Miracle-dz/UniFAR-FTUs huggingface dataset:
Premalignant Oligodendrocyte Precursor Cells Stall in a Heterogeneous State of Replication Stress Prior to Gliomagenesis

Profiling premalignant cell states in a mouse model of glioma uncovers regulatory heterogeneity in glioma cells-of-origin and defines a state of replication stress that precedes tumor initiation. Cancer evolves from premalignant clones that adopt unusual cell states to achieve transformation. We previously pinpointed the oligodendrocyte precursor cell (OPC) as a cell of origin for glioma, but the early changes of mutant OPCs during premalignancy remained unknown. Using mice engineered for inducible Nf1-Trp53 loss in OPCs, we acutely isolated labeled mutant OPCs by laser-capture microdissection, determined global gene-expression changes by bulk RNA sequencing, and compared with cell-state fluctuations at the single-cell level by stochastic profiling, which uses RNA-sequencing measurements from random pools of 10 mutant cells. At 12 days after Nf1-Trp53 deletion, bulk differences were mostly limited to mitotic hallmarks and genes for ribosome biosynthesis, and stochastic profiling revealed a spectrum of stem-progenitor (Axl, Aldh1a1), proneural, and mesenchymal states as potential starting points for gliomagenesis. At 90 days, bulk sequencing detected few differentially expressed transcripts, whereas stochastic profiling revealed cell states for neurons and mural cells that do not give rise to glial tumors, suggesting cellular dead-ends for gliomagenesis. Importantly, mutant OPCs that strongly expressed key effectors of nonsense-mediated decay (Upf3b) and homology-dependent DNA repair (Rad51c, Slx1b, Ercc4) were identified along with DNA-damage markers, suggesting transcription-associated replication stress. Analysis of 10-cell transcriptomes at 90 days identified a locus of elevated gene expression containing an additional repair endonuclease (Mus81) and Rin1, a Ras-Raf antagonist and possible counterbalance to Nf1 loss, which was microdeleted or downregulated in gliomas at 150 days. These hidden cell-state variations uncover replication stress as a potential bottleneck that must be resolved for glioma initiation. Significance: Profiling premalignant cell states in a mouse model of glioma uncovers regulatory heterogeneity in glioma cells-of-origin and defines a state of replication stress that precedes tumor initiation. See related articles by Singh and colleagues, p. 1840 and Schaff and colleagues, p. 1853
High proton conductivity and low fuel crossover polymer electrolyte membranes derived from branched sulfonated poly(ether ether ketone)s and silica sulfonic acid nanoparticles

With the objective of improving water uptake and proton conductivity, silica sulfonic acid (SSA) nanoparticles were successfully prepared via the sulfonation of silica (SiO2) with sulfuryl chloride and a series of branched sulfonated poly(ether ether ketone) (BSPEEK)-based hybrid membranes with varying contents of SSA were fabricated by the solution-casting method as proton electrolyte materials. The hybrid membranes exhibited improved water uptake, excellent thermal stability, and enhanced mechanical strength. Compared with the methanol permeability, with the incorporation of SSA particles, the proton conductivity enhanced more significantly. The selectivity of the hybrid membranes increased with the increasing SSA contents, and the highest value was 8.2 × 105 S s cm−3, which was 2.6 times higher than that of Nafion 117. Therefore, these BSPEEK-SSA hybrid membranes could be considered as promising materials for direct methanol fuel cell applications.
Disaccharide Type Affected Phenolic and Volatile Compounds of Citrus Fiber-Blackberry Cream Fillings

The food industry is continuously developing ingredients, processing methods and packaging materials to improve the quality of fruit products. The aim of this work was to study the possibility of using citrus fiber in the preparation of blackberry cream fillings in combination with disaccharides (sucrose, maltose and trehalose). Evaluations of the phenolics, proanthocyanidins, antioxidant activity, color and volatiles of blackberry cream fillings were conducted after preparation and after three months of storage. Blackberry cream fillings were prepared from citrus fiber (5%), blackberry juice and disaccharides (50%). Disaccharide type had an effect on all investigated parameters. The highest phenol content was in fillings with trehalose (4.977 g/100 g) and the lowest was in fillings prepared with sucrose (4.249 g/100 g). The same tendency was observed after storage. Fillings with maltose had the highest proanthocyanidins content (473.05 mg/100 g) while fillings with sucrose had the lowest amount (299.03 mg/100 g) of these compounds. Regarding volatile compounds, terpenes and aldehydes and ketones were evaluated in the highest concentration. Terpenes were determined in the highest concentration in fillings with trehalose (358.05 µg/kg), while aldehydes and ketones were highest in fillings with sucrose (250.87 µg/kg). After storage, concentration of volatiles decreased. These results indicate that the selection of adequate disaccharides is very important since it can influence the final quality of the product.
Development and Validation of the Perceived Authenticity Scale for Cheese Specialties with Protected Designation of Origin

Authenticity has become increasingly important in the modern market as consumers seek products more resonant of tradition and originality. This study aimed to develop and validate a perceived authenticity scale for food specialties. Furthermore, this work exposed the causal relationship between authenticity and consumer behaviour, by quantitatively analysing the effects of perception of authenticity and identification with a product on consumers’ willingness to consume the cheese Algovian Emmentaler, an iconic dairy product produced in southern Germany and protected with the designation of origin. Three surveys were conducted over two different timeframes. One served as a pre-test in Germany with a representative sample for the second two in Germany and Italy with a gourmet sample. Both objective authenticity and subjective authenticity were considered, with the former comprising concepts such as whether the respondent was sure of the cheese’s origin and the latter what the cheese embodied. Identification with Algovian Emmentaler was also surveyed. Exploratory factor analysis and confirmatory factor analysis were conducted on the survey data in order to construct an authenticity scale. Based on this scale, structural equation models were constructed. Objective authenticity was found to positively contribute to stated willingness to consume, as well as mediate subjective authenticity, which itself mediated the effects of identification. Subjective authenticity was a large contributing factor to willingness to consume among German consumers, whereas the effects of objective authenticity were higher in Italy compared with the former. Expectedly, identification with Algovian Emmentaler also had a high direct effect on willingness to consume in Germany.
Reducing medical device alarms by an order of magnitude: A human factors approach

The intensive care unit (ICU) is one of the most technically advanced environments in healthcare, using a multitude of medical devices for drug administration, mechanical ventilation and patient monitoring. However, these technologies currently come with disadvantages, namely noise pollution, information overload and alarm fatigue—all caused by too many alarms. Individual medical devices currently generate alarms independently, without any coordination or prioritisation with other devices, leading to a cacophony where important alarms can be lost amongst trivial ones, occasionally with serious or even fatal consequences for patients. We have called this approach to the design of medical devices the single-device paradigm, and believe it is obsolete in modern hospitals where patients are typically connected to several devices simultaneously. Alarm rates of one alarm every four minutes for only the physiological monitors (as recorded in the ICUs of two hospitals contributing to this paper) degrades the quality of the patient’s healing environment and threatens patient safety by constantly distracting healthcare professionals. We outline a new approach to medical device design involving the application of human factors principles which have been successful in eliminating alarm fatigue in commercial aviation. Our approach comprises the networked-device paradigm, comprehensive alarms and humaniform information displays. Instead of each medical device alarming separately at the patient’s bedside, our proposed approach will integrate, prioritise and optimise alarms across all devices attached to each patient, display information more intuitively and hence increase alarm quality while reducing the number of alarms by an order of magnitude below current levels.
Fabrication of Co3O4 from Cobalt/2,6-Napthalenedicarboxylic Acid Metal-Organic Framework as Electrode for Supercapacitor Application

In this study, cobalt-based metal-organic framework (MOF) powder was prepared via the solvothermal method using 2,6-naphthalenedicarboxylic acid (NDC) as the organic linker and N,N-dimethylformamide (DMF) as the solvent. The thermal decomposition of the pristine cobalt-based MOF sample (CN-R) was identified using a thermogravimetric examination (TGA). The morphology and structure of the MOFs were modified during the pyrolysis process at three different temperatures: 300, 400, and 500 °C, which labeled as CN-300, CN-400, and CN-500, respectively. The results were evidenced via field-emission scanning electron microscopy (FESEM), energy dispersive X-ray spectroscopy (EDX) and X-ray diffraction (XRD). The crystallite size of all samples was calculated using Scherrer’s equation. The smallest crystallite size of 7.77 nm was calculated for the CN-300 sample. Fourier transform infrared spectroscopy (FTIR) spectra were acquired for all the samples. The graphical study of the cyclic voltammogram (CV) gave the reduction and oxidation peaks. The charge transfer resistance and ionic conductivity were studied using electrical impedance spectroscopy (EIS). The galvanostatic charge–discharge (GCD) responses of all samples were analyzed. The relatively high specific capacitance of 229 F g−1 at 0.5 A g−1 was achieved in the sample CN-300, whereby 110% of capacitance was retained after 5000 cycles. These findings highlighted the durability of the electrode materials at high current densities over a long cycle.
Composição química e atividade alelopática do óleo volátil de Hydrocotyle bonariensis Lam (araliaceae)

Os oleos essenciais sao liquidos aromaticos obtidos de materiais vegetais (flores, folhas, ramos, sementes, ervas, madeira, frutos, raizes e cascas), sendo constituidos por misturas complexas, dentre outras, de terpenoides que podem conter ate 100 ou mais compostos orgânicos. Os terpenos encontrados com maior frequencia nos oleos essenciais sao os monoterpenos, sesquiterpenos e com menor frequ-encia os diterpenos. Seus constituintes terpenicos podem apresentar diversas funcoes orgânicas, como alcoois, cetonas, eteres, esteres e aldeidos. Os terpenos possuem, tambem, diversas funcoes nas plantas atuando como fitoalexinas, repelentes de insetos, agentes de atracao polinica, agentes de defesa contra herbivoros, feromonios, hormonios vegetais, moleculas de sinalizacao e aleloquimicos.
Selective Inhibition of Human Monoamine Oxidase B by 5-hydroxy-2-methyl-chroman-4-one Isolated from an Endogenous Lichen Fungus Daldinia fissa

Inhibitory activities against monoamine oxidases (MAOs) and cholinesterases (ChEs) and antioxidant activity were evaluated for 195 extracts from Ukraine-derived endogenous lichen fungi (ELF). Among them, an ELF13 (identified as Daldinia fissa) extract showed the highest inhibitory activity against MAO-B, and 5-hydroxy-2-methyl-chroman-4-one (HMC) was isolated as a ~ 4-fold selective inhibitor of MAO-B (IC50 = 3.23 µM) compared to MAO-A (IC50 = 13.97 µM). HMC is a reversible competitive inhibitor with a Ki value of 0.896 µM. No cytotoxicity was observed in normal and cancer cells at 50 µM of HMC. HMC showed blood–brain barrier permeability and high gastrointestinal absorption in silico pharmacokinetics. The docking simulation results showed that the binding affinity of HMC for MAO-B (−7.3 kcal/mol) was higher than that of MAO-A (−6.1 kcal/mol) and that HMC formed a hydrogen bond interaction with Cys172 of MAO-B (distance: 3.656 Å), whereas no hydrogen bonding was predicted with MAO-A. These results suggest that HMC can be considered a candidate for the treatment of neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease.
Treatment generalization from trained /ɹ/ to untrained /l/: a case study of persisting distortion errors

ABSTRACT The extent to which treatment of speech errors that are phonetic in nature (i.e., distortions) produces generalization to untrained sounds is not well understood. This case study reports a child referred for treatment of a velarized distortion of American English /ɹ/, who also demonstrated an inconsistent velarized distortion of /l/. Acoustic analysis revealed evidence of a covert contrast between /ɹ/ and /l/ prior to treatment. Ultrasound biofeedback treatment and perceptual training targeted /ɹ/ only, but progress was tracked for both /ɹ/ and /l/. Substantial improvements in perceptually rated accuracy and significant changes in acoustic features were observed for both sounds, indicating generalization. These results highlight that generalization from trained to untrained sounds is possible for children with residual speech errors characterized by phonetic distortions.
Reductive Dissolution of Ferric Iron Minerals by Acidiphilium SJH

The acidophilic heterotrophic eubacterium Acidiphilium SJH was shown to catalyze the reductive dissolution of a wide range of ferric iron? containing minerals (akageneite, goethite, jarosite, natrojarosite, and amorphous ferric hydroxide) and of the mixed ferrous/ferric mineral magnetite. The specific rates of dissolution varied with the structural stabilities of the minerals, such that amorphous ferric hydroxide was the most rapid and jarosite and akageneite were the slowest of the minerals tested. The reductive dissolution of both amorphous ferric hydroxide and magnetite was faster in pH 2.0 than in higher pH (2.8? 3.0) cultures, even though Acidiphilium SJH has a pH optimum close to pH 3. Contact between bacteria and ferric mineral was not necessary for reductive dissolution to occur. Adding EDTA or diethylenetriamine pentaacetic acid to bacterial cultures accelerated the solubilization of goethite and amorphous ferric hydroxide. Although cell-free spent media and heat-killed Acidiphilium SJH also appear.
Influence of Artefact Correction and Recording Device Type on the Practical Application of a Non-Linear Heart Rate Variability Biomarker for Aerobic Threshold Determination

Recent study points to the value of a non-linear heart rate variability (HRV) biomarker using detrended fluctuation analysis (DFA a1) for aerobic threshold determination (HRVT). Significance of recording artefact, correction methods and device bias on DFA a1 during exercise and HRVT is unclear. Gas exchange and HRV data were obtained from 17 participants during an incremental treadmill run using both ECG and Polar H7 as recording devices. First, artefacts were randomly placed in the ECG time series to equal 1, 3 and 6% missed beats with correction by Kubios software’s automatic and medium threshold method. Based on linear regression, Bland Altman analysis and Wilcoxon paired testing, there was bias present with increasing artefact quantity. Regardless of artefact correction method, 1 to 3% missed beat artefact introduced small but discernible bias in raw DFA a1 measurements. At 6% artefact using medium correction, proportional bias was found (maximum 19%). Despite this bias, the mean HRVT determination was within 1 bpm across all artefact levels and correction modalities. Second, the HRVT ascertained from synchronous ECG vs. Polar H7 recordings did show an average bias of minus 4 bpm. Polar H7 results suggest that device related bias is possible but in the reverse direction as artefact related bias.
Comparison of Proteomic Technologies for Blood-Based Detection of Colorectal Cancer

Blood-based protein biomarkers are increasingly being explored as supplementary or efficient alternatives for population-based screening of colorectal cancer (CRC). The objective of the current study was to compare the diagnostic potential of proteins measured with different proteomic technologies. The concentrations of protein biomarkers were measured using proximity extension assays (PEAs), liquid chromatography/multiple reaction monitoring–mass spectrometry (LC/MRM-MS) and quantibody microarrays (QMAs) in plasma samples of 56 CRC patients and 99 participants free of neoplasms. In another approach, proteins were measured in serum samples of 30 CRC cases and 30 participants free of neoplasm using immunome full-length functional protein arrays (IpAs). From all the measurements, 9, 6, 35 and 14 protein biomarkers overlapped for comparative evaluation of (a) PEA and LC/MRM-MS, (b) PEA and QMA, (c) PEA and IpA, and (d) LC/MRM-MS and IpA measurements, respectively. Correlation analysis was performed, along with calculation of the area under the curve (AUC) for assessing the diagnostic potential of each biomarker. DeLong’s test was performed to assess the differences in AUC. Evaluation of the nine biomarkers measured with PEA and LC/MRM-MS displayed correlation coefficients >+0.6, similar AUCs and DeLong’s p-values indicating no differences in AUCs for biomarkers like insulin-like growth factor binding protein 2 (IGFBP2), matrix metalloproteinase 9 (MMP9) and serum paraoxonase lactonase 3 (PON3). Comparing six proteins measured with PEA and QMA showed good correlation and similar diagnostic performance for only one protein, growth differentiation factor 15 (GDF15). The comparison of 35 proteins measured with IpA and PEA and 14 proteins analyzed with IpA and LC/MRM-MS revealed poor concordance and comparatively better AUCs when measured with PEA and LC/MRM-MS. The comparison of different proteomic technologies suggests the superior performance of novel technologies like PEA and LC/MRM-MS over the assessed array-based technologies in blood-protein-based early detection of CRC.
Sex-Based Language Differences in Female Pelvic Medicine and Reconstructive Surgery Fellowship Recommendation Letters

Supplemental digital content is available in the text. Introduction Letters of recommendation (LORs) are a significant component of residency and fellowship applications. Applicant sex may play a role in the language used in letters, which could hinder progress in academic fields, particularly for women. Although differences in language based on applicant sex have been identified in other fields, no prior studies have evaluated LORs for female pelvic medicine and reconstructive surgery (FPMRS) fellowships. Methods Letters of recommendations for applicants to an urban, tertiary care academic medical FPMRS fellowship from 2017 to 2019 were collected. Using the Linguistic Inquiry and Word Count program, a licensed text analysis software for academic purposes, we analyzed LORs based on 16 categories. The Wilcoxon rank sum test, Fisher exact test, and a generalized linear mixed model were used for statistical analyses. Results A total of 97 fellowship applications were analyzed, yielding 354 LORs; 32 applicants were male, whereas 65 were female. Letters written for male applicants contained significantly more power words (P = 0.022) and significantly less affiliation words (P = 0.025) compared with female counterparts. Differences were maintained after adjusting for age, race/ethnicity, step 1 to step 3 scores, Phi Beta Kappa status, Alpha Omega Alpha status, and writer’s sex. Conclusions Significant linguistic differences based on applicant sex exist in FPMRS fellowship LORs. Differences are consistent with previous analyses within science and medical fields. These findings did not show a significant association with an applicant’s ability to match; however, we did not analyze whether the matched institution was the preferred choice for each applicant.
Gastro-Protective Effects of Albizia anthelmintica Leaf Extract on Indomethacin-Induced Gastric Ulcer in Wistar Rats: In Silico and In Vivo Studies

We have previously reported that the leaf extract of Albizia anthelmintica exhibited substantial antioxidant, anti-inflammatory, analgesic, and antipyretic properties in vivo. We also comprehensively characterized the active phytoconstituents and found several flavonoids and galloyl glucosides derivatives. In the current work, we explored the gastroprotective effects of the leaf extract in an indomethacin-induced ulcer model and the mechanisms involved. The rats being pretreated with the tested extract (100 and 200 mg kg−1) significantly prevented gastric lesions by 87.4% and 92.3%, respectively, and they had no structural derangements in the gastric mucosa. The extract significantly reduced the elevated levels of IKκB, NF-κB, TNF-α, IL-6, iNOS, and lipid peroxidation; increased the reduced level of glutathione peroxidase (GPx) activity; and reduced glutathione (GSH) in the indomethacin-induced ulcer model. The protective activities of the extract were similar in most aspects to those exerted by the known anti-ulcer drug famotidine. These activities might be attributed to the anti-inflammatory and antioxidant activities, and the reduction of iNOS levels. In conclusion, Albizia anthelmintica is a potential candidate for management of gastric ulcers with antioxidant properties.
Thermal Characteristics of Breast Surface Temperature in Healthy Women

Thermography is widely used in the medical field, including in the detection of breast disorders. The aim of the research was to characterize the range of breast surface temperature values, taking into account the entire area of the mammary gland and, independently, the nipple, in healthy women. An additional aim was to assess the symmetry of the breast temperature distribution (using an IR camera) and the correlation of temperatures with the content of adipose tissue. Thermograms were made for the right and left breasts, each time delineating the area of the entire breast and a separate area of the nipple, chest, and abdomen. Analyzing the intergroup differences in temperature of selected body areas (Tmean), it was shown that, in all cases, they were significantly higher in younger women. Statistical analysis showed no significant differences between breast and nipple temperatures in relation to the body sides. The highest temperatures within the mammary gland were recorded for the nipple area. The use of the high-resolution digital infrared thermal imaging method in early and screening preventive diagnoses of changes in the mammary gland requires individual interpretation of the results, taking into account the assessment of the physiological pattern of temperature distribution in both breasts.