Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeting SRC Family Kinases in Mesothelioma: Time to Upgrade

Malignant mesothelioma (MM) is a deadly tumor mainly caused by exposure to asbestos. Unfortunately, no current treatment is able to change significantly the natural history of the disease, which has a poor prognosis in the majority of patients. The non-receptor tyrosine kinase SRC and other SRC family kinase (SFK) members are frequently hyperactivated in many cancer types, including MM. Several works have indeed suggested that SFKs underlie MM cell proliferation, survival, motility, and invasion, overall affecting multiple oncogenic pathways. Consistently, SFK inhibitors effectively counteracted MM cancerous features at the preclinical level. Dasatinib, a multi-kinase inhibitor targeting SFKs, was also assessed in clinical trials either as second-line treatment for patients with unresectable MM or, more recently, as a neoadjuvant agent in patients with resectable MM. Here, we provide an overview of the molecular mechanisms implicating SFKs in MM progression and discuss possible strategies for a more successful clinical application of SFK inhibitors. Our aim is to stimulate discussion and further consideration of these agents in better designed preclinical and clinical studies to make the most of another class of powerful antitumoral drugs, which too often are lost in translation when applied to MM.
Stereological and histopathological evaluation of doxorubicin-induced toxicity in female rats’ ovary and uterus and palliative effects of quercetin and vitamin E

Doxorubicin (DOX) is a widely used chemotherapeutic agent with demonstrated reproductive toxicity. This study sought to determine the DOX-induced toxicity in the ovary and uterus and the preventive effects of quercetin (QCT) and vitamin E (Vit.E). Female rats were divided into six groups as follows: control, QCT (20 mg/kg), Vit.E (200 mg/kg), DOX (accumulative 15 mg/kg), DOX/QCT, and DOX/Vit.E. After 3 weeks, the toxicity of DOX in ovarian and uterine tissues and the potential palliative effects of QCT and Vit.E were evaluated by histopathological–stereological methods. The findings indicate a dramatic decline in the number of ovarian follicles (p < 0.001), ovarian and its associated structures volume, the volume of the uterus, its layers, and related structures (p < 0.05). Coadministration of QCT and Vit.E with DOX-treated rats demonstrated an alleviative effect on most of the studied parameters. Nevertheless, few adverse effects were recognized concerning these antioxidants administration (p < 0.05). In conclusion, the findings of this study support the protective role of these dietary supplements in the prevention of DOX-induced toxicity in uterine and ovarian tissues.
The ARRIVE guidelines 2.0: updated guidelines for reporting animal research

Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work adequately, evaluate its methodological rigour, and reproduce the methods and results. Despite considerable levels of endorsement by funders and journals over the years, adherence to the guidelines has been inconsistent, and the anticipated improvements in the quality of reporting in animal research publications have not been achieved. Here, we introduce ARRIVE 2.0. The guidelines have been updated and information reorganised to facilitate their use in practice. We used a Delphi exercise to prioritise and divide the items of the guidelines into 2 sets, the ‘ARRIVE Essential 10,’ which constitutes the minimum requirement, and the ‘Recommended Set,’ which describes the research context. This division facilitates improved reporting of animal research by supporting a stepwise approach to implementation. This helps journal editors and reviewers verify that the most important items are being reported in manuscripts. We have also developed the accompanying Explanation and Elaboration document, which serves (1) to explain the rationale behind each item in the guidelines, (2) to clarify key concepts, and (3) to provide illustrative examples. We aim, through these changes, to help ensure that researchers, reviewers, and journal editors are better equipped to improve the rigour and transparency of the scientific process and thus reproducibility.
Molecular Mechanisms and Potential Therapeutic Reversal of Pancreatic Cancer-Induced Immune Evasion

Pancreatic cancer ranks high among the causes of cancer-related mortality. The prognosis of this grim condition has not improved significantly over the past 50 years, despite advancement in imaging techniques, cancer genetics and treatment modalities. Due to the relative difficulty in the early detection of pancreatic tumors, as low as 20% of patients are eligible for potentially curative surgery; moreover, chemotherapy and radiotherapy (RT) do not confer a great benefit in the overall survival of the patients. Currently, emerging developments in immunotherapy have yet to bring a significant clinical advantage among pancreatic cancer patients. In fact, pancreatic tumor-driven immune evasion possesses one of the greatest challenges leading to immunotherapeutic resistance. Most of the immune escape pathways are innate, while poor priming of hosts’ immune response and immunoediting constitute the adaptive immunosuppressive machinery. In this review, we extensively discuss the pathway perturbations undermining the anti-tumor immunity specific to pancreatic cancer. We also explore feasible up-and-coming therapeutic strategies that may restore immunity and address therapeutic resistance, bringing hope to eliminate the status quo in pancreatic cancer prognosis.
Retinol-binding protein 4 is associated with arterial stiffness in early postmenopausal women.

OBJECTIVE Recent evidence in postmenopausal women suggested lack of association between serum levels of retinol-binding protein 4 (RBP4) and subclinical atherosclerosis; however, associations with arterial stiffness in this population remain unexplored. We evaluated the association among RBP4 and cardiovascular risk factors, including homocysteine, a marker involved in retinoic acid synthesis, and indices of arterial stiffness, in a sample of apparently healthy postmenopausal women. METHODS This cross-sectional study included 123 healthy postmenopausal women, not on hormone therapy, antihypertensive, or hypolipidemic treatment and with a menopausal age 10 years or less. We performed biochemical/hormonal assessment and sonographic evaluation, including carotid-femoral pulse wave velocity (PWV) and carotid artery stiffness index (SI). RESULTS Univariate analysis showed that RBP4 values correlated with age, low-density lipoprotein-cholesterol and estradiol levels. There was a trend of association of SI and PWV with homocysteine and triglycerides. RBP4 differed according to PWV, using the median PWV value as cut-off (RBP4, PWV ≤8.1 vs >8.1 m/s: 10.09 ± 2.05 vs 10.85 ± 1.91 ng/mL, analysis of covariance P value 0.014 adjusted for age, menopausal age, estradiol, pulse pressure). Linear regression analysis showed that PWV was independently associated with RBP4, age, and pulse pressure, whereas SI was independently associated with RBP4. An increase of one standard deviation in RBP4 levels (2.54 ng/mL) was associated with an increase of 0.577 m/s in PWV. CONCLUSIONS RBP4 serum levels are associated with arterial stiffness, in a sample of healthy postmenopausal women. If this association is causative, serum RBP4 levels could serve as a marker of arterial stiffness. Prospective studies are required to investigate the significance of our findings. : Video Summary:http://links.lww. com/MENO/A621.
Pain Neuroscience Education Plus Usual Care Is More Effective than Usual Care Alone to Improve Self-Efficacy Beliefs in People with Chronic Musculoskeletal Pain: A Non-Randomized Controlled Trial

Self-efficacy beliefs are associated with less physical impairment and pain intensity in people with chronic pain. Interventions that build self-efficacy beliefs may foster behavioral changes among this population. A non-randomized trial has been carried out to evaluate the effectiveness of pain neuroscience education (PNE) plus usual care in modifying self-efficacy beliefs, pain intensity, pain interference and analgesics consumption in people with chronic musculoskeletal pain. Participants were allocated to an experimental (PNE plus usual care, n = 49) and a control (usual care alone, n = 51) group. The primary outcome was self-efficacy beliefs (Chronic Pain Self-Efficacy Scale), and the secondary outcomes were pain intensity, pain interference (Graded Chronic Pain Scale) and analgesics consumption. The participant’s pain knowledge (revised Neurophysiology of Pain Questionnaire) after PNE intervention was also assessed to analyze its influence on every outcome measure. All the outcome measures were assessed at the baseline and at four-week and four-month follow-ups. PNE plus usual care was more effective than usual care alone to increase self-efficacy beliefs and decrease pain intensity and pain interference at all follow-up points. No differences between groups were found in terms of analgesics consumption. Knowledge of pain neurophysiology did not modify the effects of PNE plus usual care in any of the outcome measures. These results should be taken with caution because of the non-randomized nature of this design, the limited follow-ups and the uncertainty of the presence of clinical changes in self-efficacy for participants. Larger, methodological sound trials are needed.
Shiga Toxin Uptake and Sequestration in Extracellular Vesicles Is Mediated by Its B-Subunit

Shiga toxin (Stx)-stimulated blood cells shed extracellular vesicles (EVs) which can transfer the toxin to the kidneys and lead to hemolytic uremic syndrome. The toxin can be taken up by renal cells within EVs wherein the toxin is released, ultimately leading to cell death. The mechanism by which Stx is taken up, translocated, and sequestered in EVs was addressed in this study utilizing the B-subunit that binds to the globotriaosylceramide (Gb3) receptor. We found that Stx1B was released in EVs within minutes after stimulation of HeLa cells or red blood cells, detected by live cell imaging and flow cytometry. In the presence of Retro-2.1, an inhibitor of intracellular retrograde trafficking, a continuous release of Stx-positive EVs occurred. EVs from HeLa cells possess the Gb3 receptor on their membrane, and EVs from cells that were treated with a glycosylceramide synthase inhibitor, to reduce Gb3, bound significantly less Stx1B. Stx1B was detected both on the membrane and within the shed EVs. Stx1B was incubated with EVs derived from blood cells, in the absence of cells, and was shown to bind to, and be taken up by, these EVs, as demonstrated by electron microscopy. Using a membrane translocation assay we demonstrated that Stx1B was taken up by blood cell- and HeLa-derived EVs, an effect enhanced by chloropromazine or methyl-ß-cyclodextrin, suggesting toxin transfer within the membrane. This is a novel mechanism by which EVs derived from blood cells can sequester their toxic content, possibly to evade the host response.
FUNCTIONAL MORPHOLOGY OF INSECT WINGS

Despite the extensive and long-standing use of wing characters in insect systematics, serious experimental investigations of the functional sense be­ hind insect wing design are virtually confined to the past two decades. Functional discussion in earlier writing is speculative and curiously scarce. Most notably, Rohdendorf attempted to interpret the evolution of wing form in Diptera (115) and insects in general (114) in functional terms, and Edmunds & Traver (52) discussed the ground plan and early evolution of wings with reference to possible changes in flight technique, but these and other workers were hampered by the limited information then available on the movements of wings in flight, and on flapping-flight aerodynamics in general. Studies in both these areas progressed significantly in the 1950s and 1960s through investigations of the flight of tethered insects (95, 119-121, 125), but insect flight and wing morphology remained essentially separate disciplines until the early 1970s, when a coincident series of technical and intellectual developments at last prepared the way for a synthesis. The scanning electron microscope became widely available, allowing a stepwise improvement in detailed morphology. Weis-Fogh (125) and Norberg (104) pioneered high­ speed cinematography of insects flying freely, and hence displaying a far
Performance and Carcass Characteristics of Broiler Chicks Fed Diets Supplemented with Commercial Zinc-Methionine

This work was conducted to study the effect of three levels of commercial organic mineral of zinc-methionine as commercial product in starter and finisher diets of broiler chicks. One hundred and ninety two unsexed Hubbard broiler chicks at three week of age were divided into four treatments (48 birds each), each treatment contained 4 replicates of 12 birds. The experimental treatments were as follows: Treatment 1: Chicks were fed the control diet. Treatment 2: Chicks were fed the control diet + 0.3 g Zn + Mth /Kg diet. Treatment 3: Chicks were fed the control diet + 0.4 g Zn + Mth /Kg diet. Treatment 4: Chicks were fed the control diet + 0.5 g Zn + Mth /Kg diet. Chicks fed the diet supplemented with com. Zn Meth diet at the level of 0.5g Zn Meth. /Kg diet had the highest value of live body weight (LBW) at 49 days of age (2473.2 g). Chicks fed the diet supplemented with 0.5 g Zn Meth. /Kg diet had the heaviest live body weight gain (LBWG) during the period from 21 to 49 days of age (1777.9 g). Chicks fed the diet supplemented with 0.3 g Zn Meth. /Kg diet had the lowest feed intake (FI) during the period from 21 to 49 days of age (3531.5 g). Chicks fed the diet supplemented with 0.3 g Zn Meth. /Kg diet had the best feed conversion (FC), crude protein conversion (CPC) and caloric conversion (CCR) during the period from 36 to 42 days of age (2.14, 0.384 and 6.65 g, respectively). Chicks fed the diet supplemented with 0.5 Zn Meth. /Kg diet had the highest values of GR during the period 21-49 days (0.868). Chicks fed the diet supplemented with 0.3 g Zn Meth. /Kg diet had the highest value of performance index (PI) during the period from 36-42 days (115.37) and chicks fed the diet supplemented with 0.5 g Zn Meth. /Kg diet had the highest value of PI during the periods 21-28 and 43-49 days (49.26 and 115.8, respectively). No significant differences were found among dietary treatments in chemical composition of broiler meat and carcass traits. Chicks fed the diet supplemented with 0.4 Zn Meth. /Kg diet had the highest value of GPT. Economical efficiency (EEF) value at 42 days of age was improved in chicks diet supplemented with Zn Meth. as
Additions to the bryophyte flora of Bulgaria

New and noteworthy records of bryophytes from Bulgaria are reported. Bartramia stricta, Bryum funckii, Calypogeia integristipula, Dicranella humilis, Dicranoweisia compacta, Ditrichum gracile, Grimmia anomala, G. lisae, G. meridionalis, Hedwigia ciliata var. leucophaea, Hypnum bambergeri, Hypnum recurvatum, Schistidium crassipilum, S. elegantulum, S. robustum, S. singarense and Tortella bambergeri are new to Bulgaria, and some additional species are new to different regions of Bulgaria. Mosses/ liverworts/new records / distribution / Bulgaria The collections for this article were made during excursions with the Nordic Bryological Society from 10 to 15 July 2005 throughout Bulgaria, invited and led by Anna Ganeva and Rayna Natcheva,, and during two subsequent weeks travelling with Florian Hans through the country. Specimens are depos- ited in SOM and in the private herbarium of the author, or as otherwise indicated. Nomenclature and distribution data are based on the two check-lists of Bulgaria (GANEVA & NATCHEVA 2003, NATCHEVA & GANEVA 2005), which contain 2 species of hornworts, 173 liverworts and 531 mosses. In a country like Bulgaria, with high diversity of climate, geology and morphology, about 800-1000 species of bryophytes could be expected. So there is a high probability of further dis- coveries. The novelties are indicated by an asterisk (*). Liverworts *Calypogeia integristipula Steph.
Cross-cultural adaptation, reliability and validity of the Persian version of the Victorian Institute of Sport Assessment-Achilles questionnaire (VISA-A)

Abstract Purpose Achilles tendinopathy is a prevalent overuse injury among athletes and in those with a sedentary lifestyle. Current evidence indicates that the Victorian Institute of Sport Assessment-Achilles (VISA-A) questionnaire is a valid, reliable and disease-specific outcome measure for assessing the clinical symptoms in patients with Achilles tendinopathy. The objective of this study was to translate and cross-culturally adapt the VISA-A questionnaire into Persian (VISA-A-P) and evaluating its psychometric properties. Materials and methods Cultural adaptation of VISA-A-P was conducted according to Beaton’s guideline. The final version of VISA-A-P was handed to 61 patients for analysis of psychometric properties. Test–retest reliability, internal consistency, concurrent validity, item-total correlation, and floor/ceiling effect were evaluated in patients with Achilles tendinopathy. To assess test–retest reliability, 35 patients refilled the VISA-A-P twice within 5–7 days. Known-group validity was evaluated using 50 healthy individuals. Results VISA-A-P showed excellent test–retest reliability (ICC = 0.90), excellent internal consistency (Cronbach’s alpha = 0.95), strong correlation with FAAM, and moderate to strong correlation with FAOS questionnaires. There was a significant difference between the average score of patients (34.55 ± 18.24) and the healthy group (73.1 ± 20.10). VISA-A-P showed neither ceiling nor floor effect. Conclusions The VISA-A-P is a reliable and valid instrument for measuring the symptoms in Persian speaking populations with Achilles tendinopathy. Implications for rehabilitation Achilles tendinopathy is a debilitating overuse injury that insidiously affects tendoAchilles. VISA-A-P revealed acceptable validity and reliability and it could be used by Persian speaking clinicians and researchers to assess pain and function in people with Achilles tendinopathy.
The Effect of Dietary Exposure to Coal Ash Contaminants within Food Ration on Growth and Reproduction in Daphnia magna

Coal ash contains numerous contaminants and is the focus of regulatory actions and risk assessments due to environmental spills. We exposed Daphnia magna to a gradient of coal ash contamination under high and low food rations to assess the sublethal effects of dietary exposures. Whereas exposure to contaminants resulted in significant reductions in growth and reproduction in daphnids, low, environmentally relevant food rations had a much greater effect on these endpoints. Environ Toxicol Chem 2020;39:1998–2007. © 2020 SETAC
Alteration of p53 and NF-kB pathways by E7 protein from cutaneous Human Papillomavirus type 38

Viral infections contribute to 15–20% of all human cancers. Studying the mechanisms employed by the oncogenic viruses to induce cellular transformation is essential for a better understanding of the resulting cancers and the discovery of new mechanisms involved in cancer development which can be targeted in therapeutic approaches. Human papillomaviruses (HPVs) are small dsDNA viruses which have been clearly associated with certain cancers. They were first isolated from the skin of patients suffering from Epidermodysplasia Verruciformis (EV) having an increased susceptibility to infection by specific HPV types and to the development of non-melanoma skin cancer (NMSC). Certain cutaneous HPV types, such as 5, 8, and 38, are suspected to play a role in skin cancer development. However the direct role of cutaneous HPV in the etiology of cancer is still under debate. Previous studies from our laboratory have reported that HPV38 E6 and E7 proteins are able to immortalize human primary keratinocytes in vitro and in vivo. Cellular immortalization can be achieved through the deregulation of important signaling pathways including p53 and NF-KB. In the present work, we have investigated the molecular mechanisms of p53 and NF-KB pathways deregulation by E6 and E7 oncoproteins from HPV38 in human keratinocytes. We show here that HPV38 E6E7 induce the formation of a transcription repressor complex including IKKβ, ΔNp73α, and polycomb group members EZH2 and DNMT1. The formation of this protein complex correlates with the inhibition of several p53-target genes, such as PIG3. We also report in these studies that HPV38 E6E7 activate NF KB pathway, which plays an important role in the survival of HPV38 E6E7-immortalized human keratinocytes upon TNF-α– and UVB-mediated apoptosis. In addition our data highlight E7 being the main HPV38 protein mediating p53 and NF-KB deregulation. Our studies shed light on novel molecular mechanisms that could be important for HPV38-mediated cellular transformation
Decomposition of Metrosideros polymorpha leaf litter along elevational gradients in Hawaii

We examined interactions between temperature, soil development, and decomposition on three elevational gradients, the upper and lower ends of each being situated on a common lava flow or ash deposit. We used the reciprocal transplant technique to estimate decomposition rates of Metrosideros polymorpha leaf litter during a three‐year period at warm and cool ends of each gradient. Litter quality was poorest early in soil development or where soils were most intensely leached and waterlogged. In situ litter decomposition was slowest on the young 1855 flow (k= 0.26 and 0.14 at low and high elevation, respectively). The more fertile Laupahoehoe gradient also supported more rapid in situ decay at the warmer low elevation site (k= 0.90) than at high elevation (k= 0.51). The gradient with the most advanced soil development showed no difference for in situ decay at low and high elevations (k= 0.88 and 0.99, respectively) probably due to low soil nutrient availability at low elevation, which counteracted the effect of warmer temperature. Comparisons of in situ, common litter, and common site experiments indicated that site factors influenced decomposition more than litter quality did. The effect of temperature, however, could be over‐ridden by soil fertility or other site factors. Field gradient studies of this sort yield variable estimates of apparent Q10, even under the best conditions, due to interactions among temperature, moisture, nutrient availability, decomposer communities and litter quality. Such interactions may be as likely to occur with changing climate as they are along elevational gradients.
The Apoplast: A Key Player in Plant Survival

The apoplast comprises the intercellular space, the cell walls, and the xylem. Important functions for the plant, such as nutrient and water transport, cellulose synthesis, and the synthesis of molecules involved in plant defense against both biotic and abiotic stresses, take place in it. The most important molecules are ROS, antioxidants, proteins, and hormones. Even though only a small quantity of ROS is localized within the apoplast, apoplastic ROS have an important role in plant development and plant responses to various stress conditions. In the apoplast, like in the intracellular cell compartments, a specific set of antioxidants can be found that can detoxify the different types of ROS produced in it. These scavenging ROS components confer stress tolerance and avoid cellular damage. Moreover, the production and accumulation of proteins and peptides in the apoplast take place in response to various stresses. Hormones are also present in the apoplast where they perform important functions. In addition, the apoplast is also the space where microbe-associated molecular Patterns (MAMPs) are secreted by pathogens. In summary, the diversity of molecules found in the apoplast highlights its importance in the survival of plant cells.