Miracle-dz/UniFAR-FTUs huggingface dataset:
Botulinum Neurotoxin-A Injection in Adult Cervical Dystonia and Spastic Paresis: Results From the INPUT (INjection Practice, Usage and Training) Survey

Botulinum toxin-A (BoNT-A) is an effective treatment for cervical dystonia (CD) and spastic paresis (SP), but it requires in-depth knowledge of anatomy and injection techniques. The Ixcellence Network® is an educational programme to provide neurology, neuropaediatrics, and physical medicine and rehabilitation (PMR) specialists with access to best clinical practices and innovations regarding SP and CD management with BoNT-A. To assess the benefits of such educational programmes and identify unmet needs, a multidisciplinary scientific committee designed INPUT (INjection Practice, Usage & Training), an international multicentric survey describing training and practices among this trained and experienced population. A self-completed questionnaire was sent online to 553 trainees and 14 trainers from the Ixcellence Network®. Among the 131 respondents, 92% specialized in PMR (48%) or neurology (44%), with a mean experience of 15.5 years in their clinical fields and 10.9 years of BoNT-A injection. Most of them (98%) reported having received training before performing their first BoNT-A injection and attending specific courses on how to perform it without any instrumental guidance (76%), and with ultrasound (73%), electrical stimulation (44%) or electromyography (41%). In terms of practices, 92% of respondents reported using at least one guidance technique while injecting, with ultrasound being the most used technique (48%). Attending specific courses was significantly associated with greater self-confidence and use, e.g. for injection with ultrasound, mean self-confidence, on a scale from 1 (not confident) to 10 (fully confident), was 7.9 for trained respondents (vs 4.0 for untrained respondents, p < 0.001) of whom 70% stated that they used this technique regularly or systematically (vs. 11% of untrained healthcare professionals (HCPs), p < 0.0001). Moreover, 84% of respondents reported having trained colleagues, residents or fellows through theoretical (70%) or practical teaching in individuals (80%) or in small groups (65%). Overall, 86% of respondents reported a notable increase over the past 5 years of the number of patients treated with BoNT-A. INPUT is the first international survey describing training and practices in SP and CD management of physicians who attended a dedicated educational programme. The results highlighted the importance of training for self-confidence, and the use of specific techniques and new approaches.
Thymic Stromal Lymphopoietin and Cancer: Th2-Dependent and -Independent Mechanisms

The thymic stromal lymphopoietin (TSLP) is an IL-7-like cytokine originally cloned from a murine thymic stromal cell line, and subsequently a human homolog was identified using database search methods. Human TSLP is mostly expressed in epithelial cells, among which are keratinocytes as well as stromal cells such as fibroblasts and immune cells. Human TSLP was first described to activate myeloid dendritic cells, which prime naïve T helper cells to produce high concentrations of Th2 cytokines, thus representing a key cytokine in triggering dendritic cells-mediated allergic Th2 inflammation. TSLP and/or its receptor has been shown to be expressed in several tumor types, where TSLP expression is associated with functional activities that can be associated or not with the induction of a Th2-prone tumor microenvironment, i.e., Th2-dependent and Th2-independent mechanisms. These mechanisms involve tissue- and immune cell target-dependent tumor-promoting or tumor-suppressive functions in different or even the same tumor type. Here we report and discuss the Th2-dependent and Th2-independent roles of TSLP in cancer and possible therapeutic targeting.
Non-optimal codon usage is critical for protein structure and function of the master general amino acid control regulator CPC-1

Under amino acid starvation condition, eukaryotic organisms activate a general amino acid control response. In Neurospora crassa, Cross Pathway Control-1 (CPC-1), the ortholog of the Saccharomyces cerevisiae bZIP transcription factor GCN4, functions as the master regulator of the general amino acid control response. Codon usage biases are a universal feature of eukaryotic genomes and are critical for regulation of gene expression. Although codon usage has also been implicated in the regulation of protein structure and function, genetic evidence supporting this conclusion is very limited. Here we show that Neurospora cpc-1 has a non-optimal NNU-rich codon usage profile that contrasts with the strong NNC codon preference in the genome. Although substitution of the cpc-1 NNU codons with synonymous NNC codons elevated CPC-1 expression in Neurospora, it altered CPC-1 degradation rate and abolished its amino acid starvation-induced protein stabilization. The codon-manipulated CPC-1 protein also exhibited different sensitivity to limited protease digestion. Furthermore, CPC-1 functions in rescuing the cell growth of the cpc-1 deletion mutant and activating the expression of its target genes were impaired by the synonymous codon changes. Together, these results reveal the critical role of codon usage in regulating of CPC-1 expression and function, and establish a genetic example of the importance of codon usage in protein structure. Abstract importance General amino acid control response is critical for organisms to adapt to amino acid starvation condition. The preference to use certain synonymous codons are a universal feature of all genomes. Synonymous codon changes were previously thought to be silent mutations. In this study, we show that the Neurospora cpc-1 gene has an unusual codon usage profile compared to other genes in the genome. We found that codon optimization of the cpc-1 gene without changing its amino acid sequence resulted in elevated CPC-1 expression, altered protein degradation rate and impaired protein functions due to changes in protein structure. Together, these results reveal the critical role of synonymous codon usage in regulating of CPC-1 expression and function, and establish a genetic example of the importance of codon usage in protein structure.
EVALUATION OF MECHANICAL HARVESTING OF OLIVE TREES IN SOME DESERT RIGONS

A comb harvesting machine was locally manufactured from low cost, local material to be suitable for olive harvesting. Performance evaluation of the manufactured machine was carried out in terms of harvesting time and comb rotating velocity comparing with four traditional methods of olive harvesting (vibrating comb, shaking the brunches, beating the brunches and climbing the trees using ladder). Three different olive trees varieties (Toffahey, Agezzey and Picual) were harvested by the above mentioned harvesting methods. The results showed that quality percentages of olive were 95.5, 75, 85, 85, and 85% for the manufactured comb harvesting machine, vibrating comb, shaking the brunches, beating the brunches and climbing the trees using ladder respectively. The energy requirements values were 9.267, 14.49, 122.9, 122.9 and 122.9kW. h/ton for the same harvesting methods. While the costs values for the harvesting operation were 95.1, 322.36, 2375, 2375 and 2375LE/ton under the same harvesting methods. The best results were achieved with the use of the manufactured comb harvesting machine at comb rotating velocity of 30 rpm during the third harvesting time.
Dendrochemistry: Ecosystem Services Perspectives for Urban Biomonitoring

The worldwide increase in urban and industrial areas represents a challenge for urban green management, pollutant mitigation and environmental monitoring. We propose an analysis approach for the spatial and spatial-temporal distribution of pollutants in the environment through dendrochemistry techniques, in order to gauge the value of this discipline in urban ecosystem. The proposed analysis models can be useful to evaluate significant changes in space and time related to economic activities and to describe the “impacts” of adopted strategies, as demonstrated in the case study of the opening or closure of factories, and therefore to describe the cause-effect relation connected with human activities. Trees represent a key factor for urban planning, providing a wide variety of ecosystem services including in-depth environmental monitoring, which is one of the main elements to be included in a high quality urban design. The proposed approach aims at suggesting the dendrochemistry as a novel and feasible tool definable as a cost-saving ecosystem service in the urban context.
Long Non-coding RNA LINC00115 Contributes to the Progression of Colorectal Cancer by Targeting miR-489-3p via the PI3K/AKT/mTOR Pathway

Long non-coding RNAs (lncRNAs) are tumor-related regulators and have been found to be involved in the underlying molecular mechanisms of colorectal cancer (CRC). However, the role of lncRNA LINC00115 during CRC progression is not entirely elucidated. In this study, we discovered that LINC00115 was significantly overexpressed in CRC, and its overexpression predicted poor patient outcomes. Downregulation of LINC00115 markedly inhibited CRC cell proliferation, increased cell apoptosis, and suppressed cell migration and invasion. Moreover, downregulation of LINC00115 led to the inactivation of PI3K/AKT/mTOR signaling. Bioinformatics analysis identified miR-489-3p as a candidate target of LINC00115. Furthermore, we revealed an inverse correlation between LINC00115 and miR-489-3p in CRC tissues. Importantly, by luciferase reporter assay, we found that miR-489-3p might directly target LINC00115, and downregulation of miR-489-3p could rescue the biological effects induced by the absence of LINC0015. In conclusion, our findings demonstrated that LINC00115 serves as an oncogene in CRC metastasis. Deeper understanding of the LINC00115/miR-489-3p axis might provide potential therapeutic targets against CRC metastasis.
Induction of AmpC-Mediated β-Lactam Resistance Requires a Single Lytic Transglycosylase in Agrobacterium tumefaciens

Agrobacterium tumefaciens, a significant biotechnological tool for production of transgenic plant lines, is highly resistant to a wide variety of antibiotics, posing challenges for various applications. One challenge is the efficient elimination of A. tumefaciens from transformed plant tissue without using levels of antibiotics that are toxic to the plants. ABSTRACT The remarkable ability of Agrobacterium tumefaciens to transfer DNA to plant cells has allowed the generation of important transgenic crops. One challenge of A. tumefaciens-mediated transformation is eliminating the bacteria after plant transformation to prevent detrimental effects to plants and the release of engineered bacteria to the environment. Here, we use a reverse-genetics approach to identify genes involved in ampicillin resistance, with the goal of utilizing these antibiotic-sensitive strains for plant transformations. We show that treating A. tumefaciens C58 with ampicillin led to increased β-lactamase production, a response dependent on the broad-spectrum β-lactamase AmpC and its transcription factor, AmpR. Loss of the putative ampD orthologue atu2113 led to constitutive production of AmpC-dependent β-lactamase activity and ampicillin resistance. Finally, one cell wall remodeling enzyme, MltB3, was necessary for the AmpC-dependent β-lactamase activity, and its loss elicited ampicillin and carbenicillin sensitivity in the A. tumefaciens C58 and GV3101 strains. Furthermore, GV3101 ΔmltB3 transforms plants with efficiency comparable to that of the wild type but can be cleared with sublethal concentrations of ampicillin. The functional characterization of the genes involved in the inducible ampicillin resistance pathway of A. tumefaciens constitutes a major step forward in efforts to reduce the intrinsic antibiotic resistance of this bacterium. IMPORTANCE Agrobacterium tumefaciens, a significant biotechnological tool for production of transgenic plant lines, is highly resistant to a wide variety of antibiotics, posing challenges for various applications. One challenge is the efficient elimination of A. tumefaciens from transformed plant tissue without using levels of antibiotics that are toxic to the plants. Here, we present the functional characterization of genes involved in β-lactam resistance in A. tumefaciens. Knowledge about proteins that promote or inhibit β-lactam resistance will enable the development of strains to improve the efficiency of Agrobacterium-mediated plant genetic transformations. Effective removal of Agrobacterium from transformed plant tissue has the potential to maximize crop yield and food production, improving the outlook for global food security.
In vitro Activity of Lefamulin Against the Common Respiratory Pathogens Isolated From Mainland China During 2017–2019

Purpose Lefamulin is a novel antibiotic approved by the U.S. Food and Drug Administration in 2019 for the treatment of community-acquired bacterial pneumonia (CABP). In this study we evaluated the in vitro antimicrobial activity of lefamulin in order to better understand its antibiogram. Methods The test strains were isolated from patients across China during the period from 2017 to 2019, including 634 strains of respiratory pathogens. The minimum inhibitory concentrations (MICs) of lefamulin and comparators were determined by broth microdilution method. Results Lefamulin showed potent activity against Streptococcus pneumoniae and Staphylococcus evidenced by 100% inhibition at 0.25 mg/L, and favorable MIC50/90 (0.125/0.125 mg/L) against S. pneumoniae (penicillin MIC ≥ 2 mg/L), MIC50/90 (≤0.015/0.125 mg/L) against methicillin-resistant S. aureus, and MIC50/90 (≤0.015/0.06 mg/L) against methicillin-resistant S. epidermidis. Lefamulin also had good activity against Streptococcus pyogenes and Streptococcus agalactia (MIC50/90: ≤0.015/≤0.015 mg/L), β-lactamase-producing Haemophilus influenzae (MIC50/90: 0.5/1 mg/L), β-lactamase-negative H. influenzae (MIC50/90: 1/1 mg/L), Moraxella catarrhalis (MIC50/90: 0.25/0.25 mg/L), and Mycoplasma pneumoniae (MIC50/90: 0.03/0.03 mg/L) regardless of resistance to azithromycin. Lefamulin was generally more active than the comparators against the test strains. Conclusion In summary, lefamulin has good and broad-spectrum coverage of respiratory pathogens (methicillin-sensitive and -resistant Staphylococcus, S. pneumoniae, β-hemolytic Streptococcus, H. influenzae, M. catarrhalis and M. pneumoniae). In vitro activity supports the use of lefamulin in the treatment of CABP in China.
DNA damage and oxidizing conditions activate p53 through differential upstream signaling pathways

Stabilization and activation of the p53 tumour suppressor are triggered in response to various cellular stresses, including DNA damaging agents and elevated Reactive Oxygen Species (ROS) like H2O2. When cells are exposed to exogenously added H2O2, ATR/CHK1 and ATM/CHK2 dependent DNA damage signaling is switched on, suggesting that H2O2 induces both single and double strand breaks. These collective observations have resulted in the widely accepted model that oxidizing conditions lead to DNA damage that subsequently mediates a p53-dependent response like cell cycle arrest and apoptosis. However, H2O2 induces signaling through stress-activated kinases (SAPK, e.g., JNK and p38MAPK) that can activate p53. Here we dissect to what extent these pathways contribute to functional activation of p53 in response to oxidizing conditions. Collectively, our data suggest that p53 can be activated both by SAPK signaling and the DDR independently of each other, and which of these pathways is activated depends on the type of oxidant used. This implies that it could in principle be possible to modulate redox signaling to stimulate p53 without inducing collateral DNA damage, thereby limiting mutation accumulation in both healthy and tumor tissues.
PSO Feature Selection and ELM Algorithm for Protein Classification based Secondary Structure and Hydropathy Profile

It is important to recognize protein classes in order to understand folding patterns. In this paper, we have proposed a method to extract the features based on secondary structure sequence and hydropathy profile. A feature selection algorithm that combines particle swarm optimization and extreme learning machine was employed to select a total of 25 features. The selected features were fed to the classifier in order to classify each protein to an appropriate class. The well-known data sets, i
Outcomes of COVID-19 in Patients With Lung Cancer Treated in a Tertiary Hospital in Madrid

Background: Cancer patients represent a vulnerable population for COVID-19 illness. We aimed to analyze outcomes of lung cancer patients affected by COVID-19 in a tertiary hospital of a high-incidence region during the pandemic. Methods: We annotated 23 lung cancer patients consecutively diagnosed with COVID-19 at our institution (HGUGM; Madrid, Spain) between March 4th, 2020 and May 12th, 2020. Only patients with a confirmatory SARS-CoV-2 RT-PCR were included in the study. Results: All patients had at least 1 COVID-19 related symptom; cough (48%), shortness of breath (48%), fever (39%), and low-grade fever (30%) were the most common. Time from symptoms onset to first positive SARS-CoV-2 PCR was 5.5 days (range 1–17), with 13% of cases needed from a 2nd PCR to confirm diagnosis. There was a high variability on thoracic imaging findings, with multilobar pneumonia as the most commonly found pattern (74%). Main lab test abnormalities were low lymphocytes count (87%), high neutrophil to lymphocyte ratio -NLR- (78%), and elevated inflammatory markers: fibrinogen (91%), c-reactive protein -CRP- (87%), and D-dimer (70%). In our series, hospitalization rate was 74%, 39% of patients developed acute respiratory distress syndrome (ARDS), and the case-fatality rate was 35% (8/23). 87% of patients received anti-viral treatment (87% hydroxychloroquine, 74% lopinavir/ritonavir, 13% azithromycin), 43% corticosteroids, 26% interferon-β, 4% tocilizumab, and 82% of hospitalized patients received anticoagulation. High-oxygen requirements were needed in 39% of patients, but only 1 pt was admitted for invasive MV and was discharged 42 days after admission. Multiple variables related to tumor status, clinical baseline conditions, and inflammation markers were associated with mortality but did not remain statistically significant in a multivariate model. In patients with lung cancer receiving systemic therapy (n = 242) incidence and mortality from COVID-19 were 4.5, and 2.1%, respectively, with no differences found by type of treatment. Conclusions: Lung cancer patients represent a vulnerable population for COVID-19, according to the high rate of hospitalization, onset of ARDS, and high mortality rate. Although larger series are needed, no differences in mortality were found by type of cancer treatment. Measures to minimize the risk of SARS-CoV-2 infection remain key to protect lung cancer patients.
Phospho-β-catenin expression in primary and metastatic melanomas and in tumor-free visceral tissues

β-catenin (βcat) is an important downstream effector in the Wnt signaling pathway and plays an important role in the development and progression of many cancers including melanoma. βcat expression is regulated by GSK-3β-mediated phosphorylation at positions 33, 37 and 41. In normal cells, phosphorylation at these sites triggers proteasomal degradation, which in turn prevents accumulation of free cytoplasmic βcat. In cancer cells, stabilized β-catenin translocates into the nucleus, where it associates with TCF/Lef proteins to activate transcription of genes that promote tumorigenesis and metastasis. It has been suggested that nuclear phospho-βcat (pβcat) staining may be diagnostically useful in differentiating primary from metastatic melanoma. Also, a pβcat peptide (residues 30-39, p33) is naturally presented by melanoma cells as a T-cell target. We evaluated the expression of pS33-βcat in primary and metastatic melanoma tissues by immunohistochemistry. pS33-βcat was detected in primary and metastatic melanomas and was most commonly cytoplasmic and almost never exclusively nuclear. Interestingly, staining with pS33-βcat and pS33/37/T41-βcat antibodies was most intense in mitotic melanoma cells, consistent with prior studies demonstrating changes in the level of βcat during cell division. We observed no significant differences in pβcat staining location or intensity between primary and metastatic melanomas, suggesting that pβcat may have limited diagnostic or prognostic utility in melanoma. However, the high expression in dividing cells suggests promise as an immunotherapeutic target.
Toward Enhanced Fixation of CO2 in Aquatic Biomass: Focus on Microalgae

The need to reduce the CO2 footprint of human activities calls for the utilization of new means of production and new sources of products. Microalgae are a very promising source of a large variety of products, from fuels to chemicals for multiple industrial applications (e.g., dyes, pharmaceutical products, cosmetics, food and feed, new materials for high tech manufacture), and for processes such as wastewater treatment. Algae, as photosynthetic organisms, use light to energize the synthesis of organic matter and differently from most terrestrial plants, can be cultured on land that is not used for crop production. We describe the main factors contributing to microalgae productivity in artificial cultivation systems and discuss the research areas that still need investigation in order to pave the way to the generation of photosynthetic cell factories. We shall comment on the main caveats of the possible mode of improving photosynthetic efficiency and to optimize the partitioning of fixed C to products of commercial relevance. We address the problem of the selection of the appropriate strain and of the consequences of their diverse physiology and culture conditions for a successful commercial application. Finally, we shall provide state of the art information on cell factories chassis by means of synthetic biology approaches to produce chemicals of interest.
Linguistic Variation and Change in 250 Years of English Scientific Writing: A Data-Driven Approach

We trace the evolution of Scientific English through the Late Modern period to modern time on the basis of a comprehensive corpus composed of the Transactions and Proceedings of the Royal Society of London, the first and longest-running English scientific journal established in 1665. Specifically, we explore the linguistic imprints of specialization and diversification in the science domain which accumulate in the formation of “scientific language” and field-specific sublanguages/registers (chemistry, biology etc.). We pursue an exploratory, data-driven approach using state-of-the-art computational language models and combine them with selected information-theoretic measures (entropy, relative entropy) for comparing models along relevant dimensions of variation (time, register). Focusing on selected linguistic variables (lexis, grammar), we show how we deploy computational language models for capturing linguistic variation and change and discuss benefits and limitations.
The Role of Genetically Determined Glycemic Traits in Breast Cancer: A Mendelian Randomization Study

Background Circulating glycemic traits (GTs) have been considered a risk factor for breast cancer, but studies using GT-associated genetic variants as an instrumental variable are limited and inconclusive. Methods Our Mendelian Randomization analysis used the most recent genome-wide datasets focusing on European women. Results Of 44 single-nucleotide polymorphisms (SNPs) with GTs, 38 fasting-glucose and 6 fasting-insulin SNPs showed heterogeneous associations with breast cancer, without significant directional pleiotropy observed. Conclusion Our findings indicate a null association between genetically determined GTs and breast cancer risk among European women. Our findings may contribute to more complete characterizing of metabolic pathways in GTs and breast cancer.