Miracle-dz/UniFAR-FTUs huggingface dataset:
Spatial modulation of visual responses arises in cortex with active navigation

During navigation, the visual responses of neurons in mouse primary visual cortex (V1) are modulated by the animal’s spatial position. Here we show that this spatial modulation is similarly present across multiple higher visual areas but negligible in the main thalamic pathway into V1. Similar to hippocampus, spatial modulation in visual cortex strengthens with experience and with active behavior. Active navigation in a familiar environment, therefore, enhances the spatial modulation of visual signals starting in the cortex.
Presentation and formatting of laboratory results: a narrative review on behalf of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group “postanalytical phase” (WG-POST)

Abstract In laboratory medicine, much effort has been put into analytical quality in the past decades, making this medical profession one of the most standardized with the lowest rates of error. However, even the best analytical quality cannot compensate for errors or low quality in the pre or postanalytical phase of the total testing process. Guidelines for data reporting focus solely on defined data elements, which have to be provided alongside the analytical test results. No guidelines on how to format laboratory reports exist. The habit of reporting as much diagnostic data as possible, including supplemental information, may lead to an information overload. Considering the multiple tasks physicians have to do simultaneously, unfiltered data presentation may contribute to patient risk, as important information may be overlooked, or juxtaposition errors may occur. As laboratories should aim to answer clinical questions, rather than providing sole analytical results, optimizing formatting options may help improve the effectiveness and efficiency of medical decision-making. In this narrative review, we focus on the underappreciated topic of laboratory result reporting. We present published literature, focusing on the impact of laboratory result report formatting on medical decisions as well as approaches, potential benefits, and limitations for alternative report formats. We discuss influencing variables such as, for example, the type of patient (e.g. acute versus chronic), the medical specialty of the recipient of the report, the display of reference intervals, the medium or platform on which the laboratory report is presented (printed paper, within electronic health record systems, on handheld devices, etc.), the context in which the report is viewed in, and difficulties in formatting single versus cumulative reports. Evidence on this topic, especially experimental studies, is scarce. When considering the medical impact, it is of utmost importance that laboratories focus not only on the analytical aspects but on the total testing process. The achievement of high analytical quality may be of minor value if essential results get lost in overload or scattering of information by using a non-formatted tabular design. More experimental studies to define guidelines and to standardize effective and efficient reporting are most definitely needed.
The First Korean Case of NUP98-NSD1 and a Novel SNRK-ETV6 Fusion in a Pediatric Therapy-related Acute Myeloid Leukemia Patient Detected by Targeted RNA Sequencing

Ha Jin Lim , M.D.*, Jun Hyung Lee , M.D.*, Young Eun Lee , M.S., Hee-Jo Baek , M.D., Hoon Kook , M.D., Ju Heon Park , M.D., Seung Yeob Lee , M.D., Hyun-Woo Choi , M.D., Hyun-Jung Choi , M.D., Seung-Jung Kee , M.D., Jong Hee Shin , M.D., and Myung Geun Shin , M.D. Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, Hwasun, Korea; Brain Korea 21 Plus Project, Chonnam National University Medical School, Gwangju, Korea; Department of Pediatrics, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, Hwasun, Korea
CD36 and LC3B initiated autophagy in B cells regulates the humoral immune response

ABSTRACT Scavenger receptors are pattern recognition receptors that recognize both foreign and self-ligands, and initiate different mechanisms of cellular activation, often as co-receptors. The function of scavenger receptor CD36 in the immune system has mostly been studied in macrophages but it is also highly expressed by innate type B cells where its function is less explored. Here we report that CD36 is involved in macro-autophagy/autophagy in B cells, and in its absence, the humoral immune response is impaired. We found that CD36-deficient B cells exhibit a significantly reduced plasma cell formation, proliferation, mitochondrial mobilization and oxidative phosphorylation. These changes were accompanied by impaired initiation of autophagy, and we found that CD36 regulated autophagy and colocalized with autophagosome membrane protein MAP1LC3/LC3 (microtubule-associated protein 1 light chain 3). When we investigated T-cell-dependent immune responses, we found that mice with CD36 deficiency, specifically in B cells, exhibited attenuated germinal center responses, class switching, and antibody production as well as autophagosome formation. These findings establish a critical role for CD36 in B cell responses and may also contribute to our understanding of CD36-mediated autophagy in other cells as well as in B cell lymphomas that have been shown to express the receptor. Abbreviations: AICDA/AID: activation-induced cytidine deaminase; ATG5: autophagy related 5; ATP: adenosine triphosphate; BCR: B-cell receptor; CPG: unmethylated cytosine-guanosine; CQ: chloroquine; DC: dendritic cells; FOB: follicular B cells; GC: germinal center; Ig: immunoglobulin; LPS: lipopolysaccharide; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MFI: mean fluorescence intensity; MZB: marginal zone B cells; NP-CGG: 4-hydroxy-3-nitrophenylacetyl-chicken gamma globulin; OCR: oxygen consumption rate; oxLDL: oxidized low-density lipoprotein; PC: plasma cells; Rapa: rapamycin; SQSTM1/p62: sequestosome 1; SRBC: sheep red blood cells; Tfh: follicular helper T cells; TLR: toll-like receptor.
Amoebae can promote the survival of Francisella species in the aquatic environment

ABSTRACT Francisella tularensis, a tier 1 select agent, is the causative bacterium of tularemia, a zoonosis with a large animal reservoir. However, F. tularensis, like many other Francisella species, is assumed to have an aquatic reservoir. The mechanisms of Francisella species persistence in surface water remain poorly characterized. In this study, we deeply investigated the long-term interactions of the tularemia agent F. tularensis subsp. holarctica, F. novicida or F. philomiragia with amoebae of the Acanthamoeba species. In amoeba plate screening tests, all the Francisella species tested resisted the attack by amoebae. In in vitro infection models, intra-amoebic growth of Francisella varied according to the involved bacterial species and strains, but also the amoeba culture medium used. In co-culture models, the amoebae favoured Francisella survival over 16 days, which was likely dependent on direct contact between bacteria and amoebae for F. novicida and on amoeba-excreted compounds for F. novicida and for F. tularensis. In a spring water co-culture model, amoebae again enhanced F. novicida survival and preserved bacterial morphology. Overall, our results demonstrate that amoebae likely promote Francisella survival in aquatic environments, including the tularemia agent F. tularensis. However, bacteria-amoebae interactions are complex and depend on the Francisella species considered.
A Detailed Two-Dimensional Numerical Study of Spark Ignition Including Ionization

In this work, the spark–ignition (SI) of a methane/air mixture contained in a constant–volume chamber is investigated by numerical simulations. A cylinder–shaped vessel filled with a methane/air mixture containing two electrodes is used as simulation model. The impact of an electrical discharge at the electrodes on the surrounding gas is simulated, with detailed treatment of the ignition process involvig chemical kinetics, transport phenomena in the gas– phase and electrodynamical modeling of the interaction between spark and fuel/air mixture. For the calculations, a 2D–code to simulate the early stages of flame development, shortly after the breakdown discharge, has been developed. Computational results are shown for ignition of a methane air–mixture.
Head injury in mixed martial arts: a review of epidemiology, affected brain structures and risks of cognitive decline

ABSTRACT Background: The popularity trend of mixed martial arts (MMA) is steeply increasing, especially in the very young population. Unfortunately, MMA carries an enormous risk of head trauma. Purpose: The aim of this article is to provide review of studies on the association between head injuries and cognitive functions in MMA fighters. Methods: A systematic literature review was performed. Web of Science, PubMed, Springer, and Scopus databases were used. A total of 30 studies were identified. The inclusion criteria were as follows: studies with MMA fighters and head injuries and/or TKO/KO and/or reduction of cognitive functions in these fighters. Results: The results indicate that the incidence of head traumas ranges between 58% and 78% of all injuries. The King-Devick test seems to be a suitable rapid tool used in the studies to assess the extent of cognitive impairment. Among the detected studies, the post-fighting scores were significantly worse for fighters with head trauma during the match. We also found anomalies in MMA fighters in different brain structures, but it seems that the thalamus and caudate are the most affected. The impaired performance in processing speed, verbal memory and psychomotor speed is regularly confirmed in studies with MMA fighters. In addition, head traumatization seems to be a risk factor for the development of neurodegenerative disorders and it may be one of the possible causes of chronic traumatic encephalopathy (CTE). Several global medical societies have identified MMA as a violent and dangerous sport and have called for its ban – but unsuccessfully. Conclusion: Therefore, possible recommendations should include increased medical supervision of the fighter (during his career, but also after it) and the introduction of practical safety instructions for fighters to reduce the risk of developing CTE. With the increasing popularity of MMA, the risk of CTE should not be underestimated.
Design, Synthesis, Anticancer Activity, and Solid Lipid Nanoparticle Formulation of Indole- and Benzimidazole-Based Compounds as Pro-Apoptotic Agents Targeting Bcl-2 Protein

Cancer is a multifactorial disease necessitating identification of novel targets for its treatment. Inhibition of Bcl-2 for triggered pro-apoptotic signaling is considered a promising strategy for cancer treatment. Within the current work, we aimed to design and synthesize a new series of benzimidazole- and indole-based derivatives as inhibitors of Bcl-2 protein. The market pan-Bcl-2 inhibitor, obatoclax, was the lead framework compound for adopted structural modifications. The obatoclax’s pyrrolylmethine linker was replaced with straight alkylamine or carboxyhydrazine methylene linkers providing the new compounds. This strategy permitted improved structural flexibility of synthesized compounds adopting favored maneuvers for better fitting at the Bcl-2 major hydrophobic pocket. Anti-cancer activity of the synthesized compounds was further investigated through MTT-cytotoxic assay, cell cycle analysis, RT-PCR, ELISA and DNA fragmentation. Cytotoxic results showed compounds 8a, 8b and 8c with promising cytotoxicity against MDA-MB-231/breast cancer cells (IC50 = 12.69 ± 0.84 to 12.83 ± 3.50 µM), while 8a and 8c depicted noticeable activities against A549/lung adenocarcinoma cells (IC50 = 23.05 ± 1.45 and 11.63 ± 2.57 µM, respectively). The signaling Bcl-2 inhibition pathway was confirmed by molecular docking where significant docking energies and interactions with key Bcl-2 pocket residues were depicted. Moreover, the top active compound, 8b, showed significant upregulated expression levels of pro-apoptotic/anti-apoptotic of genes; Bax, Bcl-2, caspase-3, -8, and -9 through RT-PCR assay. Improving the compound’s pharmaceutical profile was undertaken by introducing 8b within drug-solid/lipid nanoparticle formulation prepared by hot melting homogenization technique and evaluated for encapsulation efficiency, particle size, and zeta potential. Significant improvement was seen at the compound’s cytotoxic activity. In conclusion, 8b is introduced as a promising anti-cancer lead candidate that worth future fine-tuned lead optimization and development studies while exploring its potentiality through in-vivo preclinical investigation.
Prominent Neutralizing Antibody Response Targeting the Ebolavirus Glycoprotein Subunit Interface Elicited by Immunization

The elicitation of sustained neutralizing antibody (nAb) responses against diverse ebolavirus strains remains a high priority for the vaccine field. The most clinically advanced rVSV-ZEBOV vaccine could elicit moderate nAb responses against only one ebolavirus strain, Zaire Ebola (EBOV), among the five ebolavirus strains, which last less than 6 months. ABSTRACT The severe death toll caused by the recent outbreak of Ebola virus disease reinforces the importance of developing ebolavirus prevention and treatment strategies. Here, we have explored the immunogenicity of a novel immunization regimen priming with vesicular stomatitis virus particles bearing Sudan Ebola virus (SUDV) glycoprotein (GP) that consists of GP1 and GP2 subunits and boosting with soluble SUDV GP in macaques, which developed robust neutralizing antibody (nAb) responses following immunizations. Moreover, EB46, a protective nAb isolated from one of the immune macaques, is found to target the GP1/GP2 interface, with GP binding mode and neutralization mechanism similar to those of a number of ebolavirus nAbs from human and mouse, indicating that the ebolavirus GP1/GP2 interface is a common immunological target in different species. Importantly, selected immune macaque polyclonal sera showed nAb specificity similar to that of EB46 at substantial titers, suggesting that the GP1/GP2 interface region is a viable target for ebolavirus vaccine. IMPORTANCE The elicitation of sustained neutralizing antibody (nAb) responses against diverse ebolavirus strains remains a high priority for the vaccine field. The most clinically advanced rVSV-ZEBOV vaccine could elicit moderate nAb responses against only one ebolavirus strain, Zaire Ebola (EBOV), among the five ebolavirus strains, which last less than 6 months. Boost immunization strategies are desirable to effectively recall the rVSV vector-primed nAb responses to prevent infections in prospective epidemics, while an in-depth understanding of the specificity of immunization-elicited nAb responses is essential for improving vaccine performance. Here, using nonhuman primate animal model, we demonstrated that booster immunization with a stabilized trimeric soluble form of recombinant glycoprotein derived from the ebolavirus Sudan strain following the priming rVSV vector immunization led to robust nAb responses that substantially map to the subunit interface of ebolavirus glycoprotein, a common B cell repertoire target of multiple species, including primates and rodents.
DEEP-UV CONFOCAL FLUORESCENCE IMAGING AND SUPER-RESOLUTION OPTICAL MICROSCOPY OF BIOLOGICAL SAMPLES

A wide range of techniques has been developed to image biological samples at high spatial and temporal resolution. In this paper, we report recent results from deep-UV confocal fluorescence microscopy to image inherent emission from fluorophores such as tryptophan, and structured illumination microscopy (SIM) of biological materials. One motivation for developing deep-UV fluorescence imaging and SIM is to provide methods to complement our measurements in the emerging field of X-ray coherent diffractive imaging.
Infection with Trypanosoma lewisi or Trypanosoma musculi may promote the spread of Toxoplasma gondii

Abstract Abstract Toxoplasma gondii can infect almost all warm-blooded vertebrates with pathogensis being largely influenced by the host immune status. As important epidemiological hosts, rodents are globally distributed and are also commonly found infected with haemoflagellates, such as those in the genus Trypanosoma. We here address whether and how co-infection with trypanosomes can influence T. gondii infection in laboratory models. Rats of five strains, co-infected with T. lewisi and mice of four strains, co-infected with T. musculi, were found to be more or less susceptible to T. gondii infection, respectively, with corresponding increased or decreased brain cyst burdens. Downregulation of iNOS expression and decreased NO production or reverse were observed in the peritoneal macrophages of rats or mice, infected with trypanosomes, respectively. Trypanosoma lewisi and T. musculi can modulate host immune responses, either by enhancement or suppression and influence the outcome of Toxoplasma infection.
Characterization and Genomic Analysis of ɸSHP3, a New Transposable Bacteriophage Infecting Stenotrophomonas maltophilia

S. maltophilia is an emerging global pathogenic bacterium that displays genetic diversity in both environmental and clinical strains. Transposable phages have long been known to improve the genetic diversity of bacterial strains by transposition. ABSTRACT This study describes a novel transposable bacteriophage, ɸSHP3, continuously released by Stenotrophomonas maltophilia strain c31. Morphological observation and genomic analysis revealed that ɸSHP3 is a siphovirus with a 37,611-bp genome that encodes 51 putative proteins. Genomic comparisons indicated that ɸSHP3 is a B3-like transposable phage. Its genome configuration is similar to that of Pseudomonas phage B3, except for the DNA modification module. Similar to B3-like phages, the putative transposase B of ɸSHP3 is a homolog of the type two secretion component ExeA, which is proposed to serve as a potential virulence factor. Moreover, most proteins of ɸSHP3 have homologs in transposable phages, but only ɸSHP3 carries an RdgC-like protein encoded by gene 3, which exhibits exonuclease activity in vitro. Two genes and their promoters coding for ɸSHP3 regulatory proteins were identified and appear to control the lytic-lysogenic switch. One of the proteins represses one promoter activity and confers immunity to ɸSHP3 superinfection in vivo. The short regulatory region, in addition to the canonical bacterial promoter sequences, displays one LexA and two CpxR recognition sequences. This suggests that LexA and the CpxR/CpxA two-component system might be involved in the control of the ɸSHP3 genetic switch. IMPORTANCE S. maltophilia is an emerging global pathogenic bacterium that displays genetic diversity in both environmental and clinical strains. Transposable phages have long been known to improve the genetic diversity of bacterial strains by transposition. More than a dozen phages of S. maltophilia have been characterized. However, no transposable phage infecting S. maltophilia has been reported to date. Characterization of the first transposable phage, ɸSHP3, from S. maltophilia will contribute to our understanding of host-phage interactions and genetic diversity, especially the interchange of genetic materials among S. maltophilia.
Determinants of severe acute malnutrition among under 5 children in Satar community of Jhapa, Nepal

Background Severe acute malnutrition (SAM) is the most extreme and visible form of undernutrition plagued by chronic poverty, household food insecurity, lack of education. One of the indigenous and marginalized community of Nepal, Satar/Santhal has often been neglected and is devoid of good education and are economically deprived. This predisposes under 5 children of Satar into malnutrition. The study aims to assess determinants of SAM among children under 5 years of age in Satar community of Jhapa district, Nepal. Material & methods A community based matched case control study was carried from September 2019 to February 2020 among under five children of Satar community residing in Jhapa district. Multistage random sampling technique was used to select 50 cases and 100 controls in the ratio of 1:2. Information was collected through personal interview with the parents and anthropometric measurement of the children was measured. Bivariate and multivariate conditional logistic regression analysis was used to explore the determinants of severe acute malnutrition. Results A total of 664 children between the age group of 6–59 months were screened for SAM. The prevalence of SAM was found 7.53%. Factors like, low economic status, birth interval less than 2 years, frequency of breast feeding <8 times/day and household food insecurity were found to be significant determinants of SAM. Multivariate logistic regression documented low economic status (AOR: 11.14, 95% CI 1.42 to 87.46); and frequency of breast feeding <8 times/day (AOR: 2.09, 95% CI 1.00 to 4.37) as determinants of SAM. Conclusion Low economic status and frequency of breast feeding less than 8times/day were major determinants of SAM among children under 5yrs of age. Ending malnutrition will require greater efforts and integrated approaches to eradicate extreme poverty. Multi-sector approaches have been conducting for SAM in Nepal but there are no specific approaches for marginalized community.
High expression of vinculin predicts poor prognosis and distant metastasis and associates with influencing tumor-associated NK cell infiltration and epithelial-mesenchymal transition in gastric cancer

In the process of epithelial-mesenchymal transition (EMT), epithelial cancer cells transdifferentiate into mesenchymal-like cells with high motility and aggressiveness, resulting in the spread of tumor cells. Immune cells and inflammation in the tumor microenvironment are the driving factors of EMT, but few studies have explored the core targets of the interaction between EMT and tumor immune cells. We analyzed thousands of cases of gastric cancer and gastric tissue specimens of TCGA, CPTAC, GTEx and analyzing QPCR and IHC data of 56 gastric cancer patients in SYSU Gastric Cancer Research Center. It was known that EMT has an important connection with the infiltration of NK cells, and that the expression of vinculin may be the target of the phenomenon. The increased expression of vinculin is closely related to the aggressiveness and distant metastasis of cancer, which affects the survival prognosis of the patient. Moreover, through in vitro experiments under 3D conditions, we found that vinculin, cell invasion and metastasis are clearly linked. VCL can affect EMT and tumor immunity by regulating EPCAM gene expression. The role and mechanism of action of vinculin have been controversial, but this molecule may downregulate EpCAM (epithelial cellular adhesion molecule) and its own role in gastric cancer through DNA methylation, causing NK cells to enrich into tumor cells and kill tumor cells. At the same time, it promotes the occurrence of EMT, which in turn causes tumor metastasis and thus poorer prognosis.