Miracle-dz/UniFAR-FTUs huggingface dataset:
The beneficial role of the synthetic microneurotrophin BNN20 in a focal demyelination model

BNN20, a C17‐spiroepoxy derivative of the neurosteroid dehydroepiandrosterone, has been shown to exhibit strong neuroprotective properties but its role in glial populations has not been assessed. Our aim was to investigate the effect of BNN20 on glial populations by using in vitro and in vivo approaches, taking advantage of the well‐established lysophosphatidylcholine (LPC)‐induced focal demyelination mouse model. Our in vivo studies, performed in male mice, showed that BNN20 treatment leads to an increased number of mature oligodendrocytes (OLs) in this model. It diminishes astrocytic accumulation during the demyelination phase leading to a faster remyelination process, while it does not affect oligodendrocyte precursor cell recruitment or microglia/macrophage accumulation. Additionally, our in vitro studies showed that BNN20 acts directly to OLs and enhances their maturation even after they were treated with LPC. This beneficial effect of BNN20 is mediated, primarily, through the neurotrophin receptor TrkA. In addition, BNN20 reduces microglial activation and their transition to their pro‐inflammatory state upon lipopolysaccharides stimulation in vitro. Taken together our results suggest that BNN20 could serve as an important molecule to develop blood–brain barrier‐permeable synthetic agonists of neurotrophin receptors that could reduce inflammation, protect and increase the number of functional OLs by promoting their differentiation/maturation.
Early institutionalized care disrupts the development of emotion processing in prosody

Abstract Millions of children worldwide are raised in institutionalized settings. Unfortunately, institutionalized rearing is often characterized by psychosocial deprivation, leading to difficulties in numerous social, emotional, physical, and cognitive skills. One such skill is the ability to recognize emotional facial expressions. Children with a history of institutional rearing tend to be worse at recognizing emotions in facial expressions than their peers, and this deficit likely affects social interactions. However, emotional information is also conveyed vocally, and neither prosodic information processing nor the cross-modal integration of facial and prosodic emotional expressions have been investigated in these children to date. We recorded electroencephalograms (EEG) while 47 children under institutionalized care (IC) (n = 24) or biological family care (BFC) (n = 23) viewed angry, happy, or neutral facial expressions while listening to pseudowords with angry, happy, or neutral prosody. The results indicate that 20- to 40-month-olds living in IC have event-related potentials (ERPs) over midfrontal brain regions that are less sensitive to incongruent facial and prosodic emotions relative to children under BFC, and that their brain responses to prosody are less lateralized. Children under IC also showed midfrontal ERP differences in processing of angry prosody, indicating that institutionalized rearing may specifically affect the processing of anger.
Active hematopoiesis triggers exosomal release of PRDX2 that promotes osteoclast formation

Hematopoietic disorders, particularly hemolytic anemias, commonly lead to bone loss. We have previously reported that actively proliferating cancer cells stimulate osteoclastogenesis from late precursors in a RANKL‐independent manner. We theorized that cancer cells exploit the physiological role of bone resorption to support expanding hematopoietic bone marrow and examined if hematopoietic cells can trigger osteoclastogenesis. Using phlebotomy‐induced acute anemia in mice, we found strong correlation between augmented erythropoiesis and increased osteoclastogenesis. Conditioned medium (CM) from K562 erythroleukemia cells and primary mouse erythroblasts stimulated osteoclastogenesis when added to RANKL‐primed precursors from mouse bone marrow or RAW264.7 cells. Using immunoblotting and mass spectrometry, PRDX2 was identified as a factor produced by erythroid cells in vitro and in vivo. PRDX2 was detected in K562‐derived exosomes, and inhibiting exosomal release significantly decreased the osteoclastogenic capacity of K562 CM. Recombinant PRDX2 induced osteoclast formation from RANKL‐primed primary or RAW 264.7 precursors to levels comparable to achieved with continuous RANKL treatment. Thus, increased bone marrow erythropoiesis secondary to anemia leads to upregulation of PRDX2, which is released in the exosomes and acts to induce osteoclast formation. Increased bone resorption by the osteoclasts expands bone marrow cavity, which likely plays a supporting role to increase blood cell production.
Real‐time ultrasound virtual navigation in 3D PET/CT volumes for superficial lymph‐node evaluation: innovative fusion examination

To evaluate the feasibility and clinical application of fusion imaging with virtual navigation, combining 18F‐fluorodeoxyglucose (18F‐FDG) positron emission tomography/computed tomography (PET/CT) with real‐time ultrasound imaging, in assessing superficial lymph nodes in breast‐cancer and gynecological‐cancer patients.
Identification of anti-microbial peptides and traces of microbial DNA in infrainfundibular compartments of human scalp terminal hair follicles

Background The upper follicular compartment, a well-known reservoir of cutaneous microbiota, constitutes a space for intensive cross-barrier dialogue. The lower follicle comprises the bulb and bulge, structures with relative immune-privileged status, crucial for physiological cycling, and widely considered to be microbial-free. Objectives Following our initial immunohistochemical screening for regulatory cytokines and defensin expression in anagen hair follicles, we aimed to confirm our results with a follow-up ELISA investigation. We postulated that exposure to microbial components may trigger expression, and thus opted to investigate microbial presence in this area. Materials & Methods We performed immunohistochemical staining for selected cytokines and antimicrobial peptides, and Gram and Giemsa staining on tissue sections from healthy individuals. Based on ELISA analyses, we confirmed a marked presence of IL-17A- and HBD2 in infrainfundibular compartments from plucked anagen hair follicles of 12 individuals (six females, six males; frontal and occipital scalp sites). 16S rRNA sequencing on microbial DNA extracted from lower follicles, as well as fluorescence in situ hybridization (FISH) were applied to explore bacterial presence in the infrainfundibular compartments. Results 16S rRNA sequencing yielded reproducible data of bacterial presence in infrainfundibular compartments of plucked scalp follicles; Lawsonella clevelandensis, Staphylococcaceae and Propionibacteriaceae were the most abundant bacteria. Also, FISH revealed biofilm structures formed by Cutibacterium acnes (formerly Propionibacterium acnes ) and Staphylococcus sp. below the infundibulum. Conclusion As the skin microbiome largely influences the local immune system, the presence of bacteria in proximity to follicular immune-privileged areas may be of relevance to hair cycling in health and disease.
Machine learning predictions of concentration-specific aggregate hazard scores of inorganic nanomaterials in embryonic zebrafish

Abstract The possibility of employing computational approaches like nano-QSAR or nano-read-across to predict nanomaterial hazard is attractive from both a financial, and most importantly, where in vivo tests are required, ethical perspective. In the present work, we have employed advanced Machine Learning techniques, including stacked model ensembles, to create nano-QSAR tools for modeling the toxicity of metallic and metal oxide nanomaterials, both coated and uncoated and with a variety of different core compositions, tested at different dosage concentrations on embryonic zebrafish. Using both computed and experimental descriptors, we have identified a set of properties most relevant for the assessment of nanomaterial toxicity and successfully correlated these properties with the associated biological responses observed in zebrafish. Our findings suggest that for the group of metal and metal oxide nanomaterials, the core chemical composition, concentration and properties dependent upon nanomaterial surface and medium composition (such as zeta potential and agglomerate size) are significant factors influencing toxicity, albeit the ranking of different variables is sensitive to the exact analysis method and data modeled. Our generalized nano-QSAR ensemble models provide a promising framework for anticipating the toxicity potential of new nanomaterials and may contribute to the transition out of the animal testing paradigm. However, future experimental studies are required to generate comparable, similarly high quality data, using consistent protocols, for well characterized nanomaterials, as per the dataset modeled herein. This would enable the predictive power of our promising ensemble modeling approaches to be robustly assessed on large, diverse and truly external datasets.
Ratings of Perceived Exertion during Walking: Predicting Major Mobility Disability and Effect of Structured Physical Activity in Mobility-Limited Older Adults.

BACKGROUND This study evaluated the association between ratings of perceived exertion (RPE) of walking and major mobility disability (MMD), as well as their transitions in response to a physical activity (PA) compared to a health education (HE) program. METHODS Older adults (n=1633) at risk for mobility impairment were randomized to structured PA or HE programs. During a 400m walk, participants rated exertion as "light" or "hard". An MMD event was defined as the inability to walk 400m. MMD events and RPE values were assessed every 6-months for an average of 2.6 years. RESULTS Participants rating their exertion as "hard" had a nearly 3-fold higher risk of MMD compared with those rating their exertion as "light" (HR: 2.61, 95%CI: 2.19-3.11). The association held after adjusting for disease conditions, depression, cognitive function and walking speed (HR: 2.24, 95%CI: 1.87-2.69). The PA group was 25% more likely to transition from "light" to "hard" RPE than the HE group (1.25, 1.05-1.49). Additionally, the PA group was 27% (0.73, 0.55 - 0.97) less likely to transition from a "hard" RPE to inability to walk 400m and was more likely to recover their ability to walk 400m by transitioning to a "hard" RPE (2.10, 1.39-3.17) than the HE group. CONCLUSIONS Older adults rating "hard" effort during a standardized walk test were at increased risk of subsequent MMD. A structured PA program enabled walking recovery, but was more likely to increase transition from "light" to "hard" effort, which may reflect greater capacity to perform the test.
Immunohistochemical evaluation of hepatic progenitor cells in different types of feline liver diseases

Hepatic progenitor cells are periportally resident cells capable of differentiating into mature hepatocytes or cholangiocytes to ensure hepatic regeneration. This reaction is termed a ductular reaction. In the present study, regenerative response of the feline liver to different hepatic diseases was investigated immunohistochemically. Regeneration of the liver through hepatocellular replication and proliferation of progenitor cell compartment were comparatively evaluated. Histological and immunohistochemical stainings were conducted on feline liver samples (n=40) representing various hepatobiliary diseases. Cytokeratin (CK) 7, CK19, Proliferating cell nuclear antigen (PCNA), Ki67, and Human hepatocyte marker 1 (Hep Par-1) were used. The presence of progenitor cells within feline livers was proved, both as passive cells in normal liver and as active cells (ductular reaction) in hepatic lesions. CK7 was found to be a suitable antibody for immunohistochemically detecting feline progenitor cells. In acute events, regeneration was predominantly shaped by the division of hepatocytes. In chronic events and severe acute events, hepatocytes lost their ability to divide and regeneration mainly occurred through progenitor cells. Location of the ductular reaction varied between different hepatic diseases. Parenchymal ductular reaction was detected in fulminant hepatitis, chronic hepatitis, hepatocellular lipidosis and metastatic lymphoma, whereas septal ductular reaction was detected in chronic hepatitis and metastatic lymphoma. Ductular reaction exhibited positive staining for Hep Par-1 in chronic and severe acute events. This study indicates the major role played by hepatic progenitor cells in regeneration of the feline liver. Moreover, it shows how the activation pattern of ductular reaction varies according to the hepatobiliary disease type.
Typical preschoolers’ perceptions of augmentative and alternative communication modes of a preschooler with autism spectrum disorder

Abstract Understanding typical preschoolers’ perceptions of communication modes could help guide augmentative and alternative communication (AAC) intervention for preschoolers with autism spectrum disorder (ASD). This study explored the perceptions of 16 typically developing preschoolers toward an (a) AAC application (app) on a tablet, (b) picture exchange using a binder with printed Picture Communication SymbolsTM, and (c) prelinguistic communication used by a preschooler with ASD in a series of videos the preschoolers watched. Using a multi-method design, the study implemented both quantitative (rank ordering and preference selection) and qualitative (interview) methodologies. Quantitative results revealed the typical preschoolers had a clear overall preference for the AAC app, but variation in preference existed when selecting a communication mode to use in specific social scenarios. Qualitative data show the children more easily understood the child with ASD when he used the AAC app and associated tablets with fun, which may have accounted for positive perceptions of this AAC mode. The study is exploratory in nature and limited by its size and scope. However, it provides insights useful for clinicians’ understanding not just how typical preschoolers perceive various modes of communication, but also why they may perceive some more favorably than others, in order to tailor intervention accordingly.
Post-PCI outcomes in STEMI patients with coronary ectasia: meta-analysis

ABSTRACT Background Coronary ectasia (CE) is defined as dilation of the coronary artery, 1.5 times that of the surrounding vessel. Outcomes of percutaneous intervention (PCI) in patients with CE presenting as ST-elevated myocardial infarction (STEMI) remain a topic of debate. Methods Studies comparing outcomes of PCI in CE versus no-ectasia (NE) STEMI patients were identified. Baseline angiographic characteristics include thrombolysis in myocardial infarction (TIMI) 0–1 flow, right coronary artery (RCA) involvement, and primary outcomes including thrombus aspiration, no-reflow, mortality, and TIMI-3 post-PCI. Odds ratio (OR) and 95% confidence interval (CI) were calculated. Results Six studies (n = 5746, CE-340 and NE-5406) qualified for the analysis. RCA involvement was more common in CE than NE, OR-1.39 (95%CI1.06–1.82, p-0.02). Pre-procedure TIMI-0-1 was of comparable results between the groups (p-1.13). Higher thrombus aspiration for CE (OR 2.18, 95%CI1.44–3.32;p-<0.001). CE had higher incidence of no-reflow (OR 4.07, 95%CI2.42–6.84;p-<0.001). TIMI-3 flow post-PCI was achieved less commonly in the CE group (OR-0.64, 95%CI-0.48–0.86;p-<0.001). Mortality on follow-up was comparable (0.83, 95%CI0.39–1.78;p-0.63). Metaregression analysis did not show confounding effects from comorbidities. Conclusion Coronary ectasia patients with STEMI had higher rates of PCI failure and no-reflow than NE; however, mortality during follow-up was comparable.
IsoTV: processing and visualizing functional features of translated transcript isoforms

Abstract Summary Despite the continuous discovery of new transcript isoforms, fueled by the recent increase in accessibility and accuracy of long-read RNA sequencing data, functional differences between isoforms originating from the same gene often remain obscure. To address this issue and enable researchers to assess potential functional consequences of transcript isoform variation on the proteome, we developed IsoTV. IsoTV is a versatile pipeline to process, predict and visualize the functional features of translated transcript isoforms. Attributes such as gene and isoform expression, transcript composition and functional features are summarized in an easy-to-interpret visualization. IsoTV is able to analyze a variety of data types from all eukaryotic organisms, including short- and long-read RNA-seq data. Using Oxford Nanopore long read data, we demonstrate that IsoTV facilitates the understanding of potential protein isoform function in different cancer cell types. Availability and implementation IsoTV is available at https://github.molgen. mpg.de/MayerGroup/IsoTV, with the corresponding documentation at https://isotv.readthedocs. io/. Supplementary information Supplementary data are available at Bioinformatics online.
Iprodione and chlorpyrifos induce testicular damage, oxidative stress, apoptosis and suppression of steroidogenic‐ and spermatogenic‐related genes in immature male albino rats

The fungicide iprodione (IPR) and the insecticide chlorpyrifos (CPF) are concurrently applied for early disease control in fruits and other crops. However, there are no available data about the impacts of their co‐exposure. Additionally, IPR and CPF are known as endocrine disruptors that can cause reproductive toxicity. The outcomes of their co‐exposure on the development of male reproductive organs are still unknown. Therefore, this study aimed to assess the risk of exposure to these pesticides, particularly on the postnatal development of the male albino rat reproductive system from postnatal days 23–60. The results revealed that a single IPR or CPF exposure has harmful consequences on the reproductive development and function manifested by reduced testicular weight, serious changes in sperm characteristics, reproductive hormone level imbalance, testicular enzymes, oxidative stress and apoptosis‐related enzymes, which correlated with transcription levels of steroidogenic‐ and spermatogenic‐related genes. Histopathologically, both compounds caused severe damage in the testis and accessory glands architecture. Notably, co‐exposure to IPR and CPF in rats caused more serious damage, indicative of an additive effect than individual exposure, so concurrent exposure should be avoided as it is more hazardous, especially on male fertility.
Molecular dynamics simulations of polyampholyte solutions: osmotic coefficient

Polyampholytes are charged polymers containing both positively and negatively charged monomers widely used in colloid stabilization, wetting, adhesion, lubrication, etc. Due to the randomly distributed positive and negative charges on polymer backbone, polyampholyte chains have both the contraction tendency by counter charges and the stretch tendency by similar charges, which causes difficulty to develop a reliable molecular thermodynamic model. In this work, osmotic coefficients of solutions containing neutral or non-neutral polyampholyte chains with different segment sizes and charged sequences were obtained by molecular dynamics (MD) simulation, in which the Langevin equation considering both the viscous force from solvent and the stochastic force from heat-bath is used. A molecular thermodynamic model based on chemical association theory was developed where the polyampholyte molecules are modeled as positively and negatively charged hard-sphere chains with a chain length l. Those chains and counter-ions are embedded in a continuum medium. The l-particle cavity correlation function for a polyion chain is linearly approximated by a product of nearest-neighbor two-particle cavity correlation functions, density dependence of which is analytically expressed as a function of a scaling parameter from the mean-spherical approximation (MSA). It is shown that the predicted osmotic coefficients by the model agree satisfactorily with those obtained from MD simulation for neutral polyampholytes.
Development and Validation of Measurement Traceability for In Situ Immunoassays.

BACKGROUND Immunoassays for protein analytes measured in situ support a $2 billion laboratory testing industry that suffers from significant interlaboratory disparities, affecting patient treatment. The root cause is that immunohistochemical testing lacks the generally accepted tools for analytic standardization, including reference standards and traceable units of measure. Until now, the creation of these tools has represented an insoluble technical hurdle. METHODS We address the need with a new concept in metrology-that is, linked traceability. Rather than calculating analyte concentration directly, which has proven too variable, we calculate concentration by measuring an attached fluorescein, traceable to NIST Standard Reference Material 1934, a fluorescein standard. RESULTS For validation, newly developed estrogen receptor (ER) calibrators were deployed in tandem with an array of 80 breast cancer tissue sections in a national external quality assessment program. Laboratory performance was assessed using both the ER standards and the tissue array. Similar to previous studies, the tissue array revealed substantial discrepancies in ER test results among the participating laboratories. The new ER calibrators revealed a broad range of analytic sensitivity, with the lower limits of detection ranging from 7310 to 74 790 molecules of ER. The data demonstrate, for the first time, that the variable test results correlate with analytic sensitivity, which can now be measured quantitatively. CONCLUSIONS The reference standard enables precise interlaboratory alignment of immunohistochemistry test sensitivity for measuring cellular proteins in situ. The introduction of a reference standard and traceable units of measure for protein expression marks an important milestone.
Terahertz radiation and the skin: a review

Abstract. Significance: Terahertz (THz) radiation has demonstrated a great potential in biomedical applications over the past three decades, mainly due to its non-invasive and label-free nature. Among all biological specimens, skin tissue is an optimal sample for the application of THz-based methods because it allows for overcoming some intrinsic limitations of the technique, such as a small penetration depth (0.1 to 0.3 mm for the skin, on average). Aim: We summarize the modern research results achieved when THz technology was applied to the skin, considering applications in both imaging/detection and treatment/modulation of the skin constituents. Approach: We perform a review of literature and analyze the recent research achievements in THz applications for skin diagnosis and investigation. Results: The reviewed results demonstrate the possibilities of THz spectroscopy and imaging, both pulsed and continuous, for diagnosis of skin melanoma and non-melanoma cancer, dysplasia, scars, and diabetic condition, mainly based on the analysis of THz optical properties. The possibility of modulating cell activity and treatment of various diseases by THz-wave exposure is shown as well. Conclusions: The rapid development of THz technologies and the obtained research results for skin tissue highlight the potential of THz waves as a research and therapeutic instrument. The perspectives on the use of THz radiation are related to both non-invasive diagnostics and stimulation and control of different processes in a living skin tissue for regeneration and cancer treatment.