetheless, studies have produced inconsistent results regarding the associations between religious self-regulation and IPV perpetration. Moreover, no studies have included self-reported level of religiosity in addition to religious self-regulation in predictive models of IPV perpetration. The present study sought to address the following research question: What is the association between religious self-regulation and men’s IPV perpetration, accounting for self-reported level of religiosity? A convenience sample of 289 men, who had been in their current committed heterosexual relationship for at least one year, were recruited via Amazon’s Mechanical Turk and responded to an online survey. Logistic and negative binomial regression analyses indicated that introjected religious self-regulation was significantly positively associated with physical, psychological, and sexual IPV perpetration, while identified religious self-regulation was significantly negatively associated with physical, psychological, and sexual IPV perpetration, supporting both hypotheses. These findings have implications for faith leaders and secular service providers seeking to develop effective, culturally sensitive, and empirically informed IPV intervention and prevention strategies.
Bronchiectasis and Bronchiolectasis With Severe Herniating Pattern Associated With STAT1 Gain-of-Function Mutation: Detailed Clinicopathological Findings

STAT1 gain-of-function (GOF) mutations are associated with a rare autosomal dominant immunodeficiency disorder with main clinical manifestations including chronic mucocutaneous candidiasis (CMC) and bronchiectasis. In addition, these patients show higher incidences of cerebral and extracerebral aneurysm, malignancies and various autoimmune conditions compared to the general population. Although previous publications have reported clinical findings in patients with STAT1 GOF mutation, they did not include histopathologic features. Herein, we describe the first case with detailed histologic findings in the lung of a 5-year-old patient with a de novo STAT1 GOF mutation, who presented with CMC and bronchiectasis. The biopsy showed severe bronchiolectasis with extensive airway dilatation and occasional disruptions. Peribronchiolar inflammation was not always present and evident mainly in areas of airway disruption; inflammation may have not been a main driver of the airway damage in this case. The airway dilatation often showed an interesting herniating pattern, possibly implying a connective tissue etiology. This case also demonstrates the diagnostic utility of whole exome sequencing as STAT1 GOF mutations are not detected by routine workup. The definitive diagnosis will lead to more specific treatments and increased surveillance for serious conditions, such as cerebral aneurysms and malignancies.
Diagnostic yield and safety of the ProCore versus the standard EBUS-TBNA needle in subjects with suspected sarcoidosis

ABSTRACT Background: No randomized trial has compared the yield of the ProCore needle, a novel needle for endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA), with standard needles. Research design and methods: Consecutive subjects with intrathoracic lymphadenopathy due to suspected sarcoidosis were randomized 1:1 to undergo EBUS-TBNA with either the 22-gauge ProCore (EchoTip-ProCore, Cook-Medical) or the 22-gauge standard (Vizishot, Olympus) needle. The primary outcome was the diagnostic sensitivity; the secondary outcomes included the number of adequate aspirates obtained and procedure-related complications. Results: We randomized 100 (mean age, 43.4 years; 53% women) subjects. Of the 84 subjects finally diagnosed with sarcoidosis, the sensitivity of EBUS-TBNA was higher with the ProCore (36/42, 85.7%) versus the standard needle (31/42, 73.8%), although not statistically significant (p = 0.18). We obtained adequate aspirates in 95.2% and 90.5% subjects in the ProCore and the standard needle groups, respectively (p = 0.68). One complication (transient hypoxemia) occurred in each group. There were two incidences of the ProCore needle getting bent during the procedure. Conclusions: We found no difference in the sensitivity, specimen adequacy, or safety of EBUS-TBNA when performed with the ProCore or the Olympus needle in subjects with sarcoidosis. Larger studies are required to confirm our findings. [clinicaltrials.gov: NCT03656003]
Silencing of long noncoding RNA MYLK‐AS1 suppresses nephroblastoma via down‐regulation of CCNE1 through transcription factor TCF7L2

Nephroblastoma, a pediatric kidney cancer, caused by pluripotent embryonic renal precursors. Long noncoding RNAs (lncRNAs) are commonly abnormal expressed in many cancers. In the present study, we fousced on one newly discrovered lncRNA, MYLK Antisense RNA 1 (MYLK‐AS1), and its functional role in proliferation and cycle distribution of nephroblastoma cells. Micorarray‐based analysis revealed the highly expressed Cyclin E1 (CCNE1) and MYLK‐AS1 in nephroblastoma. After nephroblastoma tissue sample collection, RT‐qPCR confirmed the upregulated expression of MYLK‐AS1 and CCNE1 in nephroblastoma tissues and cells. Kaplan–Meier curve exhibited that patients with elevated CCNE1 had lower overall survival rate in follow‐up study. RNA binding protein immunoprecipitation, chromatin immunoprecipitation, and dual‐luciferase reporter gene assay were employed to determine the relationship among MYLK‐AS1, TCF7L2, and CCNE1, which validated that transcription factor 7‐like 2 (TCF7L2) could specifically bind to MYLK‐AS1 and TCF7L2 could positively promote CCNE1. After gain‐ and loss‐of function assays, the conclusion that silencing of MYLK‐AS1 could inhibit expression of CCNE1 through the transcription factor TCF7L2 to regulate the cell proliferation and cell cycle distribution of nephroblastoma cells was obtained. Subsequently, the subcutaneous tumor formation ability of nephroblastoma cell in nude mice was observed and the silencing of MYLK‐AS1 exerts suppressive role in the tumorigenic ability of nephroblastoma cells in vivo. Taken together, MYLK‐AS1 constitutes a promising biomarker for the early detection and treatment of nephroblastoma.
Gradient of brain mosaic RHEB variants causes a continuum of cortical dysplasia

Focal cortical dysplasia (FCD) and hemimegalencephaly (HME) are related malformations with shared etiologies. We report three patients with a spectrum of cortical malformations associated with pathogenic brain‐specific somatic Ras homolog enriched in brain (RHEB) variants. The somatic variant load directly correlated with the size of the malformation, with upregulated mTOR activity confirmed in dysplastic tissues. Laser capture microdissection showed enrichment of RHEB variants in dysmorphic neurons and balloon cells. Our findings support the role of RHEB in a spectrum of cortical malformations confirming that FCD and HME represent a disease continuum, with the extent of dysplastic brain directly correlated with the somatic variant load.
Chemotherapy-Induced Upregulation of Somatostatin Receptor-2 Increases the Uptake and Efficacy of 177Lu-DOTA-Octreotate in Neuroendocrine Tumor Cells

Simple Summary The peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTA-octreotate (LuTate) is recommended for neuroendocrine tumors (NETs) which overexpress somatostatin receptors (SSTR). A combination of LuTate with chemotherapy improves its objective response in NET patients, and here we characterized chemotherapy-induced upregulation of SSTR2 receptors as a cause for this improved response to LuTate. Using multiple NET and non-NET cell lines, we examined the SSTR2 expression for up to 7 days after exposure to drugs and its effect on LuTate uptake and cell proliferation. We report that the exposure to varying doses of chemotherapeutic drugs such as temozolomide for 24 h or 5 days results in upregulation of SSTR2 receptors between 3–7 days. This effect is more pronounced in low SSTR2 expressing BON-1 cells than in high SSTR2 expressing NCI-H727 or non-NET cancer or non-cancer cells. Thus, a properly-timed pre-treatment with low doses of chemotherapy could improve therapeutic efficacy of LuTate in NET patients. Abstract The peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTA-octreotate (LuTate) is recommended for different types of neuroendocrine tumors (NETs) which overexpress somatostatin receptors (SSTR). A combination with chemotherapy improves objective response to LuTate in NET patients and here we characterized chemotherapy-induced upregulation of SSTR2 receptors as a cause for this improved response to LuTate. The NET cell lines with low (BON-1) or relatively high (NCI-H727) SSTR2-expression levels, and non-NET cancer and normal cells were treated with chemotherapeutic drugs and assessed for upregulation of SSTR2. We report that an exposure to low or high doses of drugs, such as temozolomide for 24 h or 5 day results in upregulation of SSTR2 between 3–7 days, increased LuTate uptake and decreased rate of cell proliferation. This effect is at the level of SSTR2-mRNA and is more pronounced in low SSTR2 expressing BON-1 than in high SSTR2 expressing NCI-H727 or non-NET cancer or normal cells. Thus, a properly timed pre-treatment with low-dose chemotherapy could not only improve therapeutic efficacy of LuTate in NET patients who are presently eligible for PRRT, but also allow PRRT to be administered to patients with low SSTR-expressing NETs, who would otherwise not respond to this modality because of insufficient radiation delivery.
The Distribution of Retinal Venous Pressure and Intraocular Pressure Differs Significantly in Patients with Primary Open-Angle Glaucoma

Abstract Introduction Until now, venous pressure within the eye has widely been equated with intraocular pressure (IOP). Measurements with dynamometers calibrated in instrument units or in force showed that the retinal venous pressure (RVP) may be higher than the IOP in glaucoma patients. In this study, the RVP was measured with a contact lens dynamometer calibrated in mmHg. Methods Study type: cross-sectional. Subjects: Fifty consecutive patients with primary open-angle glaucoma (POAG) who underwent diurnal curve measurement under medication. Age: 69 ± 8 years. Measurement of RVP: contact lens dynamometry. IOP measurement: dynamic contour tonometry. Results Pressures are given in mmHg. In all 50 patients, the IOP was 15.9 (13.6; 17.1) [median (Q1; Q3)], and the RVP was 17.4 (14.8; 27.2). The distribution of the IOP was normal and that of the RVP was right skewed. In the subgroup of 34 patients with spontaneous pulsation of the central retinal vein (SVP), the IOP and therefore, by definition, the RVP was 16.5 (13.7; 17.4). In the subgroup of 16 patients without SVP, the IOP was 14.8 (13.3; 16.4), and the RVP was 31.3 (26.2; 38.8) (p ≤ 0.001). In systemic treatment, the prescribed drugs were (the number of patients is given in parentheses): ACE inhibitors (20), β-blockers (17), angiotensin II-receptor blockers (13), calcium channel blockers (12), diuretics (7). No difference in RVP was observed between patients receiving these drugs and not receiving them, except in the β-blocker group. Here, the 17 patients with systemic β-blockers had a median RVP of 15.6 mmHg and without 20.2 mmHg (p = 0.003). In the 16 patients with a higher RVP than IOP, only one patient received a systemic β-blocker. The median IOP was 15.7 mmHg with systemic β-blockers and 16.1 mmHg without (p = 0.85). Conclusion In a subgroup of 16 of the 50 patients studied, the RVP was greater than the IOP by a highly statistically and clinically significant degree. According to the widely accepted thinking on the pathophysiology of retinal and optic nerve head circulation, the blood flow in these tissues may be much more compromised in this group of patients than has been assumed. They may be identified by a missing SVP. Topical and systemic medications showed no statistically significant influence on the RVP, except for the systemic β-blockers, in which the RVP was lower by 4.6 mmHg than for the patients who did not receive these drugs (p = 0.003).
The Use of MALDI-TOF Mass Spectrometry to Analyze Commensal Oral Yeasts in Nursing Home Residents

Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a rapid and accurate method to identify microorganisms in clinical laboratories. This study isolates yeast-like microorganisms in the oral washes that are collected from non-bedridden nursing home residents, using CHROMagar Candida plates, and identifies them using Bruker MALDI-TOF MS. The ribosomal DNA sequences of the isolates are then examined. Three hundred and twenty yeast isolates are isolated from the oral washes. Candida species form the majority (78.1%), followed by Trichosporon/Cutaneotrichosporon species (8.8%). Bruker MALDI-TOF MS gives a high-level confidence, with a log(score) value of ≥1.8, and identifies 96.9% of the isolates. There are six inconclusive results (1.9%), and those sequences are verified as rare clinical species, including Candida ethanolica, Cutaneotrichosporon jirovecii, Exophiala dermatitidis, and Fereydounia khargensis. Almost all of the isolates have a regular color on the CHROMagar Candida plates. If the colonies are grouped by color on the plates, a specific dominant yeast species is present in each color group, except for purple or orange isolates. In conclusion, MALDI-TOF MS is verified as a fast, accurate and practical method to analyze oral yeasts in elderly subjects.
Molecular dynamics simulations of the structure and dynamics of confined polymer melts

We performed a series of molecular dynamics simulations investigating the static and dynamic properties of polymer melts confined between planar solid surfaces. The solid–melt interface was found to be very narrow (approximately two segment diameters) and independent of chain length. Inside the interface the segment density profile was oscillatory, the bond orientation altered between directions parallel and normal to the solid surface, and the chain ends accumulated very close to the wall (in the absence of strong wall–segment attraction). The oscillations of the segment density profile were weaker and were dampened faster than those of a simple fluid density profile next to the same solid surface. This reflected the reduced ability of sequences of connected segments (chains) to layer themselves against a solid surface because of restrictions on their configurations imposed by the chain connectivity requirement. This effect made the solid–melt interface even narrower than that of a simple fluid. Only the.
Context Memory Encoding and Retrieval Temporal Dynamics are Modulated by Attention across the Adult Lifespan

Abstract Episodic memories are multidimensional, including simple and complex features. How we successful encode and recover these features in time, whether these temporal dynamics are preserved across age, even under conditions of reduced memory performance, and the role of attention on these temporal dynamics is unknown. In the current study, we applied time-resolved multivariate decoding to oscillatory electroencephalography (EEG) in an adult lifespan sample to investigate the temporal order of successful encoding and recognition of simple and complex perceptual context features. At encoding, participants studied pictures of black and white objects presented with both color (low-level/simple) and scene (high-level/complex) context features and subsequently made context memory decisions for both features. Attentional demands were manipulated by having participants attend to the relationship between the object and either the color or scene while ignoring the other context feature. Consistent with hierarchical visual perception models, simple visual features (color) were successfully encoded earlier than were complex features (scenes). These features were successfully recognized in the reverse temporal order. Importantly, these temporal dynamics were both dependent on whether these context features were in the focus of one’s attention, and preserved across age, despite age-related context memory impairments. These novel results support the idea that episodic memories are encoded and retrieved successively, likely dependent on the input and output pathways of the medial temporal lobe (MTL), and attentional influences that bias activity within these pathways across age.
Interactions of Potential Anti-COVID-19 Compounds with Multispecific ABC and OATP Drug Transporters

During the COVID-19 pandemic, several repurposed drugs have been proposed to alleviate the major health effects of the disease. These drugs are often applied with analgesics or non-steroid anti-inflammatory compounds, and co-morbid patients may also be treated with anticancer, cholesterol-lowering, or antidiabetic agents. Since drug ADME-tox properties may be significantly affected by multispecific transporters, in this study, we examined the interactions of the repurposed drugs with the key human multidrug transporters present in the major tissue barriers and strongly affecting the pharmacokinetics. Our in vitro studies, using a variety of model systems, explored the interactions of the antimalarial agents chloroquine and hydroxychloroquine; the antihelmintic ivermectin; and the proposed antiviral compounds ritonavir, lopinavir, favipiravir, and remdesivir with the ABCB1/Pgp, ABCG2/BCRP, and ABCC1/MRP1 exporters, as well as the organic anion-transporting polypeptide (OATP)2B1 and OATP1A2 uptake transporters. The results presented here show numerous pharmacologically relevant transporter interactions and may provide a warning on the potential toxicities of these repurposed drugs, especially in drug combinations at the clinic.
A Set of Cell Lines Derived from a Genetic Murine Glioblastoma Model Recapitulates Molecular and Morphological Characteristics of Human Tumors

Simple Summary Glioblastoma (GBM) is a highly aggressive and almost inevitably lethal brain tumor. Animal models for GBM are crucial to study how the tumor evolves in vivo and to test novel treatment options. Most currently available models are based on the transplantation of human GBM cells into mice with a defective immune system. However, this approach does not allow to study the contribution of immune cells to GBM growth and to test immunotherapies. Transplantation of murine GBM cells overcomes this limitation, however, up to now, only a limited number, which mostly do not mimic important characteristics of human GBM, have been available. Via in vivo passaging, we established a set of murine GBM cell lines that (i) can be easily cultivated and further genetically manipulated, (ii) upon transplantation develop tumors with phenotypic and pathological features of human GBM, and (iii) are available to be shared with the scientific community. Abstract Glioblastomas (GBM) are the most aggressive tumors affecting the central nervous system in adults, causing death within, on average, 15 months after diagnosis. Immunocompetent in-vivo models that closely mirror human GBM are urgently needed for deciphering glioma biology and for the development of effective treatment options. The murine GBM cell lines currently available for engraftment in immunocompetent mice are not only exiguous but also inadequate in representing prominent characteristics of human GBM such as infiltrative behavior, necrotic areas, and pronounced tumor heterogeneity. Therefore, we generated a set of glioblastoma cell lines by repeated in vivo passaging of cells isolated from a neural stem cell-specific Pten/p53 double-knockout genetic mouse brain tumor model. Transcriptome and genome analyses of the cell lines revealed molecular heterogeneity comparable to that observed in human glioblastoma. Upon orthotopic transplantation into syngeneic hosts, they formed high-grade gliomas that faithfully recapitulated the histopathological features, invasiveness and immune cell infiltration characteristic of human glioblastoma. These features make our cell lines unique and useful tools to study multiple aspects of glioblastoma pathomechanism and to test novel treatments in an intact immune microenvironment.
Broadband Spin-Dependent Directional Coupler via Single Optimized Metallic Catenary Antenna

With the rapid development of on-chip optics, integrated optical devices with better performance are desirable. Waveguide couplers are the typical integrated optical devices, allowing for the fast transmission and conversion of optical signals in a broad working band. However, traditional waveguide couplers are limited by the narrow operation band to couple the spatial light into the chip and the fixed unidirectional transmission of light flow. Furthermore, most of the couplers only realize unidirectional transmission under the illumination of the linear polarized light. In this work, a broadband polarization directional coupler based on a metallic catenary antenna integrated on a silicon-on-insulator (SOI) waveguide has been designed and demonstrated under the illumination of the circularly polarized light. By applying the genetic algorithm to optimize the multiple widths of the metallic catenary antenna, the numerical simulation results show that the extinction ratio of the coupler can be maintained larger than 18 dB in a wide operation band of 300 nm (from 1400 to 1700 nm). Moreover, the coupler can couple the spatial beam into the plane and transmit in the opposite direction by modulating the rotation direction of the incident light. The broadband polarization directional coupler might have great potential in integrated optoelectronic devices and on-chip optical devices.