Miracle-dz/UniFAR-FTUs huggingface dataset:
Substantively Lowered Levels of Pantothenic Acid (Vitamin B5) in Several Regions of the Human Brain in Parkinson’s Disease Dementia

Pantothenic acid (vitamin B5) is an essential trace nutrient required for the synthesis of coenzyme A (CoA). It has previously been shown that pantothenic acid is significantly decreased in multiple brain regions in both Alzheimer’s disease (ADD) and Huntington’s disease (HD). The current investigation aimed to determine whether similar changes are also present in cases of Parkinson’s disease dementia (PDD), another age-related neurodegenerative condition, and whether such perturbations might occur in similar regions in these apparently different diseases. Brain tissue was obtained from nine confirmed cases of PDD and nine controls with a post-mortem delay of 26 h or less. Tissues were acquired from nine regions that show high, moderate, or low levels of neurodegeneration in PDD: the cerebellum, motor cortex, primary visual cortex, hippocampus, substantia nigra, middle temporal gyrus, medulla oblongata, cingulate gyrus, and pons. A targeted ultra–high performance liquid chromatography—tandem mass spectrometry (UHPLC-MS/MS) approach was used to quantify pantothenic acid in these tissues. Pantothenic acid was significantly decreased in the cerebellum (p = 0.008), substantia nigra (p = 0.02), and medulla (p = 0.008) of PDD cases. These findings mirror the significant decreases in the cerebellum of both ADD and HD cases, as well as the substantia nigra, putamen, middle frontal gyrus, and entorhinal cortex of HD cases, and motor cortex, primary visual cortex, hippocampus, middle temporal gyrus, cingulate gyrus, and entorhinal cortex of ADD cases. Taken together, these observations indicate a common but regionally selective disruption of pantothenic acid levels across PDD, ADD, and HD.
Treatment of Glaucoma Patients with Flammer Syndrome

Flammer syndrome (FS) describes a phenotype characterized by the presence of primary vascular dysregulation along with a number of symptoms and signs. Although most people with FS are healthy, FS favors the occurrence of certain diseases, such as normal tension glaucoma. This is because disturbed autoregulation makes the eye more sensitive to intraocular pressure (IOP) spikes or blood pressure drops. Treatment of FS is generally appropriate when patients either suffer greatly from their symptoms or if we can assume that it has contributed to a disease. In glaucoma, this may be the case if the glaucoma damage progresses despite well-controlled IOP. Both the still sparse scientific studies and our long clinical experience suggest that FS-targeted therapy not only relieves the symptoms of FS but also slows the progression of glaucoma damage in selected cases. This description is intended not only to help affected patients but to also motivate clinicians and researchers to conduct therapy studies to confirm or refute our observations.
Mapping the Spatial Distribution of the Rumen Fluke Calicophoron daubneyi in a Mediterranean Area

Rumen flukes (Calicophoron daubneyi) represent a growing threat to the animal health, productivity and welfare of ruminants. The present study aimed to assess the spatial distribution of C. daubneyi infections in ruminants and to develop a predictive model of the environmental suitability for rumen flukes in a Mediterranean area. A cross-sectional coprological survey was conducted in 682 sheep, 73 goat and 307 cattle farms located in the Basilicata region (southern Italy). Faecal samples collected were analysed using the FLOTAC technique. Geographical Information Systems (GIS) and statistical models were developed to determine environmental risk factors and to delimitate the areas at highest risk of infections in small ruminants. The results showed 7.9% (95% CI 6.05–10.27) of sheep farms, 2.7% (95% CI 0.48–10.44) of goat farms and 55.0% (95% CI 49.62–60.99) of cattle farms were infected by C. daubneyi. The areas with high predicted risk were situated in the western part of the region. The soil texture, land use and the presence of streams and brooks were the variables statistically significant (p < 0.05) in explaining the C. daubneyi distribution in the study area. The study confirms the importance of geospatial technology in supporting parasite control strategies in livestock and demonstrates that a combined use of different geostatistical techniques can improve the prediction of the C. daubneyi infection risk in ruminants.
Associations between Digital Health Intervention Engagement and Dietary Intake: A Systematic Review

There has been a proliferation of digital health interventions (DHIs) targeting dietary intake. Despite their potential, the effectiveness of DHIs are thought to be dependent, in part, on user engagement. However, the relationship between engagement and the effectiveness of dietary DHIs is not well understood. The aim of this review is to describe the association between DHI engagement and dietary intake. A systematic search of four electronic databases and grey literature for records published before December 2019 was conducted. Studies were eligible if they examined a quantitative association between objective measures of engagement with a DHI (subjective experience or usage) and measures of dietary intake in adults (aged ≥18 years). From 10,653 citations, seven studies were included. Five studies included usage measures of engagement and two examined subjective experiences. Narrative synthesis, using vote counting, found mixed evidence of an association with usage measures (5 of 12 associations indicated a positive relationship, 7 were inconclusive) and no evidence regarding an association with subjective experience (both studies were inconclusive). The findings provide early evidence supporting an association between measures of usage and dietary intake; however, this was inconsistent. Further research examining the association between DHI engagement and dietary intake is warranted.
A Method for Detecting and Analyzing Facial Features of People with Drug Use Disorders

Drug use disorders caused by illicit drug use are significant contributors to the global burden of disease, and it is vital to conduct early detection of people with drug use disorders (PDUD). However, the primary care clinics and emergency departments lack simple and effective tools for screening PDUD. This study proposes a novel method to detect PDUD using facial images. Various experiments are designed to obtain the convolutional neural network (CNN) model by transfer learning based on a large-scale dataset (9870 images from PDUD and 19,567 images from GP (the general population)). Our results show that the model achieved 84.68%, 87.93%, and 83.01% in accuracy, sensitivity, and specificity in the dataset, respectively. To verify its effectiveness, the model is evaluated on external datasets based on real scenarios, and we found it still achieved high performance (accuracy > 83.69%, specificity > 90.10%, sensitivity > 80.00%). Our results also show differences between PDUD and GP in different facial areas. Compared with GP, the facial features of PDUD were mainly concentrated in the left cheek, right cheek, and nose areas (p < 0.001), which also reveals the potential relationship between mechanisms of drugs action and changes in facial tissues. This is the first study to apply the CNN model to screen PDUD in clinical practice and is also the first attempt to quantitatively analyze the facial features of PDUD. This model could be quickly integrated into the existing clinical workflow and medical care to provide capabilities.
Investigations of Structural and Electrical Properties of ALD Films Formed with the Ozone Precursor

The continuous development of ALD thin films demands ongoing improvements and changes toward fabricating materials with tailored properties that are suitable for different practical applications. Ozone has been recently established as a precursor, with distinct advantages over the alternative oxidizing precursors in the ALDs of advanced dielectric films. This study reports alumina (Al2O3) and hafnia (HfO2) formation using an O3 source and compares the obtained structural and electrical properties. The performed structural examinations of ozone-based materials proved homogenous high-k films with less vacancy levels compared to water-based films. The enhanced structural properties also result in the problematic incorporation of different dopants through the bulk layer. Furthermore, analysis of electrical characteristics of the MIS structures with ALD gate dielectrics demonstrated the improved quality and good insulating properties of ozone-based films. However, further optimization of the ALD technique with ozone is needed as a relatively low relative permittivity characterizes the ultra-thin films.
A Novel Digital Care Management Platform to Monitor Clinical and Subclinical Disease Activity in Multiple Sclerosis

In multiple sclerosis (MS), the early detection of disease activity or progression is key to inform treatment changes and could be supported by digital tools. We present a novel CE-marked and FDA-cleared digital care management platform consisting of (1) a patient phone/web application and healthcare professional portal (icompanion) including validated symptom, disability, cognition, and fatigue patient-reported outcomes; and (2) clinical brain magnetic resonance imaging (MRI) quantifications (icobrain ms). We validate both tools using their ability to detect (sub)clinical disease activity (known-groups validity) and real-world data insights. Surveys showed that 95.6% of people with MS (PwMS) were interested in using an MS app, and 98.2% were interested in knowing about MRI changes. The icompanion measures of disability (p < 0.001) and symptoms (p = 0.005) and icobrain ms MRI parameters were sensitive to (sub)clinical differences between MS subtypes. icobrain ms also decreased intra- and inter-rater lesion count variability and increased sensitivity for detecting disease activity/progression from 24% to 76% compared to standard radiological reading. This evidence shows PwMS’ interest, the digital care platform’s potential to improve the detection of (sub)clinical disease activity and care management, and the feasibility of linking different digital tools into one overarching MS care pathway.
Counterclockwise Drilling with Different Tapered Drills Condenses the Implant Bed—An Optical Coherence Tomography In Vitro Study

Background and Objectives: To evaluate the condensation and the microarchitecture of implant bed walls of sites prepared with counterclockwise drilling with tapered implant drills using optical coherence tomography. Materials and Methods: Four drill designs with different wall and tip angles were used. Polyurethane laminas resembling type IV bone microarchitecture were superimposed and clamped with a vice to simulate the coronal, middle, and apical aspects of the implant site. Twenty implant beds were prepared at 1200 rpm in clockwise (control) and counterclockwise (test) directions (N = 160). Optical coherence tomography (OCT) was used to evaluate the condensation and microarchitecture characteristics of the implant bed walls. The relative condensation was calculated using the Image J software Bone application. The microarchitecture was evaluated in reconstructed 3D volumes in XY, XZ, and YZ sections. Statistical analysis was performed using one-way ANOVA. Dunnet test was applied to determine differences between groups. Significance was set as p < 0.05. Results: Counterclockwise drilling (Test) condensed and changed the microarchitecture of the apical regions for all the implant beds in all of the groups when compared to clockwise drilling (control). The apical region of test groups showed the highest relative bone condensation (p = 0.026) when compared to controls. Conclusions: The direction of rotation (counterclockwise drilling) and not the design of tapered drills (tip and wall angles) is responsible for the condensation at the apical area observed in polyurethane blocks. The OCT method can be used for the evaluation of changes in density and microstructure of polyurethane blocks.
Maternal Stressful Life Events during Pregnancy and Atopic Dermatitis in Children Aged Approximately 4–6 Years

The prevalence of atopic dermatitis (AD) in children has steadily increased over time, yet it remains largely unknown how maternal factors during pregnancy are associated with child AD. Few studies have specifically assessed the relationship between prenatal stress and child AD, with inconsistent findings. In this prospective cohort study following 426 mother-child dyads from pregnancy to middle childhood, women reported stressful life events (SLEs) experienced during the 12 months before delivery and AD outcomes in children aged approximately 4–6 years, including current, location-specific, and ever AD. We used Poisson regression to estimate risk ratios (RRs) and corresponding 95% confidence intervals (CIs) associated with a 1-unit increase in prenatal SLEs, adjusting for potential confounders. We also assessed whether the association between prenatal SLEs and child AD was modified by child sex, history of maternal atopy, or prenatal maternal resilient coping. The mean (standard deviation) of prenatal SLEs reported in the overall sample was 1.4 (1.6), with 37.1% of women reporting none. A 1-unit increase in prenatal SLEs was not significantly associated with current AD (RR: 1.08, 95% CI: 0.89, 1.31), location-specific AD (RR: 1.09, 95% CI: 0.78, 1.52), or ever AD (RR: 0.97, 95% CI: 0.87, 1.09). We did not find evidence of effect modification. Findings from this study suggest no association between prenatal SLEs and AD in middle childhood, although larger longitudinal studies with enhanced case definition and higher variability of SLE experience may more fully inform this question.
Absence of Light Exposure Increases Pathogenicity of Pseudomonas aeruginosa Pneumonia-Associated Clinical Isolates

Simple Summary An often-overlooked factor when designing an experiment is light exposure. Bacterial cultures are usually grown in an uncontrolled light environment, subject to natural daylight conditions. However, light as an abiotic factor has been described as a trigger for the switch from environmental to a pathogenic host-associated lifestyle. Pseudomonas aeruginosa possesses features that allow it to sense light and adapt its behavior accordingly. In this study, clinical isolates of P. aeruginosa from the sputum of pneumonia-diagnosed patients were assayed in two extreme light exposure conditions: constant illumination and intensity of full-spectrum light, and complete absence of light. The aim was to understand the influence of this factor on P. aeruginosa pathogenic potential, studied in interface with a human pulmonary epithelial cell line model. The preliminary findings here described evidenced that growth in the dark, which would more closely mimic the conditions in the lung microenvironment, was associated with a higher cytotoxicity against host cells, concordant with an increased pathogenic potential. Given the importance of accurately interpreting bacterial responses in in vitro studies, this study raises awareness of the need to control light exposure conditions to be as similar as possible to in vivo parameters. Abstract Pseudomonas aeruginosa can alter its lifestyle in response to changes in environmental conditions. The switch to a pathogenic host-associated lifestyle can be triggered by the luminosity settings, resorting to at least one photoreceptor which senses light and regulates cellular processes. This study aimed to address how light exposure affects the dynamic and adaptability of two P. aeruginosa pneumonia-associated isolates, HB13 and HB15. A phenotypic characterization of two opposing growth conditions, constant illumination and intensity of full-spectrum light and total absence of light, was performed. Given the nature of P. aeruginosa pathogenicity, distinct fractions were characterized, and its inherent pathogenic potential screened by comparing induced morphological alterations and cytotoxicity against human pulmonary epithelial cells (A549 cell line). Growth in the dark promoted some virulence-associated traits (e.g., pigment production, LasA proteolytic activity), which, together with higher cytotoxicity of secreted fractions, supported an increased pathogenic potential in conditions that better mimic the lung microenvironment of P. aeruginosa. These preliminary findings evidenced that light exposure settings may influence the P. aeruginosa pathogenic potential, likely owing to differential production of virulence factors. Thus, this study raised awareness towards the importance in controlling light conditions during bacterial pathogenicity evaluation approaches, to more accurately interpret bacterial responses.
Herpes Simplex Virus Re-Activation in Patients with SARS-CoV-2 Pneumonia: A Prospective, Observational Study

Background: Herpes simplex 1 co-infections in patients with COVID-19 are considered relatively uncommon; some reports on re-activations in patients in intensive-care units were published. The aim of the study was to analyze herpetic re-activations and their clinical manifestations in hospitalized COVID-19 patients, performing HSV-1 PCR on plasma twice a week. Methods: we conducted a prospective, observational, single-center study involving 70 consecutive patients with severe/critical SARS-CoV-2 pneumonia tested for HSV-1 hospitalized at Azienda Ospedaliero-Universitaria of Modena. Results: of these 70 patients, 21 (30.0%) showed detectable viremia and 13 (62%) had clinically relevant manifestations of HSV-1 infection corresponding to 15 events (4 pneumonia, 5 herpes labialis, 3 gingivostomatitis, one encephalitis and two hepatitis). HSV-1 positive patients were more frequently treated with steroids than HSV-1 negative patients (76.2% vs. 49.0%, p = 0.036) and more often underwent mechanical ventilation (IMV) (57.1% vs. 22.4%, p = 0.005). In the unadjusted logistic regression analysis, steroid treatment, IMV, and higher LDH were significantly associated with an increased risk of HSV1 re-activation (odds ratio 3.33, 4.61, and 16.9, respectively). The association with the use of steroids was even stronger after controlling for previous use of both tocilizumab and IMV (OR = 5.13, 95% CI:1.36–19.32, p = 0.016). The effect size was larger when restricting to participants who were treated with high doses of steroids while there was no evidence to support an association with the use of tocilizumab Conclusions: our study shows a high incidence of HSV-1 re-activation both virologically and clinically in patients with SARS-CoV-2 severe pneumonia, especially in those treated with steroids.
First Autochthonous Infection of a Cat with Dirofilaria immitis in Austria

This case report is about a seven-year-old male neutered European Shorthair cat infected by Dirofilaria immitis as the first reported autochthonous Dirofilaria immitis infection in Austria. There was no history of periods abroad. Echocardiography showed suspected D. immitis in the right cardiac chamber with increased pulmonary pressure and ascites. Surgical removal of the heartworms was performed. Twenty adult heartworms were removed by transvenous jugular approach under general anesthesia and stored in 4% formalin. Five out of 20 specimens were examined via light and stereomicroscopy and feline heartworm infection was confirmed. Amplification of a 203 bp or 724 bp fragment of the cytochrome c oxidase subunit I gene was unsuccessful. After surgery the cat developed acute renal failure but recovered quickly. One year later, the cat underwent a control examination including echocardiography and blood work. There were no more D. immitis detectable at echocardiography. Lung pressure was mildly increased. Complete blood count and creatinine were unremarkable. The Knott’s test and Dirofilaria-Antigen-test produced negative results. The cat did not show any clinical signs during the follow-up period. The aim of this case report is to highlight the growing risk of acquiring infection with D. immitis not only for Austrian dogs, but also for cats. This case report represents the first report of autochthonous D. immitis infection in Austria. Moreover, even if the prognosis in cats with caval syndrome due to feline heartworm disease is guarded to poor, surgical removal of the filariae can be a successful treatment option.
External Model Performance Evaluation of Twelve Infliximab Population Pharmacokinetic Models in Patients with Inflammatory Bowel Disease

Infliximab is approved for treatment of various chronic inflammatory diseases including inflammatory bowel disease (IBD). However, high variability in infliximab trough levels has been associated with diverse response rates. Model-informed precision dosing (MIPD) with population pharmacokinetic models could help to individualize infliximab dosing regimens and improve therapy. The aim of this study was to evaluate the predictive performance of published infliximab population pharmacokinetic models for IBD patients with an external data set. The data set consisted of 105 IBD patients with 336 infliximab concentrations. Literature review identified 12 published models eligible for external evaluation. Model performance was evaluated with goodness-of-fit plots, prediction- and variability-corrected visual predictive checks (pvcVPCs) and quantitative measures. For anti-drug antibody (ADA)-negative patients, model accuracy decreased for predictions > 6 months, while bias did not increase. In general, predictions for patients developing ADA were less accurate for all models investigated. Two models with the highest classification accuracy identified necessary dose escalations (for trough concentrations < 5 µg/mL) in 88% of cases. In summary, population pharmacokinetic modeling can be used to individualize infliximab dosing and thereby help to prevent infliximab trough concentrations dropping below the target trough concentration. However, predictions of infliximab concentrations for patients developing ADA remain challenging.
Updated Evidence on the Epidemiology of Hepatitis C Virus in Hemodialysis

Prevalence rates of HCV infection are decreasing in hemodialysis units of most developed countries; however, nosocomial transmission of HCV continues to occur in the hemodialysis setting, not only in the emerging world. According to the Dialysis Outcomes and Practice Patterns Study (DOPPS, 2012–2015), the prevalence of HCV among patients on regular hemodialysis was 9.9%; in incident patients, the frequency of HCV was approximately 5%. Outbreaks of HCV have been investigated by epidemiologic and phylogenetic data obtained by sequencing of the HCV genome; no single factor was retrieved as being associated with nosocomial transmission of HCV within hemodialysis units. Transmission of HCV within HD units can be prevented successfully by full compliance with infection control practices; also, antiviral treatment and serologic screening for anti-HCV can be useful in achieving this aim. Infection control practices in hemodialysis units include barrier precautions to prevent exposure to blood-borne pathogens and other procedures specific to the hemodialysis environment. Isolating HCV-infected hemodialysis patients or using dedicated dialysis machines for HCV-infected patients are not currently recommended; reuse of dialyzers of HCV-infected patients should be made, according to recent guidelines. Randomized controlled trials regarding the impact of isolation on the risk of transmission of HCV to hemodialysis patients have not been published to date. At least two studies showed complete elimination of de novo HCV within HD units by implementation of strict infection control practices without isolation practices. De novo HCV within hemodialysis units has been independently associated with facility HCV prevalence, dialysis vintage, and low staff-to-patient ratio. Antiviral treatment of HCV-infected patients on hemodialysis should not replace the implementation of barrier precautions and other routine hemodialysis unit procedures.