Miracle-dz/UniFAR-FTUs huggingface dataset:
Biomarkers for Precision Urothelial Carcinoma Diagnosis: Current Approaches and the Application of Single-Cell Technologies

Simple Summary Urothelial carcinoma (UC) is the most frequently diagnosed cancer of the urinary tract and is ranked the sixth most diagnosed cancer in men worldwide. About 70–75% of newly diagnosed UCs are non-invasive or low grade. Different tests such as urine cytology and cystoscopy are used to detect UC. If abnormal tissue is found during cystoscopy, then a biopsy will be performed. Cytology has low sensitivity for low-grade cancer while cystoscopy is invasive and costly. Detecting UC early improves the chances of treatment success. Therefore, many researchers have painstakingly identified urine biological markers for non-invasive UC diagnosis. In this review, we summarize some of the latest and most promising biological markers (including FDA-approved and investigational markers). We also discuss some new technologies that can aid research efforts in biological marker discovery for early UC detection. Abstract Urothelial carcinoma (UC) is the most frequent malignancy of the urinary system and is ranked the sixth most diagnosed cancer in men worldwide. Around 70–75% of newly diagnosed UC manifests as the non-muscle invasive bladder cancer (NMIBC) subtype, which can be treated by a transurethral resection of the tumor. However, patients require life-long monitoring due to its high rate of recurrence. The current gold standard for UC diagnosis, prognosis, and disease surveillance relies on a combination of cytology and cystoscopy, which is invasive, costly, and associated with comorbidities. Hence, there is considerable interest in the development of highly specific and sensitive urinary biomarkers for the non-invasive early detection of UC. In this review, we assess the performance of current diagnostic assays for UC and highlight some of the most promising biomarkers investigated to date. We also highlight some of the recent advances in single-cell technologies that may offer a paradigm shift in the field of UC biomarker discovery and precision diagnostics.
Bacterial growth and carbon-to-phosphorus consumption in drinking water with different carbon and phosphorus levels

Bacterial growth and corresponding consumption of carbon and phosphorus were examined in which tap water samples containing a very low concentration of free chlorine were supplemented with organic carbon and/or phosphorus. The experiments were performed in a fed-batch mode under a controlled temperature of 20°C. In the phosphorus alone-added water, there was no significant increase in bacterial numbers measured as heterotrophic plate count (HPC) in the bulk water. However, bacterial growth was stimulated by the addition of carbon (e.g., bulk HPC levels increased to 10 CFU/mL) and further stimulated by the combined addition of carbon and phosphorus (e.g., bulk HPC to 10 CFU/mL). The same effects were observed in biofilm HPC and biomass formed on polyethylene (PE) slide surfaces. In the water where organic carbon and phosphorus were added together, the highest biofilm HPC and biomass (measured as extracellular polymeric substance components) densities were observed which were 7.6×10 CFU/cm and 5.3 μg/cm, respectively. In addition to the bacterial growth, additions of organic carbon and/or phosphorus resulted in different bacterial carbon-to-phosphorus (C/P) consumption ratios. Compared to a typical bacterial C/P consumption ratio of 100:1, a higher C/P ratio (590:1) occurred in the carbon alone-added water, while a lower ratio (40:1) in phosphorus alone-added water. Comparative value (80:1) of C/P ratio was also observed in the water where organic carbon and phosphorus were added together. At the given experimental conditions, bacterial growth was deemed to be more sensitive to microbially available organic carbon than phosphorus. The effect of phosphorus addition, which resulted in a lower C/P consumption ratio, seemed to be tightly associated with the presence of microbially available organic carbon. These results suggested that the control of extrinsic carbon influx seemed to be more important to minimize bacterial regrowth in drinking water system, since even low content of phosphorus naturally occurring in drinking water was enough to allow a bacterial growth. 요약문 : 잔류염소 농도가 상당히 낮은 수돗물에서 유기탄소(organic carbon)와 인(phosphorus)의 증가가 세균 생장에 미치는 영향과 세균에 의한 유기탄소와 인의 소모를 fed-batch 실험조건(20°C 수온)에서 조사하였다. 수돗물에서 단지 인의 증가만으로는 부유성 세균 의 현저한 수적 증가는 나타나지 않았다. 그러나 유기탄소의 증가는 부유성 세균을 10 CFU/mL 수준까지 증가시켰으며, 특히 유기탄소 와 함께 동반된 인의 증가는 부유성 세균을 10 CFU/mL 수준까지 증가시켰다. 이러한 효과들은 polyethylene (PE) slide 표면에 형성된 생물막 세균과 생물량 측정에서도 동일하게 나타났다. 유기탄소와 함께 인 농도가 높은 수돗물에서 PE slide 표면에 형성된 생물막 세균 과 세포외 중합체(extracellular polymeric substance) 구성 성분으로 측정된 생물량은 각각 7.6×10 CFU/cm와 5.3 μg/cm로 가장 높았다. 세균 생장과 더불어, 수돗물에서 유기탄소와 인의 증가는 세균에 의한 탄소와 인의 이용 패턴에 영향을 미치는 것으로 나타났 다. 전형적인 세균의 C/P 소모비율(100:1)과 비교했을 때, 상대적으로 높은 C/P 소모비율(590:1)은 유기탄소 농도가 높은 수돗물에서, 그리고 상대적으로 낮은 C/P 소모비율(40:1)은 인 농도가 높은 수돗물에서 관찰되었다. 또한 유기탄소와 함께 인 농도가 높은 수돗물에 서도 상대적으로 낮은 C/P 소모비율(80:1)이 관찰되었다. 주어 진 실험조건에서는 수돗물과 생물막내 세균 생장이 인의 증가보 다는 유기탄소의 증가에 더욱 민감하게 반응하는 것으로 나타났 다. 수돗물에서 인의 증가는 세균의 낮은 C/P 소모비율을 가져
Location, location, location: the organization and roles of potassium channels in mammalian motoneurons

The spatial and temporal balance of spinal α‐motoneuron (αMN) intrinsic membrane conductances underlies the neural output of the final common pathway for motor commands. Although the complete set and precise localization of αMN K+ channels and their respective outward conductances remain unsettled, important K+ channel subtypes have now been documented, including Kv1, Kv2, Kv7, TASK, HCN and SK isoforms. Unique kinetics and gating parameters allow these channels to differentially shape and/or modify αMN firing properties, and recent immunohistochemical localization of K+‐channel complexes reveals a framework in which their spatial distribution and/or focal clustering within different surface membrane compartments is highly tuned to their physiological function. Moreover, highly evolved regulatory mechanisms enable specific channels to operate over variable levels of αMN activity and contribute to either state‐dependent enhancement or diminution of firing. While recent data suggest an additional, non‐conducting role for clustered Kv2.1 channels in the formation of endoplasmic reticulum–plasma membrane junctions postsynaptic to C‐bouton synapses, electrophysiological evidence demonstrates that conducting Kv2.1 channels effectively regulate αMN firing, especially during periods of high activity in which the cholinergic C‐boutons are engaged. Intense αMN activity or cell injury rapidly disrupts the clustered organization of Kv2.1 channels in αMNs and further impacts their physiological role. Thus, αMN K+ channels play a critical regulatory role in motor processing and are potential therapeutic targets for diseases affecting αMN excitability and motor output, including amyotrophic lateral sclerosis.
Changes in clinical scenarios, management, and perspectives of patients with chronic hepatitis C after viral clearance by direct-acting antivirals

ABSTRACT Introduction Hepatitis C virus (HCV) causes a systemic infection inducing hepatic and extrahepatic diseases. These latter involve cardiovascular system, kidney, brain, endocrine, glucose, and lipid metabolism, and the immune system. HCV infection is associated with an increased risk of morbidity and mortality for both hepatic and extrahepatic events. Direct-acting antivirals (DAA), introduced in the most recent years for HCV treatment, are effective in up to 99% of cases and have changed the clinical scenarios and management of these patients. Areas covered The literature on the impact of HCV clearance by DAA on both hepatic and extrahepatic disease outcomes has been analyzed and discussed in this review in order to summarize the full therapeutic potential and its weaknesses. Expert opinion Patients achieving HCV clearance have improved hepatic and extrahepatic diseases, quality of life and survival. They have lower incidence of cardiovascular disease, type 2 diabetes, kidney damage, and immuno-mediated manifestations. However, the improvements are related to the degree of pre-treatment organ damage. Therefore, a significant percentage of patients with advanced disease remains at risk of morbidity and mortality and must be monitored in the post-treatment. In addition, data emphasize the importance of starting treatment during the early stages of HCV infection.
Beneficial Effects of Liquid Crystalline Phases in Solid‐State Dye‐Sensitized Solar Cells

Two novel double‐alkyl functionalized imidazolium ionic liquid crystals have successfully been utilized to demonstrate the benefits of the liquid crystalline phase on the ssDSSC performance. In particular, a good balance between dye regeneration and hole transport is only realized in the liquid crystalline phase. Devices that employ a single component ionic liquid based electrolyte show a remarkably stable efficiency during 1000 h under outdoor operation temperature conditions and 1 sun illumination.
Whole Genome Sequencing Reveals the Effects of Recent Artificial Selection on Litter Size of Bamei Mutton Sheep

Simple Summary Bamei mutton sheep is a Chinese domestic sheep breed developed by crossing German Mutton Merino sheep and indigenous Mongolian sheep for meat production. There is large variation in the reproductive abilities of Bamei mutton sheep. After recent artificial selection, the average lambing rate of the Bamei mutton nucleus group was over 150%. We used the FST (Fixation Index) and XP-EHH (The Cross-Population Extended Haplotype Homozygosity) statistical approach to detect the selective sweeps between high- and low-fecundity Bamei mutton sheep groups. JUN (JUN proto-oncogene, AP-1 transcription factor subunit), ITPR3 (inositol 1,4,5-trisphosphate receptor type 3, PLCB2 (phospholipase C beta 2), HERC5 (HECT and RLD domain containing E3 ubiquitin protein ligase 5), and KDM4B (lysine demethylase 4B) were detected that are potential responsible for litter size. These observations provide a new opportunity to research the genetic variation influencing fecundity traits within a population evolving under artificial selection. Abstract Bamei mutton sheep is a Chinese domestic sheep breed developed by crossing German Mutton Merino sheep and indigenous Mongolian sheep for meat production. Here, we focused on detecting candidate genes associated with the increasing of the litter size in this breeds under recent artificial selection to improve the efficiency of mutton production. We selected five high- and five low-fecundity Bamei mutton sheep for whole-genome resequencing to identify candidate genes for sheep prolificacy. We used the FST and XP-EHH statistical approach to detect the selective sweeps between these two groups. Combining the two selective sweep methods, the reproduction-related genes JUN, ITPR3, PLCB2, HERC5, and KDM4B were detected. JUN, ITPR3, and PLCB2 play vital roles in GnRH (gonadotropin-releasing hormone), oxytocin, and estrogen signaling pathway. Moreover, KDM4B, which had the highest FST value, exhibits demethylase activity. It can affect reproduction by binding the promoters of estrogen-regulated genes, such as FOXA1 (forkhead box A1) and ESR1 (estrogen receptor 1). Notably, one nonsynonymous mutation (p.S936A) specific to the high-prolificacy group was identified at the TUDOR domain of KDM4B. These observations provide a new opportunity to research the genetic variation influencing fecundity traits within a population evolving under artificial selection. The identified genomic regions that are responsible for litter size can in turn be used for further selection.
Antibacterial activity of silver nanoparticles activated by photodynamic therapy in infected root canals.

BACKGROUND Root canal disinfection includes mechanical, chemical and biological struggle against microorganisms (MOs). Photodynamic therapy (PDT) and nanoparticle (NP) agents may be proposed as an alternative for use against intracanal infections due to their ability to disrupt biofilm and prevent bacterial adhesion to dentin. The use of NP agents in combination with light/photosensitizer (PS) agents increases the efficiency of PDT in root canal disinfection. OBJECTIVES The aim of the study was to evaluate the effect of light application - PDT - on the antibacterial activity of the combination of a PS agent (toluidine blue O -TBO) and an NP agent (silver nanoparticles - AgNPs) for the disinfection of the root canals inoculated with Enterococcus faecalis (E. faecalis). MATERIAL AND METHODS In this study, concentrations of 20 ppm of TBO and 10 ppm of AgNPs, which showed the highest antibacterial activity against E. faecalis in the TBO/AgNPs combination, were used according to the preliminary studies. After instrumentation, 120 human, single-rooted, straight-canal mandibular premolars of a standard length of 13 mm were contaminated with bacteria, and experimental procedures were conducted against 21-day-old mature biofilm. The teeth were randomly divided into 5 main experimental groups: TBO/light; AgNPs; TBO/AgNPs; AgNPs/light; and TBO/AgNPs/light. Then, these main groups were divided into 2 subgroups each, according to the 2 application time periods (30 s and 60 s) (n = 10). The remaining 20 teeth constituted positive and negative control groups. The data was analyzed with the Kolmogorov-Smirnov test, one-way analysis of variance (ANOVA), Tukey's honestly significant difference (HSD) test, and the Bonferroni correction. RESULTS The NaOCl group provided a bacterial reduction that was higher than in all other groups in a statistically significant manner. Light application on the TBO/AgNPs combination was the group that provided the highest bacterial reduction after NaOCl. CONCLUSIONS The photoactivation of the TBO/AgNPs combination led to an increase in the effect of PDT, and it has the potential to be used as an adjunct for disinfection of the root canal system.
Imaging biomarkers of vascular and axonal injury are spatially distinct in chronic traumatic brain injury

Traumatic Brain Injury (TBI) is associated with both diffuse axonal injury (DAI) and diffuse vascular injury (DVI), which result from inertial shearing forces. These terms are often used interchangeably, but the spatial relationships between DAI and DVI have not been carefully studied. Multimodal magnetic resonance imaging (MRI) can help distinguish these injury mechanisms: diffusion tensor imaging (DTI) provides information about axonal integrity, while arterial spin labeling (ASL) can be used to measure cerebral blood flow (CBF), and the reactivity of the Blood Oxygen Level Dependent (BOLD) signal to a hypercapnia challenge reflects cerebrovascular reactivity (CVR). Subjects with chronic TBI (n = 27) and healthy controls (n = 14) were studied with multimodal MRI. Mean values of mean diffusivity (MD), fractional anisotropy (FA), CBF, and CVR were extracted for pre-determined regions of interest (ROIs). Normalized z-score maps were generated from the pool of healthy controls. Abnormal ROIs in one modality were not predictive of abnormalities in another. Approximately 9-10% of abnormal voxels for CVR and CBF also showed an abnormal voxel value for MD, while only 1% of abnormal CVR and CBF voxels show a concomitant abnormal FA value. These data indicate that DAI and DVI represent two distinct TBI endophenotypes that are spatially independent.
Web-based education of the elderly improves drug utilization literacy: A randomized controlled trial

The aim of this study was to explore the effects of web-based education in the field of drug utilization on elderly individuals’ knowledge of, concerns about and self-assessed understanding of drug utilization. The 260 included participants were randomized to a control group or an intervention group. To assess drug utilization literacy, we used a questionnaire containing 20 multiple-choice questions on drug utilization and ten statements about drug utilization (to which participants graded their response using a Likert scale: two about common concerns and eight about their self-assessed understanding of drug utilization). The Beliefs about Medicines Questionnaire-General was also used. The intervention group scored higher on the knowledge questions (p < 0.001) and on six of the eight statements about self-assessed understanding of drug utilization at the first check after 2 weeks (p < 0.05). At a second check 6 months later, the difference remained for the knowledge questions, but there was no difference in self-assessed understanding of drug utilization between the groups. There were no differences in the concerns about drug utilization or beliefs about medication at any time. We conclude that a web-based education can improve drug utilization literacy in elderly individuals and might contribute to the safer use of medications.
The WNT/ROR Pathway in Cancer: From Signaling to Therapeutic Intervention

The WNT pathway is one of the major signaling cascades frequently deregulated in human cancer. While research had initially focused on signal transduction centered on β-catenin as a key effector activating a pro-tumorigenic transcriptional response, nowadays it is known that WNT ligands can also induce a multitude of β-catenin-independent cellular pathways. Traditionally, these comprise WNT/planar cell polarity (PCP) and WNT/Ca2+ signaling. In addition, signaling via the receptor tyrosine kinase-like orphan receptors (RORs) has gained increasing attention in cancer research due to their overexpression in a multitude of tumor entities. Active WNT/ROR signaling has been linked to processes driving tumor development and progression, such as cell proliferation, survival, invasion, or therapy resistance. In adult tissue, the RORs are largely absent, which has spiked the interest in them for targeted cancer therapy. Promising results in preclinical and initial clinical studies are beginning to unravel the great potential of such treatment approaches. In this review, we summarize seminal findings on the structure and expression of the RORs in cancer, their downstream signaling, and its output in regard to tumor cell function. Furthermore, we present the current clinical anti-ROR treatment strategies and discuss the state-of-the-art, as well as the challenges of the different approaches.
Bioinspired hydrogel surfaces to augment corneal endothelial cell monolayer formation

Corneal endothelial cells (CECs) have limited proliferation ability leading to corneal endothelium (CE) dysfunction and eventually vision loss when cell number decreases below a critical level. Although transplantation is the main treatment method, donor shortage problem is a major bottleneck. The transplantation of in vitro developed endothelial cells with desirable density is a promising idea. Designing cell substrates that mimic the native CE microenvironment is a substantial step to achieve this goal. In the presented study, we prepared polyacrylamide (PA) cell substrates that have a microfabricated topography inspired by the dimensions of CECs. Hydrogel surfaces were prepared via two different designs with small and large patterns. Small patterned hydrogels have physiologically relevant hexagon densities (∼2000 hexagons/mm2), whereas large patterned hydrogels have sparsely populated hexagons (∼400 hexagons/mm2). These substrates have similar elastic modulus of native Descemet's membrane (DM; ∼50 kPa) and were modified with Collagen IV (Col IV) to have biochemical content similar to native DM. The behavior of bovine corneal endothelial cells on these substrates was investigated and results show that cell proliferation on small patterned substrates was significantly (p = 0.0004) higher than the large patterned substrates. Small patterned substrates enabled a more densely populated cell monolayer compared to other groups (p = 0.001 vs. flat and p < 0.0001 vs. large patterned substrates). These results suggest that generating bioinspired surface topographies augments the formation of CE monolayers with the desired cell density, addressing the in vitro development of CE layers.
Adsorption of α‐amylase in a fixed bed: Operating efficiency and kinetic modeling

Kinetic studies on the adsorption of α-amylase from Aspergillus oryzae on the anion exchanger, Duolite A-568, and the hydrophobic resin, Duolite XAD-761, were carried out in a fixed bed. The efficiency with respect to the adsorbate and adsorbent was determined to estimate the performance of the process of adsorption. The effect of flow rate, α-amylase inlet concentration, temperature, and particle size of the packing was analyzed. In addition, the transient response, in the form of experimental breakthrough curves, was fitted using a phenomenological mathematical model accounting for the external-film and pore-diffusion mass-transfer mechanisms as well as axial dispersion along the column. Also, a Langmuir isotherm was included in the model to account for the extent of the equilibrium of adsorption. The model described satisfactorily the experimental breakthrough curves and it proved to predict successfully the behavior of a scaled-up bed using the kinetic and equilibrium parameters estimated previously. Thus, the mathematical model can be considered a reliable tool for process design and scale-up of similar systems.
Quantitative proteomic analysis of temporal lysosomal proteome and the impact of the KFERQ-like motif and LAMP2A in lysosomal targeting

ABSTRACT Autophagic pathways are regulated mechanisms that play important roles in lysosome-mediated cellular degradation. Yet, the contribution of different autophagic pathways in lysosomal targeting, and characterization of the extent and specificity in their degradome remains largely uncharacterized. By undertaking a multiplex quantitative mass spectrometry approach, we have previously analyzed the lysosomal proteome during chaperone-mediated autophagy (CMA)-stimulated conditions in cancer cells. Here, we have extended our multiplex quantitative mass spectrometry and bioinformatics analysis on the proteome from isolated lysosomes to gain a comprehensive view of the temporal enriched lysosomal content upon non-macroautophagy-activated conditions. In parallel, we describe the functional dependency of LAMP2A on, and to what degree the presence of KFERQ-like motifs in proteins influences, their lysosomal targeting. These findings establish a framework for a better understanding of the degradome mediated by autophagic pathways beyond macroautophagy, and present characterization of the impact of LAMP2A in lysosomal targeting in cancer cells. Abbreviations: CMA: chaperone-mediated autophagy; ER: endoplasmic reticulum; EIF4A1: eukaryotic translation initiation factor 4A1; eMI: endosomal microautophagy; FC: fold change; GO: gene ontology; ISR: integrated stress response; LAMP2A: lysosomal associated membrane protein 2A; MA: macroautophagy; MI: microautophagy; MS: mass spectrometry; PCA: principal component analysis; TAX1BP1: Tax1 binding protein 1.
A Method to Quantify Mean Hypertension Treatment Daily Dose Intensity Using Health Care System Data

Key Points Question Can the intensity of hypertension treatment by total dose burden for older patients be accurately quantified using only health system administrative pharmacy fill data? Findings In this cross-sectional study, dose intensity measured using pharmacy data in a national health care system was highly correlated with dose intensity documented in clinical notes by using a new algorithm that can be applied to an individual patient on any given day. Meaning This study suggests that intensity of hypertension treatment can be measured using pharmacy data at a more detailed level than using medication counts or blood pressure alone for quality comparison or as a research tool.