Miracle-dz/UniFAR-FTUs huggingface dataset:
A Preliminary Study on Cranio-Facial Characteristics Associated with Minor Neurological Dysfunctions (MNDs) in Children with Autism Spectrum Disorders (ASD)

Background. Craniofacial anomalies and minor neurological dysfunction (MNDs) have been identified, in literature, as risk factors for neurodevelopmental disorders. They represent physical indicators of embryonic development suggesting a possible contributory role of complications during early, even pre-conceptional, phases of ontogeny in autism spectrum disorders (ASD). Limited research has been conducted about the co-occurrence of the two biomarkers in children with ASD. This study investigates the associative patterns of cranio-facial anomalies and MNDs in ASD children, and whether these neurodevelopmental markers correlate with intensity of ASD symptoms and overall functioning. Methods. Caucasian children with ASD (n = 33) were examined. Measures were based on five anthropometric cranio-facial indexes and a standardized and detailed neurological examination according to Touwen. Relationships between anthropometric z-scores, MNDs and participant characteristics (i.e., age, cognitive abilities, severity of autistic symptoms measured using the Childhood Autism Rating Scale (CARS) checklist) were assessed. Results. With respect to specific MNDs, significant positive correlations were found between Cephalic Index and Sensory deficits (p-value < 0.001), which did not correlate with CARS score. Importantly, CARS score was positively linked with Intercanthal Index (p-value < 0.001), and negatively associated with posture and muscle tone (p-value = 0.027) and Facial Index (p-value = 0.004). Conclusion. Our data show a link between a specific facial phenotype and anomalies in motor responses, suggesting early brain dysmaturation involving subcortical structures in cerebro-craniofacial development of autistic children. This research supports the concept of a “social brain functional morphology” in autism spectrum disorders.
Neonatal Intensive Care Unit Admission Temperatures of Infants 1500 g or More

Background: Smaller preterm infants often receive extra attention with implementation of additional thermoregulation interventions in the delivery room. Yet, these bundles of interventions have largely remained understudied in larger infants. Purpose: The purpose of this study was to evaluate initial (or admission) temperatures of infants born weighing 1500 g or more with diagnoses requiring admission to the neonatal intensive care unit (NICU). Methods: Retrospective medical record review of 388 infants weighing 1500 g or more admitted to the NICU between January 2016 and June 2017. Result: In total, 42.5% of infants weighing 1500 g or more were admitted hypothermic (<36.5°C), 54.4% with a normothermic temperature, and 2.8% were hyperthermic. Of those infants admitted hypothermic, 30.4% had an admission temperature ranging from 36°C to 36.4°C and 12.1% had an admission temperature of less than 36°C. When compared with infants weighing less than 1500 g, who were born at the same institution and received extra thermal support interventions, there was a statistically significant difference (P < .001) between admission temperatures where infants less than 1500 g were slightly warmer (36.8°C vs 36.5°C). Implications for Practice: Ongoing admission temperature monitoring of all infants requiring NICU admission regardless of birth weight or admission diagnosis is important if we are going to provide the best support to decrease mortality and morbidity for this high-risk population. Implications for Research: While this study examined short-term outcomes, effects on long-term outcomes were not addressed. Findings could be used to design targeted interventions to support thermal regulation for all high-risk infants. Conclusion: Neonates admitted to the NICU weighing 1500 g or more are at high risk for developing hypothermia, similar to smaller preterm infants.
WingMesh: A Matlab-Based Application for Finite Element Modeling of Insect Wings

Simple Summary Manual modeling of complicated insect wings presents considerable practical challenges. To overcome these challenges, therefore, we developed WingMesh. This is an application for simple yet precise automatic modeling of insect wings. Using a series of examples, we showed the performance of our application in practice. We expect WingMesh to be particularly useful in comparative studies, especially where the modeling of a large number of insect wings is required within a short time. Abstract The finite element (FE) method is one of the most widely used numerical techniques for the simulation of the mechanical behavior of engineering and biological objects. Although very efficient, the use of the FE method relies on the development of accurate models of the objects under consideration. The development of detailed FE models of often complex-shaped objects, however, can be a time-consuming and error-prone procedure in practice. Hence, many researchers aim to reach a compromise between the simplicity and accuracy of their developed models. In this study, we adapted Distmesh2D, a popular meshing tool, to develop a powerful application for the modeling of geometrically complex objects, such as insect wings. The use of the burning algorithm (BA) in digital image processing (DIP) enabled our method to automatically detect an arbitrary domain and its subdomains in a given image. This algorithm, in combination with the mesh generator Distmesh2D, was used to develop detailed FE models of both planar and out-of-plane (i.e., three-dimensionally corrugated) domains containing discontinuities and consisting of numerous subdomains. To easily implement the method, we developed an application using the Matlab App Designer. This application, called WingMesh, was particularly designed and applied for rapid numerical modeling of complicated insect wings but is also applicable for modeling purposes in the earth, engineering, mathematical, and physical sciences.
Gut-Pancreas-Liver Axis as a Target for Treatment of NAFLD/NASH

Non-alcoholic fatty liver disease (NAFLD) represents the most common form of chronic liver disease worldwide. Due to its association with obesity and diabetes and the fall in hepatitis C virus morbidity, cirrhosis in NAFLD is becoming the most frequent indication to liver transplantation, but the pathogenetic mechanisms are still not completely understood. The so-called gut-liver axis has gained enormous interest when data showed that its alteration can lead to NAFLD development and might favor the occurrence of non-alcoholic steatohepatitis (NASH). Moreover, several therapeutic approaches targeting the gut-pancreas-liver axis, e.g., incretins, showed promising results in NASH treatment. In this review, we describe the role of incretin hormones in NAFLD/NASH pathogenesis and treatment and how metagenomic/metabolomic alterations in the gut microbiota can lead to NASH in the presence of gut barrier modifications favoring the passage of bacteria or bacterial products in the portal circulation, i.e., bacterial translocation.
The relation of 25-hydroxy vitamin D concentrations to liver histopathology, seasonality and baseline characteristics in chronic hepatitis C virus genotype 2 or 3 infection

Background and objectives The hydroxylation to 25-hydroxy vitamin D (25(OH)D) occurs in the liver and the impact of liver disease on vitamin D is unclear. This study evaluated the relationship between vitamin D concentrations and hepatic histopathology, seasonality and patient characteristics in well-characterized patients having undergone a liver biopsy. Method 25(OH)D was measured post-hoc in pre-treatment serum from 331 North European patients with chronic HCV genotype 2 or 3 infection (NORDynamIC study). Liver biopsies were scored for fibrosis and inflammation according to the Ishak protocol, and graded for steatosis. Non-invasive markers of hepatic fibrosis as well as baseline viral and host characteristics, including genetic polymorphisms rs2228570, rs7975232, and rs10877012 were also evaluated. Results Mean 25(OH)D concentration was 59 ±23 nmol/L, with 41% having values <50 nmol/L and 6% were <30 nmol/L. 25(OH)D correlated with fibrosis (r = -0.10, p ≤0.05) in univariate but not in multivariate analyses. No association was observed between 25(OH)D and hepatic inflammation, but with steatosis in HCV genotype 2 infected patients. None of the genetic polymorphisms impacted on 25(OH)D levels or fibrosis. 25(OH)D levels were significantly inversely correlated to BMI (r = -0.19, p = 0.001), and was also associated with season and non-Caucasian ethnicity. Conclusion Fibrosis was not independently associated with 25(OH)D concentration and no association was seen with hepatic inflammation, but HCV genotype 2 infected patients with moderate-to-severe steatosis had lower 25(OH)D levels compared to those without steatosis. A high percentage had potential risk of 25(OH)D deficiency, and BMI, seasonality and ethnicity were independently associated with 25(OH)D as previously reported.
Long-Tailed Characteristic of Spiking Pattern Alternation Induced by Log-Normal Excitatory Synaptic Distribution

Studies of structural connectivity at the synaptic level show that in synaptic connections of the cerebral cortex, the excitatory postsynaptic potential (EPSP) in most synapses exhibits sub-mV values, while a small number of synapses exhibit large EPSPs ( $\gtrsim 1.0$ [mV]). This means that the distribution of EPSP fits a log-normal distribution. While not restricting structural connectivity, skewed and long-tailed distributions have been widely observed in neural activities, such as the occurrences of spiking rates and the size of a synchronously spiking population. Many studies have been modeled this long-tailed EPSP neural activity distribution; however, its causal factors remain controversial. This study focused on the long-tailed EPSP distributions and interlateral synaptic connections primarily observed in the cortical network structures, thereby having constructed a spiking neural network consistent with these features. Especially, we constructed two coupled modules of spiking neural networks with excitatory and inhibitory neural populations with a log-normal EPSP distribution. We evaluated the spiking activities for different input frequencies and with/without strong synaptic connections. These coupled modules exhibited intermittent intermodule-alternative behavior, given moderate input frequency and the existence of strong synaptic and intermodule connections. Moreover, the power analysis, multiscale entropy analysis, and surrogate data analysis revealed that the long-tailed EPSP distribution and intermodule connections enhanced the complexity of spiking activity at large temporal scales and induced nonlinear dynamics and neural activity that followed the long-tailed distribution.
Protein Expression Knockdown in Cancer Cells Induced by a Gemini Cationic Lipid Nanovector with Histidine-Based Polar Heads

A histidine-based gemini cationic lipid, which had already demonstrated its efficiency as a plasmid DNA (pDNA) nanocarrier, has been used in this work to transfect a small interfering RNA (siRNA) into cancer cells. In combination with the helper lipid monoolein glycerol (MOG), the cationic lipid was used as an antiGFP-siRNA nanovector in a multidisciplinary study. Initially, a biophysical characterization by zeta potential (ζ) and agarose gel electrophoresis experiments was performed to determine the lipid effective charge and confirm siRNA compaction. The lipoplexes formed were arranged in Lα lamellar lyotropic liquid crystal phases with a cluster-type morphology, as cryo-transmission electron microscopy (cryo-TEM) and small-angle X-ray scattering (SAXS) studies revealed. Additionally, in vitro experiments confirmed the high gene knockdown efficiency of the lipid-based nanovehicle as detected by flow cytometry (FC) and epifluorescence microscopy, even better than that of Lipofectamine2000*, the transfecting reagent commonly used as a positive control. Cytotoxicity assays indicated that the nanovector is non-toxic to cells. Finally, using nano-liquid chromatography tandem mass spectrometry (nanoLC-MS/MS), apolipoprotein A-I and A-II followed by serum albumin were identified as the proteins with higher affinity for the surface of the lipoplexes. This fact could be beyond the remarkable silencing activity of the histidine-based lipid nanocarrier herein presented.
Early Intervention in Ulcerative Colitis: Ready for Prime Time?

Growing evidence shows that ulcerative colitis (UC) is a progressive disease similar to Crohn’s disease (CD). The UC-related burden is often underestimated by physicians and a standard step-up therapeutic approach is preferred. However, in many patients with UC the disease activity is not adequately controlled by current management, leading to poor long-term prognosis. Data from both randomized controlled trials and real-world studies support early intervention in CD in order to prevent disease progression and irreversible bowel damage. Similarly, an early disease intervention during the so-called “window of opportunity” could lead to better outcomes in UC. Here, we summarize the literature evidence on early intervention in patients with UC, highlighting strengths and limitations of this approach.
A 3D Tissue Model of Traumatic Brain Injury with Excitotoxicity That Is Inhibited by Chronic Exposure to Gabapentinoids

Injury progression associated with cerebral laceration is insidious. Following the initial trauma, brain tissues become hyperexcitable, begetting further damage that compounds the initial impact over time. Clinicians have adopted several strategies to mitigate the effects of secondary brain injury; however, higher throughput screening tools with modular flexibility are needed to expedite mechanistic studies and drug discovery that will contribute to the enhanced protection, repair, and even the regeneration of neural tissues. Here we present a novel bioengineered cortical brain model of traumatic brain injury (TBI) that displays characteristics of primary and secondary injury, including an outwardly radiating cell death phenotype and increased glutamate release with excitotoxic features. DNA content and tissue function were normalized by high-concentration, chronic administrations of gabapentinoids. Additional experiments suggested that the treatment effects were likely neuroprotective rather than regenerative, as evidenced by the drug-mediated decreases in cell excitability and an absence of drug-induced proliferation. We conclude that the present model of traumatic brain injury demonstrates validity and can serve as a customizable experimental platform to assess the individual contribution of cell types on TBI progression, as well as to screen anti-excitotoxic and pro-regenerative compounds.
Oxidative Stress and Inflammation Induced by Waterpipe Tobacco Smoking Despite Possible Protective Effects of Exercise Training: A Review of the Literature

The prevalence of waterpipe tobacco smoking (WTS), which is also known as ghalyan, shisha or hookah, is increasing rapidly around the world, especially among youth. Growing interest in this form of tobacco smoking can be traced, in part, to the use of flavored tobacco products, social acceptability as a safer option than cigarettes, and its consideration as a relaxation method or entertainment. However, there is a well-established association between WTS and oxidative stress that causes irreversible chronic pathological conditions such as cardiovascular and respiratory problems, as well as different types of cancers, and thus increases the risk of mortality. Clearly, induction of inflammation status through increased reactive oxygen species (ROS), which in turn leads to oxidative stress and harm to lipids, DNA, and proteins, is the most plausible mechanism to explain the potential harmful effects of WTS. Unlike WTS, well-designed exercise training programs increase ROS to the extent that it is beneficial to the body. In this study, we aimed to review available evidence on the impact of exercise training on oxidative stress and inflammation status. We also summarize the effect of acute and chronic WTS on different exercise capacities.
Differentiation of a Contractile, Ureter-Like Tissue, from Embryonic Stem Cell-Derived Ureteric Bud and Ex Fetu Mesenchyme.

BACKGROUND There is intense interest in replacing kidneys from stem cells. It is now possible to produce, from embryonic or induced pluripotent stem cells, kidney organoids that represent immature kidneys and display some physiologic functions. However, current techniques have not yet resulted in renal tissue with a ureter, which would be needed for engineered kidneys to be clinically useful. METHODS We used a published sequence of growth factors and drugs to induce mouse embryonic stem cells to differentiate into ureteric bud tissue. We characterized isolated engineered ureteric buds differentiated from embryonic stem cells in three-dimensional culture and grafted them into ex fetu mouse kidney rudiments. RESULTS Engineered ureteric buds branched in three-dimensional culture and expressed Hoxb7, a transcription factor that is part of a developmental regulatory system and a ureteric bud marker. When grafted into the cortex of ex fetu kidney rudiments, engineered ureteric buds branched and induced nephron formation; when grafted into peri-Wolffian mesenchyme, still attached to a kidney rudiment or in isolation, they did not branch but instead differentiated into multilayer ureter-like epithelia displaying robust expression of the urothelial marker uroplakin. This engineered ureteric bud tissue also organized the mesenchyme into smooth muscle that spontaneously contracted, with a period a little slower than that of natural ureteric peristalsis. CONCLUSIONS Mouse embryonic stem cells can be differentiated into ureteric bud cells. Grafting those UB-like structures into peri-Wolffian mesenchyme of cultured kidney rudiments can induce production of urothelium and organize the mesenchyme to produce rhythmically contracting smooth muscle layers. This development may represent a significant step toward the goal of renal regeneration.
The impact of temporal fine structure and signal envelope on auditory motion perception

The majority of psychoacoustic research investigating sound localization has utilized stationary sources, yet most naturally occurring sounds are in motion, either because the sound source itself moves, or the listener does. In normal hearing (NH) listeners, previous research showed the extent to which sound duration and velocity impact the ability of listeners to detect sound movement. By contrast, little is known about how listeners with hearing impairments perceive moving sounds; the only study to date comparing the performance of NH and bilateral cochlear implant (BiCI) listeners has demonstrated significantly poorer performance on motion detection tasks in BiCI listeners. Cochlear implants, auditory protheses offered to profoundly deaf individuals for access to spoken language, retain the signal envelope (ENV), while discarding temporal fine structure (TFS) of the original acoustic input. As a result, BiCI users do not have access to low-frequency TFS cues, which have previously been shown to be crucial for sound localization in NH listeners. Instead, BiCI listeners seem to rely on ENV cues for sound localization, especially level cues. Given that NH and BiCI listeners differentially utilize ENV and TFS information, the present study aimed to investigate the usefulness of these cues for auditory motion perception. We created acoustic chimaera stimuli, which allowed us to test the relative contributions of ENV and TFS to auditory motion perception. Stimuli were either moving or stationary, presented to NH listeners in free field. The task was to track the perceived sound location. We found that removing low-frequency TFS reduces sensitivity to sound motion, and fluctuating speech envelopes strongly biased the judgment of sounds to be stationary. Our findings yield a possible explanation as to why BiCI users struggle to identify sound motion, and provide a first account of cues important to the functional aspect of auditory motion perception.
Macrobioerosion of dead branching Porites, 4 and 6 years after coral mass mortality

Internal bioerosion by macroborers (polychaetes, sipunculans, bivalves, and sponges) was investigated in dead Porites branches collected from 8 coral reefs along the Kenyan coast, 4 and 6 yr after the 1998 mass mortality of corals. Levels of nutrients, benthic cover, and numbers of grazing and invertebrate-eating fish and sea urchins were measured and evaluated for their influence on macrobioerosion. The macroboring community composition was influenced by the grazer composition on each reef; worms were the major macroboring agent where sea urchin biomass was high, and sponges were the dominant agent where herbivorous fish biomass was high. Bivalves accounted for a small proportion of the internal bioerosion and were not mea- surably influenced by consumers or water quality. The total macrobioerosion rates in Porites branches ranged from 534 ± 70 to 1134 ± 44 g CaCO3 m �2 (4 yr after the coral death) and 837 ± 111 to 2149 ± 314 g CaCO3 m �2 (6 yr after the coral death). The macrobioerosion rates were linearly and positively correlated with chlorophyll a concentrations (chl a) in the water column 4 and 6 yr after the coral death. Sponge boring rates were also positively correlated to chl a 6 yr after coral death but not after the initial 4 yr. Consequently, the macrobioerosion rates responded to nutrient status, but the community of borers changed with the dominant grazers, which in turn were influ- enced by fisheries management.
The FMS like Tyrosine Kinase 3 (FLT3) Is Overexpressed in a Subgroup of Multiple Myeloma Patients with Inferior Prognosis

Therapy resistance remains a major challenge in the management of multiple myeloma (MM). We evaluated the expression of FLT3 tyrosine kinase receptor (FLT3, CD135) in myeloma cells as a possible clonal driver. FLT3 expression was analyzed in bone marrow biopsies of patients with monoclonal gammopathy of undetermined significance or smoldering myeloma (MGUS, SMM), newly diagnosed MM (NDMM), and relapsed/refractory MM (RRMM) by immunohistochemistry (IHC). FLT3 gene expression was analyzed by RNA sequencing (RNAseq) and real-time PCR (rt-PCR). Anti-myeloma activity of FLT3 inhibitors (midostaurin, gilteritinib) was tested in vitro on MM cell lines and primary MM cells by 3H-tymidine incorporation assays or flow cytometry. Semi-quantitative expression analysis applying a staining score (FLT3 expression IHC-score, FES, range 1–6) revealed that a high FES (>3) was associated with a significantly shorter progression-free survival (PFS) in NDMM and RRMM patients (p = 0.04). RNAseq and real-time PCR confirmed the expression of FLT3 in CD138-purified MM samples. The functional relevance of FLT3 expression was corroborated by demonstrating the in vitro anti-myeloma activity of FLT3 inhibitors on FLT3-positive MM cell lines and primary MM cells. FLT3 inhibitors might offer a new targeted therapy approach in a subgroup of MM patients displaying aberrant FLT3 signaling.