Miracle-dz/UniFAR-FTUs huggingface dataset:
Population Growth Rates of Aedes atropalpus (Diptera: Culicidae) Are Depressed at Lower Temperatures Where Aedes japonicus japonicus (Diptera: Culicidae) Are Naturally Abundant in Rock Pools

Abstract Recent studies report extensive reductions in the abundance of the North American rock pool mosquito, Aedes atropalpus (Diptera: Culicidae), following the invasion of Ae. japonicus japonicus in the United States. Although developmental temperature is recognized as an important component of the invasion biology of Ae. j. japonicus, its impacts on the population growth and fitness of Ae. atropalpus remain largely undefined. In this study we reared Ae. atropalpus larvae at three temperature ranges reflecting ecologically important temperatures in natural rock pools: a low temperature range (mean: 19°C) where Ae. j. japonicus is common and Ae. atropalpus is often rare, a middle temperature range (mean: 25°C) where both species are naturally found in similar relative abundances, and a higher temperature range (mean: 31°C) where Ae. atropalpus is the dominant species. We measured survival, development time, wing length, and fecundity to calculate a finite population growth rate at each temperature. Our results indicate that Ae. atropalpus population growth suffers in colder rock pools, which informs the perceived displacement of the species in temperate habitats. The population growth rate was highest in the middle temperature range, but not significantly higher than in the highest temperature range used in this study. The developmental success of Ae. atropalpus at the intermediate temperature range suggests that competition with Ae. j. japonicus in rock pools within that range may significantly impact natural Ae. atropalpus populations.
New distribution and molecular diversity of the reniform nematode Rotylenchulus macrosoma Dasgupta, Raski and Sher, 1968 (Nematoda: Rotylenchulinae) in Europe.

Reniform nematodes of the genus Rotylenchulus are semiendoparasites of numerous herbaceous and woody plant roots and occur largely in regions with temperate, subtropical and tropical climates. In this study, we provide new records of the nematode R. macrosoma in eight European countries (Czech Republic, France, Germany, Hungary, Italy, Romania, Serbia and Portugal), in addition to the six Mediterranean countries (Greece, Israel, Jordan, Spain, Syria, and Turkey) where it has previously been reported. Four new host species (corn, pea, wheat and an almond-peach hybrid rootstock) are added to the recorded host species (bean, chickpea, hazelnut, peanut, soybean, wild and cultivated olive). Molecular analyses based on the coxI and D2-D3 segments of 28S RNA markers showed high diversity and pronounced genetic structure of populations of R. macrosoma. However, the complexity of phylogeographic patterns in plant-parasitic nematodes may be related to the intrinsic heterogeneity in the distribution of soil organisms, a rare occurrence of a species, or the potential human impact associated with agricultural practices.
Global Lysine Crotonylation Profiling of Mouse Liver

Lysine crotonylation (Kcr) is a recently discovered post‐translational modification that potentially regulates multiple biological processes. With an objective to expand the available crotonylation datasets, LC‐MS/MS is performed using mouse liver samples under normal physiological conditions to obtain in vivo crotonylome. A label‐free strategy is used and 10 034 Class I (localization probabilities > 0.75) crotonylated sites are identified in 2245 proteins. The KcrE, KcrD, and EKcr motifs are significantly enriched in the crotonylated peptides. The identified crotonylated proteins are mostly enzymes and primarily located in the cytoplasm and nucleus. Functional enrichment analysis based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes shows that the crotonylated proteins are closely related to the purine‐containing compound metabolic process, ribose phosphate metabolic process, carbon metabolism pathway, ribosome pathway, and a series of metabolism‐associated biological processes. To the best of the authors' knowledge, this research provides the first report on the mouse liver crotonylome. Furthermore, it offers additional evidence that crotonylation exists in non‐histone proteins, and is likely involved in various biological processes. The mass spectrometry proteomics data have been deposited in the ProteomeXchange Consortium with the dataset identifiers PXD019145.
Cell surface GRP78 signaling: An emerging role as a transcriptional modulator in cancer

Cancer cells acquire dysregulated gene expression to establish specific transcriptional dependencies and their underlying mechanisms that are ultimately responsible for this addictions have not been fully elucidated. Glucose‐regulated protein 78 (GRP78) is a stress‐inducible, multifunctional, prosurvival, endoplasmic reticulum chaperone in the heat shock protein 70 family. Expression of cell surface GRP78 (CS‐GRP78) is associated with increased malignant behavior and resistance to chemotherapy and radiotherapy by endowing various cancer cells with increased proliferative ability, altered metabolism, improved survival, and augmented invasive and metastatic potential. Emerging evidence has highlighted an unusual role of CS‐GRP78 in regulating transcription factors (TFs) by mediating various signaling pathways involved in malignant transformation, metabolic reprogramming, and tumor progression. During the last decade, we targeted CS‐GRP78 with C38 monoclonal antibody (C38 Mab) in numerous studies, which have highlighted the epigenetic interplay between CS‐GRP78 and various TFs including c‐MYC, Yes‐associated protein/transcriptional coactivator with PDZ‐binding motif, c‐Fos, and histone acetylation to potentiate subsequent modulation of tumorigenesis, invasion, and metastasis. Here, we summarize the current state of knowledge about the role of CS‐GRP78 in cancer development and progression, including epigenetic regulation and sheds light on CS‐GRP78 as vulnerable target for cancer therapy. Overall, this review focuses on the mechanisms of TFs that are behind the transcriptional dysregulation in cancer and lays the groundwork for rational therapeutic use of C38 Mab based on CS‐GRP78 biology.
A Review of Therapeutic Effects and the Pharmacological Molecular Mechanisms of Chinese Medicine Weifuchun in Treating Precancerous Gastric Conditions

Patients with precancerous gastric conditions are at a high risk for gastric carcinoma. The Chinese medicine Weifuchun (WFC) is used in treating chronic superficial gastritis and in postoperative adjuvant treatment of gastric cancer. Both monotherapy and combination therapy of WFC with other drugs can result in a favorable therapeutic outcome. WFC can dramatically improve clinical outcomes in patients with gastric precancerous lesions by targeting multiple pathways including pathways involved in the pharmacological action of Radix Ginseng Rubra (red ginseng), Rabdosia amethystoides, and fried Fructus Aurantii, including regulation of NF-κB, RUNX3/TGF-beta/Smad, Hedgehog (Hh) and Wnt signaling pathways, modulation of the expression of oncogenes and tumor suppressor genes, and indirect inhibition of Helicobacter pylori (Hp) by maintaining gastric microbial ecosystem. In this review, we will discuss the clinical efficacy and therapeutic regimen of WFC for gastric precancerous lesions and the molecular mechanisms involved. This review will highlight WFC-based therapeutic strategies in disrupting progress to gastric cancer and provide more information on the pharmacological mechanisms of WFC and its clinical application for the treatment of precancerous gastric lesions.
Massive Ascites Caused by Primary Diffuse Large B-cell Lymphoma of the Jejunum: A Case of a Rare Initial Symptom

A 74-year-old man presented with abdominal swelling. Computed tomography revealed massive ascites and localized thickening of the small intestinal wall. Enteroscopy showed ulcerative lesions along the circumference of the jejunum. Histological examination showed dense proliferation of large lymphoid atypical cells, and immunohistochemistry showed CD20 and CD10 positivity, CD3 negativity, and Ki67 labeling index >80%. Cytology of the ascitic fluid revealed large lymphoid cells. These findings suggest that small intestine primary diffuse large B-cell lymphoma (DLBCL) caused the ascites. Massive ascites as an initial symptom of primary DLBCL of the jejunum is rare. Herein, we describe this unusual presentation.
Structures and biological evaluation of phenylpropanoid derivatives from Dendrobium Sonia

Abstract Two new phenylpropanoid derivatives (1-2), together with eight known compounds (3-10) were isolated from the stems of Dendrobium sonia. The structures of these compounds were elucidated on the basis of spectroscopic analyses, including HRESIMS, 1 D and 2 D NMR experiments. All of the isolated compounds were tested for their Nitric Oxide (NO) Inhibitory Activities. The results of bioactive screening showed that compounds 2, 8, 9 and 10 exerted inhibitory effects on NO production with IC50 values in the range of 26.3 to 31.6 μM. Compound 8 and 9 exhibited stronger anti-inflammatory activities with IC50 values 26.3 and 27.7 μM, comparable to that of the positive control. Graphical Abstract
Current trends in the management and prevention of human papillomavirus (HPV) infection.

PURPOSE Herein, we critically evaluate and discuss current literature in the field of human papillomavirus (HPV) pathogenesis, treatment, and prevention. METHODS Screening of the literature and selection of studies was performed until May 31st, 2019. RESULTS HPV is considered the commonest heterosexual and homosexual sexually transmitted infection globally. Low-risk HPV subtypes are associated with genital warts, whereas persistent infection with high-risk HPV 16 and 18 subtypes is closely associated with premalignant and invasive lesions in the anogenital and oropharyngeal region. E6 and E7 genes are the main drivers of oncogenic transformation in cervix since they promote all aspects of cancer hallmarks. Importantly, the implementation of screening has reduced the HPV-associated disease burden. In this field, a shift from cytology to HPV testing is currently being observed. Furthermore, vaccination programmes have shown high effectiveness in preventing HPV infection and HPV-related lesions, whereas their future implementation on a larger scale would further enhance our primary prevention strategies. CONCLUSION Although HPV constitutes an evolving paradigm in cancer prevention, optimizing screening test performance, and cost-effectiveness remains debatable.
Changes in primary and secondary hemostasis in patients with CLL treated with venetoclax and ibrutinib

Abstract Bleeding is a common adverse event following ibrutinib monotherapy. However, it remains unclear how hemostasis is affected by venetoclax in combination with ibrutinib. Here we investigated hemostasis in patients with chronic lymphocytic leukemia (CLL) at baseline, during ibrutinib monotherapy, and during venetoclax and ibrutinib combination therapy or venetoclax monotherapy. Primary hemostasis, assessed by Multiplate using adenosine diphosphate (ADP), arachidonic acid (AA), and thrombin receptor agonist peptide (TRAP-6), was impaired in all CLL patients at baseline, remained unchanged upon ibrutinib monotherapy, and improved significantly following venetoclax added to ibrutinib or as monotherapy. Secondary hemostasis assessed by thromboelastography (TEG) was normal and unchanged throughout treatment. The frequency of clinical bleeding events was the highest during ibrutinib monotherapy, in line with the demonstrated improved primary hemostasis upon addition of venetoclax, thus pointing toward a treatment option for CLL patients with increased bleeding risk.
Profiles of bystanders' motivation to defend school bully victims from a self‐determination perspective

Abstract This study was aimed at exploring which latent profiles emerge based on ratings of self‐determined motivation to defend victims of bullying, and to explore if they are related to bystander roles and victimization in bullying, as well as student–teacher relations. Data were collected from 1,800 Swedish and Italian students, with an age range between 10 and 18 years (M = 12.6, standard deviation = 1.74). The students completed a survey in their classrooms. Latent profile analysis was used to explore the possible clusters of individuals with similar ratings on the motivational variables. Multivariate analysis of variances were conducted to explore differences between the profiles in relation to their roles when witnessing bullying and to student–teacher relationships. Four latent profiles emerged. The profiles represented respondents (a) high in prosocial motivation, (b) high in externally extrinsic motivation, (c) intermediate in externally extrinsic motivation, and (d) with identified/introjected motivation. Multivariate analyses showed that reports of bystander roles when witnessing bullying, teacher–student relationships, and bullying victimization, significantly differed over the motivational profiles. The bystanders were unevenly distributed across the four groups and most individuals were categorized in the prosocial motivation group. Female and male bystanders were evenly distributed across clusters. The prosocial motivation group experienced victimization to a lesser extent than the other profile groups. Students in the intermediate externally extrinsic group were more likely to take the pro‐bully and outsider role during bullying. Concerning student–teacher relationships, the prosocial motivation group reported the closest relationships with their teachers, while the intermediate externally extrinsic group reported the most conflictual relationships.
Quaternary variations in the structural assembly of N‐acetylglucosamine‐6‐phosphate deacetylase from Pasteurella multocida

N‐acetylglucosamine 6‐phosphate deacetylase (NagA) catalyzes the conversion of N‐acetylglucosamine‐6‐phosphate to glucosamine‐6‐phosphate in amino sugar catabolism. This conversion is an essential step in the catabolism of sialic acid in several pathogenic bacteria, including Pasteurella multocida, and thus NagA is identified as a potential drug target. Here, we report the unique structural features of NagA from P. multocida (PmNagA) resolved to 1.95 Å. PmNagA displays an altered quaternary architecture with unique interface interactions compared to its close homolog, the Escherichia coli NagA (EcNagA). We confirmed that the altered quaternary structure is not a crystallographic artifact using single particle electron cryo‐microscopy. Analysis of the determined crystal structure reveals a set of hot‐spot residues involved in novel interactions at the dimer‐dimer interface. PmNagA binds to one Zn2+ ion in the active site and demonstrates kinetic parameters comparable to other bacterial homologs. Kinetic studies reveal that at high substrate concentrations (~10‐fold the KM), the tetrameric PmNagA displays hysteresis similar to its distant neighbor, the dimeric Staphylococcus aureus NagA (SaNagA). Our findings provide key information on structural and functional properties of NagA in P. multocida that could be utilized to design novel antibacterials.
Genetics of skeletal muscle strength and its determinants in healthy, untrained males

It is well accepted that inter-individual variability exists in muscle strength (more specifically maximal voluntary contraction torque), and many of its determinants. The extent of this inter-individual variability, however, has yet to be quantified despite many researchers suggesting genetic factors contribute. The aims of the present thesis were to first quantify the inter-individual variability within skeletal muscle phenotypes in a homogenous population, and secondly to investigate the contribution of multiple genetic polymorphisms to the inter-individual variability within these phenotypes. Genotype and phenotype data was collected from 120 untrained Caucasian males (aged 18-39 yr). Considerable inter-individual variability in muscle strength phenotypes and many of its determinants was observed. Subsequently, polymorphisms in the CNTF, TTN, PTK2, TRHR and ACTN3 genes demonstrated significant associations with one or more of the skeletal muscle phenotypes, but neither ACE nor COL5A1 were found to associate with any of the measured phenotypes. Adopting a polygenic approach that incorporated all of these genetic polymorphisms did not account for the inter-individual variability observed within VL muscle size (inter-individual variability = 13-20%; P ≥ 0.166) or strength (14-19%; P ≥ 0.220). The results identified novel genetic associations between TTN, CNTF and skeletal muscle architecture, in addition to providing the first independent replications of associations between PTK2 and specific force, and TRHR and lean mass. In conclusion, there appears to be a genetic influence on skeletal muscle phenotypes, however, further research is necessary to replicate the associations observed within the current thesis in comparable and different populations. Nonetheless, the work presented here has applications for improving physical performance, in addition to enhancing our understanding of skeletal muscle disorders, which may have implications for how individuals exercise and how skeletal muscle disorders are treated and/or prevented in future.
App-Based Delivery of Clinical Emotional Freedom Techniques: Cross-Sectional Study of App User Self-Ratings

Background The burgeoning area of mobile health (mHealth) has experienced rapid growth in mobile apps designed to address mental health issues. Although abundant apps offer strategies for managing symptoms of anxiety and stress, information regarding their efficacy is scarce. Objective This study aimed to assess the effect of an mHealth app on user self-ratings of psychological distress in a sample of 270,461 app users. The Tapping Solution App guides users through the therapeutic protocols of Clinical Emotional Freedom Techniques (EFT), an evidence-based psychophysiological intervention that combines acupressure with elements of cognitive and exposure therapies. Methods App users provided self-ratings of emotional intensity before and after app sessions (termed “tapping meditations”) using an 11-point Subjective Units of Distress scale. App user data for 23 tapping meditations, which addressed psychological symptoms of anxiety and stress, were gathered between October 2018 and October 2019, totaling 380,034 completed app sessions. Results Across 12 anxiety-tapping meditations, the difference in emotional intensity ratings from presession (mean 6.66, SD 0.25) to postsession (mean 3.75, SD 0.30) was statistically significant (P<.001; 95% CI −2.92 to −2.91). Across 11 stress-tapping meditations, a statistically significant difference was also found from presession (mean 6.91, SD 0.48) to postsession (mean 3.83, SD 0.54; P<.001; 95% CI −3.08 to −3.07). The results are consistent with the literature on the efficacy of Clinical EFT for anxiety and stress when offered in conventional therapeutic formats. Conclusions The findings provide preliminary support for the effectiveness of the mHealth app in the immediate reduction of self-rated psychological distress. As an adjunct to professional mental health care, the app promises accessible and convenient therapeutic benefits.
Production of [68 Ga]Ga-PSMA: Comparing a manual kit-based method with a module-based automated synthesis approach.

The labelling of peptides with gallium-68 is often initially performed by manual labelling, but with high clinical demand, other alternatives are needed. Kit-based or automated synthesis are viable options for standardized methods and deemed pharmaceutically more acceptable. This study compares these [68 Ga]Ga-PSMA-11 production methods. Data from 40 kit-based and 40 automated syntheses of [68 Ga]Ga-PSMA-11 were analysed. Pre-set criteria were evaluated including radiochemical purity, radionuclidic purity, chemical purity, physiological acceptability and sterility. The operator time and radiation dose received were measured. The robustness and repeatability of each method were assessed and a comparison of the running costs of each method is also provided. For both the methods all the analysed products met the release criteria. No differences were found in radiochemical purity, radiochemical identity, radionuclidic purity, and sterility. However, radiochemical yield and apparent molar activity showed significant differences. For both methods, whole body radiation exposure to operators was lower than with manual labelling (25 - 40 μSv). The exposure during kit-based labelling (14.5 ± μSv) was seven times higher than that of automated synthesis (2.05 ± 0.99 μSv). The automated synthesis was the more expensive method. Both methods are sound alternatives to manual synthesis and offer higher quality, better radiation protection and a more reliable manufacturing of radiopharmaceuticals.
Hypothalamic–vagal oxytocinergic neurocircuitry modulates gastric emptying and motility following stress

Stress triggers and exacerbates the symptoms of functional gastrointestinal disorders, such as delayed gastric emptying and impaired gastric motility. Understanding the mechanisms by which the neural circuits, impaired by stress, are restored may help to identify potential targets for more effective therapeutic interventions. Oxytocin administration or release ameliorates the stress‐induced delayed gastric emptying and motility. However, is it unclear whether the effects are mediated via the hypothalamic‐pituitary‐adrenocortical axis or the oxytocinergic projections from the paraventricular nucleus of the hypothalamus to brainstem neurones of the dorsal vagal complex. We used Cre‐inducible designer receptors exclusively activated by designer drugs to demonstrate the fundamental role of the oxytocinergic hypothalamic–vagal projections in the gastric adaptation to stress.
Comparative transcriptomic analysis of cerebral organoids and cortical neuron cultures derived from human induced pluripotent stem cells.

Human induced pluripotent stem cells (iPSCs) can be differentiated along various neuronal lineages to generate two-dimensional neuronal cultures as well as three-dimensional brain organoids. Such iPSC-derived cellular models are being utilized to study the basic biology of human neuronal function and to interrogate the molecular underpinnings of disease biology. The different cellular models generated from iPSCs have varying properties in terms of the diversity and organization of the cells as well as the cellular functions that are present. In order to understand transcriptomic differences in iPSC-derived monolayer neuronal cultures and three-dimensional brain organoids, we differentiated eight human iPSC lines from healthy control subjects to generate cerebral organoids and cortical neuron monolayer cultures from the same set of iPSC lines. We undertook RNA-seq experiments in these model systems and analyzed the gene expression data to identify genes that are differentially expressed in cerebral organoids and two-dimensional cortical neuron cultures. In cerebral organoids, gene ontology analysis showed enrichment of genes involved in tissue development, response to stimuli and the interferon-γ pathway while two-dimensional cortical neuron cultures showed enrichment of genes involved in nervous system development and neurogenesis. We also undertook comparative analysis of these gene expression profiles with transcriptomic data from the human fetal prefrontal cortex (PFC). This analysis showed greater overlap of the fetal PFC transcriptome with cerebral organoid gene expression profiles compared to monolayer cortical neuron culture profiles. Our studies delineate the transcriptomic differences between cortical neuron monolayer cultures and three-dimensional cerebral organoids and can help inform the appropriate use of these model systems to address specific scientific questions.