Miracle-dz/UniFAR-FTUs huggingface dataset:
Auditory brainstem responses obtained with randomised stimulation level

Abstract Objective To present randomised stimulation level (RSL) – a stimulation paradigm in which the level of the stimuli is randomised, rather than presented sequentially as in the conventional paradigm. Design The value of RSL was evaluated by (i) comparing the morphology of auditory brainstem responses (ABRs) elicited by the conventional and RSL paradigms, and by (ii) an online survey investigating the hearing comfort of the stimulus sequence. Study sample ABRs were obtained from 11 normal-hearing adults (8 females, 25–29 years). The online survey was administered to 238 adults from the general community. Results Results showed that (i) both stimulation paradigms elicit ABR signals of similar morphology, (ii) RSL provides a faster comprehensive representation of the ABR session, and that (iii) the general population found RSL stimuli to be more comfortable. Conclusions The simultaneous evaluation of all ABR traces of the session provided by RSL has potential to improve the identification of ABR components by enabling clinicians to make use of the response tracking strategy from the start of the test, which is critical in situations where ABRs present an abnormal morphology. New research opportunities and the clinical potential of RSL are discussed.
Pathogen Stimulation of Interleukin-8 from Human Vaginal Epithelial Cells through CD40

Most bacterial and fungal pathogens cause disease across mucosal, and to a lesser extent, skin barriers with the help of induced chemokines from epithelial cells. In this study, we showed that potential vaginal pathogens Staphylococcus aureus, group A and B streptococci, some Enterococcus faecalis strains, Escherichia coli, and Candida albicans use the immune costimulatory molecule CD40 to induce the chemokine interleukin-8 production. ABSTRACT Many bacterial and fungal pathogens cause disease across mucosal surfaces, and to a lesser extent through skin surfaces. Pathogens that potentially cause disease vaginally across epithelial cells include Staphylococcus aureus, group A and B streptococci, Escherichia coli, Neisseria gonorrhoeae, and Candida albicans. We have previously shown that staphylococcal and streptococcal superantigens induce inflammatory chemokines from vaginal epithelial cells through the immune costimulatory molecule CD40 through use of a CRISPR cas9 knockout mutant and complemented epithelial cell line. In this study, we show that the potential vaginal pathogens S. aureus, group A and B streptococci, E. coli, an Enterococcus faecalis strain, and C. albicans in part use CD40 to stimulate interleukin-8 (IL-8) production from human vaginal epithelial cells. In contrast, N. gonorrhoeae does not appear to use CD40 to signal IL-8 production. Normal flora Lactobacillus crispatus and an Enterococcus faecalis strain that produces reutericyclin do not induce IL-8. These data indicate that many potential pathogens, but no normal commensals, induce IL-8 to help disrupt the human vaginal epithelial barrier through CD40, thus providing a potential therapeutic target for drug development. IMPORTANCE Most bacterial and fungal pathogens cause disease across mucosal, and to a lesser extent, skin barriers with the help of induced chemokines from epithelial cells. In this study, we showed that potential vaginal pathogens Staphylococcus aureus, group A and B streptococci, some Enterococcus faecalis strains, Escherichia coli, and Candida albicans use the immune costimulatory molecule CD40 to induce the chemokine interleukin-8 production. In contrast, Neisseria gonorrhoeae does not use CD40 to stimulate interleukin-8. Normal flora lactobacilli and at least one E. faecalis strain do not induce interleukin-8.
Wnt signaling pathway: A comprehensive review

Wnt signaling is an evolutionary cell‐to‐cell coordination mechanism and it is highly critical for a variety of physiological processes of an organism's body, including stem cell regeneration, proliferation, division, migration, polarity of a cell, determining fate of the cell and specification of neural crest, neural symmetry and morphogenesis. Wnts are extracellular secreted glycol proteins, consisted of a family of 19 human proteins that represent the complex nature of the regulatory structure and physiological efficiency of signaling. Moreover, a Wnt/β‐catenin‐dependent pathway and the β‐catenin‐independent pathway that is further classified into the Planar Cell Polarity and Wnt/Ca2+ pathways have been established as key signaling nodes downstream of the frizzled (Fz/Fzd) receptor, and these nodes are extensively analyzed at biochemical and molecular levels. Genetic and epigenetic activities that ultimately characterize the pathway and its subsequent responses contribute to Wnt‐β‐catenin signaling pathway hypo or hyper‐activation and is associated with the variety of human disorders progression most significantly cancers. Recognizing how this mechanism operates is crucial to the advancement of cancer prevention therapies or regenerative medicine methods.
Rapid and Gentle Immunopurification of Brain Synaptic Vesicles

Current methods to isolate synaptic vesicles (SVs), the organellar quanta of synaptic transmission, require highly specialized materials and up to 24 h. These technical obstacles have thus far limited the study of SVs in models of synaptic function and pathophysiology. Here, we describe techniques for the rapid isolation of SVs by immunoprecipitation with widely available antibodies conjugated to magnetic beads. We report that the inexpensive rho1D4 monoclonal antibody binds SVs and show that elution with the 1D4 peptide yields native vesicles that are ≥ 10-fold purer than those obtained with classical techniques. These methods substantially widen the accessibility of SVs, enabling their purification in 60–90 min for downstream analyses including mass spectrometry and cryo-electron microscopy. Immunopurified SV preparations from mouse brain contained apolipoprotein E, the LDL receptor Lrp1, and enzymes involved in lipid metabolism, suggesting that SVs may play direct roles in lipid homeostasis and lipoprotein trafficking at the nerve terminal. SIGNIFICANCE STATEMENT SVs are small organelles that form and recycle at nerve terminals to enable synaptic transmission. Much remains unknown about the processes that enable the formation and function of SVs. Moreover, nerve terminals appear to be particularly vulnerable to pathophysiologic processes underlying neurodegenerative diseases and schizophrenia. Although techniques to purify synaptic vesicles thus have the potential to yield significant insights into physiology and pathophysiology of nerve terminals, current methods rely on either esoteric materials or expression of transgenes. This article addresses these problems by establishing robust, efficient methods for SV purification using widely available materials, and it highlights several promising areas of future study arising from proteomic analyses of immunopurified SVs.
Using a Convolutional Neural Network and Convolutional Long Short-term Memory to Automatically Detect Aneurysms on 2D Digital Subtraction Angiography Images: Framework Development and Validation

Background It is hard to distinguish cerebral aneurysms from overlapping vessels in 2D digital subtraction angiography (DSA) images due to these images’ lack of spatial information. Objective The aims of this study were to (1) construct a deep learning diagnostic system to improve the ability to detect posterior communicating artery aneurysms on 2D DSA images and (2) validate the efficiency of the deep learning diagnostic system in 2D DSA aneurysm detection. Methods We proposed a 2-stage detection system. First, we established the region localization stage to automatically locate specific detection regions of raw 2D DSA sequences. Second, in the intracranial aneurysm detection stage, we constructed a bi-input+RetinaNet+convolutional long short-term memory (C-LSTM) framework to compare its performance for aneurysm detection with that of 3 existing frameworks. Each of the frameworks had a 5-fold cross-validation scheme. The receiver operating characteristic curve, the area under the curve (AUC) value, mean average precision, sensitivity, specificity, and accuracy were used to assess the abilities of different frameworks. Results A total of 255 patients with posterior communicating artery aneurysms and 20 patients without aneurysms were included in this study. The best AUC values of the RetinaNet, RetinaNet+C-LSTM, bi-input+RetinaNet, and bi-input+RetinaNet+C-LSTM frameworks were 0.95, 0.96, 0.92, and 0.97, respectively. The mean sensitivities of the RetinaNet, RetinaNet+C-LSTM, bi-input+RetinaNet, and bi-input+RetinaNet+C-LSTM frameworks and human experts were 89% (range 67.02%-98.43%), 88% (range 65.76%-98.06%), 87% (range 64.53%-97.66%), 89% (range 67.02%-98.43%), and 90% (range 68.30%-98.77%), respectively. The mean specificities of the RetinaNet, RetinaNet+C-LSTM, bi-input+RetinaNet, and bi-input+RetinaNet+C-LSTM frameworks and human experts were 80% (range 56.34%-94.27%), 89% (range 67.02%-98.43%), 86% (range 63.31%-97.24%), 93% (range 72.30%-99.56%), and 90% (range 68.30%-98.77%), respectively. The mean accuracies of the RetinaNet, RetinaNet+C-LSTM, bi-input+RetinaNet, and bi-input+RetinaNet+C-LSTM frameworks and human experts were 84.50% (range 69.57%-93.97%), 88.50% (range 74.44%-96.39%), 86.50% (range 71.97%-95.22%), 91% (range 77.63%-97.72%), and 90% (range 76.34%-97.21%), respectively. Conclusions According to our results, more spatial and temporal information can help improve the performance of the frameworks. Therefore, the bi-input+RetinaNet+C-LSTM framework had the best performance when compared to that of the other frameworks. Our study demonstrates that our system can assist physicians in detecting intracranial aneurysms on 2D DSA images.
Validation of actinic keratosis diagnosis and treatment codes among veterans living with HIV

Actinic keratoses (AK) diagnosis, billing, and pharmacy codes have not been validated among people living with human immunodeficiency virus (HIV), preventing use in epidemiologic and clinical research. We aimed to calculate the positive predictive value (PPV) of AK diagnosis codes, procedural codes for destruction of pre‐malignant lesions, and pharmacy codes for topical 5‐fluorouracil.
Factors associated with acute pancreatitis in patients with impacted duodenal papillary stones: a retrospective cohort study

Abstract Objective Impaction of a stone at the duodenal papilla can obstruct biliopancreatic outflow and thereby lead to acute pancreatitis. But not all patients with an impacted papillary stone (IPS) had the clinical features of pancreatitis. This study aimed to identify factors associated with acute pancreatitis in patients with IPS. Methods We retrospectively analyzed patients with IPS who underwent endoscopic retrograde cholangiopancreatography (ERCP) at Tianjin Nankai Hospital. Clinical factors were compared between patients with/without acute pancreatitis before ERCP. Factors associated with acute pancreatitis were identified by univariable and multivariable binary logistic regression. Results The final analysis included 174 patients with acute pancreatitis (pancreatitis group, PG) and 130 patients without acute pancreatitis (non-pancreatitis group, NPG). Preoperative incidences of jaundice (85.6 vs. 72.3%), acute cholangitis (54.6 vs. 33.8%), and hyperlipidemia (39.1 vs. 22.3%) were higher in the PG than in the NPG (p < .05). High tension in the duodenal papilla (83.3 vs. 71.5%), circular papillary orifice (82.8 vs. 70.0%), and distal stone impaction (90.8 vs. 82.3%) were more common in the PG than in the NPG (p < .05), whereas stone diameter and common bile duct diameter did not differ significantly between groups. Multivariable logistic regression revealed that jaundice, acute cholangitis, hyperlipidemia, and dot/circular papillary orifice were independently associated with acute pancreatitis (p < .05). Conclusions Jaundice, acute cholangitis, and hyperlipidemia are independent risk factors for acute pancreatitis in patients with IPS. Prompt ERCP in patients with these features might reduce acute pancreatitis risk. Dot/circular papillary orifice may be an anatomical factor of acute pancreatitis, which needs more evidence.
Larval parasitism in a specialist herbivore is explained by phenological synchrony and host plant availability.

1. Parasitism is a key factor in the population dynamics of many herbivorous insects, although its impact on host populations varies widely, for instance, along latitudinal and altitudinal gradients. Understanding the sources of geographical variation in host-parasitoid interactions is crucial for reliably predicting the future success of the interacting species under a context of global change. 2. Here, we examine larval parasitism in the butterfly Aglais urticae in south-west Europe, where it is a mountain specialist. Larval nests were sampled over two years along altitudinal gradients in three Iberian mountain ranges, including the Sierra Nevada, home to its southernmost European population. Additional data on nettle condition and adult butterflies were obtained in the study areas. 3. These data sources were used to investigate whether or not differences in parasitism rates are related to the geographical position and phenology of the host, and to the availability of the host plants. 4. Phenological differences in the host populations between regions were related to the severity of summer drought and the corresponding differences in host plant availability. At the trailing-edge of its distribution, the butterfly's breeding season was restricted to the end of winter and spring, while in its northern Iberian range the season was prolonged until mid-summer. Although parasitism was an important source of mortality in all regions, parasitism rates and parasitoid richness were highest in the north and lowest in the south. Moreover, within a region, there was a notable increase in parasitism rates over time, which probably led to selection against an additional late-summer host generation in northern regions. Conversely, the shorter breeding season in Sierra Nevada resulted in a loss of synchrony between the host and one important late-season parasitoid, Sturmia bella, which may partly explain the high density of this butterfly species at the trailing-edge of its range. 5. Our results support the key role of host phenology in accounting for differences in parasitism rates between populations. They also provide insights into how climate through host plant availability affects host phenology and, ultimately, the impact of parasitism on host populations.
Idiopathic normal pressure hydrocephalus-like MRI features in patients with progressive supranuclear palsy: a comparative case-control study

ABSTRACT Background The occurrence of neurodegenerative disease in patients with normal pressure hydrocephalus (NPH) is emphasized in recent reports. Based on this common co-occurrence, some of the hydrocephalic disorders appearing in late adulthood have been hypothesized to result from initially unapparent parenchymal abnormalities of neurodegenerative origin. Among these diseases, progressive supranuclear palsy (PSP) has been specifically remarked on. We aimed to comparatively investigate the neuroimaging clues of iNPH in our PSP subjects. Methods Eighteen patients with a clinical diagnosis of PSP, 44 with Parkinson’s disease (PD), and 44 healthy control (HC) individuals were enrolled. The disproportionately enlarged subarachnoid space hydrocephalus (DESH) score, the Evans’ index (EI), and the callosal angle (CA) were measured on the conventional magnetic resonance imaging (MRI). The comparative analyses were performed using IBM SPSS Statistics 26. Results We found that dilated Sylvian fissures score (p = 0.016) and focal sulcal dilatation score (p = 0.037) were higher in the PSP group in comparison to HC whereas the CA score was higher in PSP subjects in comparison to both PD patients and HC (p = 0.000). Remarkably, the DESH score was also found to be higher in the PSP group in comparison to the age-matched HC group (p = 0.024). Conclusions We found that the NPH-like MRI features were more common in PSP subjects in comparison to PD subjects and age-matched HC. These results may provide critical contributions to the literature regarding the overlap between PSP and NPH.
Infrared cavity ring-down spectroscopy for detecting non-small cell lung cancer in exhaled breath

Early diagnosis of lung cancer greatly improves the likelihood of survival and remission, but limitations in existing technologies like low-dose computed tomography have prevented the implementation of widespread screening programs. Breath-based solutions that seek disease biomarkers in exhaled volatile organic compound (VOC) profiles show promise as affordable, accessible and non-invasive alternatives to traditional imaging. In this pilot work, we present a lung cancer detection framework using cavity ring-down spectroscopy (CRDS), an effective and practical laser absorption spectroscopy technique that has the ability to advance breath screening into clinical reality. The main aims of this work were to (1) test the utility of infrared CRDS breath profiles for discriminating non-small cell lung cancer (NSCLC) patients from controls, (2) compare models with VOCs as predictors to those with patterns from the CRDS spectra (breathprints) as predictors, and (3) present a robust approach for identifying relevant disease biomarkers. First, based on a proposed learning curve technique that estimated the limits of a model’s performance at multiple sample sizes (10–158), the CRDS-based models developed in this work were found to achieve classification performance comparable or superior to like mass spectroscopy and sensor-based systems. Second, using 158 collected samples (62 NSCLC subjects and 96 controls), the accuracy range for the VOC-based model was 65.19%–85.44% (51.61%–66.13% sensitivity and 73.96%–97.92% specificity), depending on the employed cross-validation technique. The model based on breathprint predictors generally performed better, with accuracy ranging from 71.52%–86.08% (58.06%–82.26% sensitivity and 80.21%–88.54% specificity). Lastly, using a protocol based on consensus feature selection, three VOCs (isopropanol, dimethyl sulfide, and butyric acid) and two breathprint features (from a local binary pattern transformation of the spectra) were identified as possible NSCLC biomarkers. This research demonstrates the potential of infrared CRDS breath profiles and the developed early-stage classification techniques for lung cancer biomarker detection and screening.
Comparing population-level mental health of UK workers before and during the COVID-19 pandemic: a longitudinal study using Understanding Society

Objectives The COVID-19 pandemic has substantially affected workers’ mental health. We investigated changes in UK workers’ mental health by industry, socioeconomic class and occupation and differential effects by UK country of residence, gender and age. Methods We used representative Understanding Society data from 6474 adults (41 207 observations) in paid employment who participated in pre-pandemic (2017–2020) and at least one COVID-19 survey. The outcome was General Health Questionnaire-12 (GHQ-12) caseness (score: ≥4). Exposures were industry, socioeconomic class and occupation and are examined separately. Mixed-effects logistic regression was used to estimate relative (OR) and absolute (%) increases in distress before and during pandemic. Differential effects were investigated for UK countries of residence (non-England/England), gender (male/female) and age (younger/older) using three-way interaction effects. Results GHQ-12 caseness increased in relative terms most for ‘professional, scientific and technical’ (OR: 3.15, 95% CI 2.17 to 4.59) industry in the pandemic versus pre-pandemic period. Absolute risk increased most in ‘hospitality’ (+11.4%). For socioeconomic class, ‘small employers/self-employed’ were most affected in relative and absolute terms (OR: 3.24, 95% CI 2.28 to 4.63; +10.3%). Across occupations, ‘sales and customer service’ (OR: 3.01, 95% CI 1.61 to 5.62; +10.7%) had the greatest increase. Analysis with three-way interactions showed considerable gender differences, while for UK country of residence and age results are mixed. Conclusions GHQ-12 caseness increases during the pandemic were concentrated among ‘professional and technical’ and ‘hospitality’ industries and ‘small employers/self-employed’ and ‘sales and customers service’ workers. Female workers often exhibited greater differences in risk by industry and occupation. Policies supporting these industries and groups are needed.
Bottom-up physiologically based pharmacokinetic modelling for predicting the human pharmacokinetic profiles of the ester prodrug MGS0274 and its active metabolite MGS0008, a metabotropic glutamate 2/3 receptor agonist

Abstract For ester prodrugs that are used to improve the gastrointestinal absorption of highly hydrophilic, pharmacologically active substances, it is challenging to predict the human pharmacokinetics (PK) of the prodrugs and their parent compounds using only preclinical data. This research was aimed at constructing a PBPK model for predicting the human PK of the ester prodrug MGS0274 and its parent compound MGS0008 after a single oral administration of MGS0274 besylate. First, we identified carboxylesterase 1 (CES1) as the major enzyme involved in the hydrolysis of MGS0274. Second, we constructed a new compartment model to estimate the passive diffusion clearance (CLpd) of MGS0008, a critical parameter for predicting the PK of highly hydrophilic compounds, based on in vivo monkey PK data. Finally, we constructed a permeability-limited liver PBPK model incorporating the CLpd assumed to be the same in humans. We confirmed that our method reliably predicted the human PK and that the estimated CLpd was comparable to that calculated retrospectively using the PBPK model, suggesting that the methodology for estimating the CLpd was valid. Our proposed methodology is expected to be helpful for human PK prediction of ester prodrugs hydrolysed by CES1 and their hydrophilic parent compounds even during the preclinical phase.
Long‐term cost‐effectiveness of Dexcom G6 real‐time continuous glucose monitoring system in people with type 1 diabetes in Australia

Real‐time continuous glucose monitoring (rt‐CGM) allows patients with diabetes to adjust insulin dosing, potentially improving glucose control. This study aimed to compare the long‐term cost‐effectiveness of the Dexcom G6 rt‐CGM device versus self‐monitoring of blood glucose (SMBG) and flash glucose monitoring (FGM) in Australia in people with type 1 diabetes (T1D).
Choroid plexus function in neurological homeostasis and disorders: The awakening of the circadian clocks and orexins

As research regarding the role of circadian rhythms, sleep, and the orexinergic system in neurodegenerative diseases is growing, it is surprising that the choroid plexus (CP) remains underappreciated in this realm. Despite its extensive role in the regulation of circadian rhythms and orexinergic signalling, as well as acting as the primary conduit between cerebrospinal fluid (CSF) and the circulatory system, providing a mechanism by which toxic waste molecules can be removed from the brain, the CP has been largely unexplored in neurodegeneration. In this review, we explore the role of the CP in maintaining brain homeostasis and circadian rhythms, regulating CSF dynamics, and how these functions change across the lifespan, from development to senescence. In addition, we examine the relationship between the CP, orexinergic signalling, and the glymphatic system, highlighting gaps in the literature and areas that require immediate exploration. Finally, we assess current knowledge, including possible therapeutic strategies, regarding the role of the CP in neurological disorders, such as traumatic brain injury, migraine, Alzheimer’s disease, and multiple sclerosis.