Miracle-dz/UniFAR-FTUs huggingface dataset:
Extracellular Vesicle Dissemination of Epidermal Growth Factor Receptor and Ligands and Its Role in Cancer Progression

Simple Summary Overexpression of the transmembrane protein, epidermal growth factor receptor (EGFR), drives tumour progression in several cancers including breast, lung, glioblastoma and head and neck cancers. In recent years, it has been shown that tumour cells can transfer EGFR to other tumour cells and non-tumour cells using extracellular vesicles (EVs). EVs are nano-sized vesicles secreted by cells and contain protein, RNA and DNA. The function of EVs is to send messages between cells which occurs in both healthy and diseased states. In this review, we will discuss how the transfer of EGFR and EGFR ligands by EVs in cancer can promote metastases, the formation of new tumour blood vessels and decrease the anti-tumour activity of immune cells. We will also discuss how EGFR contained in EVs can be used as a non-invasive diagnostic marker of cancer, and finally, how EVs can be re-engineered to promote targeting to EGFR expressing tumours. Abstract The epidermal growth factor receptor (EGFR) pathway functions through the autocrine or paracrine activation of cellular EGFR by a number of transmembrane ligands. Amplified or mutant EGFR can lead to tumour formation due to increased cell proliferation, growth, migration and survival signals. These oncogenic effects were thought to be confined to aberrant cells hosting genetic alterations in EGFR. However, in the past decade, numerous studies identified that tumour cells could harness extracellular vesicles (EVs) to disseminate EGFR, mutant EGFR, phosphorylated EGFR and EGFR ligands to local and distant cells. This functions to impart a pro-tumourigenic phenotype in recipient cells. EVs play an essential role in intracellular communication, through receptor signalling or the release of their intra-vesicular content into recipient cells. This review will discuss the role of EVs delivering EGFR or EGFR ligands either to or from tumour cells and how this can promote metastases, pre-metastatic niche formation, osteoclastogenesis, angiogenesis and immune modulation in cancer. We will examine how circulating EVs positive for EGFR may be exploited as diagnostic, prognostic or therapeutic markers in cancers including breast, lung, glioblastoma, ovarian and prostate. Finally, we will explore recent breakthroughs in bio-engineering EVs with EGFR targeting abilities for targeted drug delivery.
Investigation of Ctenocephalides felis on domestic dogs and Rickettsia felis infection in the Democratic Republic of Sao Tome and Principe

Rickettsia felis is an obligate intracellular Gram‐negative bacterium which causes flea‐borne spotted fever in humans. In the past decades, R. felis has been detected worldwide in Ctenocephalides felis fleas and various other arthropods. However, due to its shared symptoms with other common vector‐borne diseases, human infection is prone to be underestimated or misdiagnosed, especially in the malaria‐endemic areas including sub‐Saharan Africa, where confirmatory laboratory diagnoses are not usually available. In this study, a ‘One Health’ approach was adopted to explore potential vector‐borne and zoonotic pathogens in the Democratic Republic of Sao Tome and Principe (DRSTP), an island nation in the Gulf of Guinea. By collaborating with local veterinarians, 1,187 fleas were collected from 95 domestic dogs across the country and later identified as Ct. felis using taxonomic keys. A cytochrome oxidase gene‐based phylogenetic analysis revealed that all collected fleas belonged to a single haplotype and were identical to isolates from Ivory Coast and Brazil that clustered into a clade of tropical distribution. Additional samples of 14 chigoe fleas (Tunga penetrans) were collected from the surrounding environment of the dogs’ resting spots. Rickettsia felis infection in fleas was examined by molecular methods targeting the citrate synthase (gltA)‐ and outer membrane protein A (ompA)‐coding genes as well as the R. felis‐specific pRF plasmid. The bacterial DNA was detected in 21.01% (146/695) of cat fleas but none of the chigoe fleas. Microimmunofluorescence assay was then performed to assess pathogen exposure of the residents. Of 240 dried blood spots from participants with dog contacts, 8 (3.33%) exhibited R. felis antibodies. Our findings demonstrated the presence of R. felis in DRSTP. Further extensive epidemiological studies regarding its prevalence and its role in causing febrile illness while the nation is entering pre‐elimination stage of malaria will be carried out.
Cultivated Land Change, Driving Forces and Its Impact on Landscape Pattern Changes in the Dongting Lake Basin

Comprehending the dynamic change characteristics of land use/cover and the driving factors causing the change are prerequisites for protecting land resources. This paper analyzes changes in cultivated land, the driving factors that cause them, and their tremendous impact on landscape pattern changes in the Dongting Lake Basin. For this purpose, we used mathematical statistics, buffer analysis, trend analysis, landscape pattern index, and logistic regression model to analyze the land use data of the study area from 1980 to 2018. The results show that the cultivated land showed a decreasing trend, with the total area decreased by 4.76% (or 716.13 km2) from 1980 to 2018, and the activity of mutual transformation with other land use types decreased. The spatial distribution pattern of cultivated land and landscape shows the change characteristics gradually from Dongting Lake to the surroundings. Among the driving factors of cultivated land changes, the influence of human activities was gradually increasing, while the natural factors were decreasing. The cultivated land landscape pattern index and the overall landscape pattern index have a significant positive correlation, showing relatively consistent change trend and spatial distribution characteristics. We believe that the decrease of cultivated land area has a certain relationship with the increase of landscape fragmentation in the Dongting Lake Basin. Our research is expected to provide a reference for strengthening regional cultivated land management and rational development and utilization of regional land resources.
Puerarin sensitized K562/ADR cells by inhibiting NF‐κB pathway and inducing autophagy

Puerarin is an isoflavone isolated from Pueraria lobata (Willd.) Ohwi. In the present study, reversal effect and underlying mechanisms of puerarin on multidrug resistance (MDR) were investigated in K562/ADR cells. K562/ADR cells exhibited adriamycin (ADR) resistance and higher levels of MDR1 expression compared with K562 cells. Puerarin enhanced the chemosensitivity of K562/ADR cells and increased the ADR accumulation in K562/ADR cells. The expression levels of MDR1 were down‐regulated by puerarin in K562/ADR cells. Luciferase reporter assay further demonstrated the inhibitory effect of puerarin on TNF‐α‐induced NF‐κB activation. The phosphorylation of IκB‐α was significantly suppressed by puerarin. In silico docking analyses suggested that puerarin well matched with the active sites of IκB‐α. Moreover, a large number of autophagosomes were found in the cytoplasm of K562/ADR cells after puerarin treatment. The significant increase in LC3‐II and beclin‐1 was also observed, indicating autophagy induction by puerarin in K562/ADR cells. Puerarin induced cell cycle arrest and apoptosis in K562/ADR cells. Finally, puerarin inhibited phosphorylation of Akt and JNK. In conclusion, puerarin‐sensitized K562/ADR cells by downregulating MDR1 expression via inhibition of NF‐κB pathway and autophagy induction via Akt inhibition.
The Impact of the COVID‐19 Pandemic on Cardiac Electrophysiology Training: A Survey Study

The coronavirus disease 2019 (COVID‐19) pandemic has resulted in a significant decrease in volume of electrophysiology (EP) procedures. There has been concern that trainees may not achieve the procedural numbers required to graduate as independent electrophysiologists within the usual timeline. We sought to determine the impact of the COVID‐19 pandemic on the percentage of clinical cardiac EP (CCEP) fellows in jeopardy of not meeting procedural volume requirements and overall sentiments regarding preparedness of fellows for independent practice.
Pulse Consumption among Portuguese Adults: Potential Drivers and Barriers towards a Sustainable Diet

The transition from diets rich in animal products to plant-based protein foods—like pulses—is crucial, for both environmental sustainability and human health. The aim of this study was to characterize the current consumption and to describe the drivers of and barriers to pulse intake in Portugal. Using a quantitative approach, a semi-structured questionnaire was distributed online, and 1174 valid responses were obtained. The most consumed pulses were beans and peas, consumed at least once a week by 48.3% and 44.4% of the sample, respectively. When participants were asked about the possibility of replacement, even partially, of animal products for pulses, 15.0% stated they would not substitute even in a food scarcity scenario. In the qualitative study, ten individuals involved at different steps of pulses’ supply and value chain were interviewed in order to study individual behaviors and experiences linked knowledge and consumption of pulses. It was noticed that the lack of recognition of their nutritional value, the high cooking time and the effect of the anti-nutritional factors were commonly pointed out as barriers. The identification and understanding of perceived barriers for that low consumption will leverage the development of new strategies to promote this promising alternative.
Healthy Living and Co-Production: Evaluation of Processes and Outcomes of a Health Promotion Initiative Co-Produced with Adolescents

Co-production is an approach to designing, delivering, and evaluating public services through strict collaboration among professionals and the people using services with an equal and reciprocal relationship. Health promotion initiatives that include education services rarely use the co-production approach. Nevertheless, the value of co-production is widely recognized, although it is considered a normative good, and scarce and mixed evidence is available in literature. The purpose of this paper is to provide evidence supporting the hypothesis that a co-production approach, applied to an intervention for preventing obesity, can be effective and efficient. To this end, an evaluation of the processes, outputs meant as intermediate results, and behavioral and economic outcomes of a public health-promotion initiative co-produced and co-delivered with adolescents (beFood) was conducted. Mixed methods were used, including field-observations, two self-reported questionnaires, and an opportunity–cost analysis that compared beFood to traditional approaches of public health promotion. The co-production model was successfully implemented and appears to be effective—more than 5000 adolescents were reached by only 49 co-producer adolescents, who reported behavioral changes (e.g., eating better and practicing more physical activity). The cost analysis showed that the co-production approach was also efficient, producing relevant savings and potentially making available more than 3000 h of professionals’ time. This research can support a re-thinking of public institutions’ organization, public initiatives’ design, and public servants’ role.
Development of Test Equipment for Pedestrian-Automatic Emergency Braking Based on C-NCAP (2018)

In order to evaluate the effectiveness of a pedestrian-automatic emergency braking (PAEB) system on pedestrian protection, a set of PAEB test equipment was developed according to the test requirement of China-New Car Assessment Program (C-NCAP) (2018) in this study. In the aspect of system control strategy, global positioning system (GPS) differential positioning was used to achieve the required measurement and positioning accuracy, the collaborative control between the PAEB test equipment and automated driving robot (ADR) was achieved by wireless communication, and the motion state of the dummy target in the PAEB system was controlled by using the S-shaped-curve velocity control method. Part of the simulations and field tests were conducted according to the scenario requirements specified in C-NCAP (2018). The experimental and simulated results showed that the test equipment demonstrated high accuracy and precision in the process of testing, the dummy target movement was smooth and stable, complying with the requirements of PAEB tests set forth in C-NCAP (2018), and yielding satisfactory results as designed. Subsequently, the performance of the AEB of a vehicle under test (VUT) was conducted and the score for star-rating to evaluate the performance level of AEB calculated. Results indicated the developed test equipment in this study could be used to evaluate the performance of the PAEB system with effectiveness.
Cardiac and Metabolic Impact of Functional Foods with Antioxidant Properties Based on Whey Derived Proteins Enriched with Hemp Seed Oil

The impaired ability to feed properly, evident in oncologic, elderly, and dysphagic patients, may result in malnutrition and sarcopenia. Increasing the consumption of dietary proteins by functional foods and enriching their composition by adding beneficial nutrients may represent an adjuvant therapy. We aimed to evaluate the safety and the positive effects of a standard diet (SD) supplemented with whey-derived protein puddings (WDPP), with appropriate rheological properties, and hemp seed oil (HSO), rich in polyphenols. Rats were assigned to SD, WDPP, WDPP plus hemp seed oil (HSOP), and HSO supplemented diets for eight weeks. “Anthropometric”, metabolic, and biochemical variables, oxidative stress, tissue injury, liver histology, and cardiac susceptibility to ischemia/reperfusion were analyzed. All the supplementations did not induce significant changes in biochemical and metabolic variables, also in relation to glucose tolerance, and livers did not undergo morphological alteration and injury. An improvement of cardiac post-ischemic function in the Langendorff perfused heart model and a reduction of infarct size were observed in WDPP and HSOP groups, thanks to their antioxidant effects and the activation of Akt- and AMPK-dependent protective pathways. Data suggest that (i) functional foods enriched with WDPP and HSOP may be used to approach malnutrition and sarcopenia successfully under disabling conditions, also conferring cardioprotection, and that (ii) adequate rheological properties could positively impact dysphagia-related problems.
Neuron Loss in Alzheimer’s Disease: Translation in Transgenic Mouse Models

Transgenic mouse models represent an essential tool for the exploration of Alzheimer’s disease (AD) pathological mechanisms and the development of novel treatments, which at present provide only symptomatic and transient effects. While a variety of mouse models successfully reflects the main neuropathological hallmarks of AD, such as extracellular amyloid-β (Aβ) deposits, intracellular accumulation of Tau protein, the development of micro- and astrogliosis, as well as behavioral deficits, substantial neuron loss, as a key feature of the disease, seems to be more difficult to achieve. In this review, we summarize information on classic and more recent transgenic mouse models for AD, focusing in particular on loss of pyramidal, inter-, and cholinergic neurons. Although the cause of neuron loss in AD is still a matter of scientific debate, it seems to be linked to intraneuronal Aβ accumulation in several transgenic mouse models, especially in pyramidal neurons.
Profiles of Pediatric Leprosy: A Report from a University Hospital of Nepal in the Post-Elimination Era.

Because pediatric leprosy strongly indicates continuous disease transmission in the community, knowing the profiles of pediatric leprosy is of great value for a leprosy-free world. We conducted this study to assess the clinical profiles of pediatric leprosy in Nepal. This retrospective study analyzed the 7-year record from 2011 to 2017. There were a total of 68 pediatric leprosy cases. Male (63.2%) cases outnumbered female cases. The minimum age of the leprosy-affected children was 6 years, with the mean age 12.17 (±1.95) years. Contact history was present in 26 (38.2%) children. Most of them (83.8%) had positive slit-skin smear. Lepra reaction was present in 14.7%. Nine had a disability, with 4/9 (44.4%) of them having grade 2 disability. More than two-thirds (70.6%) were multi-bacillary cases. Some (2.9%) even had lepromatous leprosy. Leprosy continues to be a disease of concern in the post-elimination era even in the pediatric population.
Selection of DNA Aptamers for Subcellular Localization of RBSDV P10 Protein in the Midgut of Small Brown Planthoppers by Emulsion PCR-Based SELEX

Rice black-streaked dwarf virus (RBSDV), classified under the Reoviridae, Fijivirus genus, caused an epidemic in the eastern provinces of China and other East Asian countries and resulted in severe yield loss in rice and wheat production. RBSDV is transmitted by the small brown planthopper (SBPH, Laodelphax striatellus Fallén) in a persistent manner. In order to provide a stable and cost-effective detection probe, in this study we selected three DNA aptamers (R3, R5 and R11) by an optimized, standardized and time saving emulsion PCR-based SELEX, for the detection of RBSDV outer-shell P10 protein for in situ localization studies in the midgut of SBPH. The specificity of these three DNA aptamers was tested through detection of the P10 protein using an enzyme-linked oligonucleotide assay (ELONA) and aptamer-based dot-blot ELISA. All three DNA aptamers can be used to detect RBSDV P10 protein by immunofluorescent labeling in the midgut of RBSDV-infected SBPH. These data show that the selected aptamers can be used for the detection of RBSDV P10 protein in vitro and in vivo. This is the first report of aptamers being selected for detection of a rice virus capsid protein.
Characteristics and outcomes of hospitalised patients with acute kidney injury and COVID-19

Introduction COVID-19 has spread globally to now be considered a pandemic by the World Health Organisation. Initially patients appeared to have a respiratory limited disease but there are now increasing reports of multiple organ involvement including renal disease in association with COVID-19. We studied the development and outcomes of acute kidney injury (AKI) in patients with COVID-19, in a large multicultural city hospital trust in the UK, to better understand the role renal disease has in the disease process. Methods This was a retrospective review using electronic records and laboratory data of adult patients admitted to the four Manchester University Foundation Trust Hospitals between March 10 and April 30 2020 with a diagnosis of COVID-19. Records were reviewed for baseline characteristics, medications, comorbidities, social deprivation index, observations, biochemistry and outcomes including mortality, admission to critical care, mechanical ventilation and the need for renal replacement therapy. Results There were 1032 patients included in the study of whom 210 (20.3%) had AKI in association with the diagnosis of COVID-19. The overall mortality with AKI was considerably higher at 52.4% compared to 26.3% without AKI (p-value <0.001). More patients with AKI required escalation to critical care (34.8% vs 11.2%, p-value <0.001). Following admission to critical care those with AKI were more likely to die (54.8% vs 25.0%, p-value <0.001) and more likely to require mechanical ventilation (86.3% vs 66.3%, p-value 0.006). Discussion We have shown that the development of AKI is associated with dramatically worse outcomes for patients, in both mortality and the requirement for critical care. Patients with COVID-19 presenting with, or at risk of AKI should be closely monitored and appropriately managed to prevent any decline in renal function, given the significant risk of deterioration and death.
Distinguishing Non-Small Cell Lung Cancer Subtypes in Fine Needle Aspiration Biopsies by Desorption Electrospray Ionization Mass Spectrometry Imaging.

BACKGROUND Distinguishing adenocarcinoma and squamous cell carcinoma subtypes of non-small cell lung cancers is critical to patient care. Preoperative minimally-invasive biopsy techniques, such as fine needle aspiration (FNA), are increasingly used for lung cancer diagnosis and subtyping. Yet, histologic distinction of lung cancer subtypes in FNA material can be challenging. Here, we evaluated the usefulness of desorption electrospray ionization mass spectrometry imaging (DESI-MSI) to diagnose and differentiate lung cancer subtypes in tissues and FNA samples. METHODS DESI-MSI was used to analyze 22 normal, 26 adenocarcinoma, and 25 squamous cell carcinoma lung tissues. Mass spectra obtained from the tissue sections were used to generate and validate statistical classifiers for lung cancer diagnosis and subtyping. Classifiers were then tested on DESI-MSI data collected from 16 clinical FNA samples prospectively collected from 8 patients undergoing interventional radiology guided FNA. RESULTS Various metabolites and lipid species were detected in the mass spectra obtained from lung tissues. The classifiers generated from tissue sections yielded 100% accuracy, 100% sensitivity, and 100% specificity for lung cancer diagnosis, and 73.5% accuracy for lung cancer subtyping for the training set of tissues, per-patient. On the validation set of tissues, 100% accuracy for lung cancer diagnosis and 94.1% accuracy for lung cancer subtyping were achieved. When tested on the FNA samples, 100% diagnostic accuracy and 87.5% accuracy on subtyping were achieved per-slide. CONCLUSIONS DESI-MSI can be useful as an ancillary technique to conventional cytopathology for diagnosis and subtyping of non-small cell lung cancers.
Cell Wall Composition as a Marker of the Reprogramming of the Cell Fate on the Example of a Daucus carota (L.) Hypocotyl in Which Somatic Embryogenesis Was Induced

Changes in the composition of the cell walls are postulated to accompany changes in the cell’s fate. We check whether there is a relationship between the presence of selected pectic, arabinogalactan proteins (AGPs), and extensins epitopes and changes in cell reprogramming in order to answer the question of whether they can be markers accompanying changes of cell fate. Selected antibodies were used for spatio-temporal immunolocalization of wall components during the induction of somatic embryogenesis. Based on the obtained results, it can be concluded that (1) the LM6 (pectic), LM2 (AGPs) epitopes are positive markers, but the LM5, LM19 (pectic), JIM8, JIM13 (AGPs) epitopes are negative markers of cells reprogramming to the meristematic/pluripotent state; (2) the LM8 (pectic), JIM8, JIM13, LM2 (AGPs) and JIM11 (extensin) epitopes are positive markers, but LM6 (pectic) epitope is negative marker of cells undergoing detachment; (3) JIM4 (AGPs) is a positive marker, but LM5 (pectic), JIM8, JIM13, LM2 (AGPs) are negative markers for pericycle cells on the xylem pole; (4) LM19, LM20 (pectic), JIM13, LM2 (AGPs) are constitutive wall components, but LM6, LM8 (pectic), JIM4, JIM8, JIM16 (AGPs), JIM11, JIM12 and JIM20 (extensins) are not constitutive wall components; (5) the extensins do not contribute to the cell reprogramming.