Miracle-dz/UniFAR-FTUs huggingface dataset:
ONECUT2 upregulation is associated with CpG hypomethylation at promoter‐proximal DNA in gastric cancer and triggers ACSL5

Many studies have focused on global hypomethylation or hypermethylation of tumor suppressor genes, but less is known about the impact of promoter hypomethylation of oncogenes. We previously showed that promoter methylation may gradually increase or decrease during the transition from gastric mucosa (GM) to intestinal metaplasia (IM) to gastric cancer (GC). In our study, we focused on regional CpG hypomethylation of the promoter‐proximal DNA of the transcription factor ONECUT2 (OC2) in IM and GC cells. We validated the hypomethylation of promoter‐proximal DNA of OC2 in 160 primary GCs, in which methylation level correlated negatively with OC2 mRNA level. IM and GC cells stained positively for OC2, whereas GM cells did not. Stable transfection of OC2 in GC cells promoted colony formation, cell migration, invasion and proliferation. Moreover, OC2 knockdown with a short hairpin RNA suppressed tumorigenesis in nude mice. In addition, chromatin immunoprecipitation coupled with DNA sequencing and RNA‐seq analyses revealed that OC2 triggered ACSL5, which is strongly expressed in IM of the stomach but not in GM, indicating that OC2 and ACSL5 are early‐stage biomarkers for GC. We also observed a high correlation between the levels of OC2 and ACSL5 mRNAs in the GENT database These results suggest that epigenetic alteration of OC2 upregulates its expression, which then activates ACSL5; thus, OC2 is induced in IM by epigenetic alteration and triggers ACSL5 expression, and thus OC2 and ACSL5 may cooperatively promote intestinal differentiation and GC progression.
Effect of Microbial Biomass and Humic Acids on Abiotic and Biotic Magnetite Formation.

Magnetite (Fe3O4) is an environmentally ubiquitous mixed-valent iron (Fe) mineral which can form via biotic or abiotic transformation of Fe(III) (oxyhydr)oxides such as ferrihydrite (Fh). It is currently unclear whether environmentally relevant biogenic Fh from Fe(II)-oxidizing bacteria, containing cell-derived organic matter, can transform to magnetite. We compared abiotic and biotic transformation: 1) abiogenic Fh (aFh); 2) abiogenic Fh coprecipitated with humic acids (aFh-HA); 3) biogenic Fh produced by phototrophic Fe(II)-oxidizer Rhodobacter ferrooxidans SW2 (bFh); 4) biogenic Fh treated with bleach to remove biogenic organic matter (bFh-bleach). Abiotic or biotic transformation of Fh was promoted by Fe2+aq or Fe(III)-reducing bacteria. Fe2+aq-catalyzed abiotic reaction with aFh and bFh-bleach led to complete transformation to magnetite. In contrast, aFh-HA only partially (68%) transformed to magnetite, and bFh (17%) transformed to goethite. We hypothesize that microbial biomass stabilized bFh against reaction with Fe2+aq. All four Fh substrates were transformed into magnetite during biotic reduction, suggesting that Fh remains bioavailable even when associated with microbial biomass. Additionally, there were poorly ordered magnetic components detected in the biogenic end-products for aFh and aFh-HA. Nevertheless, abiotic transformation was much faster than biotic transformation, implying that initial Fe2+aq concentration, passivation of Fh and/or sequestration of Fe(II) by bacterial cells and associated biomass play major roles in the rate of magnetite formation from Fh. These results improve our understanding of factors influencing secondary mineralization of Fh in the environment.
Control of Saliva-Borne Infections: An Epidemic of Influenza

THE perusal of an article in the February number of this Journal by Cumming [1] on" Saliva-borne Disease Control: Eradication,"and a very pertinent letter by the p,rofessor of Hygiene 12] in referenc~ to this article in the same number, suggested that a most exceUeht'Opportlmity of testing Cumming's conclusions, or at least of carrying out investigations on similar lines, was actually available at that very time in the Aldershot Command. An epidemic of influenza of moderate intensity was actually in progress' in the Aldershot· Command, and considerable numbers of men in many units in different barracks were being, or had been, admitted to hospital with the disease. Permission was therefore obtained to carry out an investigation to see whether there appeared to be any relationship between the rate of incidence in the various units in different areas arid any possible difference in the washing-up arrangements' of feeding ntensils in vogue in these units. ( Cumming in his article indicates that what he cans the" mess-kit wash water" was the actual link by which· saliva. -borne organisms were transferred from the infected man to the non-infected susceptible. He also shows that so important is this chain of infection that proper sterilization oLtness utensils canses a reduction of the" influenza rate to 1 per cent
Effect of Elevated Pulmonary Artery Systolic Pressure on Short-Term Prognosis in Patients With Acute Myocardial Infarction

Pulmonary artery systolic pressure (PASP) may increase because of cardiac alterations that result in increased filling pressures after acute myocardial infarction (AMI). We hypothesized that PASP might be a useful maker to predict the risk of cardiac death after AMI. We carried out a retrospective study from 2013 to 2017 involving 5401 patients with AMI. Patients were grouped according to their admission PASP result, and the primary end point was cardiac death in 6 months after AMI. Pulmonary artery systolic pressure was associated with age, AMI site, Killip classification, and decreased ejection fraction. After adjustments for clinical and echocardiographic parameters in a Cox model, PASP was found to be significantly related to cardiac death. In receiver operating characteristic analysis, PASP >30 mm Hg had a sensitivity of 59.8% and a specificity of 62.5% for predicting 6-month cardiac death after AMI. In conclusion, PASP at the index admission may be a useful marker predicting short-term cardiac death. These results have implications for future research and management of patients with AMI.
Migration patterns and immigrants characteristics in North-Western Europe

This report provides an overview of recent immigration and settlement patterns for the four study countries. The most recent available statistics are used and patterns over the past decade are described. Characteristics of the immigration flows (among other origin, age, and gender), as well as, other issues related to settlement (for example nationality and citizenship) are discussed. Different immigration flows, including asylum seekers and refugees, are presented. This part provides as much detail and comparability as possible by using different data sources. Special emphasis is put on migrants coming from Africa and Latin America. We make use of existing data and complement it with material specifically gathered and analyzed for the purpose of this study.
Altered task-induced cerebral blood flow and oxygen metabolism underlies motor impairment in multiple sclerosis

The neural mechanisms underlying motor impairment in multiple sclerosis (MS) remain unknown. Motor cortex dysfunction is implicated in blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) studies, but the role of neural–vascular coupling underlying BOLD changes remains unknown. We sought to independently measure the physiologic factors (i.e., cerebral blood flow (ΔCBF), cerebral metabolic rate of oxygen (ΔCMRO2), and flow–metabolism coupling (ΔCBF/ΔCMRO2), utilizing dual-echo calibrated fMRI (cfMRI) during a bilateral finger-tapping task. We utilized cfMRI to measure physiologic responses in 17 healthy volunteers and 32 MS patients (MSP) with and without motor impairment during a thumb-button-press task in thumb-related (task-central) and surrounding primary motor cortex (task-surround) regions of interest (ROIs). We observed significant ΔCBF and ΔCMRO2 increases in all MSP compared to healthy volunteers in the task-central ROI and increased flow–metabolism coupling (ΔCBF/ΔCMRO2) in the MSP without motor impairment. In the task-surround ROI, we observed decreases in ΔCBF and ΔCMRO2 in MSP with motor impairment. Additionally, ΔCBF and ΔCMRO2 responses in the task-surround ROI were associated with motor function and white matter damage in MSP. These results suggest an important role for task-surround recruitment in the primary motor cortex to maintain motor dexterity and its dependence on intact white matter microstructure and neural–vascular coupling.
Synthesis, DNA binding and antimicrobial studies on rhodium(II) complexes of dicyandiamide

Abstract The synthesis and characterization on four rhodium(II) complexes with the formula [Rh2(CH3COO)2(AMUH)2(dcda)2](CH3COO)2(1),[Rh2(CH3COO)2(AEUH)2(dcda)2](CH3COO)2(2),[Rh2(CH3COO)2(APrnUH)2(dcda)2](CH3COO)2(3),[Rh2(CH3COO)2(ABnUH)2(dcda)2](CH3COO)2(4), where AMUH = 1-amidino-O-methylurea, AEUH = 1-amidino-O-ethylurea, APrnUH = 1-amidino-O-n-propylurea, ABnUH = 1-amidino-O-n-butylurea, dcda = dicyandiamide are reported. The complexes were prepared by the reaction of dicyandiamide with rhodium(II) acetate in methanol (1), ethanol (2), n-propanol (3) and n-butanol (4) respectively and characterized by various techniques such as C, H, N analysis, FTIR, UV-Visible, EPR, conductance, SEM, EDX, powder XRD pattern and mass spectral studies. The interaction studies of the complexes with CT-DNA suggested the non-intercalative mode of binding for these complexes. The antimicrobial activity of the complexes against the tested microorganisms viz. Bacillus subtilis, Enterococcus faecium, Staphylococcus aureus and Escherichia coli, using the standard antibiotics streptomycin as positive control is also reported.
Intratumoral Delivery of a PD-1–Blocking scFv Encoded in Oncolytic HSV-1 Promotes Antitumor Immunity and Synergizes with TIGIT Blockade

Oncolytic virus activity is often limited by an immunosuppressive tumor microenvironment. The antitumor efficacy of oncolytic herpes simplex virus is improved by delivering a single-chain variable fragment specific for PD-1. Pairing this with TIGIT blockade enhances antitumor responses. Oncolytic virotherapy can lead to systemic antitumor immunity, but the therapeutic potential of oncolytic viruses in humans is limited due to their insufficient ability to overcome the immunosuppressive tumor microenvironment (TME). Here, we showed that locoregional oncolytic virotherapy upregulated the expression of PD-L1 in the TME, which was mediated by virus-induced type I and type II IFNs. To explore PD-1/PD-L1 signaling as a direct target in tumor tissue, we developed a novel immunotherapeutic herpes simplex virus (HSV), OVH-aMPD-1, that expressed a single-chain variable fragment (scFv) against PD-1 (aMPD-1 scFv). The virus was designed to locally deliver aMPD-1 scFv in the TME to achieve enhanced antitumor effects. This virus effectively modified the TME by releasing damage-associated molecular patterns, promoting antigen cross-presentation by dendritic cells, and enhancing the infiltration of activated T cells; these alterations resulted in antitumor T-cell activity that led to reduced tumor burdens in a liver cancer model. Compared with OVH, OVH-aMPD-1 promoted the infiltration of myeloid-derived suppressor cells (MDSC), resulting in significantly higher percentages of CD155+ granulocytic-MDSCs (G-MDSC) and monocytic-MDSCs (M-MDSC) in tumors. In combination with TIGIT blockade, this virus enhanced tumor-specific immune responses in mice with implanted subcutaneous tumors or invasive tumors. These findings highlighted that intratumoral immunomodulation with an OV expressing aMPD-1 scFv could be an effective stand-alone strategy to treat cancers or drive maximal efficacy of a combination therapy with other immune checkpoint inhibitors.
The link between auditory salience and emotion intensity

ABSTRACT To ensure that listeners pay attention and do not habituate, emotionally intense vocalizations may be under evolutionary pressure to exploit processing biases in the auditory system by maximising their bottom-up salience. This “salience code” hypothesis was tested using 128 human nonverbal vocalizations representing eight emotions: amusement, anger, disgust, effort, fear, pain, pleasure, and sadness. As expected, within each emotion category salience ratings derived from pairwise comparisons strongly correlated with perceived emotion intensity. For example, while laughs as a class were less salient than screams of fear, salience scores almost perfectly explained the perceived intensity of both amusement and fear considered separately. Validating self-rated salience evaluations, high- vs. low-salience sounds caused 25% more recall errors in a short-term memory task, whereas emotion intensity had no independent effect on recall errors. Furthermore, the acoustic characteristics of salient vocalizations were similar to those previously described for non-emotional sounds (greater duration and intensity, high pitch, bright timbre, rapid modulations, and variable spectral characteristics), confirming that vocalizations were not salient merely because of their emotional content. The acoustic code in nonverbal communication is thus aligned with sensory biases, offering a general explanation for some non-arbitrary properties of human and animal high-arousal vocalizations.
Incomplete Excision of Cutaneous Squamous Cell Carcinoma; Systematic Review of the Literature

The treatment of choice for cutaneous squamous cell carcinoma is complete surgical excision. Incomplete excision of cutaneous squamous cell carcinoma has an increased risk of local recurrence, deep subclinical progression, and metastasis. This study aimed to investigate the proportion and risk factors of incomplete excised cutaneous squamous cell carcinoma. A systematic review of the literature was performed. Incomplete excision rates for cutaneous squamous cell carcinoma ranged from 0.4% to 35.7%. The pooled incomplete excision risk estimate was 13% (95% confidence interval 9-17%). Risk factors noted in more than one study for incomplete excision included tumor depth and size, type of operator, head and neck localization, and former incomplete excision. We found an overall incomplete excision rate of 13% for cutaneous squamous cell carcinoma. Risk factors should be taken into account in the management of cutaneous squamous cell carcinoma surgical treatment.
Androgen therapy in inherited bone marrow failure syndromes: analysis from the Canadian Inherited Marrow Failure Registry

Progressive cytopenia is a serious complication among paediatric patients with inherited bone marrow failure syndromes (IBMFS). Androgens have been used to improve blood counts in different bone marrow failure conditions. Little is known about efficacy and toxicity with new androgens (i.e., danazol) in different types of IBMFS. We identified 29 patients from the Canadian Inherited Marrow Failure Registry, who received oxymetholone or danazol. Sixteen (55%) had haematological response including patients with unclassified IBMFS (45%). Danazol showed a better toxicity profile and similar efficacy compared to oxymetholone. Androgens are an effective and safe option to ameliorate bone marrow failure in IBMFS.
The role of learning and environmental geometry in landmark-based spatial reorientation of fish (Xenotoca eiseni)

Disoriented animals and humans use both the environmental geometry and visual landmarks to guide their spatial behavior. Although there is a broad consensus on the use of environmental geometry across various species of vertebrates, the nature of disoriented landmark-use has been greatly debated in the field. In particular, the discrepancy in performance under spontaneous choice conditions (sometimes called “working memory” task) and training over time (“reference memory” task) has raised questions about the task-dependent dissociability of mechanisms underlying the use of landmarks. Until now, this issue has not been directly addressed, due to the inclusion of environmental geometry in most disoriented navigation paradigms. In the present study, therefore, we placed our focus on landmark-based navigation in fish (Xenotoca eiseni), an animal model that has provided fruitful research in spatial reorientation. We began with a test of spontaneous navigation by geometry and landmarks (Experiment 1), showing a preference for the correct corner, even in the absence of reinforced training. We then proceeded to test landmarks without the influence of informative geometry through the use of square environments (Experiment 2–4), varying the numerosity of present landmarks, the distance of landmarks from the target corner, and the type of task (i.e., spontaneous cued memory or reference memory). We found marked differences in landmark-use in the absence of environmental geometry. In the spontaneous memory task, visual landmarks acquired perceptive salience (and attracted the fish) but without serving as a spatial cue to location when they were distal from the target. Across learning in the reference memory task, the fish overcame these effects and gradually improved in their performance, although they were still biased to learn visual landmarks near the target (i.e., as beacons). We discuss these results in relation to the existing literature on dissociable mechanisms of spatial learning.
Composition-based prediction and rational manipulation of prion-like domain recruitment to stress granules

Significance Many RNA-binding proteins contain aggregation-prone prion-like domains (PrLDs), and mutations in several of these have been linked to degenerative diseases. Additionally, many of these proteins are associated with stress granules, which are membraneless organelles that form under stress, in part through reversible protein assembly. Although the mechanisms of stress granule assembly are unclear, PrLDs can play a role in this process. In order to further understand how PrLDs respond to stress, we analyzed the assembly propensities of a selection of different PrLDs from yeast. We find that many PrLDs are efficiently recruited to stress-induced assemblies and that this recruitment is predominantly dependent on the amino acid composition of the PrLDs. Mutations in a number of stress granule-associated proteins have been linked to various neurodegenerative diseases. Several of these mutations are found in aggregation-prone prion-like domains (PrLDs) within these proteins. In this work, we examine the sequence features governing PrLD localization to stress granules upon stress. We demonstrate that many yeast PrLDs are sufficient for stress-induced assembly into microscopically visible foci that colocalize with stress granule markers. Additionally, compositional biases exist among PrLDs that assemble upon stress, and these biases are consistent across different stressors. Using these biases, we have developed a composition-based prediction method that accurately predicts PrLD assembly into foci upon heat shock. We show that compositional changes alter PrLD assembly behavior in a predictable manner, while scrambling primary sequence has little effect on PrLD assembly and recruitment to stress granules. Furthermore, we were able to design synthetic PrLDs that were efficiently recruited to stress granules, and found that aromatic amino acids, which have previously been linked to PrLD phase separation, were dispensable for this recruitment. These results highlight the flexible sequence requirements for stress granule recruitment and suggest that PrLD localization to stress granules is driven primarily by amino acid composition, rather than primary sequence.
Anadromy and Marine Habitat Use of Lake Trout (Salvelinus namaycush) From the Central Canadian Arctic.

Anadromy was documented in 16 lake trout, Salvelinus namaycush, from Canada's central Arctic using capture data and otolith microchemistry. For the first time, estuarine/marine habitat use was described for five individuals using acoustic telemetry. Age-at-first migration to sea was variable (10-39 years) among individuals and most S. namaycush undertook multiple anadromous migrations within their lifetime. Telemetry data suggested that S. namaycush do not travel far into marine habitats and prefer surface waters (< 2 m). These results further our overall understanding of the marine ecology of Arctic S. namaycush. This article is protected by copyright. All rights reserved.
Does occupational noise matter amongst manufacturing (small and medium enterprises) workers? Empirical evidence from Magaba, Mbare, Zimbabwe

Background The significance of how occupational noise can influence attitudes towards occupational noise exposure, susceptibility to hearing loss and job performance has generally been neglected in the past studies. Objectives The aim of this study was to determine the impact of occupational noise on attitudes towards occupational noise exposure, susceptibility to hearing loss and job performance of manufacturing small and medium enterprises (SMEs) workers in Zimbabwe. Method A survey was conducted involving 250 respondents, including manufacturing SME workers, and the hypotheses were analysed by applying structural equation modelling. Results Occupational noise had a positive and significant effect on attitudes towards occupational noise exposure and perceived susceptibility to hearing loss amongst manufacturing SME workers. In addition, attitudes towards exposure to occupational noise and the perceived susceptibility of hearing loss have had a positive and significant impact on manufacturing SME workers’ job performance. Conclusion The novelty of the research is its analysis of occupational noise as an indicator of attitudes towards occupational noise exposure and susceptibility to hearing loss as well as job performance. This study provides practitioners with beneficial implications. Collective knowledge on occupational noise could help manufacturing SME managers in recognising the perceptions of employees on occupational noise and how it ultimately affects job performance. Moreover, this study is intended to add new knowledge to the current body of African occupational noise literature – a context that has not received much research attention in developing countries.