Miracle-dz/UniFAR-FTUs huggingface dataset:
miR-20a/Foxj2 Axis Mediates Growth and Metastasis of Colorectal Cancer Cells as Identified by Integrated Analysis

Background MicroRNAs (miRNAs) have a significant regulatory effect on the proliferation, migration, and invasion of cells, and have been widely reported to have oncogenic or tumor-suppressive impacts on various tumors. In the present study we assessed the regulation and function of miR-20a on colorectal cancer (CRC) cell lines. Material/Methods qPCR was used to quantify miR-20a expression. Luciferase reporter assay was conducted to confirm Foxj2 3′UTR associations. In addition, the function of miR-20a and Foxj2 in CRC was detected using MTT, colony formation, transwell assays, and cell cycle analysis. Results Our data revealed that miR-20a expression was elevated in the CRC cell lines, and cell migration, proliferation, and invasion abilities were promoted by the overexpression of miR-20a. Moreover, Foxj2 was authenticated as a direct target gene of miR-20a in CRC cells. Furthermore, we found that the ectopic Foxj2 dramatically suppressed miR-20a-promoted proliferation, migration, invasion, and xenografts in vitro and in vivo, and induced cell cycle arrest at G1 stage. Conclusions Our results showing the roles of miR-20a/Foxj2 in carcinogenesis of CRC may help improve treatment of CRC.
Four-Hour Double Staining for In Situ Hybridization and Immunohistochemistry

Abstract We describe a novel rapid double histochemical staining method for in situ hybridization (ISH) and immunohistochemistry (IHC) of formalin fixed, paraffin embedded tissue sections. For this purpose, 3 cases of Epstein-Barr virus (EBV) positive gastric carcinoma tissues and 5 cases each of pulmonary adenocarcinoma and squamous cell carcinoma tissues were used. The method employs the Micro Probe System, which is based on capillary action, to sequentially supply, incubate, and remove liquid reagents, including antibodies, probe solution, and substrates for histochemical staining of tissue sections. The method consists of ISH with EBV-encoded small RNA (EBER-1) or epidermal growth factor receptor (EGFR) for the first cycle, and IHC with anti-pan keratin antibody (AEl/AE3), anti-T cell (CD45R0, UCHL-1), or anti-B cell (CD20, L26) antibody or antibody to Ki-67 antigen for the second. To block cross reactivity, probes and protein reagents bound to tissue were removed by microwave oven heating with citrate buffer prior to IHC. By this method, we effectively identified both the expression of nucleic acid sequences and localization of proteins in tissue sections in less than 4 hr. This simple, reliable and sensitive method may be useful in many areas of diagnosis and research. (The J Histotechnol 23:321, 2000)
Ablation of TRPV1+ Afferent Terminals by Capsaicin Mediates Long-Lasting Analgesia for Trigeminal Neuropathic Pain

Abstract Trigeminal neuropathic pain (TNP) is often resistant to current pharmacotherapy, and there is a pressing need to develop more efficacious treatments. Capsaicin is a pungent ingredient of chili peppers and specifically activates transient receptor potential vanilloid subtype 1 (TRPV1), a Ca2+-permeable ion channel. Topical capsaicin invariably induces burning pain. Paradoxically, the transient pain is often followed by prolonged attenuation of the preexisting pathologic pain from the same region. However, the mechanisms underlying capsaicin-induced analgesia are not well understood. Although the reports of the involvement of TRPV1 and TRPV1+ afferents in neuropathic pain are controversial, we recently demonstrated that TRPV1 and TRPV1+ afferents are involved in mechanical hyperalgesia in mice with chronic constriction injury of the infraorbital nerve (ION-CCI). Consistently, chemogenetic inhibition of TRPV1-lineage (TRPV1-LN) afferents attenuated mechanical hyperalgesia and ongoing pain. In mice with ION-CCI, we found that a single focal injection of capsaicin into facial skin led to attenuation of mechanical hyperalgesia over two weeks. Capsaicin treatment also attenuated secondary hyperalgesia in extraterritorial mandibular skin. Furthermore, capsaicin treatment decreased ongoing pain. Longitudinal in vivo two-photon imaging of cutaneous nerve fibers showed that such capsaicin-induced analgesia is correlated with cutaneous nerve terminal density. Furthermore, preventing capsaicin-induced ablation of afferent terminals by co-administration of capsaicin with MDL28170, an inhibitor of calpain, abolished capsaicin-induced analgesia. These results suggest that a single focal injection of capsaicin induces long-lasting analgesia for neuropathic pain via selective ablation of TRPV1+ afferent terminals and that TRPV1+ afferents contribute to the maintenance of TNP.
Genomic structure and chromosome mapping of the genes encoding clathrin-associated adaptor medium chains μ1A (Ap1m1) and μ1B (Ap1m2)

The protein μ1B is a member of the medium chain family of the clathrin-associated adaptor complex and is expressed exclusively in epithelial cells. We determined the genomic structure of previously cloned murine genes for μ1B (Ap1m2) and its closely related homolog, μ1A (Ap1m1). Comparison of their genomic structures revealed that the positions of introns are identical between these two genes, except for the insertion of an additional intron in Ap1m1 (intron 4). By contrast, these structures are different from that of the more distantly related Ap2m1 gene encoding μ2. Taken together with the similarity of amino acid sequences among these genes, the data presented in this study suggest that Ap1m1/2 and Ap2m1 diverged long before the separation of Ap1m1 and Ap1m2, which most likely resulted from a relatively recent gene duplication. We also mapped AP1M2 to human chromosome 19p13.2 and Ap1m2 to the proximal region of mouse chromosome 9. The results are consistent with the fact that these regions are syntenic.
Block and Random Practice: A Wii Fit Dynamic Balance Training in Older Adults

ABSTRACT Purpose: To compare the effectiveness of blocked and random practice schedules of balance training in dynamic balance abilities of older adults using Wii Fit balance game tasks. Method: Forty-one participants who were not receiving hospice care or living in a nursing home participated. Three Wii Fit balance tasks (tasks A, B, and C) were selected for training, and one task (task D) was selected as the transfer test among the nine tasks in the Wii Fit balance game software. Scores for tasks A and D were evaluated. Completion times for tasks B and C were evaluated. Moved distance for the functional reach test (FRT), completion time for the timed up and go test (TUG), and performance score for the Tinetti performance‐oriented mobility assessment (POMA) were also tested as clinical balance assessment outcomes. Results: The training significantly improved the performance outcomes of clinical balance assessments and task D. There were no significant group × time interaction effects and no significant main effects by group during the acquisition and retention periods of tasks A, B, and C. However, significant main effects by time were observed for tasks A, B, and C. Conclusions: When dynamic balance training such as the Wii Fit balance system is administered to older adults in a clinical setting, either a block or a random practice schedule can be effectively used to improve the dynamic balance skills. Wii Fit–based balance training is clinically effective for improving the dynamic balance ability.
A novel deep learning method for predictive modeling of microbiome data

With the development and decreasing cost of next-generation sequencing technologies, the study of the human microbiome has become a rapid expanding research field, which provides an unprecedented opportunity in various clinical applications such as drug response predictions and disease diagnosis. It is thus essential and desirable to build a prediction model for clinical outcomes based on microbiome data that usually consist of taxon abundance and a phylogenetic tree. Importantly, all microbial species are not uniformly distributed in the phylogenetic tree but tend to be clustered at different phylogenetic depths. Therefore, the phylogenetic tree represents a unique correlation structure of microbiome, which can be an important prior to improve the prediction performance. However, prediction methods that consider the phylogenetic tree in an efficient and rigorous way are under-developed. Here, we develop a novel deep learning prediction method MDeep (microbiome-based deep learning method) to predict both continuous and binary outcomes. Conceptually, MDeep designs convolutional layers to mimic taxonomic ranks with multiple convolutional filters on each convolutional layer to capture the phylogenetic correlation among microbial species in a local receptive field and maintain the correlation structure across different convolutional layers via feature mapping. Taken together, the convolutional layers with its built-in convolutional filters capture microbial signals at different taxonomic levels while encouraging local smoothing and preserving local connectivity induced by the phylogenetic tree. We use both simulation studies and real data applications to demonstrate that MDeep outperforms competing methods in both regression and binary classifications. Availability and Implementation: MDeep software is available at https://github.com/lichen-lab/MDeep Contact:chen61@iu.edu.
OPEN TRACHEOSTOMY FOR COVID19 POSITIVE PATIENTS: A METHOD TO MINIMIZE AEROSOLIZATION AND REDUCE RISK OF EXPOSURE

Abstract Introduction The COVID-19 virus is highly contagious and thus there is a potential of infecting operating staff when operating on these patients. This case series describes a method of performing open tracheostomy for COVID-19 patients while minimizing potential aerosolization of the virus using typically available equipment and supplies. Methods This is a case series of 18 patients who were COVID-19 positive and underwent open tracheostomy in the operating room under a negative pressure plastic hood created using readily available equipment and supplies. Patients had to be intubated for at least 14 days, be convalescing from their cytokine storm, and deemed to survive for at least 14 more days. Other indications for tracheostomy were altered mental status, severe deconditioning, respiratory failure and failed extubation attempts. Results There were 14 men and 4 women with severe SARS-CoV2 infection requiring long-term intubation since March 23 or later. The mean age was 61.7, BMI was 32.6, and the pre-tracheostomy ventilator day was 20.4. The indications for tracheostomy were altered mental status, severe deconditioning and continued respiratory with hypoxia. Failed extubation attempt rate was 16.7% and hemodialysis rate was 38.9%. All patients were hemodynamically stable, without any evidence of accelerating cytokine storm. To date there was one minor bleeding due to postoperative therapeutic anticoagulation. Conclusion This report describes a method of performing open tracheostomy with minimal aerosolization using readily available equipment and supplies in most hospitals.
Biomarkers and Disease Severity in Children With Community-Acquired Pneumonia

In this prospective cohort study of children with suspected CAP, we evaluate the association between conventional host biomarkers and disease severity. BrightcoveDefaultPlayer10.1542/6145807516001PEDS-VA_2019-3728 Video Abstract BACKGROUND: Host biomarkers predict disease severity in adults with community-acquired pneumonia (CAP). We evaluated the association of the white blood cell (WBC) count, absolute neutrophil count (ANC), C-reactive protein (CRP), and procalcitonin with the development of severe outcomes in children with CAP. METHODS: We performed a prospective cohort study of children 3 months to 18 years of age with CAP in the emergency department. The primary outcome was disease severity: mild (discharged from the hospital), mild-moderate (hospitalized but not moderate-severe or severe), moderate-severe (eg, hospitalized with receipt of intravenous fluids, supplemental oxygen, complicated pneumonia), and severe (eg, intensive care, vasoactive infusions, chest drainage, severe sepsis). Outcomes were examined within the cohort with suspected CAP and in a subset with radiographic CAP. RESULTS: Of 477 children, there were no statistical differences in the median WBC count, ANC, CRP, or procalcitonin across severity categories. No biomarker had adequate discriminatory ability between severe and nonsevere disease (area under the curve [AUC]: 0.53–0.6 for suspected CAP and 0.59–0.64 for radiographic CAP). In analyses adjusted for age, antibiotic use, fever duration, and viral pathogen detection, CRP was associated with moderate-severe disease (odds ratio 1.12; 95% confidence interval, 1.0–1.25). CRP and procalcitonin revealed good discrimination of children with empyema requiring chest drainage (AUC: 0.83) and sepsis with vasoactive infusions (CRP AUC: 0.74; procalcitonin AUC: 0.78), although prevalence of these outcomes was low. CONCLUSIONS: WBC count, ANC, CRP, and procalcitonin are generally not useful to discriminate nonsevere from severe disease in children with CAP, although CRP and procalcitonin may have some utility in predicting the most severe outcomes.
The molecular basis of how buried human leukocyte antigen polymorphism modulates natural killer cell function

Significance In humans, a key class of natural killer (NK) receptors are termed killer cell immunoglobulin-like receptors (KIRs), which interact with human leukocyte antigen (HLA) class I molecules. This KIR–HLA axis plays an important role in immunity, including, for example, HIV control. Nevertheless, how HLA polymorphism shapes KIR recognition was unknown. We show how buried polymorphic residues within the peptide-binding cleft of HLA impact KIR recognition by modulating the conformation of the bound peptide. Accordingly, we provide a mechanistic basis for the differing clinical associations between KIR and HLA polymorphism. Micropolymorphisms within human leukocyte antigen (HLA) class I molecules can change the architecture of the peptide-binding cleft, leading to differences in peptide presentation and T cell recognition. The impact of such HLA variation on natural killer (NK) cell recognition remains unclear. Given the differential association of HLA-B*57:01 and HLA-B*57:03 with the control of HIV, recognition of these HLA-B57 allomorphs by the killer cell immunoglobulin-like receptor (KIR) 3DL1 was compared. Despite differing by only two polymorphic residues, both buried within the peptide-binding cleft, HLA-B*57:01 more potently inhibited NK cell activation. Direct-binding studies showed KIR3DL1 to preferentially recognize HLA-B*57:01, particularly when presenting peptides with positively charged position (P)Ω-2 residues. In HLA-B*57:01, charged PΩ-2 residues were oriented toward the peptide-binding cleft and away from KIR3DL1. In HLA-B*57:03, the charged PΩ-2 residues protruded out from the cleft and directly impacted KIR3DL1 engagement. Accordingly, KIR3DL1 recognition of HLA class I ligands is modulated by both the peptide sequence and conformation, as determined by the HLA polymorphic framework, providing a rationale for understanding differences in clinical associations.
Barriers and facilitating factors in the prevention of diabetes type 2 and gestational diabetes in vulnerable groups: A scoping review

Aims Type 2 diabetes mellitus (T2DM) and gestational diabetes (GDM) are globally on the rise, accompanied by comorbidities and associated health costs. Increased physical activity, healthy nutrition, and weight loss have shown the potential to prevent T2DM/GDM. Despite this, reaching vulnerable groups remains a key challenge. The aim of this scoping review was to identify barriers and facilitating factors in the prevention of T2DM/GDM in vulnerable groups. Methods We conducted a systematic literature search in May 2018, updated in September 2019, in several databases (e.g. PubMed, Embase) to identify barriers and facilitating factors in the prevention of T2DM/GDM in vulnerable groups. Two reviewers independently screened the results. Extracted data was charted, categorized, and summarized. Results We included 125 articles. Ninety-eight studies were extracted, and eight categories of barriers and facilitating factors were formed. The most common categories of barriers were limited knowledge, family/friends, and economic factors, and the most common categories of facilitating factors were family/friends, social support, and knowledge. Conclusion This scoping review identified various barriers and facilitating factors in vulnerable groups. Preventive interventions should consider these barriers and facilitating factors in developing preventive interventions or in adapting existing ones.
MOLECULAR INVESTIGATION OF VECTOR-BORNE PATHOGENS IN RED FOXES (VULPES VULPES) FROM SOUTHERN FRANCE

Abstract: Because of their free-ranging nature, the probability of wild animals being exposed to vector-borne pathogens is likely higher than that of humans and pets. Recently, the red fox (Vulpes vulpes) has been suspected as being a reservoir or host of several pathogens of veterinary and public health importance. We conducted a molecular survey on 93 red foxes hunted in 2008–18, in the departments of Bouches-du-Rhône and Var, in southeastern France, for pathogens including Leishmania infantum, Piroplasmida, Hepatozoon spp. , nematodes, Coxiella burnetii, Borrelia spp. , Rickettsia spp. , and Anaplasmataceae. Spleen samples were screened for the presence of vector-borne pathogens by PCR followed by sequencing. Pathogens were detected in 94% (87/93) of red foxes, and coinfections were identified in 24% (22/93) of foxes. We identified DNA from Hepatozoon canis, L. infantum, and Babesia vogeli in 92% (86/93), 15% (14/93), and 3% (3/93) of red foxes, respectively. We also found DNA of nematodes in 3% (3/93) of foxes; Spirocerca vulpis was identified in one fox and Dirofilaria immitis in the two others. Interestingly, C. burnetii genotype 3, previously described in humans from the same region, was identified in 3% (3/93) of foxes and Anaplasma platys in 2% (2/93) of foxes. We did not detect DNA of Borrelia spp. , Bartonella spp. , or Rickettsia spp. In our study, the prevalence of pathogens did not vary by fox origin, sex, or tick carriage. Molecular evidence of B. vogeli, H. canis, S. vulpis, D. immitis, C. burnetii, and A. platys in red foxes has not previously, to our knowledge, been reported from southern France. We propose that red foxes are potential reservoirs for several pathogens, including major zoonotic agents such as L. infantum. They could be incidental hosts for pathogens, such C. burnetii. The high prevalence for H. canis suggests an important role of foxes in domestic dog (Canis lupus familiaris) infection. These animals may pose a threat to human and animal health.
A Novel Lysophosphatidic Acid Acyltransferase of Escherichia coli Produces Membrane Phospholipids with a cis-vaccenoyl Group and Is Related to Flagellar Formation

Lysophosphatidic acid acyltransferase (LPAAT) introduces fatty acyl groups into the sn-2 position of membrane phospholipids (PLs). Various bacteria produce multiple LPAATs, whereas it is believed that Escherichia coli produces only one essential LPAAT homolog, PlsC—the deletion of which is lethal. However, we found that E. coli possesses another LPAAT homolog named YihG. Here, we show that overexpression of YihG in E. coli carrying a temperature-sensitive mutation in plsC allowed its growth at non-permissive temperatures. Analysis of the fatty acyl composition of PLs from the yihG-deletion mutant (∆yihG) revealed that endogenous YihG introduces the cis-vaccenoyl group into the sn-2 position of PLs. Loss of YihG did not affect cell growth or morphology, but ∆yihG cells swam well in liquid medium in contrast to wild-type cells. Immunoblot analysis showed that FliC was highly expressed in ∆yihG cells, and this phenotype was suppressed by expression of recombinant YihG in ∆yihG cells. Transmission electron microscopy confirmed that the flagellar structure was observed only in ∆yihG cells. These results suggest that YihG has specific functions related to flagellar formation through modulation of the fatty acyl composition of membrane PLs.
Stored xylem sap from wheat and barley in drying soil contains a transpiration inhibitor with a large molecular size

Xylem sap was collected from wheat and barley growing in a drying soil, and the effect of the sap on transpiration was detected by a bioassay with detached wheat leaves. The inhibitory activity of fresh sap was small, and could be largely accounted for by the abscisic acid content (about 2×10-5mol m-3). When fresh sap was stored at -20°C for several days, the activity increased. Maximum activity developed after a week. This increase in activity was due to a compound that increased in size with storage at -20°C. When fresh sap was fractionated with filters of different molecular size exclusion characteristics, and the separated fractions stored at -20°C for a week, activity developed only in the fraction containing compounds smaller than 0·3 kDa. However, when sap already stored at -20°C was fractionated, activity was only in fractions containing compounds larger than 0·3 kDa. The increase in activity and in size did not occur with storage in liquid nitrogen (-196°C) or at -80°C. These results suggest that storage at -20°C causes the aggregation or polymerization of a small compound with low activity to form a large compound with high activity. This change is not catalysed by an enzyme because it can occur in a fraction from which molecules larger than 0·3 kDa are removed. It is probably promoted by high solute concentrations when ice crystals form. Sap collected from plants in soils of high water potential had little or no activity after storage at -20°C.
Identification of pathogenic TRAIL-expressing innate immune cells during HIV-1 infection in humanized mice by scRNA-seq.

Depletion of CD4+ T cells during HIV-1 infection is mostly mediated by inflammatory cells via indirect but not clearly defined mechanisms. In this report we employed the single-cell RNA sequencing (scRNA-seq) technology to study HIV-induced transcriptomic change in innate immune cells in lymphoid organs. We performed scRNA-seq on hCD45+hCD3-hCD19- human leukocytes isolated from spleens of humanized NOD/Rag2-/-/γc-/- (NRG) mice transplanted with human CD34+ hematopoietic stem-progenitor cells (NRG-hu HSC mice). We identified major populations of innate immune cells including plasmacytoid dendritic cells (pDC), myeloid dendritic cells (mDC), macrophage, nature killer (NK) cells and innate lymphoid cells (ILC). HIV-1 infection significantly upregulated genes involved in type-I interferon inflammatory pathways in each of the innate immune subsets. Interestingly, we found that the TNF-related apoptosis-inducing ligand (TRAIL) was upregulated in the innate immune populations including pDC, mDC, macrophage, NK and ILC. We further demonstrated that blockade of TRAIL signaling pathway in NRG-hu HSC mice prevented HIV-1 induced CD4+ T cell depletion in vivo. In summary, we characterized HIV-induced transcriptomic changes of innate immune cells in the spleen at single-cell levels, identified the TRAIL+ innate immune cells and defined an important role of TRAIL signaling pathway in HIV-1 induced CD4+ T cell depletion in vivo.