Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of the Large-Conductance Ca2+-Regulated Potassium Channel in Mitochondria of Human Bronchial Epithelial Cells

Mitochondria play a key role in energy metabolism within the cell. Potassium channels such as ATP-sensitive, voltage-gated or large-conductance Ca2+-regulated channels have been described in the inner mitochondrial membrane. Several hypotheses have been proposed to describe the important roles of mitochondrial potassium channels in cell survival and death pathways. In the current study, we identified two populations of mitochondrial large-conductance Ca2+-regulated potassium (mitoBKCa) channels in human bronchial epithelial (HBE) cells. The biophysical properties of the channels were characterized using the patch-clamp technique. We observed the activity of the channel with a mean conductance close to 285 pS in symmetric 150/150 mM KCl solution. Channel activity was increased upon application of the potassium channel opener NS11021 in the micromolar concentration range. The channel activity was completely inhibited by 1 µM paxilline and 300 nM iberiotoxin, selective inhibitors of the BKCa channels. Based on calcium and iberiotoxin modulation, we suggest that the C-terminus of the protein is localized to the mitochondrial matrix. Additionally, using RT-PCR, we confirmed the presence of α pore-forming (Slo1) and auxiliary β3-β4 subunits of BKCa channel in HBE cells. Western blot analysis of cellular fractions confirmed the mitochondrial localization of α pore-forming and predominately β3 subunits. Additionally, the regulation of oxygen consumption and membrane potential of human bronchial epithelial mitochondria in the presence of the potassium channel opener NS11021 and inhibitor paxilline were also studied. In summary, for the first time, the electrophysiological and functional properties of the mitoBKCa channel in a bronchial epithelial cell line were described.
The Clinical Relevance of Target Lymph Node Biopsy after Primary Systemic Therapy in Initially Node-Positive Breast Cancer Patients

Simple Summary Currently, the optimal axillary surgical approach for breast cancer patients with initial node-positive disease and conversion to clinically node-negative status after primary systemic therapy is unclear. The aim of our study was to evaluate the clinical impact of removing the initially most suspicious, labeled axillary lymph node in addition to the sentinel lymph node. Metastatic target lymph nodes were found in five out of 63 patients (7.9%), while the sentinel lymph node was either tumor-free or not detected. The removal of the target lymph node influenced the adjuvant systemic therapy in only one case (1.6%). However, complete axillary dissection was indicated in all five cases. Furthermore, with fewer than three sentinel lymph nodes removed, the target lymph node reduced the false-negative rate to less than 10%. We therefore conclude that although the target lymph node has a minor impact on adjuvant systemic therapy, it is relevant for surgical axillary management. Abstract Purpose: To assess the impact of the removal of the target lymph node (TLN) on therapy after the completion of primary systemic therapy (PST) in initially node-positive breast cancer patients. Methods: Pooled data analysis of participants of the prospective CLIP- and TATTOO-study at the University of Rostock was performed. Results: A total of 75 patients were included; 63 of them (84.0%) converted to clinically node-negative after PST. Both TLN and sentinel lymph node (SLN) were identified in 41 patients (51.2%). In five out of 63 patients (7.9%), the TLN was metastatic after PST and the SLN was either tumor-free or not detected. Axillary lymph node dissection (ALND) was conducted in all five patients. In one patient, systemic therapy recommendation was influenced by the TLN; adjuvant radiotherapy was influenced by the TLN in zero patients. For patients with fewer than three removed SLNs, the FNR was 28.6% for the SLN biopsy alone and 7.1% for targeted axillary dissection (TAD). Conclusions: Removal of the TLN in addition to the SLN after PST has only minimal impact on the type of adjuvant systemic therapy and radiotherapy. However, the extent of axillary surgery was relevantly affected and FNR was improved by TAD.
Endothelial cell loss after accelerated corneal crosslinking using pachymetry-guided hypo-osmolar riboflavin dosing in thin keratoconic corneas

Accelerated corneal crosslinking with only hypo-osmolar riboflavin solution throughout the procedure in thin corneas is effective but seems to result in a significant endothelial cell density decrease postoperatively. Purpose: To report the intraoperative changes in corneal pachymetry, as well as the efficacy and safety of accelerated corneal crosslinking (A-CXL) treatment using only hypo-osmolar riboflavin (HO-RF) solution in progressive keratoconus patients with thin corneas. Setting: University of Health Sciences, Prof. Dr. Cemil Tascioglu Education and Research Hospital, Istanbul, Turkey Design: Retrospective study. Methods: Thin keratoconic corneas (<400 m without epithelium) who had A-CXL (9 mW/cm2-10 minutes) with HO-RF solution application were enrolled in the study. Intraoperative corneal pachymetric changes and uncorrected and corrected distance visual acuities (UDVA and CDVA), refraction power values, topographic values, and endothelial cell density (ECD) measurements were recorded preoperatively and at 1st, 3rd, 6th, and 12th month follow-up postoperatively. Results: 31 eyes of 25 patients (mean age: 24.17 ± 3.07 years) included in this study. The mean thickness increased to 438 μm (P = .001) after the application of HO-RF solution, and it was reduced to 424 μm (P = .001) after ultraviolet irradiation. At all postoperative visits after month 1, there was a significant increase in both UDVA (P < .05) and CDVA (P < .01) values and a significant decrease in both maximum keratometry (P < .05) and ECD (P < .01) values. Conclusions: Accelerated CXL with only HO-RF solution application throughout the procedure in thin corneas was effective but seemed to result in a significant ECD decrease postoperatively.
Clinical Applications of Liquid Biopsy in Non-Small Cell Lung Cancer Patients: Current Status and Recent Advances in Clinical Practice

Recent advances in targeted and immune therapies have enabled tailored treatment strategies for advanced lung cancer. Identifying and understanding the genomic alterations that arise in the course of tumor evolution has become hugely valuable, but tissue biopsies are often insufficient for representing the whole cancer genome due to tumor heterogeneity. A liquid biopsy refers to the isolation and analysis of any tumor-derived material in the blood, and recent studies of this material have mostly focused on cell-free tumor DNA (ctDNA) in plasma. Indeed, liquid biopsy analysis is now expected to expand in utility and scope in clinical practice. In this review, we assess the biology and technical aspects of ctDNA analysis and discuss how it is currently applied in the clinic. Key points: Liquid biopsy is a potentially powerful tool in the era of personalized medicine for guiding targeted therapies in non-small cell lung cancer.
A Microbial Monitoring System Demonstrated on the International Space Station Provides a Successful Platform for Detection of Targeted Microorganisms

Closed environments such as the International Space Station (ISS) and spacecraft for other planned interplanetary destinations require sustainable environmental control systems for manned spaceflight and habitation. These systems require monitoring for microbial contaminants and potential pathogens that could foul equipment or affect the health of the crew. Technological advances may help to facilitate this environmental monitoring, but many of the current advances do not function as expected in reduced gravity conditions. The microbial monitoring system (RAZOR® EX) is a compact, semi-quantitative rugged PCR instrument that was successfully tested on the ISS using station potable water. After a series of technical demonstrations between ISS and ground laboratories, it was determined that the instruments functioned comparably and provided a sample to answer flow in approximately 1 hour without enrichment or sample manipulation. Post-flight, additional advancements were accomplished at Kennedy Space Center, Merritt Island, FL, USA, to expand the instrument’s detections of targeted microorganisms of concern such as water, food-borne, and surface microbes including Salmonella enterica serovar Typhimurium, Pseudomonas aeruginosa, Escherichia coli, and Aeromonas hydrophilia. Early detection of contaminants and bio-fouling microbes will increase crew safety and the ability to make appropriate operational decisions to minimize exposure to these contaminants.
Central Administration of Ampelopsin A Isolated from Vitis vinifera Ameliorates Cognitive and Memory Function in a Scopolamine-Induced Dementia Model

Neurodegenerative diseases are characterized by the progressive degeneration of the function of the central nervous system or peripheral nervous system and the decline of cognition and memory abilities. The dysfunctions of the cognitive and memory battery are closely related to inhibitions of neurotrophic factor (BDNF) and brain-derived cAMP response element-binding protein (CREB) to associate with the cholinergic system and long-term potentiation. Vitis vinifera, the common grapevine, is viewed as the important dietary source of stilbenoids, particularly the widely-studied monomeric resveratrol to be used as a natural compound with wide-ranging therapeutic benefits on neurodegenerative diseases. Here we found that ampelopsin A is a major compound in V. vinifera and it has neuroprotective effects on experimental animals. Bath application of ampelopsin A (10 ng/µL) restores the long-term potentiation (LTP) impairment induced by scopolamine (100 μM) in hippocampal CA3-CA1 synapses. Based on these results, we administered the ampelopsin A (10 ng/µL, three times a week) into the third ventricle of the brain in C57BL/6 mice for a month. Chronic administration of ampelopsin A into the brain ameliorated cognitive memory-behaviors in mice given scopolamine (0.8 mg/kg, i.p.). Studies of mice’s hippocampi showed that the response of ampelopsin A was responsible for the restoration of the cholinergic deficits and molecular signal cascades via BDNF/CREB pathways. In conclusion, the central administration of ampelopsin A contributes to increasing neurocognitive and neuroprotective effects on intrinsic neuronal excitability and behaviors, partly through elevated BDNF/CREB-related signaling.
Artificial Intelligence Based Algorithms for Prostate Cancer Classification and Detection on Magnetic Resonance Imaging: A Narrative Review

Due to the upfront role of magnetic resonance imaging (MRI) for prostate cancer (PCa) diagnosis, a multitude of artificial intelligence (AI) applications have been suggested to aid in the diagnosis and detection of PCa. In this review, we provide an overview of the current field, including studies between 2018 and February 2021, describing AI algorithms for (1) lesion classification and (2) lesion detection for PCa. Our evaluation of 59 included studies showed that most research has been conducted for the task of PCa lesion classification (66%) followed by PCa lesion detection (34%). Studies showed large heterogeneity in cohort sizes, ranging between 18 to 499 patients (median = 162) combined with different approaches for performance validation. Furthermore, 85% of the studies reported on the stand-alone diagnostic accuracy, whereas 15% demonstrated the impact of AI on diagnostic thinking efficacy, indicating limited proof for the clinical utility of PCa AI applications. In order to introduce AI within the clinical workflow of PCa assessment, robustness and generalizability of AI applications need to be further validated utilizing external validation and clinical workflow experiments.
Stability of Non-Linear Dirichlet Problems with ϕ-Laplacian

We study the stability and the solvability of a family of problems −(ϕ(x′))′=g(t,x,x′,u)+f* with Dirichlet boundary conditions, where ϕ, u, f* are allowed to vary as well. Applications for boundary value problems involving the p-Laplacian operator are highlighted.
Continuing Orthohantavirus Circulation in Deer Mice in Western Montana

Hantavirus pulmonary syndrome (HPS) is an often-fatal disease caused by New World hantaviruses, such as Sin Nombre orthohantavirus (SNV). In the US, >800 cases of HPS have been confirmed since it was first discovered in 1993, of which 43 were reported from the state of Montana. The primary cause of HPS in the US is SNV, which is primarily found in the reservoir host Peromyscus maniculatus (deer mouse). The reservoir host covers most of the US, including Montana, where multiple studies found SNV in local deer mouse populations. This study aimed to check the prevalence of SNV in the deer mice at popular recreation sites throughout the Bitterroot Valley in Western Montana as compared to previous studies in western Montana. We found high prevalence (up to 20%) of deer mice positive for SNV RNA in the lungs. We were unable to obtain a SNV tissue culture isolate from the lungs but could passage SNV from lung tissue into naïve deer mice. Our findings demonstrate continuing circulation of SNV in western Montana.
Tellurium: A Rare Element with Influence on Prokaryotic and Eukaryotic Biological Systems

Metalloid tellurium is characterized as a chemical element belonging to the chalcogen group without known biological function. However, its compounds, especially the oxyanions, exert numerous negative effects on both prokaryotic and eukaryotic organisms. Recent evidence suggests that increasing environmental pollution with tellurium has a causal link to autoimmune, neurodegenerative and oncological diseases. In this review, we provide an overview about the current knowledge on the mechanisms of tellurium compounds’ toxicity in bacteria and humans and we summarise the various ways organisms cope and detoxify these compounds. Over the last decades, several gene clusters conferring resistance to tellurium compounds have been identified in a variety of bacterial species and strains. These genetic determinants exhibit great genetic and functional diversity. Besides the existence of specific resistance mechanisms, tellurium and its toxic compounds interact with molecular systems, mediating general detoxification and mitigation of oxidative stress. We also discuss the similarity of tellurium and selenium biochemistry and the impact of their compounds on humans.
Multi-Odor Discrimination by Rat Sniffing for Potential Monitoring of Lung Cancer and Diabetes

The discrimination learning of multiple odors, in which multi-odor can be associated with different responses, is important for responding quickly and accurately to changes in the external environment. However, very few studies have been done on multi-odor discrimination by animal sniffing. Herein, we report a novel multi-odor discrimination system by detection rats based on the combination of 2-Choice and Go/No-Go (GNG) tasks into a single paradigm, in which the Go response of GNG was replaced by 2-Choice, for detection of toluene and acetone, which are odor indicators of lung cancer and diabetes, respectively. Three of six trained rats reached performance criterion, in 12 consecutive successful tests within a given set or over 12 sets with a success rate of over 90%. Through a total of 1300 tests, the trained animals (N = 3) showed multi-odor sensing performance with 88% accuracy, 87% sensitivity and 90% specificity. In addition, a dependence of behavior response time on odor concentrations under given concentration conditions was observed, suggesting that the system could be used for quantitative measurements. Furthermore, the animals’ multi-odor sensing performance has lasted for 45 days, indicating long-term stability of the learned multi-odor discrimination. These findings demonstrate that multi-odor discrimination can be achieved by rat sniffing, potentially providing insight into the rapid, accurate and cost-effective multi-odor monitoring in the lung cancer and diabetes.
The M35 Metalloprotease Effector FocM35_1 Is Required for Full Virulence of Fusarium oxysporum f. sp. cubense Tropical Race 4

Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4) causes Fusarium wilt of banana, the most devastating disease on a banana plant. The genome of Foc TR4 encodes many candidate effector proteins. However, little is known about the functions of these effector proteins on their contributions to disease development and Foc TR4 virulence. Here, we discovered a secreted metalloprotease, FocM35_1, which is an essential virulence effector of Foc TR4. FocM35_1 was highly upregulated during the early stages of Foc TR4 infection progress in bananas. The FocM35_1 knockout mutant compromised the virulence of Foc TR4. FocM35_1 could interact with the banana chitinase MaChiA, and it decreased banana chitinase activity. FocM35_1 induced cell death in Nicotiana benthamiana while suppressing the INF1-induced hypersensitive response (HR), and its predicted enzymatic site was required for lesion formation and the suppression to INF1-induced HR on N. benthamiana leaves. Importantly, treatment of banana leaves with recombinant FocM35_1 accelerates Foc TR4 infection. Collectively, our study provides evidence that metalloprotease effector FocM35 seems to contribute to pathogen virulence by inhibiting the host immunity.
One-Step Construction of Multi-Walled CNTs Loaded with Alpha-Fe2O3 Nanoparticles for Efficient Photocatalytic Properties

The aggregation and the rapid restructuring of the photoinduced electron−hole pairs restructuring in the process of photoelectric response remains a great challenge. In this study, a kind of Multi-walled carbon nanotubes loaded Alpha-Fe2O3 (CNTs/α-Fe2O3) heterostructure composite is successfully prepared via the one-step method. Due to the synergistic effect in the as-prepared CNTs/α-Fe2O3, the defect sites and oxygen-containing functional groups of CNTs can dramatically improve the interface charge separation efficiency and prevent the aggregation of α-Fe2O3. The improved photocurrent and enhanced hole–electron separation rate in the CNTs/α-Fe2O3 is obtained, and the narrower band gap is measured to be 2.8 ev with intensive visible-light absorption performance. Thus, the CNTs/α-Fe2O3 composite serves as an excellent visible light photocatalyst and exhibits an outstanding photocatalytic activity for the cationic dye degradation of rhodamine B (RhB). This research supplies a fresh application area forα-Fe2O3 photocatalyst and initiates a new approach for design of high efficiency photocatalytic materials.
Physical Activity, Sedentary Behavior and Sleep Time: Association with Cardiovascular Hemodynamic Parameters, Blood Pressure and Structural and Functional Arterial Properties in Childhood

An association between movement behavior (MB) components (sleep time (ST), physical activity (PA) and sedentary behavior (SB)) and the state of the cardiovascular (CV) system in children has been postulated. However, it is still controversial whether MB components and/or sub-components (domains) during childhood are independently associated with aortic and peripheral blood pressure (BP), and structural or functional arterial properties. Aims: (1) to evaluate MB components and subcomponents associations with CV characteristics, (2) to analyze the explanatory capacity of interindividual variations in MB on CV properties inter-individual variations at the beginning of school age. Methods: Anthropometric, aortic and peripheral BP, hemodynamic levels (cardiac output, systemic vascular resistances), wave reflection indexes, and arterial structural (diameter, intima–media thickness) and functional (blood flow velocities, Doppler-indexes, local and regional arterial stiffness) parameters of elastic (carotids), transitional (brachial) and muscular (femoral) arteries and time spent in MB (PA questionnaires) were assessed in 816 children (5–6 years). Cardiovascular variables were standardized (z-scores), using age- and sex-related mean values and standard deviations obtained from subjects non-exposed to CV risk factors (CRFs) and who complied with 24 h MB recommendations (reference subgroup). Multiple linear regression models were constructed considering the CV z-scores as dependent variables and CRFs and MB components and subcomponents as independent variables. Results: CV variables showed independent association with MB variations. However, their explanatory capacity on CV characteristics was lesser than that of anthropometric indexes, sex and/or high BP. Conclusions: MB components and sub-components were associated with CV characteristics regardless of other factors, but their capacity to explain variations was lesser than that of anthropometric data, sex or high BP state. MB subcomponents (e.g., sedentary play and screen time in case of SB) showed different (even opposite) associations with CV parameters. ST was associated mainly with indexes of the ventricle ejective function, rather than with CV structural characteristics. SB component and subcomponents were associated with BP, but not with structural parameters. PA component and subcomponents were associated with both BP and structural parameters. The different arterial types, as well central and peripheral parameters showed independent associations with MB components and subcomponents. None of these were independently associated with arterial stiffness.
Heparin-Tagged PLA-PEG Copolymer-Encapsulated Biochanin A-Loaded (Mg/Al) LDH Nanoparticles Recommended for Non-Thrombogenic and Anti-Proliferative Stent Coating

Drug-eluting stents have been widely implanted to prevent neointimal hyperplasia associated with bare metal stents. Conventional polymers and anti-proliferative drugs suffer from stent thrombosis due to the non-selective nature of the drugs and hypersensitivity to polymer degradation products. Alternatively, various herbal anti-proliferative agents are sought, of which biochanin A (an isoflavone phytoestrogen) was known to have anti-proliferative and vasculoprotective action. PLA-PEG diblock copolymer was tagged with heparin, whose degradation releases heparin locally and prevents thrombosis. To get a controlled drug release, biochanin A was loaded in layered double hydroxide nanoparticles (LDH), which are further encapsulated in a heparin-tagged PLA-PEG copolymer. LDH nanoparticles are synthesized by a co-precipitation process; in situ as well as ex situ loading of biochanin A were done. PLA-PEG-heparin copolymer was synthesized by esterification reaction, and the drug-loaded nanoparticles are coated. The formulation was characterized by FTIR, XRD, DSC, DLS, and TEM. In vitro drug release studies, protein adhesion, wettability, hemocompatibility, and degradation studies were performed. The drug release was modeled by mathematical models to further emphasize the mechanism of drug release. The developed drug-eluting stent coating is non-thrombogenic, and it offers close to zero-order release for 40 days, with complete polymer degradation in 14 weeks.