Miracle-dz/UniFAR-FTUs huggingface dataset:
Data enabled prediction analysis assigns folate/biopterin transporter (BT1) family to 36 hypothetical membrane proteins in Leishmania donovani

Leishmaniasis is a neglected tropical disease caused by the pathogenic protozoan Leishmania donovani and it is transmitted by an infected sand fly. Approximately 0.4 million cases of Visceral Leishmaniasis are reported across the globe every year, of which 67% is from the Indian subcontinent. The currently available drugs have not been effective owing to their high toxicity levels, inadequate specificity, drug resistance, extended treatment periods and/or prohibitive prices. For this reason, hypothetical proteins in this pathogen, which constitute about 67% of its proteome, must be distinctly characterized and studied for their potential role as drug targets for Leishmaniasis. Domain information from PFAM and functional information from GO has been used to assign putative functions to 36 hypothetical membrane proteins in this protozoan. Furthermore, as a case study, we have performed a thorough sequence level characterization of a hypothetical protein E9BPD7 from the BT1 family of membrane proteins that transports folate/biopterin. Phylogenetic analyses of E9BPD7 have revealed interesting evolutionary correlations to BT1 family and MFS superfamily, which have significant roles in a number of diseases and drug resistance pathways.
The Association of Perioperative Serum Lactate Levels with Postoperative Delirium in Elderly Trauma Patients

Background Several studies have shown the utility of lactate level as a predictor of early outcomes in trauma patients. We conducted this study to evaluate the association of perioperative serum lactate levels with postoperative delirium (POD) in elderly trauma patients. Materials and Methods This study included 466 elderly trauma patients with measurements of serum lactate levels on admission and 1 h after surgery. The associations of POD with serum lactate levels (on admission and 1 h after surgery) and lactate clearance were analyzed using Kendall's correlation. Perioperative serum lactate levels and lactate clearance as predictors of POD were evaluated using univariate and multivariable analyses. Results The incidence of POD in the present study was 38.1%. Serum lactate levels on admission and at 1 h after surgery were significantly higher in major trauma than in minor trauma. In univariate analysis of perioperative serum lactate levels and lactate clearance as predictors of POD, the odds ratio (OR) for serum lactate level on admission was 4.19 (P < 0.01, 2.91 < 95% confidence interval (CI) < 6.02) and that 1 h after surgery was 3.83 (P < 0.01, 2.79 < 95% CI < 5.25); however, the OR for serum change of lactate level was 0.99 ((P < 0.09, 0.99 < 95% CI < 1.00). In multivariable analysis for predictors of POD, the OR for serum lactate level on admission was 2.40 (P < 0.09, 0.87 < 95% CI < 6.7), that for serum lactate 1 h after surgery was 2.83 (P=0.01, 1.28 < 95% CI < 6.24), that for ICU admission was 3.01 (P=0.01, 2.09 < 95% CI < 6.03), and that for ISS was 1.47 (P < 0.01, 1.27 < 95% CI < 3.70). Conclusions Taking together the results of univariate and multivariable analyses, serum lactate level 1 h after surgery may be used as a prediction model of POD development in elderly trauma patients.
Myoferlin, a Membrane Protein with Emerging Oncogenic Roles

Myoferlin (MYOF), initially identified in muscle cells, is a member of the Ferlin family involved in membrane fusion, membrane repair, and membrane trafficking. Dysfunction of this protein is associated with muscular dysfunction. Recently, a growing body of studies have identified MYOF as an oncogenic protein. It is overexpressed in a variety of human cancers and promotes tumorigenesis, tumor cell motility, proliferation, migration, epithelial to mesenchymal transition, angiogenesis as well as metastasis. Clinically, MYOF overexpression is associated with poor outcome in various cancers. It can serve as a prognostic marker of human malignant disease. MYOF drives the progression of cancer in various processes, including surface receptor transportation, endocytosis, exocytosis, intercellular communication, fit mitochondrial structure maintenance and cell metabolism. Depletion of MYOF demonstrates significant antitumor effects both in vitro and in vivo, suggesting that targeting MYOF may produce promising clinical benefits in the treatment of malignant disease. In the present article, we reviewed the physiological function of MYOF as well as its role in cancer, thus providing a general understanding for further exploration of this protein.
Five New Meroterpenoids from the Fruiting Bodies of the Basidiomycete Clitocybe clavipes with Cytotoxic Activity

Five new meroterpenoids, clavipols A–B (1–2) with a 12-membered ether ring and clavilactones G–I (3–5) having a 10-membered carbocycle connected to a hydroquinone and an α,β-epoxy/unsaturated lactone, were obtained from the fruiting bodies of the basidiomycete Clitocybe clavipes. Their structures were determined by comprehensive analysis of their spectroscopic data, and the absolute configuration of 1 was established by quantum chemical calculations of electronic circular dichroism (ECD). All the isolated compounds (1–5) were tested for their cytotoxic activity against three human tumor cell lines (Hela, SGC-7901, and SHG-44) in vitro after treatment for 48 h. Compound 4 exhibited moderate cytotoxic activity against Hela and SGC-7901 tumor cell lines, with IC50 values of 23.5 and 14.5 µM, respectively.
Optimization of Polyethylene Glycol-Mediated Transformation of the Pepper Anthracnose Pathogen Colletotrichum scovillei to Develop an Applied Genomics Approach

Colletotrichum acutatum is a species complex responsible for anthracnose disease in a wide range of host plants. Strain C. acutatum KC05, which was previously isolated from an infected pepper in Gangwon Province of South Korea, was reidentified as C. scovillei using combined sequence analyses of multiple genes. As a prerequisite for understanding the pathogenic development of the pepper anthracnose pathogen, we optimized the transformation system of C. scovillei KC05. Protoplast generation from young hyphae of KC05 was optimal in an enzymatic digestion using a combined treatment of 2% lysing enzyme and 0.8% driselase in 1 M NH4Cl for 3 h incubation. Prolonged incubation for more than 3 h decreased protoplast yields. Protoplast growth of KC05 was completely inhibited for 4 days on regeneration media containing 200 μg/ml hygromycin B, indicating the viability of this antibiotic as a selection marker. To evaluate transformation efficiency, we tested polyethylene glycol-mediated protoplast transformation of KC05 using 19 different loci found throughout 10 (of 27) scaffolds, covering approximately 84.1% of the entire genome. PCR screening showed that the average transformation efficiency was about 17.1% per 100 colonies. Southern blot analyses revealed that at least one transformant per locus had single copy integration of PCR-screened positive transformants. Our results provide valuable information for a functional genomics approach to the pepper anthracnose pathogen C. scovillei.
Genomics Analysis of Metabolic Pathways of Human Stem Cell-Derived Microglia-Like Cells and the Integrated Cortical Spheroids

Brain spheroids or organoids derived from human pluripotent stem cells (hiPSCs) are still not capable of completely recapitulating in vivo human brain tissue, and one of the limitations is lack of microglia. To add built-in immune function, coculture of the dorsal forebrain spheroids with isogenic microglia-like cells (D-MG) was performed in our study. The three-dimensional D-MG spheroids were analyzed for their transcriptome and compared with isogenic microglia-like cells (MG). Cortical spheroids containing microglia-like cells displayed different metabolic programming, which may affect the associated phenotype. The expression of genes related to glycolysis and hypoxia signaling was increased in cocultured D-MG spheroids, indicating the metabolic shift to aerobic glycolysis, which is in favor of M1 polarization of microglia-like cells. In addition, the metabolic pathways and the signaling pathways involved in cell proliferation, cell death, PIK3/AKT/mTOR signaling, eukaryotic initiation factor 2 pathway, and Wnt and Notch pathways were analyzed. The results demonstrate the activation of mTOR and p53 signaling, increased expression of Notch ligands, and the repression of NF-κB and canonical Wnt pathways, as well as the lower expression of cell cycle genes in the cocultured D-MG spheroids. This analysis indicates that physiological 3-D microenvironment may reshape the immunity of in vitro cortical spheroids and better recapitulate in vivo brain tissue function for disease modeling and drug screening.
Excess Glutamate May Cause Dilation of Retinal Blood Vessels in Glutamate/Aspartate Transporter-Deficient Mice

Purpose To investigate the longitudinal findings of fundus features and spectral-domain optical coherence tomography (SD-OCT) to characterize the morphologic features in a mouse model of defective glutamate/aspartate transporter (GLAST−/− mice). Materials and Methods The fundus findings and SD-OCT images were longitudinally recorded at five time points from postnatal (P) 22 to P156 in GLAST−/− mice. As a control wild type, age-matched C57BL/6J mice were employed. The mouse retina was subdivided into five layers, and the thickness of each layer was longitudinally measured by InSight® using SD-OCT pictures. The SD-OCT findings were compared with the histologic appearances. The diameter of the retinal blood vessels was measured by the ImageJ® software program using SD-OCT images. The data were statistically compared between both age-matched mouse groups. Results The retinal blood vessels appeared more dilated in GLAST−/− mice than in wild-type mice. This tendency was statistically significant at all time points after P44 by analyses using SD-OCT images. The ganglion cell complex (GCC) and outer nuclear layer (ONL) were significantly thinner in GLAST−/− mice at all time points after P80 than in the wild-type mice. This tendency was more clearly indicated by SD-OCT than histologic sections. Discussion In the present study, we found for the first time the dilation of the retinal blood vessels and the thinning of the ONL in GLAST−/− mice, in addition to the thinning of the GCC.
Connection the Rhizomicrobiome and Plant MAPK Gene Expression Response to Pathogenic Fusarium oxysporum in Wild and Cultivated Soybean

Little known the connections between soybeans mitogen-activated protein kinase (MAPK) gene expression and the rhizomicrobiome upon invasion of the root pathogen Fusarium oxysporum. To address this lack of knowledge, we assessed the rhizomicrobiome and root transcriptome sequencing of wild and cultivated soybean during the invasion of F. oxysporum. Results indicated F. oxysporum infection enriched Bradyrhizobium spp. and Glomus spp. and induced the expression of more MAPKs in the wild soybean than cultivated soybean. MAPK gene expression was positively correlated with Pseudomonadaceae but negatively correlated with Sphingomonadaceae and Glomeraceae in both cultivated and wild soybean. Specifically, correlation profiles revealed that Pseudomonadaceae was especially correlated with the induced expression of GmMAKKK13-2 (Glyma.14G195300) and GmMAPK3-2 (Glyma.12G073000) in wild and cultivated soybean during F. oxysporum invasion. Main fungal group Glomeraceae was positively correlated with GmMAPKKK14-1 (Glyma.18G060900) and negatively correlated with GmRaf6-4 (Glyma.02G215300) in the wild soybean response to pathogen infection; while there were positive correlations between Hypocreaceae and GmMAPK3-2 (Glyma.12G073000) and between Glomeraceae and GmRaf49-3 (Glyma.06G055300) in the wild soybean response, these correlations were strongly negative in the response of cultivated soybean to F. oxysporum. Taken together, MAPKs correlated with different rhizomicrobiomes indicating the host plant modulated by the host self-immune systems in response to F. oxysporum.
Janus kinase inhibitors for the treatment of rheumatoid arthritis demonstrate similar profiles of in vitro cytokine receptor inhibition

Janus kinase (JAK) inhibitors have emerged as an effective class of therapies for various inflammatory diseases such as rheumatoid arthritis (RA). JAK inhibitors function intracellularly by modulating the catalytic activity of JAKs and disrupting the receptor‐mediated signaling of multiple cytokines and growth factors, including those with pro‐inflammatory activity. Understanding the inhibition profiles of different JAK inhibitors, based on the associated cytokine receptors and downstream inflammatory pathways affected, is important to identify the potential mechanisms for observed differences in efficacy and safety. This study applied an integrated modeling approach, using in vitro whole blood cytokine inhibition potencies and plasma pharmacokinetics, to determine JAK‐dependent cytokine receptor inhibition profiles, in the context of doses estimated to provide a similar clinical response in RA clinical trials. The calculated profiles of cytokine receptor inhibition for the JAK inhibitors tofacitinib, baricitinib, upadacitinib, and filgotinib and its metabolite, were generally similar when clinically efficacious doses for RA were considered. Only minor numerical differences in percentage cytokine receptor inhibition were observed, suggesting limited differentiation of these inhibitors based on JAK pharmacology, with each showing a differential selectivity for JAK1 heterodimer inhibition. Nevertheless, only robust clinical testing involving head‐to‐head studies will ultimately determine whether there are clinically meaningful differences between these JAK inhibitors. Furthermore, ongoing and future research into inhibitors with alternative JAK selectivity remains of clinical importance. Thus, all JAK inhibitors should be characterized via thorough preclinical, metabolic and pharmacological evaluation, adequate long‐term clinical data, and when available, real‐world experience.
The Rheology of Saliva

The rheology of saliva affects the coating and lubrication of oral surfaces and the consistency of ingested foods. Salivary gland dysfunction can cause tissue damage and dysphagia. Therefore, we have considered the problem of designing a synthetic saliva for medical management. Also, we have measured certain rheological properties [shear-dependent viscosity η (k)] and the frequency-dependent moduli [G′(f) and η′(f)] of normal stimulated whole saliva. Analysis of the rheological data and consideration of requirements for using artificial saliva have resulted in a better understanding of the rheological functions of natural saliva and the desirable characteristics of synthetic saliva. In addition, we have measured rheological properties of two commercial saliva substitutes for comparison.
SUPPLEMENT

Verbal Learning Tasks: An ENIGMA Mega-Analysis. Table S1: Summary characteristics of the underlying datasets (citations) (C = Control, LC = LIMBIC-CENC) Full Cohort descriptions are available in Supplementary Table S1. NDA datasets refer to multiple individual studies from the NIMH Data Archive. ‘Mean Total Raw Score’ refers to the raw sum of trials over the number of exposures in the learning portion of the tests. *No individual reference because data come from multiple studies.
Acoustic emission monitoring of tool wear during the face milling of steels and aluminium alloys using a fibre optic sensor. Part 2: Frequency analysis

Abstract This paper describes the application of acoustic emission (AE) frequency analysis to cutting tool wear monitoring in finish milling operations. AE detection was achieved using a fibre optic interferometer which, unlike conventional piezoelectric transducers, allows absolute measurements of the frequency content of the signals, generated during face milling of various steels and aluminium alloys, to be made. A model detailing the expected variations in AE mean frequency with various forms of tool wear in the different processes is presented and is validated by the practical set of tool wear tests using the fibre optic interferometer.
Use of Human Minor Salivary Glands in Basic and Applied Secretion Research

Previous findings from studies utilizing human labial and palatine minor salivary glands are reviewed. These studies took histopathological, biochemical, and ultrastructural approaches, and focused on control and diseased glands. Disease-oriented summarizations are used, and control results are discussed in the context of disease-related findings. Findings are reviewed separately for electrolytes, macromolecules, and ultrastructure. In control subjects, minor gland salivary electrolyte concentrations are dependent on flow rate, and this dependence may be altered by diseases such as cystic fibrosis as-well as by inflammatory situations such as graft-versus-host disease. There is also evidence that salivary electrolyte secretion processes are not similar in labial and palatine minor glands. Studies of salivary macromolecular composition are reviewed for control subjects and for patients with graft-versus-host disease and Sjögren's syndrome. The findings indicate that the macromolecular contents of labial and palatine gland saliva are similar, but that both are significantly different from that for major gland saliva. Finally, studies attempting to measure disease-related changes in intracellular composition are reviewed. It is concluded that the minor salivary glands are important models for the study of exocrine gland physiology and pathophysiology in man.
Latent tuberculosis and the use of immunomodulatory agents

Latent Mycobacterium tuberculosis infection (LTBI) is defined as a state of persistent immune response to stimulation by M. tuberculosis antigens without evidence of active tuberculosis. (1) The World Health Organization estimates that one fourth of the world population is infected with M. tuberculosis. (2) The main strategy for reducing the risk of developing the disease in individuals infected with M. tuberculosis, who are at increased risk of progression to active tuberculosis, is LTBI treatment,(1) which is able to reduce this risk by 60-90%(3) and is one of the main components of the World Health Organization’s End TB strategy. (4)
Distributed Optimization for Disturbed Second-Order Multiagent Systems Based on Active Antidisturbance Control

In this article, the distributed optimization problem is studied for second-order multiagent systems with both mismatched and matched disturbances. For this problem, a distributed active antidisturbance control framework is established, which consists of both disturbance estimation/compensation and distributed feedforward-feedback composite control design. In the first stage, some disturbance estimators are utilized to estimate various types of matched/mismatched disturbances for each agent. In the second stage, for each agent, based on the disturbance estimates, the information exchanges between the neighboring agents, and the gradient of the local cost function only accessible to itself, a kind of distributed composite controllers are proposed. Under these controllers, all the agents’ outputs asymptotically reach consensus to the minimizer of the global cost function, which is the sum of all the local cost functions. The closed-loop system convergence is proven based on a new Lyapunov function, convex analysis, and an input-to-state stability criterion. Simulations demonstrate the effectiveness of the proposed control scheme.
Goniozus omanensis (Hymenoptera: Bethylidae) an important parasitoid of the lesser date moth Batrachedra amydraula Meyrick (Lepidoptera: Batrachedridae) in Oman

A new species of bethylid parasitoid wasp, Goniozus omanensis Polaszek sp. n. , is described based on morphology and DNA sequence data. The species is currently known only from the lesser date moth Batrachedra amydraula, a pest of economic importance, but can be reared on two factitious host species. G. omanensis is compared with G. swirskiana, known from the same host in Israel. We summarise current knowledge of G. omanensis life-history, and its potential as an agent of biological pest control.
Successful Use of Cidofovir in an Immunocompetent Child With Severe Adenoviral Sepsis

A case of severe adenoviral sepsis in an immunocompetent host successfully treated with cidofovir challenges the paradigm that this therapy should be reserved for children who are immunocompromised. Adenovirus infection is common in childhood and is generally associated with self-limited disease. Cidofovir, a viral DNA polymerase inhibitor, is used to treat adenovirus infection in select populations but is not often recommended for immunocompetent patients because of limited antiviral activity and nephrotoxicity. Here, we report a case of fulminant adenovirus infection associated with lymphopenia and multiple organ failure requiring extracorporeal membrane oxygenation support in a previously healthy child. After 1 week of supportive therapy, the patient had persistent organ failure and continued to have adenoviremia of >560 000 copies per mL. Weekly doses of cidofovir with concurrent probenecid for renal protection was initiated. Adenovirus blood load declined after the first cidofovir dose, becoming undetectable after 3 doses. The patient was successfully decannulated from extracorporeal membrane oxygenation, extubated, and eventually discharged at his functional baseline without need for ongoing respiratory support. Lymphopenia improved after viremia resolved, and a subsequent immunologic workup revealed no evidence of primary immunodeficiency. The viral isolate was genotyped as adenovirus type 7. This case reveals the successful use of cidofovir for management of severe adenovirus infection in a previously healthy child. To date, there are no universally accepted recommendations for the use of cidofovir in this population. Further study is warranted to determine the potential role of cidofovir in treating severe adenovirus infections in immunocompetent children.
Mismatch repair status predicts survival after adjuvant treatment in stage II colon cancer patients

Stage II colon cancer is primarily a surgical disease. Only a still not well‐defined subset of patients may benefit from postoperative adjuvant chemotherapy. The relationship between adjuvant chemotherapy and survival after relapse is furthermore still not definitely explored in this group of patients. A number of reports suggest some association between defective mismatch repair (dMMR) and colorectal cancer stage II prognosis, but due to contradictory results from existing studies, the exact predictive role is still not fully understood.
Blood product administration during high risk neuroblastoma therapy

Abstract The increasing intensity of high-risk neuroblastoma (HR NB) treatment over the last decades has resulted in improved survival at the expense of prolonging therapy and exposure to additional potentially toxic agents. Anemia and thrombocytopenia requiring transfusion are common during therapy for HR NB. Risks of cumulative red blood cell and platelet transfusions are incompletely defined in pediatric oncology patients, however, risks of transfusional iron overload are well described in other populations. This study aimed to determine the number of packed red blood cell (pRBC) and platelet transfusions throughout treatment for HR NB and how these numbers have changed with modern therapy. We performed a retrospective review of 92 patients with HR NB from June 2002 until September 2017. Patients received a median of 20 pRBC and 32 platelet transfusions. Our results demonstrated large numbers of transfusions with significantly increased blood product exposures among patients who received intensified therapy, either with additional induction chemotherapy, tandem autologous stem cell transplants, or dinutuximab plus cytokines with isotretinoin. Similar volumes of pRBC transfusions have been associated with iron overload in other populations and warrant further discussion of guidelines for long-term follow up of HR NB patients.