Miracle-dz/UniFAR-FTUs huggingface dataset:
IL-12 Family Cytokines in Cancer and Immunotherapy

Simple Summary The IL-12 family cytokines play an important role in regulating the tumor immune contexture. Recent efforts geared towards the development of better immune therapeutic approaches have identified the need to overcome immune suppression and improve the quantity and quality of anti-tumor effector immune cells within the tumor milieu. In this review, we summarize the recent findings on IL-12 family cytokines in regulating anti-tumor immunity as well as the effectiveness and benefits of enhancing anti-tumor immunity in pre-clinical and clinical settings by targeting IL-12 family cytokines. Abstract The IL-12 family cytokines are a group of unique heterodimeric cytokines that include IL-12, IL-23, IL-27, IL-35 and, most recently, IL-39. Recent studies have solidified the importance of IL-12 cytokines in shaping innate and adaptive immune responses in cancer and identified multipronged roles for distinct IL-12 family members, ranging from effector to regulatory immune functions. These cytokines could serve as promising candidates for the development of immunomodulatory therapeutic approaches. Overall, IL-12 can be considered an effector cytokine and has been found to engage anti-tumor immunity by activating the effector Th1 response, which is required for the activation of cytotoxic T and NK cells and tumor clearance. IL-23 and IL-27 play dual roles in tumor immunity, as they can both activate effector immune responses and promote tumor growth by favoring immune suppression. IL-35 is a potent regulatory cytokine and plays a largely pro-tumorigenic role by inhibiting effector T cells. In this review, we summarize the recent findings on IL-12 family cytokines in the control of tumor growth with an emphasis primarily on immune regulation. We underscore the clinical implications for the use of these cytokines either in the setting of monotherapy or in combination with other conventional therapies for the more effective treatment of malignancies.
Thermal conduction in two-phase materials with spherical and non-spherical inclusions

Two-phase materials have been assumed to contain spherical particles arranged in a three-dimensional cubic geometry. The arrangement has been divided into unit cells each of which contains a sphere. The resistor model has been applied to determine the effective thermal conductivity (ETC) of the unit cell. A sphericity term has been introduced to account for the ETC of materials with non-spherical particles. A porosity correction term has also been applied to the present model and other models cited in the literature. Reported results have been discussed in the light of the proposed model and suggested modifications.
THE SOLUBILITY OF BENZODIAZEPINES IN SODIUM SALICYLATE SOLUTION AND A PROPOSED MECHANISM FOR HYDROTROPIC SOLUBILIZATION

Abstract The influence of simple structural modification on the solubility of a series of poorly soluble benzodiazepines in sodium salicylate solution was investigated. Results of solubility and spectral studies indicate that an electrostatic force of the donor—acceptor type plays an important role in the solubilization of these compounds by hydrotropy. In an attempt to explain the characteristic positive deviation in hydrotropic solubilization diagrams, the solution properties of sodium salicylate were studied. Conductivity experiments indicate molecular aggregation of sodium salicylate at a concentration of 0.67 M at 25°C. The aggregation concentration increases as a function of temperature. Results obtained from density, viscosity and diffusion studies are consistent with those of conductivity measurements. The remarkable increase in the solubilizing effect of sodium salicylate is probably associated with aggregate formation. Inclusion of the benzodiazepine molecules in the sodium salicylate aggregates is thought to be the mechanism responsible for the solubilization of these drugs. A donor-acceptor interaction between sodium salicylate and benzodiazepine molecules is assumed to stabilize such an inclusion and determine the degree of solubility of the benzodiazepines in sodium salicylate solution. Nevertheless, further studies are necessary to substantiate these results.
Infrared Spectra of Poly(acetylene)

The infrared spectra of poly(acetylene), poly(acetylene-d2), copoly(acety+acetylene-d2), and copoly(acetylene+acetylene-d1+acetylene-d2) prepared by the Ti(OC4H9)4–Al(C2H5)3 system over a wide temperature range (ca. −100 to 180°C) are reported. A tentative assignment of the observed spectra is made on the basis of model structures in which infinite planar chains of all trans, all trans–cisoid, and all cis–transoid configurations are assumed. The spectral data are best interpreted on the basis of an all cis-transoid (or an all trans-cisoid) structure for the polymers prepared at temperatures lower than −78°C, and an all trans structure for the polymers prepared at temperatures higher than 150°C.Simplified calculations of the C-H and C-D out-of-plane deformation frequencies are made for various model chains. It has been concluded from a comparison of the observed and calculated frequencies that the cis-opening of the triple bond occurs in a polymerization reaction with the Ti(OC4H9)4–Al(C2H5)3 catalyst system at low temperatures.
Cbl-b Is Upregulated and Plays a Negative Role in Activated Human NK Cells

Key Points Cbl-b is induced in IL-15/IL-2/K562–activated primary human NK cells. Abrogation of Cbl-b enhances cytotoxicity of primary human NK cells. The E3 ubiquitin ligase Cbl-b has been characterized as an intracellular checkpoint in T cells; however, the function of Cbl-b in primary human NK cells, an innate immune anti-tumor effector cell, is not well defined. In this study, we show that the expression of Cbl-b is significantly upregulated in primary human NK cells activated by IL-15, IL-2, and the human NK cell–sensitive tumor cell line K562 that lacks MHC class I expression. Pretreatment with JAK or AKT inhibitors prior to IL-15 stimulation reversed Cbl-b upregulation. Downregulation of Cbl-b resulted in significant increases in granzyme B and perforin expression, IFN-γ production, and cytotoxic activity against tumor cells. Collectively, we demonstrate upregulation of Cbl-b and its inhibitory effects in IL-15/IL-2/K562–activated human NK cells, suggesting that Cbl-b plays a negative feedback role in human NK cells.
Lung Ultrasound Is Often, but Not Always, Normal in Healthy Subjects: Considerations for COVID-19 Pandemic

Background: Lung ultrasound (LU) is becoming an increasingly important diagnostic tool in detecting lung involvement in Corona Virus Disease 2019 (COVID-19). The aim of this study was to ascertain the likelihood of finding LU abnormalities; mimicking lung involvement; in COVID-19 negative healthy individuals. Methods: We performed LU on 265 healthcare workers; not presenting COVID-19 major symptoms and in good health; during the course of a serological screening program for COVID-19 in our General Hospital. LU results were reported as total Lung Ultrasound Score (LUS) using a 12-zone method of reporting. Results: 250/265 subjects were included in the COVID-19 negative group. LU was not completely normal (LUS ≠ 0) in 65/250 COVID-19 negative subjects (26%) and in 12/15 (80%) poorly symptomatic COVID-19 positive subjects; with a multifocal pattern in 12.7% vs. 66.7% of cases respectively. Age and COVID-19 positivity were independent predictors of total LUS. A total LUS ≥ 2 had a sensitivity of 66.67% and a specificity of 85.60% in detecting COVID-19 positivity. Conclusions: A slightly altered LU can be quite frequent in healthy COVID-19 negative subjects. LU can have a role in confirming but not screening COVID-19 poorly symptomatic cases.
A Destruction Model of the Vascular and Lymphatic Systems in the Emergence of Psychiatric Symptoms

Simple Summary Impairment of the immune-barrier system in the aged brain is manifested in neurodegenerative diseases, such as Alzheimer’s disease. Cerebrospinal fluid flow and drainage system of meningeal lymph scavenge the waste products in the brain parenchyma. Recent accumulating attention to the immune system in the brain is now accompanied by the expanding knowledge of the breakdown mechanism of the blood-brain barrier and increased permeability of activated immune cells at the glymphatic system, in developing brains, and in the situation of infections. These disruptions of the immune-barrier function between vasculature and brain parenchyma, where neurons locate, would also occur by infection of viruses or microorganisms, vascular injury, cerebral hemorrhage, neurological diseases, and other external factors like stress. Those activate microglia, brain-resident immune cells, and allow the infiltration of immune cells, such as macrophages, neutrophils, and T cells. Aberrant immunity disrupts the functions of neurons and prevents the maturation of glia (e.g., oligodendrocytes and astrocytes), which may cause the emergence of the highly variable psychiatric symptoms seen in schizophrenia, autism spectrum disorders, Alexander disease, and developmental disorders via an abnormality of brain activities at both cellular and organism levels. Therefore, this hypothesis challenges the longstanding neuron-centric view of neurodegenerative and psychiatric diseases. Abstract The lymphatic system is important for antigen presentation and immune surveillance. The lymphatic system in the brain was originally introduced by Giovanni Mascagni in 1787, while the rediscovery of it by Jonathan Kipnis and Kari Kustaa Alitalo now opens the door for a new interpretation of neurological diseases and therapeutic applications. The glymphatic system for the exchanges of cerebrospinal fluid (CSF) and interstitial fluid (ISF) is associated with the blood-brain barrier (BBB), which is involved in the maintenance of immune privilege and homeostasis in the brain. Recent notions from studies of postmortem brains and clinical studies of neurodegenerative diseases, infection, and cerebral hemorrhage, implied that the breakdown of those barrier systems and infiltration of activated immune cells disrupt the function of both neurons and glia in the parenchyma (e.g., modulation of neurophysiological properties and maturation of myelination), which causes the abnormality in the functional connectivity of the entire brain network. Due to the vulnerability, such dysfunction may occur in developing brains as well as in senile or neurodegenerative diseases and may raise the risk of emergence of psychosis symptoms. Here, we introduce this hypothesis with a series of studies and cellular mechanisms.
Noncontact Body Temperature Measurement: Uncertainty Evaluation and Screening Decision Rule to Prevent the Spread of COVID-19

The need to measure body temperature contactless and quickly during the COVID-19 pandemic emergency has led to the widespread use of infrared thermometers, thermal imaging cameras and thermal scanners as an alternative to the traditional contact clinical thermometers. However, limits and issues of noncontact temperature measurement devices are not well known and technical–scientific literature itself sometimes provides conflicting reference values on the body and skin temperature of healthy subjects. To limit the risk of contagion, national authorities have set the obligation to measure body temperature of workers at the entrance to the workplace. In this paper, the authors analyze noncontact body temperature measurement issues from both clinical and metrological points of view with the aim to (i) improve body temperature measurements accuracy; (ii) estimate the uncertainty of body temperature measurement on the field; (iii) propose a screening decision rule for the prevention of the spread of COVID-19. The approach adopted in this paper takes into account both the traditional instrumental uncertainty sources and clinical–medical ones related to the subjectivity of the measurand. A proper screening protocol for body temperature measurement considering the role of uncertainty is essential to correctly choose the threshold temperature value and measurement method to access critical places during COVID-19 pandemic emergency.
Circuit selectivity in drug versus natural reward seeking behaviors

Substance use disorder (SUD) is characterized, in part by behavior biased toward drug use and away from natural sources of reward (e.g., social interaction, food, sex). The neurobiological underpinnings of SUDs reveal distinct brain regions where neuronal activity is necessary for the manifestation of SUD‐characteristic behaviors. Studies that specifically examine how these regions are involved in behaviors motivated by drug versus natural reward allow determinations of which regions are necessary for regulating seeking of both reward types, and appraisals of novel SUD therapies for off‐target effects on behaviors motivated by natural reward. Here, we evaluate studies directly comparing regulatory roles for specific brain regions in drug versus natural reward. While it is clear that many regions drive behaviors motivated by all reward types, based on the literature reviewed we propose a set of interconnected regions that become necessary for behaviors motivated by drug, but not natural rewards. The circuitry is selectively necessary for drug seeking includes an Action/Reward subcircuit, comprising nucleus accumbens, ventral pallidum, and ventral tegmental area, a Prefrontal subcircuit comprising prelimbic, infralimbic, and insular cortices, a Stress subcircuit comprising the central nucleus of the amygdala and the bed nucleus of the stria terminalis, and a Diencephalon circuit including lateral hypothalamus. Evidence was mixed for nucleus accumbens shell, insular cortex, and ventral pallidum. Studies for all other brain nuclei reviewed supported a necessary role in regulating both drug and natural reward seeking. Finally, we discuss emerging strategies to further disambiguate the necessity of brain regions in drug‐ versus natural reward‐associated behaviors.
TMD-Unet: Triple-Unet with Multi-Scale Input Features and Dense Skip Connection for Medical Image Segmentation

Deep learning is one of the most effective approaches to medical image processing applications. Network models are being studied more and more for medical image segmentation challenges. The encoder–decoder structure is achieving great success, in particular the Unet architecture, which is used as a baseline architecture for the medical image segmentation networks. Traditional Unet and Unet-based networks still have a limitation that is not able to fully exploit the output features of the convolutional units in the node. In this study, we proposed a new network model named TMD-Unet, which had three main enhancements in comparison with Unet: (1) modifying the interconnection of the network node, (2) using dilated convolution instead of the standard convolution, and (3) integrating the multi-scale input features on the input side of the model and applying a dense skip connection instead of a regular skip connection. Our experiments were performed on seven datasets, including many different medical image modalities such as colonoscopy, electron microscopy (EM), dermoscopy, computed tomography (CT), and magnetic resonance imaging (MRI). The segmentation applications implemented in the paper include EM, nuclei, polyp, skin lesion, left atrium, spleen, and liver segmentation. The dice score of our proposed models achieved 96.43% for liver segmentation, 95.51% for spleen segmentation, 92.65% for polyp segmentation, 94.11% for EM segmentation, 92.49% for nuclei segmentation, 91.81% for left atrium segmentation, and 87.27% for skin lesion segmentation. The experimental results showed that the proposed model was superior to the popular models for all seven applications, which demonstrates the high generality of the proposed model.
Hit the brakes – a new perspective on the loop extrusion mechanism of cohesin and other SMC complexes

ABSTRACT The three-dimensional structure of chromatin is determined by the action of protein complexes of the structural maintenance of chromosome (SMC) family. Eukaryotic cells contain three SMC complexes, cohesin, condensin, and a complex of Smc5 and Smc6. Initially, cohesin was linked to sister chromatid cohesion, the process that ensures the fidelity of chromosome segregation in mitosis. In recent years, a second function in the organization of interphase chromatin into topologically associated domains has been determined, and loop extrusion has emerged as the leading mechanism of this process. Interestingly, fundamental mechanistic differences exist between mitotic tethering and loop extrusion. As distinct molecular switches that aim to suppress loop extrusion in different biological contexts have been identified, we hypothesize here that loop extrusion is the default biochemical activity of cohesin and that its suppression shifts cohesin into a tethering mode. With this model, we aim to provide an explanation for how loop extrusion and tethering can coexist in a single cohesin complex and also apply it to the other eukaryotic SMC complexes, describing both similarities and differences between them. Finally, we present model-derived molecular predictions that can be tested experimentally, thus offering a new perspective on the mechanisms by which SMC complexes shape the higher-order structure of chromatin. Summary: Co-existing mechanisms underlying sister chromatid tethering and loop extrusion by structural maintenance of chromosomes (SMC) cohesins complex are discussed. The model is extended to include all eukaryotic SMC complexes.
Analysis of Point Shear Wave Elastography and Biochemical Markers for the Detection of Liver Fibrosis

Background and Objectives: This work focuses on the possibility of using the point shear wave elastography (pSWE) method for detecting biochemical markers in diffuse liver diseases. Additionally, this study addresses the issue of the influence of ultrasound factors on the pSWE quality indicators of the obtained measurements. Materials and Methods: A pSWE examination was performed on 139 patients (69 female and 70 male) diagnosed with diffuse liver disease. The average age for all patients was 50.7 ± 15.0 years (female: 52.7 ± 15.2 years; male: 48.8 ± 14.6 years). Of these 139 patients, 65 met the inclusion criteria regarding biochemical parameters. The pSWE quality indicators were related to abnormalities found in B-mode ultrasound. Results: A strong positive correlation was found between the results of the pSWE and all biochemical indexes analysed, with the exception of age/platelet count (PLT), for which an average correlation was obtained. The greatest correlation was observed between the elastography and King’s Score index. There was no correlation observed between elastography and any of the analysed parameters or biochemical indexes considered. The pSWE measurements were impaired by factors such as thick soft tissue, uneven hepatic surface, hepatomegaly and female gender. No statistically significant difference in pSWE quality indicators parameters was found between disease entities. Conclusions: pSWE seems to be a complementary method for detecting biochemical indexes, but its results can be influenced by numerous factors.
Effects of Strength vs. Plyometric Training Programs on Vertical Jumping, Linear Sprint and Change of Direction Speed Performance in Female Soccer Players: A Systematic Review and Meta-Analysis

The main purpose of this systematic review and meta-analysis was to compare the effects of strength training (ST) and plyometric training (PT) on vertical jump, linear sprint and change of direction (COD) performance in female soccer players. A systematic search of the PubMed, Web of Science, Google Scholar and SportDiscus databases revealed 12 studies satisfying the inclusion criteria. The inverse-variance random-effects model for meta-analyses was used. Effect sizes (ES) were represented by the standardized mean difference and presented alongside 95% confidence intervals (CI). The magnitude of the main effect was small to moderate (vertical jump (ES 0.53 (95% CI—0.11, 0.95), Z = 2.47 (p = 0.01); linear sprint (ES −0.66 (95% CI—2.03, −0.21), Z = 2.20 (p = 0.03); COD (ES −0.36 (95% CI—0.68, −0.03), Z = 2.17 (p = 0.03)). Subgroup analyses were performed (i.e., ST and PT duration, frequency, session duration and total number of sessions), revealing no significant subgroup differences (p = 0.12–0.88). In conclusion, PT provides better benefits than ST to improve vertical jump, linear sprint and COD performance in female soccer players. However, significant limitations in the current literature prevent assured PT and ST prescription recommendations being made.
Standardized Method for Defining a 1-mm2 Region of Interest for Calculation of Mitotic Rate on Melanoma Whole Slide Images.

CONTEXT. — Mitotic rate counting is essential in pathologic evaluations in melanoma. The American Joint Committee on Cancer recommends reporting the number of mitotic figures (MFs) in a 1-mm2 area encompassing the "hot spot. " There is currently no standard procedure for delineating a 1-mm2 region of interest for MF counting on a digital whole slide image (WSI) of melanoma. OBJECTIVE. — To establish a standardized method to enclose a 1-mm2 region of interest for MF counting in melanoma based on WSIs and assess the method's effectiveness. DESIGN. — Whole slide images were visualized using the ImageScope viewer (Aperio). Different monitors and viewing magnifications were explored and the annotation tools provided by ImageScope were evaluated. For validation, we compared mitotic rates obtained from WSIs with our method and those from glass slides with traditional microscopy with 30 melanoma cases. RESULTS. — Of the monitors we examined, a 32-inch monitor with 3840 × 2160 resolution was optimal for counting MFs within a 1-mm2 region of interest in melanoma. When WSIs were viewed in the ImageScope viewer, ×10 to ×20 magnification during screening could efficiently locate a hot spot and ×20 to ×40 magnification during counting could accurately identify MFs. Fixed-shape annotations with 500 × 500-μm squares or circles can precisely and efficiently enclose a 1-mm2 region of interest. Our method on WSIs was able to produce a higher mitotic rate than with glass slides. CONCLUSIONS. — Whole slide images may be used to efficiently count MFs. We recommend fixed-shape annotation with 500 × 500-μm squares or circles for routine practice in counting MFs for melanoma.
Controlled-release urea improved rice yields by providing nitrogen in synchrony with the nitrogen requirements of plants.

BACKGROUND Excessive application of nitrogen(N) fertilizer and low N-use efficiency (NUE) are prevalent problems in rice production. Controlled-release urea (CRU) is widely adopted to increase rice yields, but the synchronicity of N release from CRU with uptake of N by plants has rarely been studied. A 2-year field experiment involving CRU and urea applications at three different N rates (240, 192 and 144 kg N ha-1 , equal to 100%, 80% and 60% of the recommended rate, respectively) was performed to compare their effects on N uptake, soil N content and rice yields. RESULTS The successive release curves of CRU in the soil matched the corresponding N uptake curves of rice plants, and significant linear correlations were observed. Grain yield and N uptake under the CRU treatment increased by 5.25-7.88% and 7.13-17.94% than urea treatments, at the same N rate, and no obvious difference was found between CRU60% and Urea100%. CRU80% and CRU60% presented the highest NUE. The contents of NH4 + -N, NO3 - -N, and total N and the chlorophyll relative value-SPAD values of the leaves under the CRU treatments were significantly higher than those under the urea treatments from heading to harvest. The contents of exchangeable Na+ and Ca2+ and the cation exchange capacity increased in response to CRU. CONCLUSION CRU increased rice yields by providing N strongly in synchrony with the N requirements of the plants, and applying CRU at 192 kg N ha-1 was an effective strategy to conserve N fertilizer, increase soil N contents and enhance NUE. This article is protected by copyright. All rights reserved.